Thesis (M.Med. (Radiation Oncology)) -- University of Limpopo, 2022 / Background Hypothyroidism in head and neck cancer patients after radiotherapy is known to occur, yet thyroid function tests are not routinely monitored in all patients post radiation therapy. Routine post radiation therapy thyroid function testing is currently not part of the follow-up protocol in these patients at Pietersburg Hospital. The aim of this study is to evaluate post radiation therapy hypothyroidism among head and neck cancer patients treated with radiotherapy at Pietersburg Hospital Methods A prospective (cohort) observational study was carried out among head and neck cancer patients receiving radiotherapy at the radiation oncology department in Pietersburg Hospital. Sample size of n=37 was calculated using Statistica V13.0. Thyroid function tests were performed at the start of radiation therapy and repeated on the first day of follow up, 6 weeks after completing radiation therapy. During follow up, participants were also interviewed for the presence of symptoms of hypothyroidism such as dry skin, dry hair, fatigue, cold intolerance, or weight gain. Data analysis was done with STATA version 16. Descriptive statistics were used to characterise variables, and summarised in tables, graphs and charts. Changes in thyroid function tests and other variables were analysed. A p-value of 0.05 was deemed statistically significant. Results Thirty-seven patients were enrolled in the study, 26 males and 11 females. The mean age of the patients was 53.1 ±12.3 standard deviation [SD]) with a range of 40.8 to 65.4 years. The most common diagnoses were cancer of the larynx and hypopharynx, forming 29.7% and oral cavity cancer, 29.7%. Only three patients (8%) had an early stage cancer (Stages 1 and 2), 11 patients (29.7%) moderately advanced cancer (Stage 3) while the majority (62%; n =23) had locally advanced cancer (Stage 4). Majority of the patients received 70Gy in 35 daily fractions, five fractions per week via 3-D conformal radiotherapy. Only 29 patients who had complete pre- and post radiotherapy thyroid function tests were included in the final analysis. Of these, none had clinical hypothyroidism at 3 months. Two patients (6.8%) had sub-clinical hypothyroidism, with post radiation therapy TSH values greater than 3.5mIU/ml. The mean post radiation therapy TSH values increased by 8.3% and the mean fT4 values decreased by 2.05% compared to the pre-radiation therapy values. Both changes were not statistically significant (p=0.99 and p=0.82 respectively). There was no statistically significant correlation between changes in TSH and fT4 versus age (p=0.88 and p=0.92 respectively), sex (p=0.55 and p=0.15 respectively), cancer stage (p=0.21 and p=0.78 respectively), and cancer site (p=0.17 and p=0.74 respectively). The most common post radiotherapy symptom was fatigue (62%) followed by cold intolerance (54%), weight gain (43%) and dry skin or dry hair (43% each). Conclusion The results of the study suggest that sub-clinical hypothyroidism is detectable early post radiation therapy presenting as clinical symptoms.

No description available.

Thesis (D. Tech. (Clinical Technology )) - Central University of Technology, Free State, 2013 / The HIV pandemic in South-Africa has created a new form of vulnerability for households with regards to food security and nutritional status which are vital components in the general care of HIV-infected individuals. The risk of nutritional deficiencies and malnutrition are predictors of disease progression and treatment in resource limited settings. Furthermore, HIV affects nutritional status by increasing the energy requirements, reducing food intake, affecting nutrient absorption and metabolism inadequacies due to cytokine activity and diarrhea. Several vitamins and minerals are important in fighting HIV infection because they are required by the immune system and major organs to attack infectious pathogens. Many of these micronutrients have been found to be deficient in HIVinfected persons and several studies were launched worldwide to investigate the feasibility of food assistance and nutrient supplementation. Nutritional supplementation has been advocated in HIV-infected persons especially in lowincome countries such as South Africa. Therefore, a study to evaluate the role of nutritional supplementation in HIV-positive patients becomes necessary, especially in a developing country such as South Africa. It is against this background that the present research was initiated to examine the influence of a nutritional supplement on the immune status and health status of HIVpositive/ AIDS adult individuals. The aim of the investigation was to determine if supplementation with a mixture comprised from specific minerals, vitamins and herbs over a period of one year, affected the haematological status, immune status, viral load and pulmonary function in forty (40) HIV-infected individuals living in the Mangaung Metropolitan, RSA. viii A quantitative, open-labeled, before-after clinical trial was conducted at the Central University of Technology, in Bloemfontein, Free State Province in the RSA. Socio-demographic and dietary intake questionnaires were completed. All data pertaining to anthropometric measurements, haematological status, immune status, viral load and pulmonary function were obtained my means of using standard procedures and technological equipment. The data were subjected to parametric and non-parametric statistical analysis. The results of the present investigation show that the eating pattern of this urbanized group of individuals reflects high energy (KJ) and macronutrient intakes coinciding with sub-optimal intake of Vitamin D and iodine. Of all the haematological variables the only statistical significant changes observed were increases in the median erythrocyte sedimentation rate (ESR) (p=0.0219) and mean cell haemoglobin concentration (MCHC) (p=0.0245) after six months of nutritional supplementation. At 12 months a statistical significant decrease in the median CD/CD8 ratio (p<0.0048), median Hematocrit concentration (p<0.0312), median mean cell volume (MCV) (p<0.0359), and median RDW (p<0.0273) accompanied a statistically significant increase in the MCHC (p<0.0003) at 12 months after supplementation. At 6 months 89% (CI95%: 73%; 96%) of the individuals showed a decline in viral load counts with a median percentage decline of 34% (CI95%: 73%; 96%). At 12 months 85% [CI95%: 68%; 94%] of the individuals show a decrease in viral load counts with a median percentage decline of 62.9% (CI95%: 50%; 78.6%) following the intake of the supplement. The main findings of the present investigation reveal that 68% (50%-81%) of the individuals show a statistical median increase (p=0.0302) of 16.9% (11.5%; ix 36.1%) in the Peak Expiratory Flow (PEF) at six months. A significant decrease (p=0.0484) in the median FEF75 of 28.1% (14%; 35.3%) is observed in 70% (53%-83%) of the individuals after 12 months of exposure to the supplement. No statistical significant changes are observed for FVC, FEV1, FEV1/FVC and FEF50 over the entire trial period. The present results suggest that a significant measurable decrease in viral load in HIV-infected individuals can be obtained by means of subjecting individuals to a nutritional fortification supplement strategy for 6 months or more.

PhD / The overall objective of this thesis is to provide additional data to assist clinicians and experimental neurologists alike in the quest for better understanding, more accurately diagnosing and more successfully treating patients suffering from Parkinson’s disease (PD). The general theme of the thesis is the interaction between certain environmental stimuli, including the exposure to adverse events during early central nervous system (CNS) development and the manifestation of elements of neurodegeneration, whether by means of neurochemical changes or expressed as a dysfunctional voluntary motor system. The first chapter provides a general introduction to the research theme of the thesis. This includes, in particular, a discussion on current understanding concerning the etiology and clinical profile of PD, the relative contribution made by genetic factors compared to environmental ones, and current treatment strategies for treating the disease. Mention is also made of the failure of these therapeutic applications for reversing or protecting against the disease, due to the side-effects associated with them. The material covered in chapter 1 provides the basis for the more complete discussion concerning these various aspects, contained in the chapters to follow. The overall aim was also to characterise the effects of commonly used toxin-induced animal models of PD, and the extent of vulnerability that the CNS displays towards them. The destruction of dopaminergic neurons following the administration of 6-OHDA at targeted points along the nigrostriatal tract is used extensively to model PD pathology in rats and is an established animal model of the disease. However, mature or even aged animals are mainly used in these studies, while the effects that the toxin might have on the developing CNS remain unclear. The study reported in chapter 4 aimed to elucidate some of 6-OHDA’s actions on the young adolescent (35 days-old) CNS by comparing the motor and biochemical effects of a unilateral infusion of the toxin into two anatomically distinct basal ganglia loci: The medial forebrain bundle (MFB) and the striatum. Animals were randomly assigned to receive either a direct delivery of 6-OHDA (12μg/4μl) into the MFB or an indirect injection, into the striatum. Although both lesion types were used, the MFB model is considered a more accurate portrayal of end-stage PD, while the striatum-model better reflects the long-term progressive pathology of the disease. The different lesions’ effects on motor function were determined by observing animal’s asymmetrical forelimb use to correct for weigh shifting during the vertical exploration of a cylindrical enclosure. Following the final behavioral assessment, the concentration of dopamine (DA) and DA metabolites remaining in the post-mortem brains were determined using 4 HPLC electrochemistry (HPLC-EC) and the levels compared between the two groups. The HPLC-EC results revealed a compensatory effect for DA production and DA turnover on the lesioned hemisphere side of the toxin-infused animal group. Thus, following 6-OHDA treatment, there appears to be extensive adaptive mechanisms in place within the remaining dopaminergic terminals that may be sufficient for maintaining relatively high extracellular and synaptic concentrations of DA. However, since substantial changes in motor-function were observed, it is suggested that the capacity of the remaining dopaminergic neurons to respond to increased functional demands may be limited. In addition, the behavioral results indicate that the distinct indices relating to different functional deficits depend on the lesioning of anatomically distinct structures along the nigrostrial tract. It has long been known that far fewer women are diagnosed with PD than men are. This seeming protection offered to females against degenerative disease of the CNS may relate to estrogen, although the hormone’s mechanism of action on the dopaminergic system is poorly defined. With an estimated 10-15 million women using oral contraceptives (OCs) in the United States alone, the aim of chapter 2 was to examine the evidence for a possible relationship between PD and the female reproductive hormone estrogen. A review of the current literature available on the topic was performed by consulting Medline, and by performing a search of the case-reports contained within the World Health Organization’s (WHO) International Drug Monitoring database, for possible PD-related symptoms that may arise from estrogen replacement therapy (ERT). The results, whilst conflicting, seem to suggest that estrogen protects women from obtaining the disease, or at least some features of it. Intensive research efforts are called for, with sufficient power to establish the relationship between ERT and the onset and development of parkinsonism. Chapter 3 reports on the results obtained from an experiment that subjected young Sprague-Dawley rats, 35 days of age, to a lower and a higher dose of 6-OHDA delivered to the MFB. Control rats received equivalent saline infusions. At 14 days post-surgery, the rats were evaluated for forelimb akinesia. For the higher dose of 6- OHDA the female rats were less impaired than males in making adjustment steps in response to a weight shift and in the vibrissae-evoked forelimb placing test. In addition, Tyrosine hydroxylase (TH) immunoreactivity was significantly higher for the female rats. Early gender differences in cell survival factors and/or other promoters of neuroplasticity may have contributed to the beneficial outcome seen in the females. For example, nerve growth factor (NGF) was found to be higher in the female rats following administration of the DA neurotoxin. It is unclear whether gonadal steroids are involved, and, if so, whether female hormones are protective or whether male hormones are prodegenerative. Determining the mechanisms for the improved outcome seen in the young female rats may lead to potential treatment strategies against PD. 5 Many studies have shown that early life stress may lead to impaired brain development, and may be a risk factor for developing psychiatric diseases, including clinical depression. However, few studies have investigated the impact that early stress may have on the onset and development of neurodegenerative disorders such as PD. The study reported on in chapter 5 conjointly subjected rat pups to a maternal separation (MS) paradigm that is a well characterised model of adverse early life events, and a unilateral, intrastriatal injection of 6- OHDA. The combined effects of these models on motor deficits and brain protein levels were investigated. Specifically, the animals were assessed for behavioral changes at 28 days postlesion with a battery of tests that are sensitive to the degree of DA loss sustained. The results show that animals that had been subjected to MS display poorer performance in the vibrissae and single-limb akinesia test compared to non-MS control animals (that had also been subjected to the toxin exposure). In addition, there was a significant increase in the loss of TH staining in MS rats compared to non-MS ones. The results from this study therefore suggest that exposure to adverse experiences during the early stages of life may contribute towards making dopaminergic neurons more susceptible to subsequent insults to the CNS occurring during mature stages of life. Therefore, taken together, early exposure to stress may predispose an individual towards the onset and development of neurodegenerative disease, which especially becomes a threat during the later stages of adult life. Moreover, within the framework of these characteristics, the capacity of a widely-used pharmacological agent (statins) was tested for possible future therapeutic application in PD (chapter 7). Although the precise cause of sporadic PD remains an enigma, evidence suggests that it may associate with defective activity of complex I of the mitochondrial electron transport chain. Mitochondrial DNA transmit and express this defect in host cells, resulting in increased oxygen free radical production, depressed antioxidant enzyme activities, and greater susceptibility to apoptotic cell death. Simvastatin is a member of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) group of drugs that are widely used for lowering cholesterol levels in patients who display elevated concentrations of low-density lipoprotein cholesterol. The study aimed to investigate the effects that statin-treatment have on motor-function and at the mitochondrial-protein level, using rotenone, a mitochondrial complex I inhibitor, as a rat-model of PD. Adult male Sprague-Dawley rats were treated either with simvastatin (6mg/day for 14 days) or with a placebo. Two different tests to assess motor function were used: The apomorphine-rotation test, and the vibrissae-elicited forelimb placement test. Following the drug administration protocol, the nigrostriatal tract was unilaterally lesioned with either rotenone (3 μg/4 μl) or, for the controls, were sham-operated by infusing the vehicle (DMSO:PEG) only. Five days later the rats were killed and a highly purified concentration of isolated mitochondria was prepared from the substantia nigra (SN) sections. 2- 6 Dimensional electrophoresis (2-DE) with subsequent identification of the spots using electronspray ionization quadruple time-of-flight mass spectrometrical (ESI-Q-TOF MS) was performed and the results BLAST-searched using bio-informatics tools for naming the identified peptides. The motor test results indicate that while unilateral rotenone causes behavioral asymmetries, treatment with simvastatin improved motor function relative to the rotenoneinduced ones. Mass Spectroscopy identified 23 mitochondrial proteins that differ significantly in protein expression (p < 0.05) following simvastatin treatment. The altered proteins were broadly classified according to their cellular function into 6 categories, with the majority involved in energy metabolism. This study effectively illustrated how neuroproteomics, with its sophisticated techniques and non-biased ability to quantify proteins, provides a methodology with which to study the changes in neurons associated with neurodegeneration. As an emerging tool for establishing disease-associated protein profiles, it also generates a greater understanding as to how these proteins interact and undergo post-translational modifications. Furthermore, due to the advances made in bioInformatics, insight is created concerning their functional characteristics. Chapter 4 summarises the most prominent proteomics techniques and discuss major advances made in the fast-growing field of neuroproteomics in PD. Ultimately, it is hoped that the application of this technology will lead towards a presymptomatic diagnosis of PD, and the identification of risk factors and new therapeutic targets at which pharmacological intervention can be aimed. The final chapter (chapter 8) provides a retrospective look at the academic work that had been performed for the purpose of this thesis, recaps on the main findings, and also highlights certain aspects of the project and provides relevant suggestions for future research. Lastly, the appendix provides a detailed overview of the methods followed for the experiments described in this thesis. It provides not only a comprehensive description of the techniques that had been followed, but provides information concerning the care taken with the animals (i.e. post-surgery) in order to control for the potential influence of experimental variables on the results.

En inhibant la formation de caillots dans le sang, les médicaments antiplaquettaires diminuent de façon importante le risque d’événements ischémiques aigus. Cependant, une sous-population de patients souffrant de maladie coronarienne présente une inhibition inadéquate de la fonction plaquettaire malgré la prise quotidienne d’acide acétylsalicylique (AAS). Le premier volet de cette thèse démontre qu’une régénération plaquettaire accélérée pourrait expliquer en partie la variabilité dans la persistance de l’effet antiplaquettaire de l’AAS chez certains sujets souffrant de maladie coronarienne. Ces données suggèrent qu’une augmentation de la fréquence d’administration d’AAS d’une à deux fois par jour pourrait être bénéfique chez ces sujets. Des méta-analyses ont suggéré qu’une réponse plaquettaire inadéquate à l’AAS pourrait augmenter le risque d’événements ischémiques récurrents. La nature rétrospective de ces analyses ne permet pas d’établir la causalité. Dans le deuxième volet de cette thèse, les résultats d’une étude prospective visant à comparer la pertinence clinique de 6 tests de fonction plaquettaire fréquemment utilisés pour évaluer la réponse plaquettaire à l’AAS est présentée. Les résultats démontrent qu’aucun des tests de fonction plaquettaire couramment employés ne prédit la survenue d’événements ischémiques aigus chez des patients souffrant de maladie coronarienne stable. Toutefois, la cessation de la prise d’AAS est un prédicteur important d’événements thrombotiques. La cessation de médicaments antiplaquettaires a souvent été associée à la survenue d’événements thrombotiques dans les jours suivant l’interruption. À savoir si la survenue de ces événements est attribuable uniquement au retrait d’un médicament protecteur ou plutôt à une sensibilisation plaquettaire, constitue un débat d’actualité. Dans le troisième volet de cette thèse, des données sont présentées démontrant que la cessation de clopidogrel après la période recommandée par les lignes directrices actuelles provoque une sensibilisation des plaquettes nouvellement formées aux stimuli plaquettaires physiologiques. Ces résultats encouragent la recherche sur différentes modalités pour atténuer le risque thrombotique accru chez ces patients souffrant de maladie coronarienne. En conclusion, cet ouvrage présente des études visant à identifier les sous-populations de patients qui sont plus à risque de complications cardiovasculaires récurrentes. Dans ce contexte, la personnalisation de traitement est une avenue thérapeutique prometteuse, où chaque patient pourra recevoir un traitement ciblé en fonction de ses besoins et de ses contre-indications. Ce changement de paradigme d’une thérapie empirique issue d’études de grande envergure sur des données populationnelles à une thérapie ajustée aux besoins individuels représente un vaste champ de recherche, où la majorité des découvertes sont à faire. / By inhibiting the formation of blood clots, antiplatelet drugs significantly reduce the risk of acute ischemic events. However, a subpopulation of patients suffering from coronary artery disease presents with an inadequate inhibition of platelet function despite taking acetylsalicylic acid (ASA) daily. The first part of this thesis demonstrates that accelerated platelet turnover could partly explain the variability in the persistence of the antiplatelet effect of ASA in some coronary artery disease patients. These results suggest that increasing the frequency of administration of ASA from once to twice daily may be beneficial in selected patients. Meta-analyses have suggested that an inadequate platelet response to ASA may increase the risk of recurrent ischemic events. The retrospective nature of these analyses forbids the inference of causality. In the second part of this thesis, the results of a prospective study comparing the clinical relevance of 6 platelet function tests commonly used to assess platelet response to ASA are presented. The results show that none of the commonly used platelet function tests predict the occurrence of acute ischemic events in stable coronary artery disease patients. However, discontinuation of ASA is an important predictor of thrombotic events. Discontinuation of antiplatelet drugs has often been associated with thrombotic events in the days following cessation. If the occurrence of these events is due solely to the withdrawal of a protective drug or rather platelet sensitization is a topic of some debate. In the third part of this thesis, data are presented demonstrating that clopidogrel discontinuation, after the period recommended by current guidelines, leads to sensitization of newly formed platelets to physiological platelet stimuli. These results encourage research on different ways to mitigate the increased risk of thrombosis in coronary artery disease patients scheduled to discontinue clopidogrel therapy. In conclusion, this dissertation presents studies aiming to identify subpopulations of patients who are at increased risk of recurrent cardiovascular events. In this context, the personalization of treatment is a promising therapeutic avenue, where each patient can receive a targeted therapy according to his needs and contraindications. This shift in paradigm from empirical therapy based on population data retrieved from large clinical studies to therapy tailored to individual needs opens a vast field of research, where the majority of discoveries remain to be made.

The aim of this study is definition reference values including reference equations for parameters PImax, PEmax and P0.1 of the normal Czech population aged 14-15 years. 102 subjects were examined for this purpose (55 boys and 47 girls). Except the reference values for boys and girls, this work includes correlations of mouth pressures with anthropometric data and also with other spirometric parameters. In case of boys were found a significant correlation of PEmax parameter with weight, BMI and PEF. In group of boys we also found a correlation of PImax with BMI and PImax with IC. Parameter P0.1 correlates only with VT. In group of girls we found a significant correlations of PImax, PEmax and P0.1 with PEF and MEF25.

A toxicidade vestibular pode ser definida como danos que uma substância química causa sobre a estrutura e a função vestibular. Entre as drogas que podem causar a vestibulotoxicidade estão os agentes antineoplásicos como os derivados da platina. OBJETIVO: Identificar a frequência de ocorrência de alteração vestibular em pacientes oncológicos tratados com derivados da platina, os sinais e sintomas vestibulares nestes pacientes, e se a alteração vestibular pré-existente exacerba os sintomas eméticos durante a quimioterapia com derivados da platina. METODOLOGIA: Amostra foi composta por pacientes adultos com câncer que realizaram tratamento com drogas derivadas da platina. O protocolo para o monitoramento vestibular foi composto pelo questionário Dizziness Handicap Inventory (DHI) Brasileiro, Testes da Função Vestibular (manobra de Dix-Hallpike e vecto-eletronistagmografia) e pela descrição de sintomas eméticos e tontura durante a quimioterapia e avaliação vestibular. RESULTADOS: Quarenta e oito pacientes realizaram a avaliação vestibular pré-quimioterapia, sendo que 23 (48%) apresentaram avaliação vestibular dentro da normalidade. Dezesseis pacientes submeteram-se ao monitoramento vestibular com avaliação antes e após tratamento, sendo que após o tratamento dois pacientes (12,5%) apresentaram avaliação vestibular dentro da normalidade e 14 (87,5%) apresentaram algum tipo de alteração vestibular, evidenciada somente pela prova calórica. Nenhum paciente referiu queixas vestibulares ao DHI na avaliação pré-tratamento, assim como quase todos os pacientes, exceto um, na avaliação pós tratamento. Apenas um (6,3%) com avaliação vestibular alterada pós-tratamento apresentou grau leve no DHI. A dose de cisplatina entre os pacientes que mostraram piora do quadro vestibular variou entre 160 e 400 mg/m² e dois pacientes foram tratados com carboplatina com dose de 2306 mg/m² e 1801 mg/m². Não houve diferença de manifestação dos sintomas eméticos/tontura durante a avaliação vestibular ou após quimioterapia entre os pacientes com e sem alteração vestibular prévia. Entretanto, os pacientes que referiram sintomas eméticos durante os ciclos de quimioterapia foram aqueles que manifestaram maior desconforto na PC, independente da dose de quimioterapia ou da alteração vestibular. CONCLUSÃO: Alteração vestibular ou a modificação do quadro vestibular ocorreu em 50% dos pacientes com câncer tratados com derivados da platina. O sinal mais frequente de alteração nos testes vestibulares foi a hiporreflexia à prova calórica, sem sintomas vestibulares relatados na vida diária destes pacientes. As alterações vestibulares pré-existentes não exacerbaram os sintomas eméticos durante a quimioterapia / Vestibular toxicity may be defined as a damage that chemical substances cause on the structure and the function of the vestibular system. Among the drugs that may cause vestibulotoxicity there are antineoplastic agents, such as those derived from platinum. OBJECTIVE: To identify the frequency of occurrence of vestibular alterations in cancer patients treated with platinum-based chemotherapy; the vestibular signs and symptoms in these patients, and whether the pre-existing vestibular alterations exacerbate emetic symptoms during chemotherapy with platinum-based drugs. METHODS: The sample was composed of adults who were treated of the cancer with platinum-based chemotherapy. The vestibular monitoring protocol involved the Brazilian Dizziness Handicap Inventory (DHI), Vestibular Function Tests (positioning nystagmus with Dix-Hallpike maneuver and vectoelectronystagmography) and the description of emetic symptoms and dizziness during chemotherapy and vestibular evaluation. RESULTS: Forty-eight subjects performed the pre-treatment vestibular evaluation, and 23 of them (48%) presented vestibular assessment within the normal range. Sixteen patients underwent the vestibular monitoring evaluation before and after treatment: after the treatment two patients (12.5%) showed normal vestibular assessment while 14 (87.5%) showed a vestibular disorder, basically in the caloric tests, but the alteration was considered a modification in their baseline stage in eight patients (50%). None of the patients reported complaints in the pre-treatment assessment, with a DHI scores within the normal range, as well as all the patients, except one, in the post treatment assessment (81,3%). Only one patient (6.3%) had a score above normal (mild complaint) with altered vestibular evaluation in the post treatment assessment. The dose of cisplatin among these patients who had a modification in the vestibular function varied from 160 to 400 mg/m² and two patients were treated with carboplatin with do of 2306 mg/m² and 1801 mg/m². There was no difference of emetic symptoms/dizziness during the chemotherapy or the vestibular evaluation among patients with or without previous vestibular alterations. However, patients who reported more emetic symptoms during chemotherapy cycles were those who showed greater discomfort in the caloric test, regardless of the dosage of chemotherapy or vestibular alteration. CONCLUSION: Vestibular alterations or modification of the baseline alteration were found in 50% of cancer patients treated with platinum-based chemotherapy. The most common sign of vestibular alteration in the vestibular tests was the hiporeflexia at the caloric test with no reported symptoms in their daily life. The preexisting vestibular alterations did not exacerbate emetic symptoms during chemotherapy

INTRODUÇÃO. A definição de insuficiência hepática pós-operatória (IHP) não é ainda padronizada, dificultando a comparação de inovações em procedimentos hepáticos e tornando complexo o uso de possíveis intervenções terapêuticas pós- operatórias em um momento adequado. CASUÍSTICA E MÉTODOS. Entre 1998 e 2002, 775 resecções hepáticas eletivas, dos quais 531 (69%) por doenças malignas e 464 (60%) consistindo em hepatectomias maiores, foram incluídas de maneira prospectiva em um banco de dados. O parênquima hepático não-tumoral foi anormal em 330 pacientes (43%) incluindo esteatose em mais que 30% dos hepatócitos em 107 (14%), fibrose sem cirrose em 237 (43%) e cirrose em 94 (12%). Foi analisado o impacto sobre a mortalidade da ocorrência de tempo de protrombina (TP) menor que 50% e bilirrubina total sérica (BT) maior que 50 µmol/L (3 mg/dl) (critério 50-50) nos dias pós-operatórios (PO) 1, 3, 5 e 7. RESULTADOS. A cinética pós-operatória do TP e da BT foram diferentes. O menor nível de TP foi no primeiro dia pós-operatório (PO) e o pico de BT foi no terceiro dia PO. A tendência ao retorno para valores pré-operatórios destes dois fatores bioquímicos se firmou claramente no quinto DPO. A mortalidade operatória global foi de 3.4% (26 pacientes), incluindo 21 (81%) casos com parênquima não-tumoral anormal e 20 (77%) após uma hepatectomia maior. O índice de mortalidade foi maior em pacientes com TP < 50% ou BT > 50 µmol/L (3 mg/dl) no pós-operatório. A conjunção de TP < 50% e BT > 50 µmol/L (3 mg/dl) no quinto DPO foi potente fator preditivo de mortalide, a qual atingiu 59% quando esta associação ocorreu. CONCLUSÕES. A partir do quinto dia PO, a associação de TP > 50% e BT > 50 µml/L (3 mg/dl) (critério 50-50) foi preditor prático e acurado de índice de mortalidade após hepatectomia. Propõe-se assim este critério como definição de insuficiência hepática pós-operatória. / INTRODUCTION. Definition of postoperative liver failure (PLF) is not standardized, rendering complex the comparison of novelties in liver procedures and also the use of possible postoperative therapeutic interventions in due time. METHODS. Between 1998 and 2002, 775 elective liver resections, whence 531 (69%) were for malignancies and 464 (60%) for major resections, were included in a prospective database. The non- tumorous hepatic parenchima was abnormal in 330 patients (43%) including steatosis > 30% in 107 (14%), non-cirrhotic fibrosis in 237 (43%) and cirrhosis in 94 (12%). The clinical impact of Prothrombin Time (PT) < 50% and Serum Bilirubin (SB) > 50µmol/L (3 mg/dl) (50-50 criteria) on postoperative days (POD) 1, 3, 5 and 7 was analyzed. RESULTS. Kinetic of postoperative PT and SB were different. Lowest PT levels were on POD1 and the peak of SB was on POD 3. The tendency to return to preoperative values of these two biochemical factors was clearly affirmed on POD 5. Operative mortality was 3.4% (26 patients), including 21 (81%) cases with abnormal liver parenchyma and 20 (77%) following major hepatectomies. Mortality rate was increased in patients with PT < 50% or SB > 50µmol/L (3mg/dl). The conjunction of PT < 50% and SB > 50µmol/L (3 mg/dl) on POD 5 was a strong predictive factor of increased mortality, which reached 59%. CONCLUSIONS We found that after postoperative day 5, the association of PT > 50% and SB > 50µml/L (3 mg/dl) (50-50 criteria) was a simple and accurate predictor of mortality after hepatectomy. These results allow us to propose this criteria as a definition of postoperative liver failure.

Introdução: A atresia transversa da maxila é a discrepância volumétrica existente entre a maxila e a mandíbula no plano transversal que, além de alterações dento-esqueléticas, gera mudanças craniofaciais importantes, como o estreitamento das cavidades nasais, a diminuição da permeabilidade nasal e a respiração bucal. A expansão palatina cirurgicamente assistida (EPCA) é a técnica cirúrgica indicada para a correção da atresia maxilar em pacientes adultos, com o crescimento ósseo finalizado. A rinometria acústica é uma técnica objetiva de estudo da respiração nasal, com a qual se avalia a geometria e o volume nasal. Já a rinomanometria trata-se de um método aerodinâmico que quantifica a pressão transnasal e a resistência ao fluxo aéreo. Objetivos: O objetivo deste estudo foi avaliar subjetiva e objetivamente a função respiratória nasal, em pacientes com atresia maxilar, submetidos à EPCA e determinar o tipo de correlação existente entre as medidas ortodônticas e as alterações de área, volume, resistência, e fluxo aéreo nasal. Casuística e Métodos: Para a realização do estudo foram avaliados 27 pacientes adultos, por meio da rinometria acústica, rinomanometria, medidas ortodônticas (perímetro e comprimento do arco maxilar, distância transversa entre caninos, prés-molares e molares superiores) em modelos de estudos e escala visual analógica da função respiratória apenas nasal, no pré-operatório, após a ativação do expansor maxilar do tipo Hyrax, instalado previamente à cirurgia, e após quatro meses da EPCA, realizada sob anestesia geral. Os exames otorrinolaringológicos foram realizados em sala ambientalizada, com e sem o uso de vasoconstritor nasal, em ambas as cavidades nasais. Resultados: Os resultados demonstraram que 59,3% da casuística era do gênero feminino, com idade média de 25,33 anos. Todas as medidas ortodônticas obtiveram um aumento estatisticamente significante (p<0,001), que mantiveram-se ao longo da tempo (p<0,001). Todas as medidas avaliadas apresentaram melhores resultados com o uso de vasoconstritor nasal. A área da cavidade nasal como um todo aumentou após a cirurgia (p<0,036). O volume médio é 2,75 maior com o uso de vasoconstritor (p < 0,001), porém não houve alterações estatisticamente significantes entre os momentos avaliados. Os fluxos expiratórios e inspiratórios aumentaram ao longo do tempo (p<0,001, para ambos). A pressão expiratória diminui no decorrer dos momentos avaliados (p<0,004). A análise subjetiva da sensação respiratória apenas pelo nariz aumentou significantemente de um momento para o outro (p<0,05). Houve correlação estatística entre perímetro do arco aumentado e resistência aérea diminuída (p=0,004) e entre o aumento de uma medida transversa com o aumento do fluxo inspiratório e expiratório, sem o uso de vasoconstritor (p=0,023 e p=0,004 respectivamente). Apenas o fluxo respiratório apresentou comportamento diferente entre os lados. Conclusões: Assim, conclui-se que o procedimento cirúrgico de EPCA promove alterações importantes nas cavidades oral e nasais que, associadas, geram melhor qualidade respiratória ao paciente e demonstram a relevância clínica otorrinolaringológica de tal procedimento cirúrgico bucomaxilofacial / Introduction: Transverse atresia of maxilla is a volumetric discrepancy existing between the maxilla and the mandible on the transversal plan that, besides dentoskeletal alterations, generates important craniofacial changes, such as nasal cavities constriction, diminution of nasal permeability and buccal breathing. The surgically assisted rapid maxillary expansion (SARME) is the surgical technique indicated for correcting maxillary atresia in adult patients, whose bone development was concluded. Acoustic rhinometry is a technique of nasal breathing, with which the nasal geometry and volume are assessed. As for rhinomanometry, it is an aerodynamic method that quantifies the transnasal pressure and resistance to aerial flow. Objectives: The purpose of this paper was evaluating subjectively and objectively the nasal respiratory function in patients with maxillary atresia, who have undergone SARME and determining the type of correlation existing between the orthodontic measures and the alterations of area, volume, resistance, and nasal aerial flow. Casuistic and Methods: For the paper accomplishment were assessed 27 adult patients, through acoustic rhinometry, rhinomanometry, orthodontic measures (perimeter and length of maxillary arch, transverse distance among canines, premolars and superior molars) in models of studies and analogical visual scale of only nasal respiratory function, on pre-surgical, after the activation of Hyrax-type maxillary expander, installed previously to the surgery, and after four months of SARME, accomplished under general anesthesia. The otorhinolaryngological tests were accomplished in an environmentally adapted room, with and without the use of nasal vasoconstrictor, in both nasal cavities. Results: The results have demonstrated that 59.3% of the casuistic was of female gender, with an average age of 25.33 years. All the orthodontic measures have obtained a statistically significant growth (p<0.001), which have maintained along the time (p<0.001). All the assessed measures have presented better results with the use of nasal vasoconstrictor. The nasal cavity area as a whole augmented after the surgery (p<0.036). The average volume is 2.75 larger with the vasoconstrictor use (p < 0.001), however, there was any statistically significant alterations between the moments assessed. The expiratory and inspiratory flows have grown along the time (p<0.001, for both). The expiratory pressure is reduced in the course of the moments assessed (p<0.004). The subjective analysis of respiratory sensation only through nose has increased significantly from one moment to the other (p<0.05). There was a statistic correlation between perimeter of augmented arch and aerial resistance diminished (p=0.004) and between the increase of a transverse measure with the growth of inspiratory and expiratory flow, with and without the use of vasoconstrictor (p=0.023 and p=0.004 respectively). Only the respiratory flow presented a different behavior between the sides. Conclusions: Thus, it is concluded that the SARME promotes important alterations on oral and nasal cavities that, associated, generate a better respiratory quality to the patient and demonstrate a clinical otorhinolaryngological relevance of such bucomaxillofacial surgical procedure

Introdução: a variabilidade clínica da fibrose cística (FC) levou ao desenvolvimento de diferentes sistemas de escores de avaliação de sua gravidade. Como nem sempre é possível fazer a monitorizarão do paciente com exames radiológicos, tomográficos, funcionais e clínicos simultaneamente, o entendimento das correlações entre esses métodos é um ponto importante para que a equipe multiprofissional dos centros de FC selecione o método mais adequado na sua rotina de atendimento. Objetivo: avaliar a gravidade das alterações clínicas, estruturais e funcionais de uma população de pacientes com fibrose cística por meio de escores clínicos, radiológicos, tomográficos e testes funcionais e analisar as correlações, por pareamento entre os escores de Shwachman-Kulczychi (E-SK), Brasfield (E. Brasfield), Bhalla (E. Bhalla), espirometria e teste de caminhada de seis minutos (TC6M). Métodos: Estudo transversal prospectivo em pacientes com idade entre 3-21 anos. Foram realizados no mesmo dia: espirometria, TC6M, radiografia de tórax (RX), tomografia computadorizada (TC) de tórax e avaliação do estadio clínico. Utilizou-se a regressão linear (coeficiente de correlação de Spearman) para a análise das correlações entre os exames. Foi construída uma Curva ROC para avaliar o melhor ponto de corte para o valor de escore de Brasfield que indicaria a presença de bronquiectasias na TC. Resultados: 43 pacientes foram avaliados, 19F/24M, 10,5 ± 4,7 anos, com mediana de E. Bhalla, E. Brasfield e E-SK de 10, 17 e 70, respectivamente. Os valores médios (% previsto) de capacidade vital forçada (CVF), volume expiratório forçado no primeiro segundo (VEF1) e fluxo expiratório forçado entre 25 e 75 % da capacidade vital (FEF25-75%) foram, respectivamente, 70,4 ± 26, 59,2 ± 26, 47,4 ± 35,8. Houve correlações significativas entre quase todos os parâmetros estudados. Apenas não houve correlação estatisticamente significativa entre escore do teste de caminhada de seis minutos (Z-TC6M) e aprisionamento + mosaico (r = -0,35), VEF1 70% e E-SK (r = -0,04); VEF1 70% e E. Bhalla (r = -0,32), VEF1 70% e E. Brasfield (r = 0,14), VEF1 70% e Z-TC6M (r =0,14). Através da Curva ROC foi determinado o ponto de corte do escore de Brasfield de 18 como o de melhor sensibilidade (83%), especificidade (92%), valor preditivo positivo (96%) e valor preditivo negativo (71%) para detecção de bronquiectasias na TC de tórax. Conclusões: Nesta casuística de pacientes com fibrose cística houve uma ampla variação quanto à gravidade da doença quando avaliada por parâmetros clínicos, radiológicos, tomográficos e funcionais. Apesar desta variação, houve correlação significativa entre a maioria dos métodos utilizados no estudo. As correlações não foram significativas nos pacientes com função pulmonar normal ou com distúrbio ventilatório obstrutivo leve, o que pode estar relacionado a uma menor capacidade discriminatória entre os diferentes métodos quando o acometimento pulmonar é de grau leve. Nessa amostra estudada, pacientes com escore de Brasfield menor ou igual a 18, tiveram uma probabilidade de 83% de apresentar bronquiectasias na TC de tórax. O teste da caminhada de seis minutos se mostrou como um método complementar alternativo que pode ser utilizado na avaliação da gravidade dos pacientes com FC / Introduction: The clinical variability of cystic fibrosis (CF) led to the development of different scoring systems to evaluate its severity. As it is not always possible to simultaneously assess CF patient with radiography, tomography, functional tests and clinical status, understanding the correlations between these methods is important for the multidisciplinary team of CF centers to select the most suitable method in their routine attendance. Objective: To assess the severity of the clinical, structural and functional characteristics of a population of CF patients by means of clinical scores, chest radiography (CXR), chest tomography (CT) and pulmonary functional tests and to analyze the correlations between Shwachman-Kulczychi score (SK), Brasfield score (Brasfield), Bhalla score (Bhalla), spirometry and six minute walk test (6-MWT). Method: A cross-sectional and prospective study including patients aged 3-21 years-old. Spirometry, 6-MWT, CRX, CT and evaluation of clinical status were performed on the same day. Linear regression (Spearman correlation coefficient) was performed to analyze the correlations between the tests. A ROC curve was constructed to assess the best value for the Brasfield score that would indicate the presence of bronchiectasis on CT. Results: A total of 43 patients were evaluated, 19F/24M, 10.5 ± 4.7 years, with median Bhalla, Brasfield and SK scores of 10, 17 and 70, respectively. Mean values (% predicted) forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and forced expiratory flow between 25 and 75% of vital capacity (FEF25-75%) were respectively 70.4 ± 26, 26 ± 59.2, 47.4 ± 35.8. There were significant correlations among almost all parameters studied. Only there was no statistically significant correlation between Z-6MWT and air trapping + mosaic perfusion (r = -0.35), FEV1 70% and SK (r = -0.04), FEV1 70% and Bhalla (r = -0.32), FEV1 70% and Brasfield (r = 0.14), FEV1 70% and Z-6MWT (r = 0.14). ROC curve determined that Brasfield score of 18 had the best sensitivity (83%), specificity (92%), positive predictive value (96%) and negative predictive value (71%) for detecting bronchiectasis on chest CT. Conclusions: These patients with cystic fibrosis had a wide variation in disease severity as assessed by clinical, radiographic, tomographic and functional scores. Despite this variation, there was a significant correlation between most methods used in the study. The correlations were not significant in patients with normal lung function or with mild obstructive lung disease, which may be related to a lower discriminate capacity between the different methods when pulmonary involvement is mild. In this study, patients with Brasfield score less than or equal to 18, had a probability of 83% to have bronchiectasis on chest CT. The six-minute walk test is a complementary method that can be used to assess the severity of patients with CF