This dissertation is structured around three original studies that offer unique insights into the challenges of change in business-to-business markets. All three studies share as an important starting point that firms rely on other firms to achieve strategic flexibility in volatile business environments. This means that firms source critical resources from business relationships in order to reduce long-term investments in times of change. From this perspective, firms' competitive advantages cross the boundaries of the firm and are embedded in their business partner networks. Thus, firms' business relationships and networks have become an important locus of organizational change in order to respond to turbulence in firms' business environments. Study one of this dissertation recognizes the importance of supplier relationships as a mechanism to react to changing business environments. The article focuses on the dynamic capabilities that enable firms to structurally reconfigure their supplier portfolios or supply networks in order to access necessary resources. The framework of relationship management capabilities introduced, is structured around three important sub-dimensions: relationship initiation, development, and ending capabilities, which collectively enable a firm to manage the reconfiguration of resource portfolios accessed via supplier relationships. The key implication for management relates to thinking beyond firms' established supply chains in times of change. While to a certain degree change can be absorbed within firms' existing supply chains, there might be a need to be 'agile', i.e. search for other suppliers who are better suited to more efficiently and effectively address such changes affecting firm competitiveness in the long run. While study one highlights the importance of firms' agility in adapting their supply chains in response to changes in their business environment, study two of this dissertation, although with a focus on the demand side of the business model, addresses the managerial challenges associated with such an agile adaptation process. Study two conceptualizes a framework for business model change and provides managers guidance to approach business model redesign. In particular, study two focuses on service business models and introduces the concepts of service infusion and defusion as important processes of business model redesign. The service infusion and defusion framework provides a pragmatic and systematic approach to understanding the nature of the business model change that companies have to manage, as well as linking these changes with knowledge creation and transfer processes. These are shown to be key for successfully managing such a business model redesign. While studies one and two assume strategy and its implementation to be key to a successful response to changes in firms' business environment, study three draws attention to the difficulties of arriving at such an appropriate or fitting response strategy in the first place, given the available information. In particular, this study examines the link between sensing changes in firms' business environments and managerial decision making in the form of strategy choice. Thereby, the study shows that strategy change causes disruptions, which eventually affect firm performance. This effect is compounded with increasing sensitivity to change as well as increasing number of factors that trigger change, and thus impairs the long term benefits of such strategy change. Thus, the effectiveness of strategy or business model changes and their implementation is inevitably contingent on distinguishing key signals from noise that disturb or misguide firms' strategic decisions.

Made available in DSpace on 2014-06-11T19:22:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2005Bitstream added on 2014-06-13T18:48:57Z : No. of bitstreams: 1 hatschbach_e_me_botfmvz.pdf: 309067 bytes, checksum: 65f60947f2e929e489c630eafea55c04 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Empregou-se a dexmedetomidina em associação com a quetamina e midazolam, ou diazepam, observando-se assim os efeitos das benzodiazepinas em cães. Esta técnica anestésica foi aplicada em 30 cães hígidos com pesos e idades variáveis, machos ou fêmeas, distribuídos em três grupos (GI, GII, GIII). O GI recebeu um pré-tratamento com atropina, na dose de 0,04 mg/kg SC, e após 15 minutos, a dexmedetomidina a 3 æg/kg IV, em dose única durante 2 minutos, seguida de dose de manutenção pela dexmedetomidina 3 æg/kg, associada à quetamina na dose de 2 mg/kg, ambas na mesma seringa completando-se o volume em 20ml de solução fisiológica para infusão contínua, no período de uma hora de aplicação. O GII recebeu o mesmo tratamento de GI, entretanto, adicionou-se à dexmedetomidina o midazolam na dose de 0,2mg/kg durante os dois minutos iniciais e outra dose, de 0,2 mg/kg com a dose de manutenção da dexmedetomidina e quetamina obedecendo volume e período de G I. Em GIII obedeceu-se o mesmo tratamento de GII substituindo-se o midazolam pelo diazepam na dose de 0,5mg/kg na dose de indução e mais 0,5mg/kg junto com a dose de manutenção. Avaliou-se o efeito das benzodiazepinas para se evitarem as contraturas causadas pela quetamina sobrepondo-se à dexmedetomidina. Observaram-se as alterações paramétricas respiratórias, oxicapnométricas, índice bispectral e período de recuperação. Conclui-se diante dos resultados obtidos que: ao se aplicar a dexmedetomidina anteriormente à quetamina, não ocorrem contraturas apesar da leve redução do índice bispectral. Já a associação com benzodiazepínicos mostrou-se mais eficiente, demonstrando ser o midazolam mais eficiente na sedação e miorrelaxamento quando comparado ao diazepam... / Dexmedetomidine in combination with ketamine and midazolam, or diazepam was used, observing the effects of the benzodiazepines in dogs. The anesthetic technique was applied in 30 healthy dogs, males or females with varied weight, divided into three groups (GI, GII and GIII). The first group (GI) received a pretreatment with atropine at 0,044 mg/kg, and 15 minutes later, dexmedetomidine at 3 æg/kg intravenous, during two minutes, for induction. For maintenance was applied the same dose of dexmedetomidine (3 æg/kg) in combination with ketamine, all diluted in 20 ml of distilled water, during one-hour infusion. Group II (GII) received the same treatment as GI, however, midazolam was administered at 0.2 mg/kg in combination with dexmedetomidine, and another dose of 0.2 mg/kg, in combination with dexmedetomidine and ketamine in one-hour infusion. Group III (GIII) received the same treatment as GII, but diazepam was used instead of midazolam, 0.5 mg/kg for induction and 0.5 mg/kg for maintenance. It was evaluated the benzodiazepines effects to prevent the cataleptic effects (contraction) caused by ketamine, even with dexmedetomidine, the respiratory and oxycapnometric parameters, bispectral index and recovery period. From the results it could be conclude that dexmedetomidine administered before ketamine does not cause muscle contractions even with less reduction in bispectral index. Benzodiazepines association with ketamine showed more reliable effects, with synergic interaction, with good sedation and muscle relaxation, being midazolam better when compared to diazepam...

Orientador: Antônio José de Araújo Aguiar / Banca: Stélio Pacca L. Luna / Banca: Silvia Gaido Cortopassi / Banca: Denise Tabacchi Fantoni / Banca: Reinaldo C. Braz / Resumo: O emprego de procedimentos de anestesia intravenosa total em cães tem sido mais freqüente, devido ao melhor conhecimento do perfil farmacocinético dos fármacos empregados. Como ainda não existe um único fármaco que produza todas as características desejáveis em uma anestesia geral, há a necessidade de se associar ao hipnótico, agentes com propriedades analgésicas. O objetivo desse estudo foi avaliar os efeitos hemodinâmicos causados pela associação do cloridrato de dexmedetomidina, nas doses de 1 e 2 μg/kg/h, e propofol na dose de 0,3 mg/kg/min, administrada em infusão intravenosa contínua em cães, bem como o tempo de recuperação anestésica após duas horas de infusão. Seis cães, clinicamente sadios, sem raça definida, pesando 17,6±1,8 kg, foram submetidos a três tratamentos com intervalo de uma semana e em seqüência aleatória. Todos os animais foram inicialmente anestesiados com isofluorano a 5V% com fluxo de 3 l/min de O2. Após a indução e intubação, os animais foram posicionados em decúbito lateral esquerdo e mantidos com isofluorano na concentração de 1,8V%. As veias cefálicas e a artéria dorsal podal foram cateterizadas e um cateter de Swan Ganz 5F foi introduzido pela veia jugular. Após fixação dos cateteres na pele, a administração do isofluorano foi interrompida. Os cães permaneceram despertos por 1 hora, e após esse período, foi realizada a avaliação das variáveis hemodinâmicas. Em seguida os cães receberam um dos seguintes tratamentos: Controle: indução com propofol (6 mg/kg/30s) e solução de NaCl 0,9% (5 ml/10min) seguida de manutenção com propofol (0.3 mg/kg/min) e NaCl 0,9% (4 ml/h); Dex 1: indução com propofol (6 mg/kg/30s) e cloridrato de dexmedetomidina (1 μg/kg/10min) seguida de manutenção com propofol (0.3 mg/kg/min)... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Total intravenous anesthesia in dogs has been more frequently used, the pharmacokinetic profile of the new drugs is better understood. No injectable anesthetic produces all of the components of a general anesthesia, it is required to associate additional analgesics with hypnotic. The aim of this study was to evaluate the hemodynamic effects caused by the association of 1 and 2 μg/kg/h of dexmedetomidine and 0,3 mg/kg/min of propofol, administered by continuous intravenous infusion, as well time of anesthetic recovery after 2 hours of infusion. Six healthy dogs weighting 17,6±1,8 kg were randomly allocated to 3 treatments with at least one week intervals between each treatment. All animals were initially anesthetized with 5V% of isoflurane and 3 l/min of oxygen. After induction and intubation, the animals were posicionated in left lateral recumbence and maintained with 1.8% end tidal. All animals were instrumented with a cephalic veins and arterial catheter and a Swan Ganz catheter in order to a monitor hemodynamic parameters. After instrumentation isoflurane was interrupted and animals were awake and remained awake for one hour. After that, baselines parameters were taken. Dogs received each one of these treatments: Control: was induced with propofol (6 mg/kg/30s) and saline (5 ml/10 min), maintenance was with propofol (0.3 mg/kg/min) and saline (4 ml/h). Dex 1 was induced with propofol (6 mg/kg30s) and dexmedetomidine (1 μg/kg10 min), maintenance with propofol (0.3 mg/kg/min) and dexmedetomidine (1 μg/kg/h). Dex 2 was induced with propofol (6 mg/kg30s) and dexmedetomidine (2 μg/kg/10min), maintenance with propofol (0.3 mg/kg/min) and dexmedetomidine (2 μg/kg/h) during 120 minutes. The parameters (HR, SBP, MAP, DAP, CI, SI, CVP, PAP, POPA, SVRI, PVRI, RR, ETCO2, SaO2, pHa, PaO2, PaCO2, HCO3, Hb, CaO2, IDO2, temperature) were taken at 15, 30, 60, 90 e 120 minutes after induction... (Complete abstract click electronic access below) / Doutor

Submitted by Sandro Camargo (sandro.camargo@unipampa.edu.br) on 2015-03-08T22:53:45Z No. of bitstreams: 1 126110002.pdf: 851420 bytes, checksum: 25b69825a19a2deff670e673e7538256 (MD5) / Made available in DSpace on 2015-03-08T22:53:46Z (GMT). No. of bitstreams: 1 126110002.pdf: 851420 bytes, checksum: 25b69825a19a2deff670e673e7538256 (MD5) Previous issue date: 2014-03-19 / Com o presente estudo, propôs-se avaliar os efeitos da clonidina como medicação pré-anestésica, sobre parâmetros cardiorrespiratórios e hematimétricos em cães anestesiados com isoflurano, associada à infusão contínua de tramadol. Para isso, foram utilizados 8 cães sem raça definida, adultos, hígidos, com peso médio de 15,3 ± 3,7 kg, oriundos do canil da Universidade Federal do Pampa mediante doação. Cada animal foi anestesiado em duas ocasiões, com intervalo mínimo de um mês. Os animais foram distribuídos em dois grupos aleatórios: grupo Clonidina (GCL; pré-medicados com clonidina, 5 μg/kg) e grupo Controle (GC; pré-medicados com solução salina). Passados 15 minutos da MPA, os animais foram induzidos à anestesia geral pela administração de propofol 8mg/kg e mantidos com isoflurano à 1 CAM. Após período de estabilização, foi realizada a aplicação do bolus de tramadol (2 mg/kg) seguido pela infusão contínua do mesmo (1,5 mg/kg/h). Foram mensurados temperatura (oC), frequência cardíaca (FC), frequência respiratória (f), eletrocardiografia, pressões arteriais sistólica, diastólica e média (PAS/PAD/PAM), pressão parcial de dióxido de carbono ao final da expiração (EtCO 2 ), saturação de oxigênio (SpO2), hemograma, leucograma, glicemia, e lactacemia, dose de indução, tempo de extubação e qualidade da recuperação anestésica. As mensurações foram realizadas nos seguintes períodos: antes da MPA, antes da indução, antes do bolus de tramadol e após início das infusões, a cada 10 minutos até se completarem 60 minutos das mesmas. Os parâmetros hematológicos, glicemia e lactacemia foram mensurados nas amostras de sangue coletadas antes da aplicação da medicação pré-anestésica, antes da indução, antes do bolus do tramadol e aos 30 e 60 minutos após início das infusões. A avaliação estatística dos resultados foi realizada utilizando-se teste de ANOVA seguido pelo teste de Tukey (p<0,05). Houve diferenças na frequência cardíaca e nas demais variáveis as diferenças não foram significativas ao longo do período experimental. A associação demonstrou-se segura em animais hígidos, sendo necessário mais estudos quanto à doses, vias de aplicação e antinocicepção na espécie. / With this study, the effects of premedication with clonidine over cardiorespiratory and hematimetry in dogs anesthetized with isoflurane and receiving continuous infusion of tramadol, were evaluated. Eight crossbreeding healthy adult dogs, weighting 15,3±3,7kg, provided from Federal University of Pampa kennel, were used. Animals were randomly anesthetized twice with a month interval and allocated in two groups (n=8), Clonidine (CLG) and Control (CG). Animals in CLG received a 5 μg kg -1 bolus of Clonidine diluted in 1mL as premed, while animals in CG received an injection of 1 mL of saline. Anesthesia was acquired with propofol 8 mg kg -1 and maintained with isoflurane (1MAC). After a stabilization period, animals received a bolus of tramadol (2 mg kg -1 ) followed by a continuous rate infusion of 1.5 mg kg -1 h of the same drug. Parameters evaluated were: body temperature (oC), heart rate (HR), respiratory frequency (f), electrocardiography, systolic, diastolic and median arterial blood pressure (SAP, DAP and MAP, respectively), end-tidal carbon dioxide (EtCO 2 ), hemoglobin saturation (SpO 2 ), hematimetric, leucocitary, glucose, lactate, propofol consumption, time of extubation and recovery quality. Data were collected before premed, before induction, before tramadol bolus, and each 10 minutes after CRI was initiated, until a 60 minutes period was achieved. Blood samples were performed before premed, before induction, before tramadol bolus and 30 and 60 minutes after CRI was initiated. Data were evaluated with ANOVA followed by Tukey`s test (p<0.05). It was observed a significant decrease in HR, while other variables showed no differences throughout the experimental period. It was concluded that the association has been shown to be safe for use in healthy animals. Further studies are necessary to determinate if this drug could enhance antinociceptive effect of tramadol in dogs.

Os equinos são comumente anestesiados com agentes voláteis em procedimentos cirúrgicos acima de 60 minutos, resultando em depressão cardiovascular dosedependente, contribuindo para uma alta taxa de mortalidade. Sendo assim, este estudo objetivou determinar se o fentanil, em infusão contínua, seria capaz de diminuir a fração expirada de isoflurano, promovendo estabilidade cardiovascular transoperatória e uma melhor recuperação após cirurgia de artroscopia, em comparação à infusão de lidocaína ou quetamina, durante a manutenção da anestesia com isoflurano. Para tanto foram utilizados 20 equinos de 3 a 8 anos e pesando 350 a 500kg, submetidos a cirurgia de artroscopia em decúbito dorsal. Os animais foram divididos aleatoriamente em 4 grupos: GL (1,5 mg/kg em bolus e infusão de 0,15mg/kg/min) ; GQ (2mg/kg em bolus e infusão de 0,2mg/kg/min); GF (7&micro;g/kg em bolus e infusão de 0,7&micro;g/kg/min) e GI que não recebeu infusão de nenhum fármaco adjuvante. Foram avaliados os parâmetros cardiovasculares (FC, PAM, PAS e PAD), ventilatórios e de oxigenação (PaO2, PaCO2, Compl e Rva), fração expirada de isoflurano [ISSO](Fexp%), e qualidade de recuperação. Em relação à [ISSO] (Fexp%) as maiores quedas foram observadas no momento 30bolus em todos os grupos, que utilizaram adjuvantes, comparados ao momento basal sendo, GL (1,50 para 0,90%) GQ (1,44 para 0,96%) e GF (1,32 para 0,96%). Observou-se que após 15 minutos da interrupção da infusão contínua de fentanil e lidocaína a fração expirada de isoflurano foi aumentada GL 25% e GF 45%. Apesar de não ter havido diferença estatística, o GF apresentou escore de recuperação menor 16,8 pontos, GL 24,6; GQ 30,0 e GI 31,8 pontos. Conclui-se então que o uso do fentanil foi capaz de reduzir a fração expirada de isoflurano em até 43%, não observando qualquer efeito colateral no momento da recuperação após re-sedação com xilazina 0,5mg/kg. / Volatile anesthetics are commonly used in horse anesthesia in surgical procedures over 60 minutes, resulting in a dose-dependent cardiovascular depression, contributing to a high mortality rate. Thus, the aimed this study was determine whether fentanyl continuous rate infusion would be able to reduce end tidal isoflurane, promoting intraoperative cardiovascular stability and a better recovery after arthroscopic surgery, when compared to lidocaine or ketamine infusion during maintenance of anesthesia with isoflurane. Therefore, 20 horses aging 3-8 years and weighing 350 to 500 kg underwent arthroscopic surgery in dorsal recumbence. The animals were randomly divided into four groups: GL (1.5 mg/kg bolus and 0.15 mg/kg/min infusion rate of lidocaine), GQ (2 mg/kg bolus and 0.2 mg/kg/min infusion of ketamine); GF (7&micro;g/kg bolus and 0.7 mg/kg/min infusion rate of fentanyl) and GI did not receive any adjuvant infusion. Cardiovascular parameters (HR, MBP, SBP and DBP), ventilatory and oxygenation (PaO2, PaCO2, Cst and Rva), end tidal isoflurano [ISO] (Fexp%), and quality of recovery were evaluated. Regarding [ISO] (Fexp%) the highest decreases were observed at the time 30bolus in all groups with adjuvants, in comparison to base line -GL (1.50 to 0.90%) GQ (1.44 to 0.96 %) and GF (1.32 to 0.96%). At 15 minutes after the end of continuous rate infusion of fentanyl and lidocaine, expired fraction of isoflurane was increased 25% for GL and 45% for GF. Although there was no statistical difference, GF showed lower recovery score - 16.8 points, while 24.6 for GL, 30.0 for GQ and 31.8 points for GI. In conclusion, fentanyl was able to reduce end tidal isoflurane to 43%, with no side effects at recovery time after re-sedation with xylazine 0.5 mg / kg.

Context: Knee injury is a common problem for runners. Knee pain is a common symptom in knee injury and is associated with alterations in knee and hip muscle activation and hip joint angles. Relieving pain through intervention may help to restore neuromuscular function. Objective: To examine the effects of ice and transcutaneous electrical nerve stimulation (TENS) combination treatment on perceived knee pain, hip frontal plane angle, and muscle activation during running in individuals with experimental knee pain (EKP). Design: Crossover. Setting: Laboratory. Subjects: 19 participants (11 males and 8 females, 23.2 ± 1.9 y, 176 ± 11.6 cm, 71.5 ± 16.9 kg; right leg dominant). Interventions: Hypertonic saline was infused into the infrapatellar fat pad for 74 minutes (total 11.1 mL). Subjects underwent 2 treatment conditions (sham; ice/TENS combination). Measurements were recorded during running at 4 time points (preinfusion, postinfusion, posttreatment, and postinterval). Main Outcome Measures: Perceived knee pain on a 100-mm visual analog scale (VAS), knee and hip muscle peak electromyography (EMG) amplitude, and hip adduction angles. Results: Hypertonic saline infusion increased perceived anterior knee pain in all participants. The average of peak perceived knee pain was 28 mm on a 100-mm VAS in EKP application. While the increased perceived knee pain level stayed consistent across time in the sham session, ice/TENS combination treatment significantly reduced perceived knee pain by 35% at 6 minutes after the treatment start (p = 0.049), and the reduced knee pain lasted for 22 minutes (p > 0.05). Peak EMG amplitude of the gluteus medius was decreased by 13.5% and 14.3% (p = 0.023; p = 0.013) during running after EKP in sham and treatment sessions, respectively. However, the peak EMG amplitude was not restored to pain-free level during running after the treatment (p = 0.026). No other muscles changed their peak EMG amplitude due to EKP or treatment. Hip adduction angles during running were also not altered by EKP or treatment (p > 0.3) in both sham and treatment sessions. Conclusions: EKP increased perceived knee pain and decreased peak muscle activation of the gluteus medius during running. Ice/TENS combination treatment reduced perceived knee pain quickly, but did not restore neuromechanics during running.

Smart infusion pump technology (SIPT) was designed to enhance safety with intravenous medication administration, but has introduced new patient safety risks and harm when nurses initiate workarounds that bypass SIPT safety features. This study sought to develop a grounded theory explaining nurses' experiences with SIPT, their perceptions of safety features, the rules and resources used in response to safety features, the actions taken in response to SIPT workflow blocks, and conditions contributing to nurse-initiated workarounds. Corbin and Strauss's (2008) grounded theory approach guided this study. Semi-structured interviews were conducted with 28 nurses who used SIPT across 13 adult patient care areas in a single Midwest teaching hospital. The grounded theory Nurse-Technology Interplay was developed through constant comparison analysis of transcribed interview data. The four categories of interacting with SIPT, making meaning, taking action, and consequences, were linked through relational statements and theoretically integrated to develop the grounded theory. The grounded theory explicates the continual interplay that occurs as nurses interact with SIPT, and the cognitive and physical processes used to resolve workflow blocks in the context of care delivery. Interacting with SIPT reflected the learning curves faced by nurses, the context of patient-care unit characteristics, and encountered workflow blocks. Making meaning reflected the cognitive processes used by nurses as they encountered workflow blocks with SIPT, and was influenced by individual perspectives, as well as shared learning. Taking action often occurred simultaneously with making meaning, and represented processes of doing, such as rechecking programming activities, seeking assistance, or engaging in workarounds. Consequences of using SIPT included patient outcomes with medication administration and the impact on practice as nurses experienced disruptions in care delivery, dependency on SIPT, a loss of calculation skills, and alarm overload. The grounded theory of Nurse-Technology Interplay provides an understanding of how nurses make sense of, and respond to, workflow blocks with SIPT safety features. The study yielded valuable insights into the complexity of SIPT implementation and the challenges nurses face while providing safe, effective, patient-centered care in the midst of juggling competing priorities. The findings have implications for nursing practice and nurse leaders. Critical to moving forward is a more purposeful approach to SIPT education and training within a patient safety framework, a systematic evaluation of organizational processes that impact SIPT, optimization the SIPT drug library to facilitate nurses' work, and promotion of a learning organization that capitalizes on the lessons that can be learned from workarounds.

<p>Pharmacotherapy for Parkinson’s disease (PD) is based on levodopa, the most effective dopaminergic drug. The development of motor complications constitutes the major challenge for new or refined therapies.</p><p>To evaluate the impact of levodopa pharmacokinetics on motor function, an observational study in the patients’ home environment was carried out. A high variability in plasma levodopa levels was found in all patients, irrespective of treatment regimen. The impact of levodopa pharmacokinetics was further studied in a crossover trial comparing sustained-release tablets and continuous daytime intestinal infusion. Infusion produced significantly decreased variability in plasma levels of levodopa, resulting in significantly normalised motor function. A permanent system for long-term levodopa infusion has been developed and 28 patients have been followed for 87 patient-years. Motor response was generally preserved during the long-term observation period, implying that there is no development of tolerance to infusion therapy. Levodopa tablets are normally used in multiples of 50 or 100 mg, thus a rough estimate of individual dosage. A new concept for individualising levodopa/carbidopa doses with microtablets of 5/1.25 mg is under development. An electronic drug-dispensing device for administering the microtablets was tested on patients with PD. All were able to handle the dispenser and most were interested in future use of the concept. Self-assessment of symptoms is accurate in PD, but traditional paper diaries are associated with low compliance. A wireless electronic diary was compared with a corresponding paper diary. The time-stamped and thus completely reliable patient compliance was 88% with the electronic diary.</p><p>To conclude, pharmacokinetics of levodopa is the major determinant for motor fluctuations in PD. Every effort to individualise dosage and to smooth out the fluctuations in levodopa concentrations should be made, e.g. by means of microtablets or enteral infusion. Electronic patient diaries for real-time data capture are suitable for PD studies.</p>

The aim of this work is to evaluate the fuzzy system for different types of patients for levodopa infusion in Parkinson Disease based on simulation experiments using the pharmacokinetic-pharmacodynamic model. Fuzzy system is to control patient’s condition by adjusting the value of flow rate, and it must be effective on three types of patients, there are three different types of patients, including sensitive, typical and tolerant patient; the sensitive patients are very sensitive to drug dosage, but the tolerant patients are resistant to drug dose, so it is important for controller to deal with dose increment and decrement to adapt different types of patients, such as sensitive and tolerant patients. Using the fuzzy system, three different types of patients can get useful control for simulating medication treatment, and controller will get good effect for patients, when the initial flow rate of infusion is in the small range of the approximate optimal value for the current patient’ type.

Dopamine increases in the nucleus accumbens after contingent and noncontingent ethanol administration in rats, but the contributions of the core, coreshell border, and shell subregions to this response are unclear. Also, it is not fully understood if increases in dopamine under these circumstances are due to the pharmacological effects of ethanol, stimuli associated with administration, or both. The studies presented in this dissertation were conducted to investigate dopamine’s role in each of these accumbal regions during ethanol administration and presentation of associated stimuli. Using microdialysis, ethanol and dopamine concentrations in accumbal subregions were measured every five minutes before, during, and after either experimenter-delivered intravenous ethanol or operant ethanol self-administration. After intravenous ethanol infusions, the increase in dopamine in the shell of the accumbens was significantly higher than that observed in the core. During operant ethanol self-administration, the core, core-shell border, and shell, all exhibited significant increases in dopamine during transfer of the animal into the operant chamber, with animals trained to drink sucrose + ethanol showing significantly higher increases when compared to those trained to drink sucrose alone. Dopamine increased significantly only in the core-shell border during ethanol consumption, and dopamine levels in the core and shell responded in a similar manner during all phases of the experiment. Together, these results suggest that dopamine responses to intravenous ethanol infusions and operant ethanol self-administration are subregion specific. Also, while increases in dopamine resulting from intravenous ethanol infusions in naïve animals appear to be due to the pharmacological effects of the drug, increases in ethanol-experienced animals during transfer into the operant chamber, and during ethanol consumption, may also be due to stimuli associated with ethanol administration. / text