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Josephs, M. B. "Functional programming with side-effects." Thesis, University of Oxford, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.375263.
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Cyphers, Benjamin. "Side Effects of 0.01% Atropine." The Ohio State University, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu161701167574429.
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Kelly, Vincent. "β–alanine: performance effects, usage and side effects." Thesis, University of Queensland, 2017. https://eprints.qut.edu.au/180848/1/43068631.pdf.
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β-alanine is a relatively new ergogenic aid and a number of questions relating to its effectiveness in enhancing high intensity exercise performance remain to be addressed. The five studies described in this thesis examined the influence of β-alanine supplementation and high intensity training on exercise capacity and considered factors that potentiallyinfluence dosage compliance and side effects – factors that may impact on the ergogenic value of β-alanine supplementation.Study 1 examined the efficacy of β-alanine supplementation in conjunction with repeated sprint and sprint interval training (and combined with a pre-exercise dose of sodium bicarbonate), on repeated-sprint ability and high intensity cycling capacity (time to fatigue at 110% of maximum power output). β-alaninesupplementation, when combined with sprint and interval training, improved repeated sprint ability but did not influence high intensity cycle capacity. Furthermore, acute sodium bicarbonate ingestion improved high intensity cycle capacity before training but had no influence on either repeated sprint ability or exercise capacity after training. It is likely that intramuscular buffer capacity increased as a result of training and that this may have outweighed the potential ergogenic buffering effects of β-alanine and sodium bicarbonate(i.e., both alone and in combination). Study 2 investigatedβ-alanine supplementation use and level of knowledge amongstprofessional rugby union (n = 87), rugby league (n = 180) and Australian Rules Football (n = 303) players. Over half the professional footballers surveyed used β-alanine, yet mostsupplemented in a manner inconsistent with recommendations. A better understanding of the environment and culture within professional football codes is required before supplement use aligns with evidence-based β-alanine supplementation recommendations. In light of these findings, Study 3 examined compliance levels to β-alanine supplementation in an applied setting. Compliance over a 28 day period was 59% (± 24%) which was significantly lower than the mean compliance rate reported by others (96%) (p < 0.0001). It was concluded that the determinants of β-alanine (non-) compliance in athletes needed to be further investigated.Study 4examined potential relationships between different β-alanine dosages and side effects. Healthy male participants were divided into low (< 75 kg) and high (> 85kg) body mass groups and completed three supplementation treatments: 1. a placebo, 2. β-alanine as a relative dose of 0.02 g·kgBM-1 and 3. β-alanine as an absolute dose of 1.6 g. For 90 min following supplementation in each condition, participants completed a questionnaire that sought responses to side effects. It was found that lighter individuals experienced fewer side effects when they supplemented with β-alanine as a dose relative to body mass; heavier individuals experienced fewer side effects when they consumed an absolute dose of 1.6 g. It was concluded that individualising the supplementation of β-alanine is likely to reduce side effects and in turn improve compliance. Finally, Study 5assessed whether the paraesthesia experienced following acute β-alanine supplementation was related to high intensity exercise performance. There was no relationship between the level of paraesthesia experienced by participants and exercise capacity. However, individual differences in side effects were found after repeated doses of β-alanine and some participants experienced side effects after consuming the slow release β-alanine formula. The findings of Study 5 highlight the need to further understand the underlying mechanismof side effects and impress the need to monitor and report side effects in future studies – particularly in β-alanine supplementation studies where participant blinding is required. Collectively, the studies described in the present thesis extend knowledge relating to β-alanine supplementation; specifically how supplementation practices can be individualised to improve compliance by practitioners and sport scientists in applied settings.
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Colagiuri, Ben. "Expectancies in Double-Blind Randomised Placebo-Controlled Trials and Placebo-Induced Side Effects." Thesis, The University of Sydney, 2009. http://hdl.handle.net/2123/8595.
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The majority of research on the placebo effect has focused on beneficial effects in patients or participants told to expect an active treatment, but who are actually given a placebo. Two important and relatively understudied aspects of the placebo effect are the extent to which expectancies influence outcomes in double-blind randomised placebo-controlled trials (RCTs) and whether the placebo effect contributes to treatment side effects. The current project investigated these two issues in both clinical and experimental settings. The first study involved reanalysing a double-blind RCT of naltrexone and acamprosate for alcohol dependence based on whether participants believed they had been allocated to receive active treatment or placebo (perceived treatment). The second study extended on this by developing an experimental model for these effects using dummy (placebo only) double-blind RCTs for cognitive performance. This allowed for the manipulation of observable changes in the form of false feedback. The third study investigated whether warning participants about side effects increases their occurrence, frequency, and/or severity in three dummy trials for sleep difficulty in healthy volunteers. The final study complemented this by examining whether first time chemotherapy patients’ expectancies for nausea were associated with their post-chemotherapy nausea. The studies on perceived treatment in double-blind RCTs indicated that participants’ beliefs about their treatment allocation can influence their actual treatment outcomes via the placebo effect and that these beliefs are affected by the feedback they receive about their performance. The studies on placebo-induced side effects indicated that the placebo effect may contribute to treatment side effects but that this effect is generally likely to be small. These findings confirm that the placebo effect can influence treatment outcomes and emphasise the importance of considering patient expectancies when delivering medical treatment. They also highlight some general limitations associated with research on the placebo effect, which include, whether conveying uncertainty undermines the placebo effect and whether measuring or manipulating expectancies is the best way to evaluate the placebo effect.
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Mischkowski, Dominik. "The Social Side Effects of Acetaminophen." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1438081282.
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Chu, Yu-Hsuan. "Custom Fluorophores for Investigating the Cellular Uptake Mechanisms and Side-Effects of Pharmaceuticals." PDXScholar, 2015. http://pdxscholar.library.pdx.edu/open_access_etds/2343.
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There is a significant current need to elucidate the molecular mechanisms of the side-effects caused by widely-used pharmaceuticals. Examples include the acute nephrotoxicity and irreversible ototoxicity promoted by the cationic drugs gentamicin and cisplatin. Gentamicin is an aminoglycoside antibiotic used for the prevention and treatment of life-threatening gram-negative bacterial infections, such as tuberculosis and meningitis. Cisplatin is used to treat a broad spectrum of cancers including head and neck, ovarian, cervical, stomach, bladder, sarcoma, lymphoma, testicular cancer and others.
The objective of this study is to design and synthesize rhodamine derivatives that can be used for the construction of geometrically well-defined cationic drug conjugates. The long-term goal is to use the conjugates as tools to aid in elucidating the properties and identities of ion channels involved in the uptake of cationic pharmaceuticals into kidney and cochlear hair cells. This will shed light on the origin and potential prevention of unwanted side effects such as nephrotoxicity and ototoxicity associated with specific cationic drugs.
A series of extended rhodamine analogs with reactive groups for biomolecule conjugation has been synthesized. These fluorophores show similar spectral properties to their prototype, Texas Red succinimidyl ester (TR-SE). However, they contain rigid linkers between the fluorophore and amine-reactive moiety. The resultant gentamicin conjugates of these materials are rigidified enabling one to assess channel pore dimensions without the confounding issue of conjugate folding. Preliminary cell studies are promising, as one observes reduced gentamicin uptake in both kidney and sensory hair cell upon systematically increasing the dimension of the fluorophore. This work has enabled us to tentatively assign the maximum dilated MET channel pore size as between 1.44 nm to 1.56 nm. However, this preliminary finding, though encouraging, needs further validation via ongoing studies with larger diameter fluorophore conjugates,
A cisplatin-Texas Red conjugate has also been synthesized to enable studies of cellular uptake mechanisms. This conjugate preserves not only the spectral properties of Texas Red after conjugation, but also the cytotoxicity of cisplatin. This has been validated in zebrafish. The series of rhodamine probes that have been conjugated to gentamicin should be similarly useful for cisplatin studies. These studies are planned. Additional future work includes the synthesis of semi-flexible (glycol) and flexible (alkyl) linkers to evaluate structure-activity relationships.
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Ahmed, Al-Obeidi Fahad. "Design, synthesis, conformation and biological activities of cyclic alpha-melanotropin and related compounds." Diss., The University of Arizona, 1988. http://hdl.handle.net/10150/184445.
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This research initiated an investigation of the structural relationships between melanocyte stimulating hormone (α-MSH) and its melanin dispersion on lizard (Anolis carolinensis) and frog (Rana pipiens) skins bioassays as representing models for mammalian and amphibian melanocytes, respectively. From previous extensive structure-activity relationships of α -MSH together with the theoretical modeling we were able to design a group of linear and cyclic peptides related to "4-10" fragment analogues of α -MSH. The solid phase synthesis of α -MSH and its related analogues using the p-methyl-benzhydrylamine resin was accomplished. The C-terminal carboxamide and N-terminal acetylamide were maintained in all peptides synthesized. The cyclic peptides were prepared in solution phase using the linear peptides generated by solid phase. All the cyclization were done by using the hydrochloride salts of the peptide and DMF as solvent with diphenylphosphoryl azide (DPPA) as a coupling reagent in the presence of K₂HPO₄ as a base. The yields of the cyclic peptides were in the range of 30-40 percent. In all the synthesized peptides the replacement of D-Phe⁷ with L-Phe⁷ causes reduction in the potency of the peptide on lizard or frog skins bioassays. Also, the reduction or increase in ring size in the cyclic peptide from a 23 membered ring diminishes the biological effect of the peptide under testing.
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Clark, Brodie. "Side Effects May Depend on the Framing of a Warning: But Does this Framing Effect Depend on Absolute Risk?" Thesis, Faculty of Science, School of Psychology, 2019. https://hdl.handle.net/2123/28535.
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Side effect warnings contribute directly to the burden of side effects. This occurs via the nocebo effect whereby negative outcomes are shaped by features of the treatment context, beyond the direct actions of the active treatment. Some studies have found that positive framing of warnings – stating the proportion of people who will not experience the side effect – reduces side effects compared to the more common-place negative framing – stating the proportion who will experience the side effect. However, findings have been mixed. It appears that the absolute risk ascribed to the side effect may determine the effect of framing, however this has not been tested. The current study employed a 2x2+1 between-subjects design to test the impact of both absolute risk and framing of a warning – as well as the inclusion of any statistical warning at all - on side effects. This was done in a model of virtual reality (VR)-induced nausea, with 130 healthy volunteers. Expectancy, anxiety and attentional bias were also measured as they have been proposed as mechanisms of framing and nocebo effects, but scantly - or in the case of attentional bias, never – previously empirically investigated. In this study, VR-induced nausea was not affected by framing or absolute risk of the warning. However, nausea was greater for participants who received no statistical warning. Relative to other groups, these participants also showed elevated anxiety – although not expectancy or attentional bias. These findings indicate that future studies and clinical practices must consider the effects of general, non-statistical warnings on nocebo side effects as they are potentially even more deleterious than more extensive, statistical warnings. These findings are also the first outside of pain studies to support a role for anxiety in nocebo effects, thereby shaping current understanding and future investigations of the poorly understood mechanisms of nocebo effects.
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McGee, Michael K. "Assessing Negative Side Effects in Virtual Environments." Thesis, Virginia Tech, 1998. http://hdl.handle.net/10919/35766.
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Virtual environment (VE) systems have been touted as exciting new technologies with many varied applications. Today VEs are used in telerobotics, training, simulation, medicine, architecture, and entertainment. The future use of VEs seems limited only by the creativity of its designers. However, as with any developing technology, some difficulties need to be overcome. Certain users of VEs experience negative side effects from being immersed into the graphically rendered virtual worlds. Some side effects that have been observed include: disorientation, headaches, and difficulties with vision. These negative side effects threaten the safety and effectiveness of VE systems.
Negative side effects have been found to develop in a variety of environments. The research focus on VE side effects thus far has been on the symptoms and not the causes. The main goals of this research is fourfold: 1) to compare a new measure for side effects with established ones; 2) begin analyzing the causes of side effects with an analysis of head-tracking; 3) to examine any adaptation that may occur within a session and between days of a session; and, 4) to examine possible predictors for users who may experience side effects.
An experiment was conducted using two different VEs with either head-tracking on or head-tracking off over four days. A questionnaire, a balance test, a vision test, and magnitude estimations of side effects were used to assess the incidence and severity of sickness experienced in the VEs. Other assessments, including a mental rotation test, perceptual style, and a questionnaire on pre-existing susceptibility to motion sickness were administered. All factors were analyzed to determine what their relationships were with the incidence and severity of negative side effects that result from immersion into the VEs.
Results showed that head-tracking induces more negative side effects than no head-tracking. The maze task environment induces more negative side effects than the office task environment. Adaptation did not occur from day to day throughout the four testing sessions. The incidence and severity of negative side effects increased at a constant rate throughout the 30 minute immersive VE sessions, but did not show any significant changes from day to day. No evidence was found for a predictor that would foretell who might be susceptible to motion sickness in VEs.Master of Science
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Rundqvist, Konrad. "Side effects of level dependent hearing protectors." Thesis, Luleå tekniska universitet, Institutionen för ekonomi, teknik och samhälle, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:ltu:diva-82150.
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Hearing protectors are used in noisy environments to attenuate damaging soundlevels. Problems are reported to arise from using hearing protectors, since usefulsounds also are attenuated. Not only are sound levels attenuated, but other humanabilities are affected by hearing protectors, such as the ability to identify and localizesounds. Manufacturers of hearing protectors also develop level-dependent hearingprotectors that are supposed to create a better listening experience for the user thandoes passive hearing protectors. This thesis investigates how the ability to identifysound is affected by hearing protectors in the Swedish processing industry and towhat extent level-dependent hearing protectors improve the user’s ability to identifysound. Semi-structured interviews were conducted by asking questions based on theprojects research questions and theories found from a literary study. A questionnairewas sent out with similar questions for verification purposes. The current literatureshows that the human ability to identify sound deteriorates by the occlusion from hearing protectors. Indications are such that hearing protectors with a level-dependent function deteriorate the ability less than does passive protectors. The relevance of this in the processing industry does not seem to be very palpable. Usersindicate that it would be dangerous for this ability to be deteriorated in theworkplace and that level-dependent hearing protectors does a better job apreserving sound identification than passive protectors, but their soundidentification ability is not deteriorated enough by passive hearing protectors forproblems to arise.
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Chumbley, Gillian Mary. "Patients' evaluation of patient controlled analgesia after surgery." Thesis, St George's, University of London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249438.
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Benson, John Arthur. "Patients' perceptions about blood pressure medication and their relationship to medicine taking." Thesis, King's College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248397.
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Ospina, Arango Juan David. "Predictive models for side effects following radiotherapy for prostate cancer." Thesis, Rennes 1, 2014. http://www.theses.fr/2014REN1S046/document.
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La radiothérapie externe (EBRT en anglais pour External Beam Radiotherapy) est l'un des traitements référence du cancer de prostate. Les objectifs de la radiothérapie sont, premièrement, de délivrer une haute dose de radiations dans la cible tumorale (prostate et vésicules séminales) afin d'assurer un contrôle local de la maladie et, deuxièmement, d'épargner les organes à risque voisins (principalement le rectum et la vessie) afin de limiter les effets secondaires. Des modèles de probabilité de complication des tissus sains (NTCP en anglais pour Normal Tissue Complication Probability) sont nécessaires pour estimer sur les risques de présenter des effets secondaires au traitement. Dans le contexte de la radiothérapie externe, les objectifs de cette thèse étaient d'identifier des paramètres prédictifs de complications rectales et vésicales secondaires au traitement; de développer de nouveaux modèles NTCP permettant l'intégration de paramètres dosimétriques et de paramètres propres aux patients; de comparer les capacités prédictives de ces nouveaux modèles à celles des modèles classiques et de développer de nouvelles méthodologies d'identification de motifs de dose corrélés à l'apparition de complications. Une importante base de données de patients traités par radiothérapie conformationnelle, construite à partir de plusieurs études cliniques prospectives françaises, a été utilisée pour ces travaux. Dans un premier temps, la fréquence des symptômes gastro-Intestinaux et génito-Urinaires a été décrite par une estimation non paramétrique de Kaplan-Meier. Des prédicteurs de complications gastro-Intestinales et génito-Urinaires ont été identifiés via une autre approche classique : la régression logistique. Les modèles de régression logistique ont ensuite été utilisés dans la construction de nomogrammes, outils graphiques permettant aux cliniciens d'évaluer rapidement le risque de complication associé à un traitement et d'informer les patients. Nous avons proposé l'utilisation de la méthode d'apprentissage de machine des forêts aléatoires (RF en anglais pour Random Forests) pour estimer le risque de complications. Les performances de ce modèle incluant des paramètres cliniques et patients, surpassent celles des modèle NTCP de Lyman-Kutcher-Burman (LKB) et de la régression logistique. Enfin, la dose 3D a été étudiée. Une méthode de décomposition en valeurs populationnelles (PVD en anglais pour Population Value Decomposition) en 2D a été généralisée au cas tensoriel et appliquée à l'analyse d'image 3D. L'application de cette méthode à une analyse de population a été menée afin d'extraire un motif de dose corrélée à l'apparition de complication après EBRT. Nous avons également développé un modèle non paramétrique d'effets mixtes spatio-Temporels pour l'analyse de population d'images tridimensionnelles afin d'identifier une région anatomique dans laquelle la dose pourrait être corrélée à l'apparition d'effets secondairesExternal beam radiotherapy (EBRT) is one of the cornerstones of prostate cancer treatment. The objectives of radiotherapy are, firstly, to deliver a high dose of radiation to the tumor (prostate and seminal vesicles) in order to achieve a maximal local control and, secondly, to spare the neighboring organs (mainly the rectum and the bladder) to avoid normal tissue complications. Normal tissue complication probability (NTCP) models are then needed to assess the feasibility of the treatment and inform the patient about the risk of side effects, to derive dose-Volume constraints and to compare different treatments. In the context of EBRT, the objectives of this thesis were to find predictors of bladder and rectal complications following treatment; to develop new NTCP models that allow for the integration of both dosimetric and patient parameters; to compare the predictive capabilities of these new models to the classic NTCP models and to develop new methodologies to identify dose patterns correlated to normal complications following EBRT for prostate cancer treatment. A large cohort of patient treated by conformal EBRT for prostate caner under several prospective French clinical trials was used for the study. In a first step, the incidence of the main genitourinary and gastrointestinal symptoms have been described. With another classical approach, namely logistic regression, some predictors of genitourinary and gastrointestinal complications were identified. The logistic regression models were then graphically represented to obtain nomograms, a graphical tool that enables clinicians to rapidly assess the complication risks associated with a treatment and to inform patients. This information can be used by patients and clinicians to select a treatment among several options (e.g. EBRT or radical prostatectomy). In a second step, we proposed the use of random forest, a machine-Learning technique, to predict the risk of complications following EBRT for prostate cancer. The superiority of the random forest NTCP, assessed by the area under the curve (AUC) of the receiving operative characteristic (ROC) curve, was established. In a third step, the 3D dose distribution was studied. A 2D population value decomposition (PVD) technique was extended to a tensorial framework to be applied on 3D volume image analysis. Using this tensorial PVD, a population analysis was carried out to find a pattern of dose possibly correlated to a normal tissue complication following EBRT. Also in the context of 3D image population analysis, a spatio-Temporal nonparametric mixed-Effects model was developed. This model was applied to find an anatomical region where the dose could be correlated to a normal tissue complication following EBRT
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Nilsson, Greger. "Cardiovascular Side Effects of Radiotherapy in Breast Cancer." Doctoral thesis, Uppsala universitet, Enheten för onkologi, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-179811.
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The aim of the thesis was to study cardiovascular side effects of radiotherapy (RT) in breast cancer (BC). In a study base of 25,171 women with BC diagnosed 1970-2000, we found a statistically significant 12% increase of stroke, compared to the stroke incidence in the background population. A case-control study of 282 cases with BC followed by a stroke and 1:1 matched controls with BC but not stroke was performed. In women irradiated to internal mammary chain (IMC) and supraclavicular lymph nodes (SCL) vs. a pooled group of women not irradiated or irradiated to targets other than IMC and SCL, a statistically significant increase of stroke with an odds ratio of 1.8 was observed. There were no associations between BC laterality, targets of RT, and hemisphere location of stroke. The radiation targets IMC and SCL, showed a statistically significant trend for an increased risk of stroke with daily fraction dose. A study of 199 patients with BC, examined by coronary angiography, detected a four- to seven-fold increase of high grade coronary artery stenosis in mid and distal left anterior descending artery (LAD), including distal diagonal branch, when comparing women with irradiated left-sided BC to those with right-sided. An increase of clinically significant coronary artery stenosis was found in pre-specified hotspot areas for radiation among women irradiated to the left breast/chest wall or to the IMC. Thus, the coronary arteries should be regarded as organs at risk in RT of BC. In a study of 15 BC patients treated with 3D conformal RT, a marked difference in dose distribution in mid and distal LAD between left- and right-sided BC was demonstrated. Irradiated right-sided BC mainly received low doses of scattered and transmitted radiation to the coronary arteries. On the contrary, tangential RT to the left breast without regional lymph node irradiation yielded coronary artery max doses of approximately 50 Gray to distal LAD, probably not safe concerning late radiation vascular effects. To conclude, we found cardiovascular side effects in women irradiated for BC, resulting in stroke and coronary artery disease, and showed an association between the targets for RT and the anatomical location of these vascular events.
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Weitoft, Tomas. "Intra-articular Glucocorticoid Treatment : Efficacy and Side Effects." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-5897.
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Heller, M. K. "The role of medication beliefs in side effects." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1563528/.
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The experience (or mere anticipation) of side effects influences patients’ beliefs about specific treatment and pharmaceuticals in general. In this thesis I postulate that beliefs about medication may also contribute to side effect reporting. Five studies were conducted to test this hypothesis and to explore putative underlying mechanisms. The majority of studies examining the relationship between medication beliefs and side effect reporting are cross-sectional, precluding inferences about the direction of the relationship. I present evidence from a prospective study showing that baseline medication beliefs predict side effect reporting in a large multinational sample of women initiating bone-loss treatment. The claim that non-pharmacological factors like medication beliefs can influence side effect reporting is supported by research on the nocebo effect (side effects to placebo). A sham trial was conducted showing that medication beliefs predict symptom reporting and attribution of symptoms as side effects in healthy volunteers taking Modafinil placebo. Many symptoms that are frequently listed as side effects are also common in patients randomized to placebo and un-medicated healthy volunteers. Using an analogue scenario I demonstrate that people with more negative beliefs about medication are more likely to misattribute a common symptom as a side effect. A related analogue study explored whether pre-existing beliefs about medication act as schemas that bias the way people process information about side effects. I show that individuals with more negative beliefs about pharmaceuticals recall and recognize fewer side effects from a patient leaflet, spend less time reading side effect information and are consequently more likely to attribute an unlisted symptom as a side effect. Finally, I present findings from a feasibility study of interventions to modify unhelpful medication beliefs in order to reduce side effect attribution. Together these findings confirm the importance of medication beliefs in side effect reporting and point to possible intervention strategies.
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Isherwood, Ruth Jayne. "Opioid-related side-effects and opioid-induced hyperalgesia." Thesis, University of Glasgow, 2015. http://theses.gla.ac.uk/6598/.
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Introduction: Opioids are widely used for the management of cancer and chronic non-cancer pain and the maintenance management of patients with a history of substance misuse. Increasingly the use of opioids is being scrutinised as patients are prescribed opioids for longer periods and the long-term effects of the opioids becomes clinically more relevant and evident. Our work has explored the prevalence of opioid-related side-effects in patients who are prescribed opioids and explored the clinically relevant phenomenon of opioid-induced hyperalgesia. . Methods: Patients were recruited who were prescribed opioids for the management of cancer and non-cancer pain or substance misuse. Quantitative data was collected to explore the prevalence and severity of opioid related side-effects, the impact of opioids on cognitive function and the effect of opioids on peripheral nerve function through quantitative sensory testing. Testing the sensory processing of patients who are on opioids has revealed altered thermal thresholds and the presence of wind-up at non-painful sites indicating central sensitisation. Qualitative description was used to explore the patient experience of an episode of opioid toxicity. Results: Patients have a significant burden of side-effects which have often not been recognised by clinicians. Using the Addenbrooke’s Cognitive Examination much more cognitive impairment has been revealed than has previously been recognised. Altered thermal thresholds and wind-up at non-painful sites suggests altered pain processing as a result of opioids. Themes from the qualitative description highlighted the coping strategies patients’ develop when managing with significant side-effects and toxicity, the covert self-management of their pain and the need to exert control. One of the most significant findings from the qualitative research was the finding of altered sensation and pain description associated with other features of opioid toxicity. Conclusions: The impact of opioids on the cognitive function of patients has significant implications in terms of patients’ involvement in decision-making and functioning in everyday life. The qualitative data reflects the burden of side effects and the descriptions of patients suggest that opioid-induced hyperalgesia exists as part of the spectrum of opioid toxicity. This finding may help physicians identify patients who are developing opioid-induced hyperalgesia and allow them to intervene earlier with a proactive approach.
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Husman, Stephen H. "Side-dress Temik® Effects on Lint Yields." College of Agriculture, University of Arizona (Tucson, AZ), 1998. http://hdl.handle.net/10150/210391.
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Temik 15G was side-dressed at a rate of 7 lb./acre and 14 lb./acre and compared to an untreated check in 4 experiments in 1996 and 1997 in Buckeye, Az. Treatments were made just prior to early bloom. Lygus counts were taken using a sweep net on weekly intervals for four to six weeks post application. A net positive return on investment (ROI) ranging from $34.79/acre to $48.19/acre was realized in three of the four experiments with the seven lb./acre rate. One experiment resulted in a net economic loss of $24.84. A net positive ROI was experienced in two of the four experiments ranging from $23.31 to $50.11 using the fourteen lb./acre Temik rate. Two of the four experiments resulted in a net loss ranging from $28.28 to $93.27 using the fourteen lb./acre rate. It appears that lint yield increase responses are due in part to a plant response to Temik, not necessarily related to lygus density as evidenced in part by the lack of measured sweep count populations.
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Husman, S. H., and B. Deeter. "Side-Dress Temik® Effects on Lint Yields." College of Agriculture, University of Arizona (Tucson, AZ), 1997. http://hdl.handle.net/10150/211107.
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Temik 15G was side -dressed at a rate of 7 lb./acre and 14 lb./acre and compared to an untreated check in two experiments in Buckeye, Az.. Treatments were made prior to the second in- season irrigation (June 3 and June 5) which was just prior to early bloom. Lygus counts were taken using a sweep net on weekly intervals for six weeks post application. The first experiment resulted in a significant increase of 123 lb. and 1241b. lint in both the 7 and 14 lb. rate treatment respectively over the untreated check. The second experiment resulted in a significant 102 lb. lint increase for the 7 lb. treatment with no significant difference for the 14 lb. treatment to the check.
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Saint-Clarke, Gwendolyn E. "Chemotherapy Side Effects at Home: A Nursing Impact." NSUWorks, 2017. https://nsuworks.nova.edu/hpd_con_stuetd/49.
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Background: Approximately 32% of all lymphoma patients experience immunocompromised severe avoidable side effects of nadir at home after discharge postchemotherapy. The certified oncology nurses employed at a large metropolitan hospital in Atlanta, Georgia, lack standardized discharge guidelines that include regulatory organizations’ recommendations to assist patients/families with at-home self-management of the avoidable side effects. Purpose: The purpose of this quality improvement project was to utilize the institution’s existing postchemotherapy discharge protocol to assess certified oncology nurses’ knowledge of severe avoidable side effects of nadir; modify the existing healthcare institution’s postchemotherapy discharge protocol to reflect standardized practice for promoting clinical practice continuity by leading organizations; conduct multifaceted training seminars to disseminate the modified postchemotherapy discharge guideline; evaluate the oncology nurses’ knowledge of severe avoidable side effects of nadir postchemotherapy after modified guideline implementation; and collaborate with the intraprofessional team to determine if the modified postchemotherapy discharge guideline was feasible and acceptable for system wide hospital implementation. Theoretical Framework: The theoretical framework used was Benner’s model of nurse proficiency: expert nurses develop skills and understanding of patient care through a sound educational base and a multitude of experiences. Methods: The existing postchemotherapy discharge protocol was used to develop a developed standardized guideline incorporating regulatory organizations’ recommendations for severe avoidable side effects of nadir postchemotherapy for nursing discharge information and patients’ at-home management. Ten oncology registered nurses on a 16-bed oncology unit participated in two 10-question Likert scale questionnaires based on the existing guideline (pretest) and the modified guideline (posttest) before and after an educational intervention. A quantitative nonparametric descriptive design was used. The questionnaires were analyzed with a two-tailed paired t test, p = 0.05, CI = 95, SD = 12. Results: Nurses significantly improved from pretest to posttest—63% before receiving modified guideline education and 83% after receiving education (p < 0.005). Conclusion: A standardized guideline that included regulatory organizations’ recommendations for at-home management of severe avoidable side effects of nadir showed significant nurses’ improvement in knowledge and competency. The effectiveness of nurses disseminating discharge information was paramount when knowledge awareness and appropriate patient/family assessment were incorporated in the discharge instructions.
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江卓庭 and Cheuk-ting Kong. "Chloramphenicol-induced toxicity on haemopoiesis." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1998. http://hub.hku.hk/bib/B3122099X.
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Gyenes, Gábor. "Cardiac side-effects of adjuvant radiotherapy for early breast cancer /." [Budapest] ; Stockholm, 1997. http://diss.kib.ki.se/1997/963-9106-04-6.
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Riley, Philip. "The prevention of oral side effects of cancer treatment." Thesis, University of Manchester, 2017. https://www.research.manchester.ac.uk/portal/en/theses/the-prevention-of-oral-side-effects-of-cancer-treatment(dee3fd53-35f7-448a-8572-591c1bf9c874).html.
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Background: Treatments for cancer can cause a range of oral side effects which can compromise patients' quality of life and even their chances of survival. The evidence for the prevention of some of these side-effects, primarily oral mucositis and salivary gland dysfunction, is often scarce or conflicting. Such evidence is needed to support the recommendations given in clinical guidelines. Aims: (i) To assess the effects of interventions for preventing oral mucositis in patients with cancer who are receiving treatment; (ii) To assess the effects of pharmacological interventions for the prevention of radiation-induced salivary gland dysfunction; (iii) To assess the quality of guidelines on the management of oral complications caused by cancer treatment. Methods: (i & ii) Systematic reviews of randomised controlled trials, using Cochrane methodology were carried out to assess the effects of interventions (oral cryotherapy and cytokines and growth factors for (i)); (iii) Guidelines published from 2005 onwards were appraised using the AGREE II instrument. The guidelines were also assessed to determine whether or not their recommendations were supported by high quality systematic reviews. Results: (i) Both oral cryotherapy and keratinocyte growth factor were found to prevent oral mucositis in patients receiving certain types of treatment. They also appeared to be relatively safe interventions; (ii) Amifostine was found to be beneficial for preventing dry mouth in the short- to medium-term in patients receiving radiotherapy to the head and neck. However, amifostine is associated with side effects; (iii) The quality of guidelines on the management of oral complications caused by cancer treatment is very poor. They are generally poorly reported, methodologically deficient, and the recommendations are rarely supported by systematic review evidence. Conclusions: More high quality randomised controlled trials are needed of interventions for preventing oral mucositis and salivary gland dysfunction. Clinical guidelines in this field should not be used without a rigorous appraisal incorporating an assessment of the evidence base for their recommendations. Different stakeholders, especially systematic reviewers and guideline developers, need to work together to improve the currently low standard of clinical guidelines.
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Gharanei, A. M. "Investigation into the cardiotoxic effects of doxorubicin and strategies for cardioprotection." Thesis, Coventry University, 2013. http://curve.coventry.ac.uk/open/items/ad712004-828e-4d9a-8ddb-17951146d414/1.
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Doxorubicin is one of the most effective anti-cancer agents; however its use is associated with adverse cardiac effects, including cardiomyopathy and progressive heart failure. Mitochondrial function and integrity are crucial for cellular processes in general and play an important role during diseased development. These characteristics of the mitochondria make them the prime target for treatments for majority of diseases and in particular of the cardiovascular system. The mitochondria are also considered to play an integral role in the manifestation of the cardiotoxic effects of compounds such as doxorubicin. The current project is designed to investigate the cardiotoxic effects of doxorubicin at tissue, cellular and protein level. In addition, it is investigated whether the inhibition of the mitochondrial permeability transition pore (mPTP) with cyclosporin A (CsA) or the inhibition of mitochondrial fission with the mitochondrial division inhibitor (mdivi-1) protects against the detrimental effects of doxorubicin on cardiac function. We also investigated whether co-treatment of doxorubicin with either CsA or mdivi-1 has any negative interaction with the cytotoxicity of doxorubicin against cancer cells. Langendorff results indicated that doxorubicin caused a time dependent reduction in the haemodynamic function of the heart as well as causing an increase in the infarct size to risk ratio in both naïve conditions and in conditions of ischaemia and reperfusion. Detrimental effects of doxorubicin on cardiac function were abrogated by co-treatment of doxorubicin with CsA or mdivi-1 in naïve conditions and in conditions of ischaemia and reperfusion. Cell viability data of isolated cardiac myocytes revealed that doxorubicin caused a concentration dependant decrease in the viability of neonatal cardiac myocytes as well as causing a reduction in the time taken to depolarisation and hypercontracture under sustained oxidative stress, all of which were prevented when co-treated with either CsA or mdivi-1. Doxorubicin significantly elevated the levels of p-Akt, p-Erk, p-Drp1 and p-p53. Co-treatment with CsA prevented the increase in the levels of p-Akt and p-Erk caused by doxorubicin in both naïve and IR condition whereas mdivi-1 prevented the increase in the levels of p-Erk, p-Drp1 and p-p53 and caused further increase in the levels of p-Akt. Using sinusoidal muscle length change during contraction and relaxation, it is demonstrated that doxorubicin caused a decrease in the power output, peak force and force during shorting. Detrimental effects of doxorubicin on work-loop contraction were abrogated when doxorubicin was co-administered with CsA. To conclude, results demonstrated that doxorubicin caused cardiotoxicity at tissue, cellular and protein level in both naïve conditions and in conditions of ischaemia and reperfusion injury. In addition, it is shown that the inhibition of mitochondrial permeability transition pore with CsA or the inhibition of the mitochondrial fission with mdivi-1 protect against doxorubicin-induced toxicity without affecting its anti-cancer properties.
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Andersson, Anne. "Long-term side effects after treatment of Hodgkin's lymphoma." Doctoral thesis, Umeå universitet, Onkologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-43287.
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Background Long-term side effects associated with the treatment of Hodgkin’s lymphoma (HL) have frequently been reported during the last decades. Studies have shown increased mortality in HL survivors. Following Hodgkin’s lymphoma, second malignancies (SM) and cardiovascular disease (CVD) are the most common causes of death in individuals treated for HL. This study investigates the incidence of side effects such as SM, CVD and infections in a cohort diagnosed with HL in Sweden between 1965 and 1995. In addition, this study identifies covariate risk factors for late side effects in order to develop strategies that prevent morbidity and mortality in HL survivors. Methods Using the Swedish Cancer Registry (SCR) at the National Board of Health and Welfare and the Multi-Generation Registry at Statistics (MGR) Sweden, we identified 6946 individuals diagnosed with HL between the years 1965 and 1995, and their first degree relatives (FDR) (n=17 858). In addition we identified the malignancies and inpatient care for CVD and infections for the HL cohort and their FDR. The standard incidence ratio (SIR) was calculated for the risk of SM, CVD and infections. For SM and CVD the risk also was stratified and calculated for family history of disease. The Swedish Hodgkin Intervention and Prevention study (SHIP), a prospective study, invited 702 individuals treated for HL at the age of 45 years or younger and who were treated in the region of Skåne, Uppsala or Umeå. The participants completed a questionnaire and were invited to an out-patient visit to an oncologist with clinical examination and blood tests. Any pathological findings were referred for further investigation. Results An increased risk for SM in HL long-term survivors was observed and seems to increase with the number of FDRs with cancer. There was also an increased risk for inpatient care due to congestive heart failure (CHF) and coronary artery disease (CAD). A family history of CHF and CAD further increased the risk for these diseases. The risk for inpatient care due to infections was increased and remained increased after 20 years or longer. The risk for infections was associated with splenectomy and hypothyroidism. Radiotherapy was an independent risk factor for cardiovascular disease in the cohort of the prospective study. ConclusionLong-term survivors from HL have an increased risk for developing late side effects such as SM, CVD and infections. Since many HL patients are young and the cure rate from the disease is high, it is of great importance to offer focused surveillance programs to selected individuals who are at high risk, e.g. individuals who received radiotherapy as part of their treatment and who have other known risk factors for cardiovascular disease such as hypertension, hypercholesterolemia, family history and smoking.
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Caliari, De Lima Lucas. "Construction Effects on the Side Shear of Drilled Shafts." Scholar Commons, 2017. http://scholarcommons.usf.edu/etd/7004.
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Design methods for side shear of drilled shafts, including the resistance factors that should be applied, do not account for any specific construction procedure. Instead, design often relies on analysis of case studies which include all construction methods used in each geomaterial type (e.g. clays, sands and rocks), or on parametric analysis. Nonetheless, literature suggests that different construction procedures result in varying side shear.
This research investigated 2 types of construction: (1) slurry stabilization in sandy soils using bentonite and polymer products that are commonly used on the field, with exposure times from near 0h to 96h, and (2) temporary casing stabilization in simulated limestone using 3 different methods for installation and extraction of the casings which included: driven, coarse-tooth rotated and fine-tooth rotated. All specimens were 1/10th scale in relation to the most common shafts sizes constructed in the field.
The results showed that bentonite slurry causes a significant reduction on the side shear within relatively short periods of time (between 2h and 4h of open excavation), whereas polymer slurry did not show appreciable variations up to 96h.
The driven and coarse-tooth rotated temporary casing exhibited lower side shear resistance than the fine-tooth rotated casings, which can be attributed to the larger annulus outside the casing and the additional crumbled pieces of rock that degrades the contact interface with the socket concrete.
Construction-based resistance factors are suggested for each construction procedure investigated in this study and clearly show the effects from different methods.
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Buijs, Ciska. "Long-term side effects of adjuvant breast cancer treatment." [S.l. : Groningen : s.n. ; University Library of Groningen] [Host], 2008. http://irs.ub.rug.nl/ppn/306087480.
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Humphries, Courtney (Courtney Elizabeth). "Side effects : the new age of AIDS in America." Thesis, Massachusetts Institute of Technology, 2004. http://hdl.handle.net/1721.1/39435.
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Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Humanities, Program in Writing and Humanistic Studies, 2004.Vita.
Includes bibliographical references (leaves 29-32).
When the cocktail of AIDS drugs called highly active antiretroviral therapy (HAART) was introduced in 1997, it radically changed the picture of HIV and AIDS in the U.S. Deaths from AIDS plummeted by two-thirds. Now, far fewer people are progressing along the once-inevitable path to illness and death. The impact of new therapy has been both dramatic and double-edged: it has spared tens of thousands from death, but has complicated their lives in countless ways. This newspaper series in five parts examines the new landscape of AIDS in the aftermath of success - a success that is still incomplete as there is still no cure. The new therapies carry literal side effects - the toxicities of drugs that infected individuals must take everyday for the rest of their lives. But the drugs have also created social and political side effects as AIDS is transformed to an increasingly chronic disease. The series relays the stories of HIV-infected individuals, clinicians, social workers, and AIDS service and prevention workers in Boston and examines how their lives and work have changed now that AIDS is no longer seen as a "crisis" in the U.S.
by Courtney Humphries.
S.M.
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ASTESANA, VALENTINA. "Alternative strategies to overcome Cisplatin side effects and resistance." Doctoral thesis, Università degli studi di Pavia, 2019. http://hdl.handle.net/11571/1231866.
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Cisplatin is one of the most effective chemotherapeutic agents used in the treatment of many type of tumours including non-small cell lung cancer, ovarian, testicular, glioblastoma, neuroblastoma and others. Cisplatin is able to form bonds with the N7 atom on guanine and adenine bases and when this damage is not repaired, DNA replication and transcription were stopped, inducing death of the cells. Despite the clinical benefit provided by Cisplatin many patients undergo phenomena of resistance and toxicity (especially ototoxicity, nephrotoxicity and neurotoxicity). Cisplatin resistance is generally multifactorial and arises through different mechanisms; one of this is correlated to high activity of PARP-1, an enzyme that modify proteins by poly-adenosine ribosylation (named PARylation). There are many targets of PARylation, one of these are histones. Moreover, high PAR levels correlate with weak infiltration by CD8+ cytotoxic lymphocytes (CTL) in human NSCLC. To overcome Cisplatin resistance and toxicity, alternative strategies were proposed: 1) the use of alternative platinum compounds, such as [Pt(O,O'-acac)(γ-acac)(DMS)], a platinum (II) complex containing acetylacetonate (acac) and a dimethylsulpide (DMS) in the coordination sphere of the metal and synthetized by the team of Prof. Fanizzi (University of Salento, Lecce), considering its activity and mechanism of action respect to Cisplatin and 2) the study of new mechanisms of resistance linked to a different immune response between Cisplatin sensitive and resistant tumour cells. For the first strategy we used human glioblastoma T98G cell line. Our results suggest that PtAcacDMS is able to induce apoptosis and necrosis with a concentration five-fold lower respect to Cisplatin (10µM respect to 40µM). Furthermore, ultrastructural analysis of TEM revealed an intense process of autophagy takes place in the cells confirm by the analysis of autophagic markers. Different cell death can be regulated by calcium and by oxidative stress. We find that PtAcacDMS induce an acute increase in [Ca2+]i respect to CDDP that was likely to be due to extracellular Ca2+ entry and enhanced both cytosolic and endoplasmic reticulum Ca2+ concentration after 48h of treatment. Increase of oxidative stress, especially the expression of ROS, can also represents a mechanism of cell death of PtAcacDMS and can be modulate the modification of chromatin and thus gene expression. Further experiments are needed to confirm these data, in particular the analysis of specific mechanisms involved in the modulation of intracellular calcium and the analysis of apoptosis and autophagy when cells growing in absence of Ca2+.
For the second stage we used mouse LLC (Lewis lung cancer) non-small cell lung cancer cell line. After generating cell lines resistant to Cisplatin, followed by their characterization with respect to PARylation, cells were injected in immunocompetent C57BL/6 mouse to evaluate the immune infiltrated. In vivo results show differences in immune infiltrate, especially in TAMs and Treg, more expressed in resistant cells, but to confirm if PARP-1 is implicated in this modulation it will be necessary to manipulate the expression of PARP-1 in the clones CDDP-resistant, silencing its expression by siRNA, to evaluate whether these injected cells exhibit the same immune infiltrate as the WT cells.
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Ewen, C. "The effects of radiation and chemotherapy on late responding tissues." Thesis, University of Manchester, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.383217.
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O'Donovan, Bernadine. "'Beyond the desired effect' : patients' experiences in identifying and managing side effects from medicines." Thesis, University of Kent, 2017. https://kar.kent.ac.uk/66995/.
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Side effects from medicines can have considerable negative impact on peoples' daily lives. As a result of an aging UK population and attendant multi-morbidity, an increasing number of medicines are being prescribed for patients, leading to increased risk of unintended side effects. The aim of this study was to explore experiences and opinions of patients and the public in identifying and managing side effects from medicines. It also sought to develop a novel causality scale for use by patients to assess suspected side effects. A mixed methods approach with four phases was selected. In Phase One surveys were distributed in pharmacies to gather information on patients' experiences of side effects and recruit potential interviewees for the following phase (935 surveys distributed; 230 returned). In-depth interviews were conducted in Phase Two with 15 people who had experienced side effects. These explored their opinions and experiences and informed Phase Three. This phase developed and validated a side effects assessment tool for patients' use (SE-PAST). The validation consisted of two strands, initial validation (by 31 assessors) followed by online validation (273 completed responses). In Phase Four 2285 patient reports to the Yellow Card Scheme were examined to learn about experiences of side effects, to investigate the value of patient reports to pharmacovigilance and to compare experiences of Yellow Card reporters to the public. This study provided novel insights into the strategies employed by patients to identify and manage their side effects. Patients seeking side effect information used a variety of information sources and the findings suggest that a key aspect of source selection may be a hierarchy of source characteristics. The strategies used to manage side effects varied, including both cognitive and behavioural responses such as non-adherence and consultation with healthcare professionals. The findings suggest that these strategies were influenced by a range of factors including established health beliefs; previous experience of side effects and cognitive biases. Areas of similarity and difference were identified between Yellow Card reporters and the general public. There was evidence of patterns in the causative drugs, the type and impacts of effects between those who report side effects and the wider public; however there was a difference in coping strategies between these groups, with non-adherence being more prevalent among Yellow Card reporters. Most on-line users of the SE-PAST agreed it would encourage them to report their side effect or talk to a healthcare professional about it. The thesis provides a unique and insightful perspective on patients' personal experiences of side effects, with implications for policy and practice. It has established that side effects can have noteworthy impacts with prolonged consequences on many aspects of patients' lives.
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Patel, Bhavesh Kantilal. "Stereospecific bioanalysis of ibuprofen and flurbiprofen : application to dispositional studies in humans." Thesis, King's College London (University of London), 2000. https://kclpure.kcl.ac.uk/portal/en/theses/stereospecific-bioanalysis-of-ibuprofen-and-flurbiprofen--application-to-dispositional-studies-in-humans(4ce11f77-500a-448e-b70d-34ae194fb662).html.
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Zahir, Sheba Adam. "Evaluating the efficacy of DNA repair biomarkers to assess human cell response to chemotherapy using imaging flow cytometry." Thesis, Brunel University, 2013. http://bura.brunel.ac.uk/handle/2438/7768.
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Chemotherapy and radiotherapy are widely accepted as common forms of treatment for cancers. The majority of cancer patients receive chemotherapy alone or in combination with radiotherapy. Most chemotherapeutic drugs cause DNA damage to the rapidly dividing cancer cells but normal cells are also damaged in the process. Therefore DNA repair levels in tumour and normal cells may determine the success of the treatment. The aim of this work was to evaluate the use of DNA repair biomarkers for assessing responses to chemotherapeutic drugs. The novel technique of imaging flow cytometry was employed to analyse the induction and resolution of γ-H2AX and RAD51 DNA repair biomarkers in DNA repair normal cell lines MRC5-SV1 and NB1-HTERT, an ATM-deficient cell line AT5BIVA (derived from an Ataxia Telangiectasia patient) and an XPF-deficient cell line GM08437B. Two cell lines were also developed, MRC5-SV1R and NB1-HTERTR which had been made resistant to HN2. A range of chemotherapeutic drugs, Adriamycin, Cisplatin and Nitrogen Mustard which have different modes of action were examined in this work. We have demonstrated distinct differences in γ-H2AX and RAD51 foci induction and resolution between the two DNA repair normal cell lines following exposure to different chemotherapeutic drugs. Additionally, it was demonstrated that both the resistant and sensitive cell lines have elevated γ-H2AX and RAD51 expression profiles in comparison to the parental cell lines over a 48 hour period post treatment with the cross-linking agent HN2. It is concluded that while both the γ-H2AX and Rad51 biomarkers may be useful for determining chemotherapeutic response, a larger cohort of cell lines and tumour samples is required for further analysis.
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Binks, Stephen Peter. "Absorption, toxicity and deposition of transition metal based pharmaceuticals following oral administration." Thesis, University of Surrey, 1988. http://epubs.surrey.ac.uk/847165/.
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The aim of this dissertation was to study the absorption, and subsequent toxic side effects of transition metal based pharmaceuticals following oral administration to rats. Administration of cisplatin (30mg/kg), carboplatin (37mg/kg) and iproplatin (42mg/kg) by oral gavage resulted in their rapid absorption so that respective peak blood levels of 2.63mug platinum/ml, 1.48mug platinum/ml and 3.13mug platinum/ml were achieved within 2-4 hours. Approximately 3-4% of the dose was excreted in the urine, but the major route of elimination was the faeces (>75%). This indicated that although rapid, absorption was relatively poor. Absorption was enhanced by employing a period of starvation prior to administration. A series of novel platinum (IV) mixed amines were absorbed to a greater extent than cisplatin and its congeners, carboplatin and iproplatin. However, absorption was somewhat slower with peak blood levels being attained some 24 hours after administration. Of the other transition metal complexes studied, auranofin and ruthenium acetylacetonate were particularly well absorbed so that peak blood levels of 12.53mug gold/ml and 6.4mug ruthenium/ml were achieved respectively. Urinary clearance of the ruthenium complex was especially significant with up to 45% of the administered dose being eliminated by this pathway within 48 hours. In vitro everted gut sac and in situ perfusion techniques confirmed the in vivo finding that cisplatin is absorbed from the small intestine more readily than carboplatin. No evidence for active or carrier-mediated transport was found and kinetic studies confirmed that absorption was by passive diffusion. Toxicology studies after oral administration of cisplatin (57 or 30mg/kg) or carboplatin (282mg/kg) indicated that the toxicities associated with the perenteral use of the complexes would also apply to the oral route. This was exemplified by the fact that oral cisplatin was profoundly nephrotoxic, whereas carboplatin was not. In addition, gastro-intestinal toxicity manifested as acute necrotizing enteritis and ulcerogenicity of the stomach was potentiated by the oral route. Studies in the ferret indicated that cisplatin is significantly more emetogenic than carboplatin. Examination of liver morphology indicated changes, such as mitochondrial swelling and vesiculation of the endoplasmic reticulum, that might indicate a higher incidence of hepatotoxic responses associated with administration of platinum complexes by the oral route. Both cisplatin and carboplatin induced a degree of myelosuppression but the most pronounced haematological lesion associated with oral administration was severe erythrocytosis which occurred as a result of a dehydration related decrease in plasma volume. Electrothermal atomic absorption analysis of tissues excised from cisplatin and carboplatin rats indicated that platinum deposition was highest in the kidney. In an attempt to explain the prolonged retention of cisplatin in this organ, the intracellular location of the compound was studied using electron microprobe analysis and subcellular fractionation. The various lysosome populations of the proximal tubule were identified as sites of concentration of platinum and it was hypothesised that sequestration within these organelles might be an important mechanism of detoxification.
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Martinez, Ramon D. "Purification and characterization of Clostridium sordellii toxins HT and LT and comparison to toxins A and B of Clostridium difficile." Diss., Virginia Polytechnic Institute and State University, 1989. http://hdl.handle.net/10919/54238.
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Clostridium sordellii cause gas gangrene in man and animals, and more recently it has been implicated as a causal agent of diarrhea and enterotoxemia in domestic animals. This organism was once believed to cause pseudomembranous colitis (PMC) in humans, however, Clostridium difficile, not C. sordellii, was found to be the causative agent of this disease. It is now known that C. difficile produces two toxins, designated A and B, that are implicated in the pathogenesis of the disease. C. sordellii produces two toxins, designated HT (Hemorrhagic Toxin) and LT (Lethal Toxin), that are similar to toxins A and B of C. difficile. The goal of my research was to purify and characterize the two toxins of C. sordellii, and compare their properties to those of C. difficile. Toxin HT was purified from C. sordellii (VPI strain 9048) culture filtrate by ultrafiltration through an XM-100 membrane filter and immunoaffinity chromatography using a monoclonal antibody to toxin A of C. difficile as the ligand. Toxin LT was purified to 80% homogeneity by ultrafiltration on an XM-100 membrane filter and ion-exchange chromatography. Toxin HT migrated as a major band with molecular weight of 525,000 and a minor band at 450,000 on non-denaturing PAGE. By SDS-PAGE the molecular weight was estimated at 300,000. Isoelectric focusing indicated a pI of 6.1. Like toxin A, toxin HT was cytotoxic to cultured cells, lethal for mice, and elicited an accumulation of hemorrhagic fluid in rabbit ileal loops. Toxin LT exhibited properties similar to toxin B, although LT was about a 1000-fold less cytotoxic than toxin B. By SDS-PAGE the molecular weight was estimated at 260,000. Immunodiffusion analysis revealed a reaction of partial identity between these toxins and their amino-terminal sequences were very similar.
Toxins HT and LT of C. sordellii have retained remarkable immunological similarities as well as physicochemical and biological properties with toxins A and B of Q. difficult however the toxins are not identical.Ph. D.
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Brown, Mary Catherine. "The impact of side effects on travellers' compliance with antimalarials." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ29663.pdf.
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Svensson, Staffan. "Medication adherence, side effects and patient-physician interaction in hypertension /." Göteborg : Department of Clinical Pharmacology, Institute of Internal Medicine, The Sahlgrenska Academy at Göteborg University, 2006. http://hdl.handle.net/2077/635.
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Brown, Mary Catherine 1964. "The impact of side effects on travellers' compliance with antimalarials /." Thesis, McGill University, 1997. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=35308.
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The association between side effects to antimalarial chemoprophylaxis and noncompliance was assessed in travellers visiting five pre-travel clinics in the greater Montreal area between February and August 1996. Participants completed pre and post-travel questionnaires to ascertain frequency and severity of side effects and compliance with malaria chemoprophylaxis. A participation rate of 83% was achieved. Of 157 travellers prescribed mefloquine and 132 travellers prescribed chloroquine, proportions experiencing symptoms or side effects were high (7% and 83%, respectively), but not statistically significantly different. Gastrointestinal side effects were more common in chloroquine users (68%) than in mefloquine users (56%) (p = 0.04). No difference was observed in proportions of psychological side effects between groups; however, they were more commonly reported in the mefloquine group. Between 26% and 33% of noncompliance was directly attributed to side effects; however, logistic regression analysis showed no significant impact of side effects on noncompliance, after controlling for other determinants.
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Lundkvist, Erik. "Side effects of being tired : burnout among Swedish sport coaches." Doctoral thesis, Umeå universitet, Institutionen för psykologi, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-98056.
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Burnout is a psychological concept that have got much attention since it was first defined in the middle of the 1970s. Although the definition of burnout differ there is consensus about exhaustion as the most important part of the concept. Burnout have also been in focus in sport psychology research. Mostly athletes have been studied but interest the coach profession have also been of interest. Research on coach burnout have mostly been directed towards demographic variables, organizational issues, behaviors and emotions and more holistic perspectives covering larger models or theories. The aims with this thesis was to try to fill some of the knowledge gaps from earlier coach burnout research with three studies. Study 1 aimed to study subjective experiences associated with perceived causes and symptoms of burnout and the subsequent recovery process. Eight elite soccer coaches who previously had been troubled with high scores of the exhaustion was interviewed. We found two burnout profiles that matched the coaches’ perceived causes of burnout. The first was associatedwith problems in handling the performance culture itself and the second had to do with the overall situation, including workload, family and health. Our findings describe coach burnout as stemming from a combination of issues, related to both home and work. When combined with work overload, coaches who have problems handling the performance culture in elite sports, and who lack the tools to enhance recovery, are particularly vulnerable to burnout. Study 2 focused on evaluating three self-report burnout measures that are available for researchers to use. Our analysis included Maslach Burnout Inventory (MBI), Oldenburg Burnout Inventory (OLBI) and Coach Burnout Questionnaire (CBQ). The main findings were that there are psychometric problems with all three measures and that MBI and OLBI cover similar definitions of burnout and CBQ cover somewhat different dimensions. Of the three methods that were tested CBQ seem to be most suitable for the coaching context. However, CBQ also have several problems and other burnout measures need to be evaluated in the coach context. Study 3 focused on the associations between workaholic tendencies and combining coaching job with having a family or a spouse, which can be a stressor since the work situation and family situation can be hard to combine. The main findings were that work seem to interfere more with family life than family life interfere with working live. Further workaholic tendencies and exhaustion was not associated. When interpreting the aggregated results from the thesis there are two main findings. First, the way coach burnout has been measured until now is unsatisfying. Although the development of a coach specific measure (CBQ) is promising, further development is needed, both when it comes to the theoretical aspects of the burnout construct and psychometric issues. Second, the symptoms and perceived causes in coach burnout is highly individual and makes burnout a very personal experience. Future research should focus on both the origins as well as the measurement of thisdetrimental concept.Utbrändhet är ett psykologiskt begrepp som har fått mycket uppmärksamhet sedan den först introducerades i mitten av 1970-talet. Även om synen på vad utbrändhet är skiljer sig åt finns en enighet om att utmattning är huvudsymptomet. Utbrändhet har studerats inom idrottspsykologisk forskning sedan början av 1980-talet. Mestadels har intresset legat på idrottare men intresse har också riktats mot tränaryrket. Forskning om tränares utbrändhet har främst intresserat sig för demografiska variabler, organisationens påverkan, beteenden och känslor samt mer övergripande modeller eller teorier som täcker flera områden. Syftet med denna avhandling var att försöka fylla en del av de kunskapsluckor som funnits i tidigare forskning med tre studier. Studie 1 syftade till att studera tränares subjektiva upplevelser av utmattning kopplat till upplevda orsaker och symptom av utbrändhet samt vägen tillbaka från utbrändhet. Åtta elitfotbollstränare som tidigare hade haft problem med utmattning intervjuades. Huvudresultatet i studien var att det fanns två sätt att uppfatta utbrändhetsprocessen. Antingen såg man miljön runt elitfotbollen som den stora orsaken eller så upplevdes hela livssituationen med små stressande händelser kopplade till arbetsbelastning, familj och hälsa som problematiska. Studie 2 fokuserade på att utvärdera tre frågeformulär som är lämpliga i en tränarkontext. I analysen ingår Maslach Burnout Inventory (MBI), som oftast använts, Oldenburg Burnout Inventory (OLBI) och Coach Burnout Questionnaire (CBQ). De viktigaste resultaten var att det dels finns problem med alla tre samt att MBI och OLBI täcker liknande definitioner av utbrändhet medan CBQ mäter lite andra aspekter. Slutsatsen från studien är att CBQ verkar passa bäst för den kontext där idrottstränare arbetar även om CBQ också har en del problematiska inslag. Studie 3 fokuserade på arbetsnarkomani och att kombinera tränarjobb med familjeliv har ett samband med utmattning. Huvudresultaten i studie 3 var att det framförallt verkar vara arbetet som störa familjelivet än familjelivet som stör arbetslivet. Ytterligare fanns inget statistiskt stöd att arbetsnarkomani skulle ha ett samband med utmattning. När det sammanlagda resultatet från hela avhandlingen tolkas utifrån vilken ny kunskap denna avhandling tillför finns två huvudbidrag. Det första är att problemen med de frågeformulär som hittills använts för att mäta utbrändhet har lyfts upp. Även om det är lovande att det utvecklats ett idrottsspecifikt formulär finns tillgängligt så finns det både teoretiska och mättekniska aspekter som behöver utvecklas. Det andra bidraget är att de symptom som ingår i upplevelsen av utbrändhet verkar vara olika för olika individer. Framtida forskning bör fokusera både på hur teoretiska och mättekninska aspekter av utbrändhetsbegreppet.
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Fraser, Douglas (Douglas H. ). "Triptycene side unit effects on compressive yield strength in polycarbonates." Thesis, Massachusetts Institute of Technology, 2006. http://hdl.handle.net/1721.1/35071.
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Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Materials Science and Engineering, 2006.Includes bibliographical references (leaf 25).
Polycarbonates have long been studied for their excellent mechanical toughness. Adding side units to polycarbonate could increase physical properties of the polymer. The role of triptycene in polycarbonate was studied by adding a low concentration of triptycene-containing polymer chains, and using compression testing. The triptycene polycarbonate was a blend created from two separate products. Differential Scanning Calorimetry was used to determine if the samples had phase separated. Thermal degradation of the samples was checked for using Thermogravimetric Analysis. Results indicated that triptycene-containing polycarbonates had higher compressive yield strengths than non-triptycene polycarbonates. The polymers were stronger due to the interlocking mechanism and the steric hindrance of the triptycene units. The design of strengthening polymers by adding triptycene units could prove useful to improve high performing polymers, or to give low molecular weight polymers more stability.
by Douglas Fraser.
S.B.
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Kallam, Kalyani. "Side chain decoration of anthocyanins : mechanisms and effects on functionality." Thesis, University of East Anglia, 2012. https://ueaeprints.uea.ac.uk/42384/.
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Anthocyanins are plant pigments offering a range of colours to fruits and flowers. Many properties of anthocyanins are influenced by the degree and type of side chain modifications. Though much is known about the biosynthesis of anthocyanins and the enzymes involved in side-chain decoration, there is limited understanding of the structural features of anthocyanin acyltransferases that determine their substrate preference. Anthocyanin acyltransferases belong to the BAHD family of enzymes and are involved in acylation. Through mutagenesis I showed that an arginine positioned close to motif-1 in aliphatic anthocyanin acyltransferase determines the enzyme’s specificity for malonyl transfer. Modification of arginine to phenylalanine in Ch3MAT, led to gain of acetylation property. This study thus suggests that CoA interacting residues are conserved in aliphatic acyltansferases. A phenylalanine in a similar position, close to motif 1 in aromatic anthocyanin acyltransferases is crucial for the specificity for aromatic-CoA of aromatic acyltransferases. To understand the influence of different side-chain modifications on the formation of anthocyanic vacuolar inclusions (AVIs), I showed that coumaroylation of anthocyanins leads to AVI formation when high levels of anthocyanins are accumulating. Malonylation does not lead to the formation of AVIs, suggesting that the ability of aromatic moieties to form intra-molecular stacks can cause formation of AVIs. Neither the presence of flavonols nor light or high amounts of anthocyanins can lead to the formation of AVIs. Therefore, the type of decoration mainly aromatic acylation of anthocyanins is responsible for AVI formation. From understanding the molecular mechanisms of acyltransferases for side chain decoration to their activity, anthocyanins can be engineered by anthocyanin acyltransferases in plants for novel functionalities. I showed that coumaroylation of anthocyanins promotes copigmentation more effectively than 5-glucosylation. 5- glucosylation, together with coumaroylation, offered stability to anthocyanins, both invitro and in-vivo. I also showed that flavonols copigment better than phenolics with anthocyanins, a property which could be useful for developing natural food colours. Thus, my study provided an in-depth investigation from molecular mechanisms to final applications of side chain decoration of anthocyanins.
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Franco, Nuno Filipe Barradas. "Business models for airport management and development: air-side effects." Master's thesis, Universidade da Beira Interior, 2009. http://hdl.handle.net/10400.6/2047.
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The civil aviation has always faced demanding challenges. One of the challenges of our days is the massification of its main product: air travel. The increased mobility in our society determines that, different airports, in a geographic area, compete for the same market. The airlines, their main clients, face a particularly difficult situation, also dealing with though competition and high operational costs, adding to this, the oil prices escalade may have restarted, thus guessing a difficult picture for the airlines in a near future and increased pressure over the airports’ taxation policies.
The quest for success in this dynamic and competitive market has driven airports to look for revenue augmentation solutions that meet the airlines’ demands of adjustment to their favour of the traditional source of airport revenue: Airport Taxes. To tackle this and at the same time answer to many passenger comfort and quality of services demands, the solution was to go commercial. Meanwhile, advances in air traffic control technology represent a window of opportunity for a more efficient use of airport structures and airspace, therefore increasing the volume of aircraft movements possible within the same infrastructure.
Many airports around the world, took advantage of the enormous passenger flow thru airport terminals, to market all kinds of services and commodities, in the airport’s premises and in the airport’s surrounding land (often airport’s property). Whether related to the aeronautical industry or not, companies, are naturally driven to seek the advantages of being located next to an airport facility, where business is alive and land prices are lower. This business model has achieved success in many airports around the world and others show signs of development in that direction, taking advantage of this new trend, in which airports make profit acting as the landlord, in what are already being called: Aerotropolis.
The regional economy is animated by the presence of a prosperous and growing airport city, but regional planning must integrate the airport city adequately, specially in what concerns to it’s transportation network that will, not only, provide access but also has the potential to expand the airport’s area of influence.A aviação civil sempre enfrentou desafios exigentes. Um dos desafios dos nossos dias é o da massificação do seu maior produto: as viagens aéreas. A elevada mobilidade da nossa sociedade determina que, diferentes aeroportos, numa dada área geográfica compitam pelo mesmo mercado. As companhias aéreas, suas principais clientes, enfrentam uma situação particularmente difícil, lidando, também com feroz competição e altos custos operacionais, adicionando a isto, a escalada dos preços do petróleo poderá ter recomeçado fazendo adivinhar um quadro difícil para estas num futuro próximo. A procura por sucesso neste dinâmico e competitivo mercado, levou os aeroportos a procurarem soluções para o aumento das receitas que vão de encontro às exigências das companhias aéreas, de ajuste a seu favor, da tradicional fonte de receitas dos aeroportos: as Taxas Aeroportuárias. Para colmatar este problema e ao mesmo tempo responder às muitas exigências de conforto e qualidade de serviços por parte dos passageiros, a solução foi a viragem para a comercialização. Entretanto avanços na tecnologia de controlo de tráfico aéreo representam uma janela de oportunidade para um uso mais eficiente das infra-estruturas aeroportuárias, incrementando assim o volume de movimentos possíveis com a infra-estrutura actual. Muitos aeroportos, pelo mundo fora, tiraram proveito do enorme fluxo de passageiros através dos terminais aeroportuários para comercializar todo o tipo de serviços e produtos, tanto nas instalações aeroportuárias como nas áreas circundantes do aeroporto (frequentemente propriedade do aeroporto). Sejam elas ligadas ou não à indústria aeronáutica, um número significativo de companhias procura as vantagens de estar localizadas junto a uma infra-estrutura aeroportuária onde o negócio está vivo e os preços da propriedade são mais baixos. Este modelo de negócio atingiu sucesso em muitos aeroportos pelo mundo fora e um número significativo deles estão a tirar vantagens desta nova tendência, em que os aeroportos realizam lucros sendo os senhorios, no que já estão a ser chamadas: Aerotropolis. A economia regional é animada pela presença de prósperas e crescentes cidades aeroporto, mas o plano de ordenamento territorial deve integrar adequadamente a cidade aeroporto, especialmente no que concerne à sua rede de transportes que, não só providenciará acesso como também tem o potencial de expandir a aérea de influência do aeroporto.
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Brookshire, Stephen William. "A Novel Bifunctional Opioid That Lacks Traditional Opioid Side Effects." Thesis, The University of Arizona, 2012. http://hdl.handle.net/10150/243897.
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Prescription opioids, such as morphine, remain an important part in the management of pain. However, their clinical utility can be limited by side effects such as constipation, nausea, and high risk of addiction. Additionally, abuse of prescription opioids has been on the rise in recent years. Therefore, it is necessary to develop effective analgesics that lack the rewarding properties of currently used opioids. The neurokinin-1 receptor (NK-1) and its endogenous ligand, Substance P (SP), have been implicated in the control of nausea and vomiting, as well as mediating the rewarding effects of opioids. Here we have characterized the side effects of a novel efficacious opioid agonist/NK-1 antagonist, TY027. TY027 fails to elicit conditioned place preference, retching or vomiting, and does not inhibit gastric motility. These findings suggest that TY027 has a superior side effect profile when compared to currently used opioids, and most importantly, it does not produce rewarding effects that may lead to addiction.
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Padayachee, Vaneshree. "Awareness regarding non-steroidal anti-inflammatory drug-related side effects in Johannesburg, South Africa." University of Western Cape, 2021. http://hdl.handle.net/11394/8370.
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>Magister Scientiae - MScNon-steroidal anti-inflammatory drugs (NSAIDs) are amongst the most commonly used medications globally, as they are highly effective and easily accessible. The NSAIDs are indicated for mild to moderate pain management. The increasing incidence of NSAID related side effects and hospitalisations has raised a concern about these medications’ safety. The prevalence of these side effects has drastic consequences to a challenged South Africanpublic healthcare system. The implications of not treating severe, potentially preventable upper gastrointestinal complications attributed to NSAIDs’ consumption continue to be a significant problem that healthcare professionals (HCP) face.
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Powers, Tiffany M. "Expression patterns of cyclin D1, D2, and D3 in the first three cell cycles in preimplantation embryo development." Virtual Press, 2004. http://liblink.bsu.edu/uhtbin/catkey/1306857.
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Cell-cycle progression in mammalian cells is coordinated by a series of control points. The D-type cyclins are a family of key cell cycle regulators that are controlled largely by mitogens and their association with and activation of cdk 4 and 6 at the G1 phase of the cell cycle. This study seeks to first analyze cyclins D1, D2, and D3 expression patterns in preimplantation mouse embryos using in vivo studies and then analyze the effects of Dilantin on the cyclin D1 expression pattern in cultured embryos. Antibody staining against cyclin D1, D2, and D3 via indirect immunofluorescence using a Zeiss Confocal Microscope and analysis of individual embryo staining intensities using Zeiss computer software were employed to evaluate expression patterns throughout the first three cell cycles. The data showed that all three D cyclins were present throughout the first three cell cycles. Cyclin D1 had peak average fluorescence intensity at the G2 phase of the second cell cycle with a decrease at the G1 in the third cell cycle. Cyclin D2 had a consistent increase of fluorescence intensity throughout all three cell cycles. Cyclin D3 had peak average fluorescence intensity at the G2 phase of the second cell cycle with an immediate decrease at the Gl phase in the third cell cycle. Cyclin D1 was localized to the nucleus in G1 phases of the cell cycle. In contrast, cyclin D2 was found in the nucleus during G2 phases of the cell cycle rather than in G1. Cyclin D3 was not localized to the nucleus in either cell cycle phase throughout the first three cell cycles. These unique nuclear staining patterns seen by D1, D2, and D3 may reflect a function in the cell cycle. Embryos cultured in the presence of l0gg/ml of Dilantin were found to be slowed in development indicated by the absence of transition from the one-cell to the two-cell stage when compared to the controls. Since the Dilantin cultured embryos never reached G1 of the second cell cycle the increase in fluorescence intensity seen was still considered to be a representation of the G2 phase of the first cell cycle. Cyclin Dl's fluorescence intensity was affected by Dilantin and accompanied with unstained nuclei during the G2 phase of the first cell cycle. The peak average fluorescence intensity occurred during the G1 phase of the second cell cycle for cyclin D1 stained CZB control, while the vehicle control, 0.001N NaOH, remained constant. Both CZB and 0.001N NaOH had similar expression patterns seen previously in the cyclin D1 in vivo data. The information gained from the in vivo and in vitro experiments will help to better understand what causes the problems associated with exposure to Dilantin, and also the effects Dilantin has on the cell cycle.Department of Biology
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Petley, Anne M. "Nicotinamide : implications for the prevention and treatment of Type I diabetes." Thesis, University of Southampton, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295712.
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Олещенко, Галина Павлівна, Галина Павловна Олещенко, Halyna Pavlivna Oleshchenko, and К. П. Гніденко. "Особливості побічних реакцій на протитуберкульозні препарати у хворих на хіміорезистентний туберкульоз." Thesis, Державна наукова установа «Науково-практичний центр профілактичної та клінічної медицини» Державного управління справами, 2019. https://essuir.sumdu.edu.ua/handle/123456789/81283.
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Кількість зареєстрованих побічних реакці досягає зазначеному Всесвітньою організацією охорони здоров'я (44-60 %) при лікуванні хіміорезистентного туберкульозу. Слід звертати увагу на моніторинг та реєстрацію побічних реакцій, що сприятиме своєчасному та повноцінному їх лікуванню, а відтак – підвищить ефективність лікування туберкульозу взагалі.
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Liu, Zhongqiu. "Mechanism of pharmacokinetic interaction between paeoniflorin and sinomenine." HKBU Institutional Repository, 2006. http://repository.hkbu.edu.hk/etd_ra/720.
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Humble, Mats B. "Obsessive-compulsive disorder, serotonin and oxytocin : treatment response and side effects." Doctoral thesis, Örebro universitet, Institutionen för medicinska vetenskaper, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-51438.
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Obsessive-compulsive disorder (OCD), with a prevalence of 1-2 %, frequently leads a chronic course. Persons with OCD are often reluctant to seek help and, if they do, their OCD is often missed. This is unfortunate, since active treatment may substantially improve social function and quality of life. Serotonin reuptake inhibitors (SRIs) have welldocumented efficacy in OCD, but delayed response may be problematic. Methods to predict response have been lacking. Because SRIs are effective, pathophysiological research on OCD has focussed on serotonin. However, no clear aberrations of serotonin have been found, thus other mechanisms ought to be involved. Our aims were to facilitate clinical detection and assessment of OCD, to search for biochemical correlates of response and side-effects in SRI treatment of OCD and to identify any possible involvement of oxytocin in the pathophysiology of OCD. In study I, we tested in 402 psychiatric out-patients the psychometric properties of a concise rating scale, “Brief Obsessive Compulsive Scale” (BOCS). BOCS was shown to be easy to use and have excellent discriminant validity in relation to other common psychiatric diagnoses. Studies II-V were based on 36 OCD patients from a randomised controlled trial of paroxetine, clomipramine or placebo. In study II, contrary to expectation, we found that the change (decrease) of serotonin in whole blood was most pronounced in non-responders to SRI. This is likely to reflect inflammatory influence on platelet turnover rather than serotonergic processes within the central nervous system. In studies IV-V, we found relations between changes of oxytocin in plasma and the anti-obsessive response, and between oxytocin and the SRI related delay of orgasm, respectively. In both cases, the relation to central oxytocinergic mechanisms is unclear. In males, delayed orgasm predicted anti-obsessive response.
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Howes, Dr Oliver. "The endocrine side effects of antipsychotic medication: prevalence, impact and treatment." Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.491902.
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Antipsychotic drugs have been known to have effects on the endocrine system since their introduction to clinical practice. However, until recently there has been little systematic investigation of the prevalence and end-organ effects of endocrine disturbance in people taking antipsychotic medications. This thesis presents a series of studies that investigate glucose-insulin homeostasis, hypothalamic-pituitary-gonadal (HPG) axis function, and the relationship between abnonnalities of the HPG axis and sexual function, bone mineral density (BMD), and glucose-insulin homeostasis in patients taking antipsychotic medication. Abnonnalities of glucose-insulin homeostasis were found in patients taking antipsychotic drugs, and switching antipsychotic treatment to clozapine was associated with the rapid development of glucoregulatory abnonnalities which were not related to changes in insulin, prolactin, insulin-like growth factor or growth honnone levels. The studies of the HPG axis found that, as expected, prolactin levels were commonly elevated in patients taking most antipsychotic drugs. Low testosterone, oestradiol and progesterone levels and high rates of sexual dysfunction were found in patients taking antipsychotic drugs, extending recent findings in a larger systematically acquired sample of subjects. However, no relationship was found between sex honnone or prolactin levels and sexual function. BMD was not found to be decreased to a clinically significant level in patients taking antipsychotic drugs, and was not related to prolactin levels. The findings presented in this thesis indicate that patients and clinicians need to be aware of the high likelihood of glucose-insulin and HPG axis disturbance, and sexual dysfunction associated with most antipsychotic treatments. Additionally these data indicate that the aetiology of sexual dysfunction and glucoregulatory abnonnalities is complex, and that the abnonnalities are not simply explained by the effects of prolactin elevation, reduced sex honnone levels, or disturbance of insulin homeostasis. A randomised controlled trial (RCT) was conducted to investigate the effects on sexual function, sex honnone levels, and bone mineral density of switching antipsychotic treatment to a relatively prolactinsparing medication compared with remaining on a relatively prolactin-raising drug. The RCT was discontinued early because inadequate recruitment and retention of subjects meant that there was insufficient power to detect differences between treatments. The factors contributing to the difficulties with the RCT are discussed and suggestions presented to guide the development of future studies to investigate treatment approaches to sexual dysfunction and hypogonadism in patients taking antipsychotic medications. 1 Supplied by The British Library - 'The world's knowledge' The thesis comprises introductory and concluding chapters, a description of the discontinued RCT and the following published papers: Howes OD, Rifkin L. Diabetic keto-acidotic (DKA) coma following olanzapine initiation in a previously euglycaemic woman and successful continued therapy with olanzapine. J Psychopharmacol (2004); 18(3): 435-7. Howes 0, Smith S. Alendronic acid for antipsychotic-related osteopenia. Am J Psychiatry (2004); 161(4): 756 Howes OD, Wheeler MJ, Pilowsky LS, Landau S, Murray RM, Smith S. Sexual function and gonadal hormones in patients taking antipsychotic treatment for schizophrenia or schizoaffective disorder. J Clin Psychiatry 2007; 68(3): 361-7. Howes OD, Wheeler MJ, Meaney AM, O'Keane V, Fogelman I, Blake G, Murray RM, Smith S. Bone mineral density and its relationship to prolactin levels in patients taking antipsychotic treatment. J Clin Psychopharmacology. 2005; 25(3): 259-61. Howes OD, Smith S, Gaughran F, Murray RM, Pilowsky LS. The relationship between prolactin levels and glucose homeostasis in antipsychotic treated schizophrenic patients. J Clin Psychopharmacology 2006: 26(6); 629-31 Howes OD, Bhatnagar A, Gaughran FP, Amiel SA, Murray RM, Pilowsky LS. A prospective study of impairment in glucose control caused by clozapine without changes in insulin resistance. American Journal of Psychiatry. 2004: 161 (2); 361-363. Howes OD, Gaughran FP, Amiel SA, Murray RM, Pilowsky LS. The Effect of Clozapine on Factors Controlling Glucose Homeostasis J Clin Psychiatry 2004; 65 (10): 1352- 1355