As crianças infectadas por HIV/Aids apresentam desnutrição e deficiências nutricionais, como anemia por deficiência de ferro e hipovitaminose A, causando prejuízo ao crescimento e desenvolvimento e imunodepressão. A fortificação de alimentos é vista como uma estratégia promissora para o combate de deficiências nutricionais. Objetivo: Desenvolver e testar aceitação e eficiência de snack de milho e pulmão bovino, rico em ferro e vitamina, na redução de anemia e hipovitaminose A, em crianças com HIV/Aids. Metodologia: Inicialmente, foi realizado um estudo transversal para caracterização do estado nutricional e alterações hematológicas - anemia e dislipidemias, em 63 crianças, com idade entre 5-10 anos, com HIV/Aids da Unidade de Infectologia do Instituto da Criança - HCFMUSP. Paralelamente, foi desenvolvido o snack rico em ferro e vitamina A, através da extrusão termoplástica, utilizando-se como matérias-primas: grits de milho degerminado e pulmão bovino liofilizado desengordurado (m/m, 90:10), como fonte de ferro heme, altamente biodisponível. A aromatização foi feita com os sabores bacon, cebola e salsa, e morango; neste processo, utilizou-se substituto de gordura e acetato de retinol para fortificação. A aceitação do snack, mediante avaliação sensorial com escala hedônica facial, foi feita por 53 crianças sadias e infectadas por HIV/Aids, com idade entre 2-10 anos, na Associação Civil Anima, SP. A intervenção nutricional ocorreu durante 2 meses; foram oferecidas 3 porções de 30g/semana de snack fortificado a 18 crianças com HIV/Aids, com idade entre 5-10 anos. Para avaliação nutricional, acompanhou-se: consumo alimentar através de recordatório de 24h, peso, altura, hemoglobina, ferro total, ferritina e retinol sérico, no início e no final da intervenção. Resultados: A desnutrição leve, moderada ou grave foi encontrada em 46% dos casos; sendo a maior freqüência no índice E/I, com escore-z de 39,7%, refletindo comprometimento de longa duração (stunting) no crescimento destas crianças. A prevalência de anemia do grupo foi de 19%. Entretanto, entre os tratados com AZT foi de 66%, observando-se associação entre prevalência de anemia e uso de AZT (zidovudina) na terapia anti-retroviral (TARV) (p=0,022). As prevalências de hipercolesterolemia e hipertrigliceridemia, considerando-se valores limítrofes e aumentados, foram respectivamente 53,5 e 51,7%; com observação de maiores freqüências nos grupos com inibidores de protease (IP) na TARV. O snack fortificado desenvolvido forneceu, em cada 100g, 5,07mg de ferro e 780?g RE de vitamina A, representando respectivamente 56% e até 78% das DRIS para crianças com idade entre 7-10 anos. O resultado da avaliação sensorial foi de aproximadamente 80% de aceitação para todos os sabores testados. A intervenção nutricional resultou em aumento da média de hemoglobina de 12,45+1,34g/dL para 12,56+1,33g/dL, sem significância estatística; e aumento do retinol sérico de 0,447+0,124 ?g RE para 0,928+0,415 ?g RE (p<0,01). Conclusão: Além de estudos de prevalência das deficiências nutricionais em grupos vulneráveis, tais como as crianças com HIV/Aids, são relevantes as intervenções nutricionais, pois contribuem como co-fator positivo no tratamento de doenças, através da melhora do estado nutricional do indivíduo. / Children infected by HIV/Aids present malnutrition and nutritional deficiency, as anaemia by iron deficiency and hypovitaminosis A, causing damage to growing and developmente. The food fortification is seen as promising strategy to the combat of nutritional deficiency. Objective: Developing and testing the efficiency of a corn snack and bovine lung. rich in iron and vitamin, in the reduction of de anaemia and hypovitaminosis A, in children with HIV/Aids. Metodology: At first, a transversal study was carried out to characterize the nutritional state and hematology alterations - anaemia and dyslipidemia, in 63 children, with age between 5-10 years old, with HIV/Aids from the Unit of Infectology from Children Institute. At the same time, the snack rich and vitamin A, was developed through the thermoplastic extrusion, using as raw material: corn grits ingeminated and bovine lung lyophilized no fat (m/m, 90:10), as source of heme iron, in highly bioavailability. In the fragrance, bacon, onion and parsley and strawberry flavors, it was used fat substitute and retinol acetate to fortification. The acceptance of the snack, through sensorial evaluation with hedonic facial scale, had been done by 53 healthy children and infected by HIV/Aids, with ages between 2-10 years old, in the Civil Anima Association, SP. Finally, the nutritional intervention was done during 2 months; it was offered 3 portions of 30g/week of strenghtened snack to 18 children with HIV/Aids, with ages between 5-10 years old. To nutritional evaluation, it was followed: food consumption through the 24-hour diary, weight, height, hemoglobin, total iron, ferreting e serum retinol, at the beginning and in the ending of the intervention. Results: The slight, moderate or severe malnutrition was found in 46% of the cases; being the most frequency when considered, the z-score of height-for-age 39,7% of malnutrited, reflecting commitment of long duration (stunting) in the growing of these children. The prevalence of anaemia was 19%, end more of 66% between the AZT treated; there was association between anaemia the AZT use (zidovudina) in the anti retroviral therapy (ARVT) (p=0,022). The prevalence of hypercholesterolemia e hypertrigliceridemia, considering low values and increased, were respctively 53,5 and 51,7%; with tendency to major frequencies in the groups with protease inhibitors (PI) in ARVT. The strengthened snack developed, per each 100g, guaranteed 5,07 mg of iron and 780 µg RE of A vitamin, representing respectively 56% and even 78% of DRIS to children with age between 7-10 years old. The result of sensorial evaluation, showed around 80% of acceptance to all tested flavors. The nutritional intervention, resulted in growth of the hemoglobin average of 12,45 +/- 1,34 g/dL to 12,56 +/- 1,33 g/dL, without statistics significance; and increasing of serum retinol of 0,447 +/- 0,124 to 0,928 +/- 0,415 (p«0,01). Conclusion: Besides the studies of prevalence of nutritional deficiency in vulnerable groups, such as children with HIV/Aids, the nutritional intervention are relevant, because contribute as co-positive factors in the didease treatments, through the improvement of the nutrition state of the individual.

Os comportamentos espectroeletroquímicos do ácido acetilsalicílico (AAS) e seu produto de hidrólise, o ácido salicílico (AS), foram estudados em soluções aquosas nas regiões de pH ácido, neutro e alcalino. Resultados para experimentos de voltametria cíclica sugeriram possíveis processos de eletro-oxidação e eletro-redução dos fármacos. O monitoramento do espectro de absorbância na região do UV-vis, simultâneo à medida de carga envolvida na eletrólise, permitiu a identificação de processos redox e o cálculo do número de elétrons envolvidos, aplicando a Lei de Faraday. O fármaco mostrou-se estável em pH ácido, reduziu em pH neutro e oxidou em pH alcalino. Tanto no processo de eletro-redução como na eletro-oxidação, os mecanismos propostos estabelecem o envolvimento de 1 elétron para a identificação de mudanças no nível molecular. Estas foram observadas pelas alterações de espectros de absorbância na região do UV-vis. Técnicas complementares, ressonância paramagnética eletrônica (RPE) e espectroscopia de transmitância FT-IR, foram usadas para a caracterização dos produtos obtidos em experimentos de eletrólise. As respostas espectrofotométricas associadas à processos eletroquímicos permitiram o desenvolvimento de método espectroeletroquímico para a detecção do fármaco em amostras reais contidas em soluções com pH neutro, utilizando a técnica de voltabsormetria derivada linear (DLVA). A interação entre os fármacos e íons de ferro no ambiente do estômago, foi simulada em experimentos in vitro, empregando eletroquímica e espectrofotometria. Na presença do AAS ocorreram interações fracas sem a interferência para a absorção de ferro pelo organismo. Em contrapartida, o AS interagiu formando um complexo estável com o Fe3+, podendo ser apontado como um potencial interferente para a absorção de ferro provocando anemia em indivíduos vegetarianos que fazem uso contínuo deste fármaco. / The spectroelectrochemical behavior of acetylsalicylic acid (ASA) and its spin off hydrolysis, salicylic acid (SA), were studied in aqueous solutions in the acid, neutral and alkaline pH regions. Results for cyclic voltammetry experiments suggested a possible electro-oxidation and electro-reduction of the drugs. The monitoring of the absorbance spectra in the region of the UV-vis, simultaneously with the measurement of the charge involved in the electrolysis, allowed the identification of redox processes and the calculation of the number of electrons involved applying Faraday\'s Law. The drug was stable in acid solutions, reduced in neutral and oxidized in alkaline ones. In electro-reduction and electro-oxidation processes, the proposed mechanisms establish the involvement of 1 electron to identify changes at the molecular level. These were observed by changes in absorbance spectra in the UV-vis region. Complementary techniques, electronic paramagnetic resonance (EPR) and FT-IR transmittance spectroscopy were used to characterize the products obtained in electrolysis experiments. The spectrophotometric responses associated to the electrochemical processes allowed the development of a spectroelectrochemical method for the detection of the drug in real samples contained in solutions with neutral pH, using the technique of derivative linear voltabsorptometry (DLVA). The interaction between drugs and iron ions in the stomach environment was simulated in in vitro experiments using electrochemistry and spectrophotometry. In the presence of ASA, weak interactions occurred without interference for the absorption of iron by the organism. On the other hand, AS interacted to form a stable complex with Fe3+ and could be considered as a potential interfering agent for the iron absorption, causing anemia in vegetarian individuals who make continuous use of this drug.

Adaptive phenotypic plasticity, the ability of a genotype to give rise to different phenotypes in different environments, evolves to allow organisms to fine-tune their life-history traits according to the varying conditions they encounter during their lives. Reproductive investment - the manner in which organisms divide their resources between survival and reproduction - is well studied in evolutionary ecology because it is a key determinant of fitness. However, whilst plasticity in reproductive effort is well understood for free-living multicellular taxa (such as insects, birds, and mammals), the application of evolutionary theory for plasticity and life history strategies to unicellular parasites and pathogens is lacking. In this thesis, I use empirical and theoretical approaches to uncover how differential resource allocation to non-replicating, sexual stages (gametocytes) versus asexually replicating stages can be harnessed by the rodent malaria parasite Plasmodium chabaudi to maximise its fitness across the often very variable conditions it encounters during infections. Differential allocation between those stages is equivalent to the fundamental life-history trade-off between survival and reproduction because gametocytes are responsible for between-host transmission (i.e. reproduction of the infection) whereas asexual parasites mediate host exploitation and within-host survival. A suite of within-host models reveal that malaria parasites could gain considerable fitness benefits in the face of low levels of drug treatment if they reduce their investment into gametocyte production ("reproductive restraint"), thereby assuring the continuity of the infection and capitalising on opportunities for future transmission. In contrast, high levels of drug treatment typically select parasites to commit all of their resources to gametocyte production ("terminal investment"), to escape a host that does not offer much opportunity for future transmission. My experiments reveal that P. chabaudi increases both its reproductive investment and its asexual replication rate in anaemic hosts (i.e. host that have a low density of red blood cells), suggesting that parasites profit from host anaemia and can afford high investment in gametocytes ("affluent investment"). I also uncover plasticity in a number of traits that underpin asexual replication rate, including invasion preference for different ages of red blood cells, but it is plasticity in the number of progeny (merozoites) per infected cell that is the main contributor to asexual replication rate. My experiments also reveal genetic variance in plasticity of the life-history traits investigated, which has profound implications for their evolution. Furthermore, plastic modification of these traits is associated with minimal costs or constraints, so that parasites can rapidly match life-history traits appropriately to the within-host environment. Severe anaemia is one of the deadliest symptoms of malaria, so observing that virulence and infectiousness increases in anaemic hosts has also fundamental clinical implications. Finally, the empirical and theoretical observations of affluent investment, reproductive restraint and terminal investment match theoretical predictions of how organisms should behave in varying environments, confirming P. chabaudi as a useful model system to test life-history theory.

Submitted by Rosivalda Pereira (mrs.pereira@ufma.br) on 2017-12-06T20:11:07Z No. of bitstreams: 1 IonePereira.pdf: 4313615 bytes, checksum: b4b18d96e95ccf2676273520e2380e31 (MD5) / Made available in DSpace on 2017-12-06T20:11:07Z (GMT). No. of bitstreams: 1 IonePereira.pdf: 4313615 bytes, checksum: b4b18d96e95ccf2676273520e2380e31 (MD5) Previous issue date: 2017-03-09 / CAPES / FAPEMA / INCT / The transient receptor potential ankyrin 1 (TRPA1) is a non-selective Ca+2 channel expressed on neuronal and non-neuronal cells, and mediates pain and inflammation; being implicated in rheumatoid arthritis (RA). Here, we evaluated the expression of TRPA1 on peripheral blood leukocytes obtained from RA patients, as well as its correlation with pain and disability, in addtition to the immune alterations in RA patients treated or not with antirheumatic drugs: the disease-modifying angent leflunomide (LFN) and the anti-TNFα adalimumab (ADA); in comparison with healthy subjects. Peripheral blood samples were taken from 15 healthy subjects (controls), 10 RA patients not undertaking anti-rheumatic therapy (NST), 15 patients treated with LFN and 15 patients treated with ADA. C reactive protein (CRP), rheumatoid factor (FR), hydrogen peroxide (H2O2), 4-hydroxynonenal (4- HNE) and tumour necrose factor α (TNFα) levels were quantified. Also, leukocyte subpopulations, the number of red blood cells, the levels of haemoglobin and the expression of TRPA1 on peripheral blood leukocytes, were evaluated. TRPA1 expression was increased on NST leukocytes and this was correlated with pain and disability and was associated with the number of polymorphonuclear cells and the activation of CD14+ cells. It was also demonstrated that treatment with either LFN or ADA attenuates anaemia in AR, with those treatments being effective in treating both the intra- and extra-articular disease. Overall, our data showns that TRPA1 influences pain and disability in RA and that its expression is reduced in patients treated with LFN or ADA. These evidences, together with the promissing data on the anti-rheumatic therapy in reducing anaemia in RA patients suggest that these drugs are effective in treating both the intra- and extra-articular alterations of RA. / O receptor de potencial transitório anquirina 1 (TRPA1) é um canal não seletivo para Ca+2 , expresso em neurônios sensoriais e células não neuronais, o qual medeia a transdução da dor e a inflamação; tendo sido implicado na artrite reumatoide (AR). Este trabalho avaliou a expressão de TRPA1 em leucócitos de sangue periférico de pacientes com AR, bem como sua correlação com a dor e a prda de função articular, além de alterações imunes encontradas em indivíduos com AR recebendo ou não terapia anti-reumática com o modificador da doença leflunomida (LFN) e ou o anti-TNFα adalimumab (ADA); em comparação à indivíduos sadios. Amostras de sangue foram coletadas de 15 indivíduos sadíos (controle), 10 pacientes artríticos não submetidos à terapia anti-reumática específica (NST), 15 pacientes tratados com LFN e 15 pacientes tratados com ADA. Os níveis circulantes de proteína C reativa (PCR), fator reumatóide (FR), peróxido de hidrogênio (H2O2), 4-hidroxinonenal (4-HNE) e fator de necrose tumoral (TNFα) foram quantificados. Ainda, avaliou-se as populações de leucócitos, o número de hemácias, os níveis de hemoglobina e a expressão de TRPA1 em leucócitos do sangue periférico. Observou-se que a expressão de TRPA1 em leucócitos de sangue periférico está aumentada em pacientes NST, e que isto está associado ao aumento do número de células polimorfonucleares e à ativação de células CD14+ . Ainda, a expressão de TRPA1 correlaciona-se com a dor e disfunção articular, alterações estas, que encontram-se reduzidas em pacientes tratados com LFN e ADA. Demonstrou-se ainda que o tratamento com LFN ou ADA previne a anemia relacionada à AR, sendo efetivos tanto no tratamento das alterações intra quanto extra articulares decorrentes da doença.. Em conjunto, os dados demonstram que o TRPA1 influencia a resposta dolorosa e a disfunção articular da AR, e que sua expressão é reduzida pelo tratamento com LFN ou ADA. Estas evidências, aliadas com dados promissores na redução da anemia dos pacientes artríticos sugerem que o tratamento com estas drogas anti-reumáticas é efetivo no tratamento de manifestações intra- e extra-articulares da AR

Background: With increasing technological advancements, healthcare providers are adopting electronic health records (EHRs) and new health information technology systems. Consequently, data from these systems is accumulating at a faster rate creating a need for more robust ways of capturing, storing and processing the data. Big data analytics is used in extracting insight form such large amounts of medical data and is increasingly becoming a valuable practice for healthcare organisations. Could these strategies be applied in disease management? Especially in rare conditions like Sickle Cell Disease (SCD)? The study answers the following research questions;1. What Data Management practices are used in Sickle Cell Anaemia management?2. What areas in the management of sickle cell anaemia could benefit from use of big data Analytics?3. What are the challenges of applying big data analytics in the management of sickle cell anaemia?Purpose: The purpose of this research was to serve as pre-study in establishing the opportunities and challenges of applying big data analytics in the management of SCDMethod: The study adopted both deductive and inductive approaches. Data was collected through interviews based on a framework which was modified specifically for this study. It was then inductively analysed to answer the research questions.Conclusion: Although there is a lot of potential for big data analytics in SCD in areas like population health management, evidence-based medicine and personalised care, its adoption is not a surety. This is because of lack of interoperability between the existing systems and strenuous legal compliant processes in data acquisition.

As crianças infectadas por HIV/Aids apresentam desnutrição e deficiências nutricionais, como anemia por deficiência de ferro e hipovitaminose A, causando prejuízo ao crescimento e desenvolvimento e imunodepressão. A fortificação de alimentos é vista como uma estratégia promissora para o combate de deficiências nutricionais. Objetivo: Desenvolver e testar aceitação e eficiência de snack de milho e pulmão bovino, rico em ferro e vitamina, na redução de anemia e hipovitaminose A, em crianças com HIV/Aids. Metodologia: Inicialmente, foi realizado um estudo transversal para caracterização do estado nutricional e alterações hematológicas - anemia e dislipidemias, em 63 crianças, com idade entre 5-10 anos, com HIV/Aids da Unidade de Infectologia do Instituto da Criança - HCFMUSP. Paralelamente, foi desenvolvido o snack rico em ferro e vitamina A, através da extrusão termoplástica, utilizando-se como matérias-primas: grits de milho degerminado e pulmão bovino liofilizado desengordurado (m/m, 90:10), como fonte de ferro heme, altamente biodisponível. A aromatização foi feita com os sabores bacon, cebola e salsa, e morango; neste processo, utilizou-se substituto de gordura e acetato de retinol para fortificação. A aceitação do snack, mediante avaliação sensorial com escala hedônica facial, foi feita por 53 crianças sadias e infectadas por HIV/Aids, com idade entre 2-10 anos, na Associação Civil Anima, SP. A intervenção nutricional ocorreu durante 2 meses; foram oferecidas 3 porções de 30g/semana de snack fortificado a 18 crianças com HIV/Aids, com idade entre 5-10 anos. Para avaliação nutricional, acompanhou-se: consumo alimentar através de recordatório de 24h, peso, altura, hemoglobina, ferro total, ferritina e retinol sérico, no início e no final da intervenção. Resultados: A desnutrição leve, moderada ou grave foi encontrada em 46% dos casos; sendo a maior freqüência no índice E/I, com escore-z de 39,7%, refletindo comprometimento de longa duração (stunting) no crescimento destas crianças. A prevalência de anemia do grupo foi de 19%. Entretanto, entre os tratados com AZT foi de 66%, observando-se associação entre prevalência de anemia e uso de AZT (zidovudina) na terapia anti-retroviral (TARV) (p=0,022). As prevalências de hipercolesterolemia e hipertrigliceridemia, considerando-se valores limítrofes e aumentados, foram respectivamente 53,5 e 51,7%; com observação de maiores freqüências nos grupos com inibidores de protease (IP) na TARV. O snack fortificado desenvolvido forneceu, em cada 100g, 5,07mg de ferro e 780?g RE de vitamina A, representando respectivamente 56% e até 78% das DRIS para crianças com idade entre 7-10 anos. O resultado da avaliação sensorial foi de aproximadamente 80% de aceitação para todos os sabores testados. A intervenção nutricional resultou em aumento da média de hemoglobina de 12,45+1,34g/dL para 12,56+1,33g/dL, sem significância estatística; e aumento do retinol sérico de 0,447+0,124 ?g RE para 0,928+0,415 ?g RE (p<0,01). Conclusão: Além de estudos de prevalência das deficiências nutricionais em grupos vulneráveis, tais como as crianças com HIV/Aids, são relevantes as intervenções nutricionais, pois contribuem como co-fator positivo no tratamento de doenças, através da melhora do estado nutricional do indivíduo. / Children infected by HIV/Aids present malnutrition and nutritional deficiency, as anaemia by iron deficiency and hypovitaminosis A, causing damage to growing and developmente. The food fortification is seen as promising strategy to the combat of nutritional deficiency. Objective: Developing and testing the efficiency of a corn snack and bovine lung. rich in iron and vitamin, in the reduction of de anaemia and hypovitaminosis A, in children with HIV/Aids. Metodology: At first, a transversal study was carried out to characterize the nutritional state and hematology alterations - anaemia and dyslipidemia, in 63 children, with age between 5-10 years old, with HIV/Aids from the Unit of Infectology from Children Institute. At the same time, the snack rich and vitamin A, was developed through the thermoplastic extrusion, using as raw material: corn grits ingeminated and bovine lung lyophilized no fat (m/m, 90:10), as source of heme iron, in highly bioavailability. In the fragrance, bacon, onion and parsley and strawberry flavors, it was used fat substitute and retinol acetate to fortification. The acceptance of the snack, through sensorial evaluation with hedonic facial scale, had been done by 53 healthy children and infected by HIV/Aids, with ages between 2-10 years old, in the Civil Anima Association, SP. Finally, the nutritional intervention was done during 2 months; it was offered 3 portions of 30g/week of strenghtened snack to 18 children with HIV/Aids, with ages between 5-10 years old. To nutritional evaluation, it was followed: food consumption through the 24-hour diary, weight, height, hemoglobin, total iron, ferreting e serum retinol, at the beginning and in the ending of the intervention. Results: The slight, moderate or severe malnutrition was found in 46% of the cases; being the most frequency when considered, the z-score of height-for-age 39,7% of malnutrited, reflecting commitment of long duration (stunting) in the growing of these children. The prevalence of anaemia was 19%, end more of 66% between the AZT treated; there was association between anaemia the AZT use (zidovudina) in the anti retroviral therapy (ARVT) (p=0,022). The prevalence of hypercholesterolemia e hypertrigliceridemia, considering low values and increased, were respctively 53,5 and 51,7%; with tendency to major frequencies in the groups with protease inhibitors (PI) in ARVT. The strengthened snack developed, per each 100g, guaranteed 5,07 mg of iron and 780 µg RE of A vitamin, representing respectively 56% and even 78% of DRIS to children with age between 7-10 years old. The result of sensorial evaluation, showed around 80% of acceptance to all tested flavors. The nutritional intervention, resulted in growth of the hemoglobin average of 12,45 +/- 1,34 g/dL to 12,56 +/- 1,33 g/dL, without statistics significance; and increasing of serum retinol of 0,447 +/- 0,124 to 0,928 +/- 0,415 (p«0,01). Conclusion: Besides the studies of prevalence of nutritional deficiency in vulnerable groups, such as children with HIV/Aids, the nutritional intervention are relevant, because contribute as co-positive factors in the didease treatments, through the improvement of the nutrition state of the individual.

Faculty of Science School of Pathology(Molecular Medicine and Haematology). 9707563v tridium@acenet.co.za / The erythrocyte carries gases between the cells and the lungs, and has to distort to negotiate narrow splenic sinuses and capillaries. This distortion necessitates a high surface area to volume ratio that is maintained by the erythrocyte membrane skeleton, a network of proteins including spectrin and protein 4.1. The skeleton anchors the lipid bilayer through attachment to integral membrane proteins, notably the anion exchange protein, band 3. Abnormalities of the erythrocyte membrane proteins cause loss of cell elasticity and ultimately the erythrocytes become prematurely trapped in the spleen where they are phagocytosed, resulting in haemolytic anaemia. Three mutations causing band 3-deficient hereditary spherocytosis (HS), a haemolytic anaemia characterised by spherical erythrocytes, were located using restriction enzyme analysis and DNA sequencing. Proband A (Black) is heterozygous for band 3 Pinhal (R490H) and has mild clinical symptoms. Proband B and his mother (Caucasian) are heterozygous for band 3 Bicetre (R490C) and have severe anaemia requiring transfusions and splenectomy, respectively. These results confirm codon 490 as a hotspot for mutations and indicate the effect of different amino acid substitutions in the same position on clinical severity. Proband C (Black) is homozygous for a novel mutation (E508K) for which her parents are heterozygous. The proband is severely affected and transfusion- dependent whereas her father has moderate anaemia and her mother is asymptomatic. It is speculated that a secondary factor modulates their clinical symptoms. All of these mutations occur in a CpG dinucleotide, a common source of DNA mutations, and are located within the highly conserved exon 13, which encodes the third to fifth α-helices and the second extracellular loop of the transmembrane region of band 3. The mutations are likely to alter the conformation of band 3, impairing its insertion into the erythrocyte membrane. No causative mutations were located in another 12 band 3-deficient HS kindred using restriction enzymes and single strand conformation polymorphism analysis. Ten protein 4.1-deficient patients with hereditary elliptocytosis, a haemolytic anaemia characterised by elliptical erythrocytes, were also studied. Immunoblot analyses ruled out abnormally sized protein 4.1 and three known DNA mutations were excluded using restriction enzyme analysis. Further studies are required to elucidate the cause of the haemolytic anaemia in these kindred. This study advanced our knowledge of the molecular basis of HS in South African kindred and highlighted the susceptibility of CpG dinucleotides to mutations.

Background: Lung cancer causes more deaths than any other cancer. Smoking causes roughly 90% of lung cancer cases. Concurrent chemoradiation therapy is the standard of care for stage IIIb patients with performance status (PS) 0-1. A less toxic approach is warranted for less fit patients. To optimize care, the understanding of common clinical variables such as haematological responses to inflammation could be much improved. Adherence to guidelines for proper clinical work-up is vital to ensure patients’ optimal care, especially for predictive assays. Screening of high-risk patients is now being implemented internationally. Chronic pulmonary obstructive disease (COPD) patients, a group at high risk to develop lung cancer, could be of interest for screening. Methods: Patient cohorts collected nationally and regionally by manual search in patient records or automated search in electronic patient records and national registries were analysed in relation to overall survival, comorbidities, medication, treatment, smoking status, biomarkers and adherence to guidelines. Standard statistics were applied to adjust for confounding factors. Results: Induction chemotherapy results in longer overall survival than radiotherapy alone (15.6 and 11.6 months respectively). The overall survival for patients with combined anaemia, leucocytosis and thrombocytosis at diagnosis is half of what could be anticipated if blood samples are normal (8.0 and 16.0 months respectively). Fifty percent of patients were overlooked in the routine work-up with EGFR analysis. Less than 40% of the patients received EGFR-tyrosine kinase inhibitors in first-line therapy. The frequency of EGFR mutation was 9.9%. COPD patients with asthma and medicating with inhaled corticosteroids, specific serotonin reuptake inhibitors (SSRI) or beta-blockers have a significantly decreased risk of lung cancer. Conclusions: Patients unfit to receive chemoradiation therapy should be considered for induction chemotherapy sequentially to radiotherapy. A patient that presents with pathological blood samples is likely to have poor prognosis and diagnostic work-up should be thorough to optimize outcome. Inadequate adherence to the national guidelines regarding treatment and EGFR analysis was shown. COPD patients medicating with ICS, beta-blockers or SSRI and with a concurrent asthma diagnosis have a decreased risk of lung cancer.

Motivation: A variety of factors including food shortage, poor hygiene and low education levels affects the nutritional status of black women. Women also have a high risk for the development of iron deficiency because they lose iron through menstruation, the birth process and a low intake of iron containing foods. All of these factors contribute to an increased risk for the development of iron deficiency anaemia in women. Objectives: The primary purpose of the study was to investigate the association between tea consumption and iron status of African females in the North West Province. To reach this purpose the specific aims were to (1) assess the iron status of women, (2) determine tea intake, and (3) determine the relationship between tea consumption and iron status, taking into account inhibiting and enhancing factors of iron absorption. Methods: A cross-sectional sample of apparently healthy females was taken from five different strata of urbanisation. The subjects were then further divided into two groups, namely younger women (younger than 45.9 years) and older women (older than 46 years). A sample of 920 subjects was used. Data were obtained from dietary, demographic and additional questionnaires, as well as from the taking of blood samples. This study was a sub-study of the THUSA study. Results: A total of 920 subjects participated of which 69.24% were younger women and 30.76% were older women. Due to missing data, the number of subjects for each parameter differed. The mean serum ferritin as well as haemoglobin concentrations were within normal ranges for both groups. The mean dietary iron intake for both groups was below recommendations. No significant correlations were found between serum ferritin or haemoglobin and total tea intake as well as a variety of other dietary factors. The low haemoglobin concentration group of the younger and older women combined had a slightly higher intake of animal protein and ascorbic acid than the high haemoglobin concentration group. On the other hand, the high serum ferritin concentration group had a significantly higher intake of animal protein than the low serum ferritin concentration group. Conclusion: The results of this study indicated that tea does not have an inhibitory effect on the iron status of the female population of the North West Province. However, the investigation of other studies conducted on the same topic had mixed results. Two of seven studies investigated and this study indicated that tea had no inhibitory effect on iron absorption. These two studies, as well as this study were not done in a controlled environment where certain factors can be controlled for, for example, time of tea intake and milk consumption with tea. The other five studies were, however, conducted in an environment where subjects were given test meals, time of tea consumption was regulated and milk consumption with tea was recorded. The conclusion can, therefore, be made that further studies on the South African population in a controlled environment are necessary to give accurate recommendations to the population. / Thesis (M.Sc. (Dietetics))--North-West University, Potchefstroom Campus, 2005.

The thesis is comprised of a comparative study of iron metabolism with particular reference to iron deficiency in the Indian and the African; Europeans were included when naterlal was available. Fifty four patients with iron deficiency anaemia were studied. There ware 43 Indians as compared with 11 Africans although the overall proportion of Indians to Africans admitted to the same ward was 1 : 4. Amongst the Indians the commonest cause of anaemia from blood loss was peptic ulceration (6 patients); while 3 had cirrhosis of the liver, one had hookworm anaemia and one was a case of ulcerative colitis. Gynaecological lesions were found in 2 patients, one had a proliferative endometrium and the other had endometrial polypi. Idiopathic iron deficiency anaemia was found in 60.5% of the Indian patients (both male and female). Amongst the Africans on the other hand, there were 2 cases of hookworm anaemia and 2 of cirrhosis of the liver while peptic ulceration was suspected in one patient who alao had amoebic dysentery and urinary hllharsiesis. None of the Africans had Idiopathic iron deficiency anaemia with the possible exception of one who had 4 Caesarean sections in rapid succession. There were 175 Indians, 175 Africans and 139 Europeans who were studied haematologlcally during pregnancy. The Incidence of iron deficiency anaemia among them was 26.7%, 2% and 4% respectively. The third aspect of the thesis is confined to an analysis of necropsy materiel for iron stores. Two hundred Africans and 58 Indians were studied. It was found that the incidence of *siderosis" in the African was high. There was a significant difference in the iron concentrations in the stores of the 2 racial groups. It was concluded that iron deficiency anaemia is common in the Indian. Diet appears to play an important role in its production. / Thesis (M.D.)-University of Natal, Durban, 1963.