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The antidepressant properties of selected methylene blue analogues / Anzelle DelportDelport, Anzelle January 2014 (has links)
The shortcomings of current antidepressant agents prompts the design of novel multimodal
antidepressants and the identification of new antidepressant targets, especially those
located at sub-cellular level. Such antidepressants should possess improved response rates
as well as safety profiles. Methylene blue (MB) is reported to possess diverse
pharmacological actions and is attracting increasing attention for the treatment of a variety of
disorders including Alzheimer’s disease, bipolar disorder, anxiety and depression. MB acts
on both monoamine oxidase (MAO) and the nitric oxide (NO)-cGMP pathway, and
possesses antidepressant activity in rodents. The principal goal of this study was to design a
close structural analogue of MB and to evaluate the effects of these structural changes on
MAO inhibition, a well-known antidepressant target. Furthermore, MAO inhibition is also
responsible for cardiovascular toxicity in clinically used MAOI inhibitors. For this purpose we
investigated the antidepressant properties of the synthetic MB analogue (ethyl-thioniniumchloride;
ETC) as well as azure B, the major metabolite of MB, in the forced swim test (FST).
ETC was synthesized with a high degree of purity from diethyl-p-phenylenediamine with 6%
yield. ETC was firstly evaluated as a potential inhibitor of recombinant human MAO-A and
MAO-B. Azure B and ETC were evaluated over a dosage range of 4-30 mg/kg for
antidepressant-like activity in the acute FST in rats, and the results were compared to those
obtained with saline, imipramine (15 mg/kg) and MB (15 mg/kg) treated rats. Locomotor
activity was evaluated to ensure that changes in swim motivation are based on
antidepressant response and not due to an indirect effect of the drug on locomotor activity.
The results document that ETC inhibits MAO-A and MAO-B with IC50 values of 0.51 μM and
0.592 μM, respectively. Furthermore, ETC inhibits MAO-A and MAO-B reversibly, while the
mode of inhibition is most likely competitive. In the acute FST, azure B and ETC were more
effective than imipramine and MB in reversing immobility, without inducing locomotor effects.
Azure B and ETC increased swimming behaviour during acute treatment, which is indicative
of enhanced serotonergic neurotransmission. Azure B and ETC did not affect noradrenergicmediated
climbing behaviour. These results suggest that azure B may be a contributor to the
antidepressant effect of MB, and acts via increasing serotonergic transmission. Secondly,
small structural changes made to MB do not abolish its antidepressant effect even though
ETC is a less potent MAO-A inhibitor than MB. / MSc (Pharmaceutical Chemistry), North-West University, Potchefstroom Campus, 2014
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The antidepressant properties of selected methylene blue analogues / Anzelle DelportDelport, Anzelle January 2014 (has links)
The shortcomings of current antidepressant agents prompts the design of novel multimodal
antidepressants and the identification of new antidepressant targets, especially those
located at sub-cellular level. Such antidepressants should possess improved response rates
as well as safety profiles. Methylene blue (MB) is reported to possess diverse
pharmacological actions and is attracting increasing attention for the treatment of a variety of
disorders including Alzheimer’s disease, bipolar disorder, anxiety and depression. MB acts
on both monoamine oxidase (MAO) and the nitric oxide (NO)-cGMP pathway, and
possesses antidepressant activity in rodents. The principal goal of this study was to design a
close structural analogue of MB and to evaluate the effects of these structural changes on
MAO inhibition, a well-known antidepressant target. Furthermore, MAO inhibition is also
responsible for cardiovascular toxicity in clinically used MAOI inhibitors. For this purpose we
investigated the antidepressant properties of the synthetic MB analogue (ethyl-thioniniumchloride;
ETC) as well as azure B, the major metabolite of MB, in the forced swim test (FST).
ETC was synthesized with a high degree of purity from diethyl-p-phenylenediamine with 6%
yield. ETC was firstly evaluated as a potential inhibitor of recombinant human MAO-A and
MAO-B. Azure B and ETC were evaluated over a dosage range of 4-30 mg/kg for
antidepressant-like activity in the acute FST in rats, and the results were compared to those
obtained with saline, imipramine (15 mg/kg) and MB (15 mg/kg) treated rats. Locomotor
activity was evaluated to ensure that changes in swim motivation are based on
antidepressant response and not due to an indirect effect of the drug on locomotor activity.
The results document that ETC inhibits MAO-A and MAO-B with IC50 values of 0.51 μM and
0.592 μM, respectively. Furthermore, ETC inhibits MAO-A and MAO-B reversibly, while the
mode of inhibition is most likely competitive. In the acute FST, azure B and ETC were more
effective than imipramine and MB in reversing immobility, without inducing locomotor effects.
Azure B and ETC increased swimming behaviour during acute treatment, which is indicative
of enhanced serotonergic neurotransmission. Azure B and ETC did not affect noradrenergicmediated
climbing behaviour. These results suggest that azure B may be a contributor to the
antidepressant effect of MB, and acts via increasing serotonergic transmission. Secondly,
small structural changes made to MB do not abolish its antidepressant effect even though
ETC is a less potent MAO-A inhibitor than MB. / MSc (Pharmaceutical Chemistry), North-West University, Potchefstroom Campus, 2014
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Stereotypical behaviour in the deer mouse (Peromyscus Maniculatus bairdii) : a pharmacological investigation of the frontal–cortico–striatal serotonergic system / Wolmarans D.Wolmarans, Petrus De Wet January 2011 (has links)
Obsessive–compulsive disorder (OCD) is a psychiatric condition that is characterized by two main symptom cohorts, namely recurrent inappropriate thoughts (obsessions) and seemingly purposeless repetitive motor actions (compulsions). In 70% of cases, the condition only re–sponds to chronic, but not sub–chronic, high dose treatment with the selective serotonin reup–take inhibitors (SSRIs), such as fluoxetine and escitalopram. This indicates a role for hyposero–tonergic functioning in the primary brain areas involved in OCD, namely the components of the cortico–striatal–thalamic–cortical (CSTC) circuit which include the prefrontal cortex, the basal ganglia, and the thalamus. A number of studies have demonstrated a lower serotonin trans–porter (SERT) availability in OCD patients compared with healthy controls, supporting the hy–pothesis of a hyposerotonergic state in OCD.
The current study focuses on the validation of the deer mouse (Peromyscus maniculatus bairdii) model of OCD and builds on previous work done in our laboratory. Deer mice that are bred and housed in confinement naturally develop two main forms of stereotypical behaviour, namely vertical jumping and pattern running. Furthermore, these behaviours can be catego–rized into various levels of severity, namely high (HSB), low (LSB) and non–stereotypic (NSB) cohorts. The seemingly purposeless and repetitive nature of these behaviours mimics the com–pulsions that characterize human OCD and constitutes the basis for the face validity of the model. However, although these two forms of stereotypy seem equally repetitive and persis–tent, stereotypical pattern runners do not complete the required number of cage revolutions per 30 minutes compared to the amount of jumps executed by stereotypical vertical jumpers. As only one set of criteria for the appraisal of the different topographies of deer mouse stereotypy has been applied in previous studies, the matter of whether pattern runners do in fact generate stereotypical behaviour of the same persistent and severe nature as opposed to the behaviour expressed by vertical jumpers, is problematic.
Therefore, the first objective of the current study was to develop a new classification system for the appraisal of the different forms of behavioural topographies of deer mice and subse–quently to evaluate whether pattern runners can indeed be categorized into non–, low– and high stereotypical cohorts. After an eight–week behavioural assessment period, deer mice express–ing the two different behavioural topographies could be classified into non–, low– and high stereotypical cohorts (NSB, LSB, and HSB respectively), applying different criteria for each be–havioural topography. Based on the weekly mean stereotypy count generated during three 30–minute intervals of highest stereotypical behaviour over the course of a 12–hour assessment period, HSB pattern runners were found to execute on average 296 cage revolutions per 30 minutes, while HSB vertical jumpers executed an average of 3063 jumps per 30 minutes. This discrepancy between the generated numbers of the different topographies of stereotypy indi–cates that one classification system for the appraisal of both behavioural topographies is indeed inappropriate, and hence requires re–evaluation and validation.
As patients with OCD present with a lower central SERT availability compared to healthy controls, the second objective of the study was to determine whether a decrease in SERT den–sity could be demonstrated in HSB animals compared to the NSB and LSB controls. After eight weeks of behavioural assessment, animals were sacrificed and frontal–cortical and striatal SERT binding was performed. HSB deer mice presented with significantly lower striatal, but not fron–tal–cortical SERT availability compared to the [NSB/LSB] control animals (p = 0.0009). As far as it concerns a lower SERT availability in HSB animals and involvement of the CSTC circuitry, this data is congruent with that demonstrated in human OCD and strengthens the construct validity of the model.
Although previous studies undertaken in our laboratory demonstrated that deer mouse stereotypy is attenuated after chronic (21–day) fluoxetine administration, OCD only responds to chronic, but not sub–chronic treatment with the SSRIs. The lack of response of deer mouse stereotypy to sub–chronic treatment has not been established and therefore the third study ob–jective was to assess the behavioural effects of sub–chronic (7–day) and chronic (28–day) SSRI treatment on expression of deer mouse stereotypy. Chronic, but not sub–chronic treatment with oral escitalopram (50 mg/kg/day) significantly increased the number of intervals over a 12–hour assessment period during which no stereotypical behaviour were expressed by HSB deer mice (p = 0.0241) and decreased the number of intervals during which high–stereotypical be–haviour were executed (p = 0.0054). Neither chronic, nor sub–chronic treatment significantly affected the behaviour of animals in the [NSB/LSB] cohort. The fact that the model demon–strates a lack of response to sub–chronic treatment with high dose SSRIs, positively contributes to the predictive validity of the deer mouse model of OCD.
The results from the current study therefore strengthens the construct and predictive valid–ity of the deer mouse model of OCD and confirm the model’s status as a prominent animal model of OCD. Not only is hyposerotonergic functioning in the CSTC circuitry implicated in the behaviour of HSB animals, but the model also demonstrates selective response to chronic SSRI–treatment - two core characteristics of human OCD. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2012.
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Stereotypical behaviour in the deer mouse (Peromyscus Maniculatus bairdii) : a pharmacological investigation of the frontal–cortico–striatal serotonergic system / Wolmarans D.Wolmarans, Petrus De Wet January 2011 (has links)
Obsessive–compulsive disorder (OCD) is a psychiatric condition that is characterized by two main symptom cohorts, namely recurrent inappropriate thoughts (obsessions) and seemingly purposeless repetitive motor actions (compulsions). In 70% of cases, the condition only re–sponds to chronic, but not sub–chronic, high dose treatment with the selective serotonin reup–take inhibitors (SSRIs), such as fluoxetine and escitalopram. This indicates a role for hyposero–tonergic functioning in the primary brain areas involved in OCD, namely the components of the cortico–striatal–thalamic–cortical (CSTC) circuit which include the prefrontal cortex, the basal ganglia, and the thalamus. A number of studies have demonstrated a lower serotonin trans–porter (SERT) availability in OCD patients compared with healthy controls, supporting the hy–pothesis of a hyposerotonergic state in OCD.
The current study focuses on the validation of the deer mouse (Peromyscus maniculatus bairdii) model of OCD and builds on previous work done in our laboratory. Deer mice that are bred and housed in confinement naturally develop two main forms of stereotypical behaviour, namely vertical jumping and pattern running. Furthermore, these behaviours can be catego–rized into various levels of severity, namely high (HSB), low (LSB) and non–stereotypic (NSB) cohorts. The seemingly purposeless and repetitive nature of these behaviours mimics the com–pulsions that characterize human OCD and constitutes the basis for the face validity of the model. However, although these two forms of stereotypy seem equally repetitive and persis–tent, stereotypical pattern runners do not complete the required number of cage revolutions per 30 minutes compared to the amount of jumps executed by stereotypical vertical jumpers. As only one set of criteria for the appraisal of the different topographies of deer mouse stereotypy has been applied in previous studies, the matter of whether pattern runners do in fact generate stereotypical behaviour of the same persistent and severe nature as opposed to the behaviour expressed by vertical jumpers, is problematic.
Therefore, the first objective of the current study was to develop a new classification system for the appraisal of the different forms of behavioural topographies of deer mice and subse–quently to evaluate whether pattern runners can indeed be categorized into non–, low– and high stereotypical cohorts. After an eight–week behavioural assessment period, deer mice express–ing the two different behavioural topographies could be classified into non–, low– and high stereotypical cohorts (NSB, LSB, and HSB respectively), applying different criteria for each be–havioural topography. Based on the weekly mean stereotypy count generated during three 30–minute intervals of highest stereotypical behaviour over the course of a 12–hour assessment period, HSB pattern runners were found to execute on average 296 cage revolutions per 30 minutes, while HSB vertical jumpers executed an average of 3063 jumps per 30 minutes. This discrepancy between the generated numbers of the different topographies of stereotypy indi–cates that one classification system for the appraisal of both behavioural topographies is indeed inappropriate, and hence requires re–evaluation and validation.
As patients with OCD present with a lower central SERT availability compared to healthy controls, the second objective of the study was to determine whether a decrease in SERT den–sity could be demonstrated in HSB animals compared to the NSB and LSB controls. After eight weeks of behavioural assessment, animals were sacrificed and frontal–cortical and striatal SERT binding was performed. HSB deer mice presented with significantly lower striatal, but not fron–tal–cortical SERT availability compared to the [NSB/LSB] control animals (p = 0.0009). As far as it concerns a lower SERT availability in HSB animals and involvement of the CSTC circuitry, this data is congruent with that demonstrated in human OCD and strengthens the construct validity of the model.
Although previous studies undertaken in our laboratory demonstrated that deer mouse stereotypy is attenuated after chronic (21–day) fluoxetine administration, OCD only responds to chronic, but not sub–chronic treatment with the SSRIs. The lack of response of deer mouse stereotypy to sub–chronic treatment has not been established and therefore the third study ob–jective was to assess the behavioural effects of sub–chronic (7–day) and chronic (28–day) SSRI treatment on expression of deer mouse stereotypy. Chronic, but not sub–chronic treatment with oral escitalopram (50 mg/kg/day) significantly increased the number of intervals over a 12–hour assessment period during which no stereotypical behaviour were expressed by HSB deer mice (p = 0.0241) and decreased the number of intervals during which high–stereotypical be–haviour were executed (p = 0.0054). Neither chronic, nor sub–chronic treatment significantly affected the behaviour of animals in the [NSB/LSB] cohort. The fact that the model demon–strates a lack of response to sub–chronic treatment with high dose SSRIs, positively contributes to the predictive validity of the deer mouse model of OCD.
The results from the current study therefore strengthens the construct and predictive valid–ity of the deer mouse model of OCD and confirm the model’s status as a prominent animal model of OCD. Not only is hyposerotonergic functioning in the CSTC circuitry implicated in the behaviour of HSB animals, but the model also demonstrates selective response to chronic SSRI–treatment - two core characteristics of human OCD. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2012.
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Single and multi-antenna MC-DS-CDMA with joint detection for broadband block-fading channelsBasilio, Daniel Jorge 23 August 2010 (has links)
In the context of broadband wireless communications using code division multiple access (CDMA), the main multiple access (MA) options include single-carrier direct sequence CDMA (SC-DS-CDMA) using time-domain direct sequence spreading [1, p. 728], multicarrier CDMA (MC-CDMA) using frequency-domain spreading [2, 3] and multicarrier DS-CDMA (MC-DS-CDMA) using time-domain direct sequence spreading of the individual sub-carrier signals [4, 5]. It was shown in [6] that MC-DS-CDMA has the highest degrees of freedom in the family of CDMA schemes that can be beneficially exploited during the system design and reconfiguration procedures. An amalgam of MC-CDMA and MC-DS-CDMA known as time and frequency domain spreading (TF-domain spreading) MC-DS-CDMA was proposed in [6]. TF-domain spreading MC-DS-CDMA has several benefits over conventional MC-DS-CDMA with regard to both capacity and performance [7]. However, in contrast to conventional MC-DS-CDMA, TF-domain spreading MC-DS-CDMA introduces MUI, which necessitates the use of joint detection at the receiver. Recently, multiple input multiple output (MIMO) or multi-antenna TF-domain spreading MC-DS-CDMA schemes have been proposed in the literature that e ciently exploit both the spatial and frequency diversity available in MIMO frequency-selective channels [8, 9]. Although an extensive amount of research has been done on single and multi-antenna TF-domain spreading MC-DS-CDMA schemes that achieve both spatial and frequency diversity in frequency-selective slow fading channels [6–9], very little research considers the time-selectivity of the wireless channels encountered. Thus, the above-mentioned schemes may not be su ciently e cient, when communicating over wireless channels exhibiting both frequency-selective and time-selective fading. There are very few MC-DS-CDMA schemes in the literature that consider the time-selectivity of the wireless channels encountered. This study considers the design of single and multi-antenna TF-domain spreading MC-DS-CDMA, for frequency-selective block-fading channels, which are capable of exploiting the full diversity available in the channel (i.e. spatial, frequency and temporal diversity), using various methods of joint detection at the receiver. It has been shown that the diversity gain in block-fading channels can be improved by coding across multiple fading blocks [10–12]. Single-antenna TF-domain spreading MC-DS-CDMA is considered for the quasi-synchronous uplink channel, and multi-antenna TF-domain spreading MC-DS-CDMA is considered for the synchronous downlink channel. Numerous simulated bit error rate (BER) performance curves, obtained using a triply selective MIMO channel platform, are presented in this study using optimal and sub-optimal joint detection algorithms at the receiver. In addition, this study investigates the impact of spatial correlation on the BER performance of the MC-DS-CDMA schemes considered. From these simulated results, one is able to conclude that TF-domain spreading MC-DS-CDMA designed for frequency-selective block-fading channels performs better than previously proposed schemes designed for frequency-selective slow fading channels, owing to the additional temporal diversity exploited under the block-fading assumption. AFRIKAANS : In die konteks van bre¨eband- draadlose kommunikasie deur die gebruik van kodeverdelingveelvuldige toegang (KVVT) behels die belangrikste veelvuldigetoegang- (VT) opsies enkel-draer direkte-sekwensie KVVT (ED-DS-KVVT), deur die gebruik van tyd-domein direkte sekwensie-verspreiding [1, p. 728], veelvuldigedraer-KVVT (VD-KVVT) deur die gebruik van frekwensiedomein-verspreiding [2, 3] en VD-DS- KVVT deur die gebruik van tyd-domein direkte sekwensie-verspreiding van die individuele sub-draerseine [4, 5]. Daar is in [6] aangetoon dat VD-DS-KVVT die hoogste vlakke van vryheid in die familie KVVT-skemas het wat voordelig benut kan word gedurende sisteemontwerp en rekonfigurasieprosedures. ’n Amalgaam van VD-KVVT en VD-DS-KVVT bekend as tyd-en-frekwensiedomeinverspreiding (TF-domeinverspreiding) VD-DS-KVVT is voorgestel in [6]. TF-domeinverspreiding VD-DS-KVVT het verskeie voordele bo konvensionele VD-DS-KVVT wat sowel kapasiteit as werkverrigting betref [7]. In teenstelling met konvensionele VD-DS-KVVT benut TF-domeinverspreiding VD-DS-KVVT multi-gebruiker-interferensie, wat die gebruik van gesamentlike opsporing by die ontvanger noodsaak. In die onlangse verlede is in die literatuur veelvuldige-inset-veelvuldige-uitset- (VIVU) of veelvuldige-antenna TF-omeinverspreiding VD-DS-KVVT-skemas voorgestel wat sowel die ruimtelike as frekwensiediversiteit wat in VIVU frekwensie-selektiewe kanale beskikbaar is, e ektief gebruik [8, 9]. Hoewel uitgebreide navorsing onderneem is oor enkel- en multi-antenna TF-domeinverspreiding VD-DS-KVVT-skemas wat sowel ruimtelike as frekwensie diversiteit in frekwensie-selektiewe stadig deinende kanale bereik [6–9], oorweeg baie min navorsing die tyd-selektiwiteit van die draadlose kanale wat betrokke is. Bogenoemde skemas mag dus nie e ektief genoeg wees nie wanneer kommunikasie plaasvind oor draadlose kanale wat sowel frekwensie-selektiewe as tyd-selektiewe wegsterwing toon. Baie min VD-DS-KVVT-skemas in die literatuur skenk aandag aan die tyd-selektiwiteit van die betrokke draadlose kanale. Die studie ondersoek die ontwerp van enkel- en multi-antenna TF-domeinverspreiding VD-DS-KVVT vir frekwensie-selektiewe blokwegsterwingkanale, wat in staat is om die volle diversiteit wat in die kanaal beskikbaar is, te benut (i.e. ruimtelike, frekwensie- en tyddiversiteit), deur die gebruik van verskeie metodes van gesamentlike opsporing by die ontvanger. Daar is aangetoon dat die diversiteitwins in blokwegsterwingkanale verbeter kan word deur kodering oor veelvuldige deinende blokke [10–12]. Enkel-antenna TF-domeinverspreiding VD-DS-KVVT word oorweeg vir die kwasi-sinchroniese opverbinding-kanaal, en multi-antenna TF-domeinverspreiding VD-DS-KVVT vir die sinchroniese afverbinding-kanaal. Talryke gesimuleerde bisfouttempo (BFT) werkverrigtingkurwes wat verkry is deur die gebruik van ’n drie-voudige selektiewe VIVU-kanaalplatform, word in hierdie studie aangebied, deur die gebruik van optimale en sub-optimale gesamentlike opsporingsalgoritmes by die ontvanger. Daarbenewens ondersoek hierdie studie die impak van ruimtelike korrelasie op die BFT-werkverrigring van die VD-DS-KVVT-skemas wat oorweeg word. Uit hierdie gesimuleerde resultate is dit moontlik om tot die gevolgtrekking te kom dat TF-domeinverspreiding VD-DS-KVVT wat ontwerp is vir frekwensie-selektiese blokwegsterwingkanale beter werkverrigting toon as vroe¨er voorgestelde skemas wat ontwerp is vir frekwensie-selektiewe stadig deinende kanale, te danke aan die ekstra tyddiversiteit wat deur die blokwegsterwing-aanname benut word. Copyright / Dissertation (MEng)--University of Pretoria, 2010. / Electrical, Electronic and Computer Engineering / unrestricted
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Bilateral processing benefit in sequentially implanted adult cochlear implant usersOosthuizen, Ilze 09 December 2011 (has links)
Bilateral cochlear implantation is accepted medical practice since 2008 in clinically suitable adults and children to enhance bilateral processing benefits. Bilateral implantation may lead to the restoration of some bilateral hearing advantages, such as improved speech recognition in noise, localisation, head shadow effect, summation, and squelch. The majority of the advantages stated in literature, though, are characteristic of the simultaneously implanted cochlear implant population. Simultaneous implantation is not yet a reality in South Africa due to funding constraints, therefore determining the bilateral processing abilities in sequentially implanted adults is essential. Determining bilateral processing benefits achievable with sequential implantation could result in evidence-based recommendations in terms of candidacy considerations, surgery protocols, motivations for medical aid funding for simultaneous cochlear implantation, and relevant measures to determine the bilateral processing benefit attainable. Furthermore, it might enhance audiologists‟ insight regarding post-implantation performance of sequentially implanted patients and enable them to counsel prospective candidates realistically. The aaim of this study was to determine the bilateral benefit attained by sequentially implanted adults. A quantitative, cross-sectional research approach was followed in a one group post-test-only exploratory research design. A purposive convenient sampling method with specified selection criteria was used to select 11 adult clients of an established cochlear implant programme in Pretoria. Tests of sound localisation in the horizontal plane and speech perception in noise were performed. During the test of sound localisation, performance with only the first or only the second implant was found to be very similar. For the majority of participants the second cochlear implant (CI 2) was the superior performing implant during xviii speech perception in noise testing, in spatially separated speech and noise conditions where noise was directed to the first implant, as well as in spatially coincident speech and noise. A statistical significant bilateral benefit (p < 0.05) was attained by sequentially implanted adults for sound localisation. A bilateral benefit for speech perception in noise was observed when noise was directed to the first implant and in the diotic listening condition with average benefits of 1.69 dB and 0.78 dB, respectively. It was not statistically significant (p > 0.05), however, and was smaller than bilateral benefit values achieved by simultaneously implanted adults in previous studies. The head shadow effect at 180° was found to be the strongest and most robust bilateral spatial benefit. Squelch and summation benefit values ranged from negative values to 2 dB and 6 dB, respectively. This corresponded with values found in previous studies. The improvement in speech perception in spatially distinct speech and noise from adding the ear with a better SNR (signal to noise ratio) indicated that the contribution of CI 2 seems to be greater than that of CI 1 for bilateral spatial benefit. It can be concluded that adults with sequential implants may achieve some extent of bilateral benefit even with many years of unilateral implant use, when speech processors differ, when the second implant is done ≥ 10 years after the first implant, and in cases of prelingual deafness. A key benefit of sequential implantation appears to be related to the advantage of having hearing on both sides so that the ear with the more favourable environmental signalto-noise ratio is always available. AFRIKAANS : Bilaterale kogleêre inplanting is sedert 2008 aanvaarde mediese praktyk vir klinies geskikte volwassenes en kinders, ten einde bilaterale prosesseringsvoordeel te verhoog. Bilaterale inplanting kan lei tot die herstel van sommige van die voordele van bilaterale gehoor, soos verbeterde spraakherkenning in lawaai, klanklokalisering, die kopskadueffek, sommering en selektiewe onderdrukking (“squelch”). Die meeste van die voordele wat in die literatuur bespreek word, is egter kenmerkend van dié persone by wie twee kogleêre inplantings gelyktydig gedoen is. Gelyktydige inplanting is as gevolg van beperkte befondsing nog nie in Suid-Afrika 'n werklikheid nie, daarom is dit noodsaaklik om te bepaal watter bilaterale prosesseringsvoordele by opeenvolgend-geïnplanteerde volwassenes voorkom. Die bepaling van watter bilaterale prosesseringsvoordele met opeenvolgende inplanting bereik kan word, sou kon lei tot getuienis-gebaseerde aanbevelings met betrekking tot besluite oor die geskiktheid van kandidate, protokol vir sjirurgie, motiverings vir die befondsing van gelyktydige kogleêre inplantings deur mediese voorsorgfondse, en toepaslike maatstawwe om te bepaal watter mate van bilaterale prosesseringsvoordeel haalbaar sou wees. Dit sou verder oudioloë se insig kon verbreed met betrekking tot die na-operatiewe prestasie van opeenvolgend-geïnplanteerde persone en hulle sodoende in staat stel om voornemende kandidate van realistiese raad te bedien. Die doel van hierdie studie was om te bepaal wat die bilaterale prosesseringsvoordele is wat deur opeenvolgend-geïnplanteerde volwassenes verkry kan word. 'n Kwantitatiewe navorsingsbenadering met 'n dwarsprofiel van „n enkelgroep is gevolg, met 'n post-toets verkennende navorsingsontwerp. 'n Doelgerigte gerieflikheidssteekproef met 'n gespesifiseerde seleksiekriteria is gebruik om 11 volwasse kliënte van 'n gevestigde kogleêre inplantprogram in Pretoria te selekteer. Klanklokalisering in die horisontale vlak en die waarneming van spraak in lawaai is getoets. Tydens die toets vir klanklokalisering is gevind dat prestasie met slegs die eerste of slegs die tweede inplanting soortgelyk was. Vir die meeste deelnemers aan die studie het die tweede kogleêre inplanting (KI 2) die beste prestasie gelewer tydens spraakwaarneming in lawaai, in omstandighede waar spraak en lawaai ruimtelik geskei is en die lawaai op die eerste inplanting gerig is, asook in omstandighede waar spraak en lawaai ruimtelik saamvoorkomend aangebied is. 'n Statisties beduidende bilaterale voordeel (p < 0.05) is deur opeenvolgend-geïnplanteerde volwassenes vir klanklokalisering behaal. 'n Bilaterale voordeel vir spraakwaarneming in lawaai is waargeneem waar lawaai op die eerste inplanting gerig is en ook in diotiese luistertoestande, met 'n gemiddelde voordeel van 1.69 dB en 0.78 dB, onderskeidelik. Dit was egter nie statisties beduidend nie en was ook kleiner as die bilaterale voordeelwaardes wat in vorige studies deur gelyktydig-geïnplanteerde volwassenes behaal is. Die kopskadu-effek by 180° was die sterkste en mees robuuste bilaterale ruimtelike voordeel. Voordeelwaardes vir selektiewe onderdrukking en sommering het gewissel van negatiewe waardes tot 2 dB en 6 dB onderskeidelik. Dit stem ooreen met waardes wat in vorige studies gevind is. Die verbetering in spraakwaarneming in ruimtelik geskeide spraak en lawaai wat verkry is deur die oor met 'n beter STR (sein-tot-ruis ratio) by te voeg, het daarop gedui dat die bydrae van KI 2 tot bilaterale ruimtelike voordeel waarskynlik groter as die bydrae van KI 1 is. Die gevolgtrekking kan gemaak word dat volwassenes met opeenvolgende inplantings 'n mate van bilaterale voordeel verkry selfs na vele jare van unilaterale inplantingsgebruik, wanneer die spraakprosesseerders in die twee inplantings van mekaar verskil, wanneer die tweede inplanting ≥ 10 jaar na die eerste plaasvind, en in gevalle van prelinguale doofheid. 'n Sleutelvoordeel van opeenvolgende inplanting hou klaarblyklik verband met die voordeel van gehoor aan albei kante te hê sodat die oor met die gunstigste sein-tot-lawaai ratio altyd beskikbaar is. / Dissertation (MCommunication Pathology)--University of Pretoria, 2011. / Speech-Language Pathology and Audiology / Unrestricted
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