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Masters Research - Masters of Medical Science / The goal of this thesis is to report on research that explored the role of cow’s milk protein in children with chronic functional constipation. The research consisted of a systematic review of the literature, two clinical crossover trials, and a qualitative exploration of the lived experience of following a milk-free diet. Chapter 1 provides the introduction to both allergy and constipation, and the relationship between the two. Causes of constipation can be organic or functional (1). Organic causes of constipation occur in relation to a primary disease classification such as endocrine or metabolic disorders, neurologic disorders, anatomic malformation, collagen vascular disease and some drugs (for example, opiates). Chronic functional constipation is defined as having one bowel motion every three to 15 days (2) and is characterised by painful bowel movements or strain in defecation, hard stools with increased diameter or pellets, and occurs with or without soiling (3). This functional constipation is defined as chronic when it persists for greater than two weeks (4). Chapter 2 details the methods used in searching the literature for evidence for a role of cow’s milk consumption in chronic functional constipation in children from 1980 to 2006. This was published as a systematic review. The literature surrounding cow’s milk and constipation was found to be limited. None of the studies previously conducted were population-based or structured to provide evidence-based evaluation or treatment guidelines at either the general practitioner or paediatric specialist level. The strongest evidence found was a double blind randomised control trial conducted by Iacono and colleagues (3). The research study by Iacono and colleagues (3) provides evidence of an association between cow’s milk and constipation. The following research questions were developed from the systematic review: 1. Can the results of the Iacono and colleagues study of children with chronic functional constipation that respond to the replacement of cow’s milk protein with soy be replicated in the Australian setting? 2. Does cow’s milk β casein A1 cause constipation in children with chronic functional constipation? 3. What are the immunological and biochemical mechanisms underlying chronic functional constipation that respond to the removal of cow’s milk protein in children? 4. What factors affect the feasibility of parents administering a cow’s milk protein free diet to their children? The four questions were addressed by two different dietary crossover trials and a qualitative study. Chapter 3 describes the participants recruited and the methods used for the crossover trials investigating milk protein and paediatric chronic functional constipation including details of the primary outcome measure (number of bowel motions during a two-week trial period) and secondary outcome measures (biochemical, immunological and faecal analysis). Chapter 4 describes the results of Trial 1, which replicated the Iacono and colleagues study in the Australian setting, investigating the effects of soy and cow’s milk β-casein A1 in children with chronic functional constipation. One hundred percent of participants experienced resolution of their constipation during the soy milk condition compared with 68% experiencing resolution during the soy milk condition in the Iacono and colleagues study (n=65). Thirteen participants were recruited to Trial 1. Nine participants returned constipation diaries for the study period. The mean (SD) number of stools for each of the conditions was: baseline, 5.1 (1.4); cow’s milk 9.9 (4.4); washout 13.0 (5.2); and soy milk 15.1 (5.0). The differences between the three dietary conditions were statistically significant, p=0.03. The results confirmed the hypothesis that children in the Australian setting with chronic functional constipation unresponsive to the usual treatments, respond to the removal of cow’s milk protein from the diet. Chapter 5 describes the results of Trial 2, the double blind crossover trial comparing the effects of cow’s milk β-casein A1 and cow’s milk β-casein A2 in children with chronic functional constipation. Thirty-nine participants were recruited to Trial 2 and 26 participants returned constipation diaries for the trial period. Unlike the soy result, the cow’s milk β casein A2 did not give 100% resolution of constipation, in fact, the percentage resolution was almost identical to the cow’s milk β casein A1 result. The fact that some children responded during the cow’s milk casein A1 condition in both trials could be caused by a threshold effect, given it was likely that participants were consuming less cow’s milk protein during the trial (400 mL with elimination of all other sources of cow’s milk protein) than on their pre-trial diet. Resolution with both the cow’s milk β casein A1 and cow’s milk β casein A2 conditions suggests that these children are able to tolerate some cow’s milk protein before the symptom of constipation occurs. This could be a food intolerance type reaction or there is some other component in cow’s milk that is causing the problem in these children. Chapter 6 describes a qualitative study of the feasibility for mothers to administer a cow’s milk protein free diet to their children. The experiences of mothers following a cow’s milk protein free diet to assist in the management of chronic functional constipation in children were reported. A number of themes were identified that are useful to health professionals educating families. Mothers found the removal of cow’s milk protein from the diets of their children challenging but persevered due to the potential benefit to their children. Many mothers planned to continue post study with a modified approach to the cow’s milk protein free diet by allowing some cow’s milk protein in the diet to make the diet more acceptable to the family but not as much as the pre-trial diet. These experiences provide health professionals with valuable insights and ideas to assist their patients to manage a cow’s milk protein free diet. Chapter 7 discusses all aspects of the research including any limitations. The results of Trial 1 confirmed the hypothesis that children in the Australian settling with chronic functional constipation unresponsive to the usual treatments respond to the removal of cow’s milk protein from the diet. Therefore, cow’s milk protein is involved in the aetiology of constipation in these children. All the study participants demonstrated an absence or low level of normal gut flora, which may affect bowel regularity. Further research into species present and absent may provide further explanations to the lack of bowel regularity in these children. The immunological and biochemical mechanisms underlying chronic functional constipation that respond to the removal of cow’s milk protein requires further investigation. Although the number of statistically significant variables between the conditions was low, there was a high degree of abnormality. Further investigations are needed, including research into food intolerance reactions that affect the nerve endings in the bowel. The results in Trial 1 and Trial 2 are suggestive of an involvement of blood factors including platelets and monocytes. Other children may have a chronic Streptococcus A infection which may be contributing to constipation as well as to liver function abnormalities. Liver function abnormalities were observed for some participants in both trials, independent of milk condition. The extent to which the research questions have been answered is evaluated in Chapter 7, which includes the conclusions and recommendations of this research. In brief, the findings were: • Children with chronic functional constipation that is unresponsive to the traditional treatments should trial a cow’s milk protein free diet for at least two weeks to determine whether this may resolve the constipation. During this period, the numbers and form of bowel motions should be recorded and results compared to a one week record collected prior to commencing the cow’s milk protein free diet. • Due to the complicated nature of a cow’s milk protein free diet, especially the number of processed foods which contain hidden cow’s milk protein, consultation with a dietitian is essential for implementation of this diet. The dietitian should consider educating the patient’s family, both parents and siblings, to ensure the best outcome in terms of acceptance and compliance of the diet, and provide adequate resources. • If this dietary modification is successful for the child and alleviates constipation, consultation with a dietitian is recommended to determine the amount tolerated and nutritional adequacy of the diet. Soy milk is recommended as a substitute for cow’s milk and a probiotic needs to be prescribed to assist with the normalisation of gut flora. • Education of health professionals such as general practitioners, paediatricians, and paediatric continence nurses, regarding a cow’s milk protein free diet for chronic functional constipation, is essential to support the child and his/her family and integral to the success of this strategy. The findings of this research will be published in the scientific literature and as conference presentations. It is hoped that these findings will assist in the management of children with chronic functional constipation unresponsive to the traditional treatments.

Masters Research - Masters of Medical Science / The goal of this thesis is to report on research that explored the role of cow’s milk protein in children with chronic functional constipation. The research consisted of a systematic review of the literature, two clinical crossover trials, and a qualitative exploration of the lived experience of following a milk-free diet. Chapter 1 provides the introduction to both allergy and constipation, and the relationship between the two. Causes of constipation can be organic or functional (1). Organic causes of constipation occur in relation to a primary disease classification such as endocrine or metabolic disorders, neurologic disorders, anatomic malformation, collagen vascular disease and some drugs (for example, opiates). Chronic functional constipation is defined as having one bowel motion every three to 15 days (2) and is characterised by painful bowel movements or strain in defecation, hard stools with increased diameter or pellets, and occurs with or without soiling (3). This functional constipation is defined as chronic when it persists for greater than two weeks (4). Chapter 2 details the methods used in searching the literature for evidence for a role of cow’s milk consumption in chronic functional constipation in children from 1980 to 2006. This was published as a systematic review. The literature surrounding cow’s milk and constipation was found to be limited. None of the studies previously conducted were population-based or structured to provide evidence-based evaluation or treatment guidelines at either the general practitioner or paediatric specialist level. The strongest evidence found was a double blind randomised control trial conducted by Iacono and colleagues (3). The research study by Iacono and colleagues (3) provides evidence of an association between cow’s milk and constipation. The following research questions were developed from the systematic review: 1. Can the results of the Iacono and colleagues study of children with chronic functional constipation that respond to the replacement of cow’s milk protein with soy be replicated in the Australian setting? 2. Does cow’s milk β casein A1 cause constipation in children with chronic functional constipation? 3. What are the immunological and biochemical mechanisms underlying chronic functional constipation that respond to the removal of cow’s milk protein in children? 4. What factors affect the feasibility of parents administering a cow’s milk protein free diet to their children? The four questions were addressed by two different dietary crossover trials and a qualitative study. Chapter 3 describes the participants recruited and the methods used for the crossover trials investigating milk protein and paediatric chronic functional constipation including details of the primary outcome measure (number of bowel motions during a two-week trial period) and secondary outcome measures (biochemical, immunological and faecal analysis). Chapter 4 describes the results of Trial 1, which replicated the Iacono and colleagues study in the Australian setting, investigating the effects of soy and cow’s milk β-casein A1 in children with chronic functional constipation. One hundred percent of participants experienced resolution of their constipation during the soy milk condition compared with 68% experiencing resolution during the soy milk condition in the Iacono and colleagues study (n=65). Thirteen participants were recruited to Trial 1. Nine participants returned constipation diaries for the study period. The mean (SD) number of stools for each of the conditions was: baseline, 5.1 (1.4); cow’s milk 9.9 (4.4); washout 13.0 (5.2); and soy milk 15.1 (5.0). The differences between the three dietary conditions were statistically significant, p=0.03. The results confirmed the hypothesis that children in the Australian setting with chronic functional constipation unresponsive to the usual treatments, respond to the removal of cow’s milk protein from the diet. Chapter 5 describes the results of Trial 2, the double blind crossover trial comparing the effects of cow’s milk β-casein A1 and cow’s milk β-casein A2 in children with chronic functional constipation. Thirty-nine participants were recruited to Trial 2 and 26 participants returned constipation diaries for the trial period. Unlike the soy result, the cow’s milk β casein A2 did not give 100% resolution of constipation, in fact, the percentage resolution was almost identical to the cow’s milk β casein A1 result. The fact that some children responded during the cow’s milk casein A1 condition in both trials could be caused by a threshold effect, given it was likely that participants were consuming less cow’s milk protein during the trial (400 mL with elimination of all other sources of cow’s milk protein) than on their pre-trial diet. Resolution with both the cow’s milk β casein A1 and cow’s milk β casein A2 conditions suggests that these children are able to tolerate some cow’s milk protein before the symptom of constipation occurs. This could be a food intolerance type reaction or there is some other component in cow’s milk that is causing the problem in these children. Chapter 6 describes a qualitative study of the feasibility for mothers to administer a cow’s milk protein free diet to their children. The experiences of mothers following a cow’s milk protein free diet to assist in the management of chronic functional constipation in children were reported. A number of themes were identified that are useful to health professionals educating families. Mothers found the removal of cow’s milk protein from the diets of their children challenging but persevered due to the potential benefit to their children. Many mothers planned to continue post study with a modified approach to the cow’s milk protein free diet by allowing some cow’s milk protein in the diet to make the diet more acceptable to the family but not as much as the pre-trial diet. These experiences provide health professionals with valuable insights and ideas to assist their patients to manage a cow’s milk protein free diet. Chapter 7 discusses all aspects of the research including any limitations. The results of Trial 1 confirmed the hypothesis that children in the Australian settling with chronic functional constipation unresponsive to the usual treatments respond to the removal of cow’s milk protein from the diet. Therefore, cow’s milk protein is involved in the aetiology of constipation in these children. All the study participants demonstrated an absence or low level of normal gut flora, which may affect bowel regularity. Further research into species present and absent may provide further explanations to the lack of bowel regularity in these children. The immunological and biochemical mechanisms underlying chronic functional constipation that respond to the removal of cow’s milk protein requires further investigation. Although the number of statistically significant variables between the conditions was low, there was a high degree of abnormality. Further investigations are needed, including research into food intolerance reactions that affect the nerve endings in the bowel. The results in Trial 1 and Trial 2 are suggestive of an involvement of blood factors including platelets and monocytes. Other children may have a chronic Streptococcus A infection which may be contributing to constipation as well as to liver function abnormalities. Liver function abnormalities were observed for some participants in both trials, independent of milk condition. The extent to which the research questions have been answered is evaluated in Chapter 7, which includes the conclusions and recommendations of this research. In brief, the findings were: • Children with chronic functional constipation that is unresponsive to the traditional treatments should trial a cow’s milk protein free diet for at least two weeks to determine whether this may resolve the constipation. During this period, the numbers and form of bowel motions should be recorded and results compared to a one week record collected prior to commencing the cow’s milk protein free diet. • Due to the complicated nature of a cow’s milk protein free diet, especially the number of processed foods which contain hidden cow’s milk protein, consultation with a dietitian is essential for implementation of this diet. The dietitian should consider educating the patient’s family, both parents and siblings, to ensure the best outcome in terms of acceptance and compliance of the diet, and provide adequate resources. • If this dietary modification is successful for the child and alleviates constipation, consultation with a dietitian is recommended to determine the amount tolerated and nutritional adequacy of the diet. Soy milk is recommended as a substitute for cow’s milk and a probiotic needs to be prescribed to assist with the normalisation of gut flora. • Education of health professionals such as general practitioners, paediatricians, and paediatric continence nurses, regarding a cow’s milk protein free diet for chronic functional constipation, is essential to support the child and his/her family and integral to the success of this strategy. The findings of this research will be published in the scientific literature and as conference presentations. It is hoped that these findings will assist in the management of children with chronic functional constipation unresponsive to the traditional treatments.

Milk and dairy products are one of the most important sources of essential trace elements in human nutrition. My thesis provides informations about the content of zinc, copper and iodine in milk during the lactation and also includes the impact of other factors on the content of elements. The experiment includes dairy cattle breedings from Hořepník and Chyšná which are located in the region Vysočina. Another breeding is from Haklovy Dvory. It is located in southern Bohemia. Milk samples were taken in the relation to performance monitoring. During the period 25 to 132 days of lactation were taken 90 samples of milk from the Hořepník breeding. From breeding Chyšná were taken 78 samples of milk in the period of 11 - 89 days of lactation and from breeding Haklovy Dvory 81 samples of milk during the period 23 to 244 days of lactation. Copper and zinc content in milk was determined by atomic absorption spektrometry. The iodine content in the milk was set by spectrometry after incineration alkaline by Sandell-Kolthoff. The average zinc content in the milk was 3.59 ? 1.15 mg-l-1. The average copper content in milk was 0.14 ? 0.12 mg-l-1and the average content of iodine in the milk was 0.18 ? 0 06 mg-l-1. The greatest variability in milk was proved to copper (V = 82,65%), the lowest zinc (V = 32,05%). The greatest effect of the duration of lactation was observed in breeding Hořepník (Zn: rxy = -0,430, Cu: rxy = -0,425, I: rxy = 0,326). The influence of the duration of lactation was insignifant in the breeding Haklovy Dvory and Chyšná. Cow's milk, according to our results, supply the iodine accounts from 19,2% for men and 52,4% for women. The milk supply the zinc accounts from 5,2 % for men and 7,2 % for women, and copper from 2,5% for both sex.

Made available in DSpace on 2014-06-11T19:29:02Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-12-04Bitstream added on 2014-06-13T19:58:28Z : No. of bitstreams: 1 verissimo_dmm_me_assis.pdf: 445435 bytes, checksum: 93b36ce929159ed46a80e679738d150a (MD5) / A maternidade é conhecida como um momento sublime na vida da mulher, mesmo em meio às transformações ocorridas no mundo contemporâneo, essa visão idealizada da maternidade é composta de fatores: sociais, culturais e históricos. A psicanálise também contribuiu na construção desta visão, tanto para uma responsabilização das mães pela estruturação psíquica das crianças, quanto para a naturalização da maternidade caracterizado-a como própria da feminilidade. Porém, inúmeros autores apontam para as dificuldades e pressões vivenciadas pelas mães da gestação ao pós-parto na relação com seu bebê, pois a vivência da maternidade sempre vem acompanhada de sentimentos conflitantes, ou seja, ambivalências. A literatura aponta também que a ambivalência se torna mais intensa quando o encontro com o bebê real é marcado por uma doença. No caso do presente trabalho, estudamos os efeitos da alergia à proteína do leite de vaca (APLV), na relação mãe-bebê, uma vez que essa doença, que vem ganhando importância no contexto pediátrico, apresenta uma particularidade: ao atingir o bebê em aleitamento, quem realiza uma dieta livre de qualquer produto lácteo é a mãe; devido à essa particularidade acreditamos que essa doença ao atingir bebês cria uma condição especial ao desenvolvimento da relação mãe-bebê. Com o objetivo de compreender as manifestações do sentimento de ambivalência em mães de bebês com a referida alergia realizamos uma investigação qualitativa psicanalítica, tendo como ponto de partida um estudo sobre os cuidados maternos ao longo da história, seguido de revisão... / Motherhood is known as a sublime moment in the life of a woman, even with the changes in the contemporary world, this idealized vision of motherhood is composed by some factors: social, cultural and historical. Psychoanalysis has also contributed in building this vision, not only the responsibility of these mothers for the psychic structure of these children, but also for the naturalization of motherhood characterized it as their own femininity. However, many authors pointed out the difficulties and pressures experienced by the these mothers from pregnancy to post partum relate to their babies, because the experience of motherhood always comes along with a conflicted feelings, and this is called ambivalence. The literature also indicates that ambivalence becomes more intense when the encounter with the real baby is marked by a disease. In the present work, we studied the effects of allergy to the protein in cow's milk (APLV) in mother-infant relationship, once that this disease which has become importance in the pediatric context ,it shows an particularity: when it get to the baby who is breastfeeding, who carries on a free diet of any dairy product is the mother because of this particularity we believe that whenever this disease reaches the baby it creates a special condition between the development of mother-infant relationship. In order to understand the manifestations of ambivalence feelings in mothers who have allergic babies , we carried out a qualitative investigation of psychoanalysis, and as a starting... (Complete abstract click electronic access below)

As proteínas do leite de vaca são os principais alérgenos relacionados à alergia alimentar em crianças e o diagnóstico inclui a realização do teste de provocação oral duplo cego placebo controlado (TPODCPC). Apesar da acurácia, este teste envolve riscos, necessita condições especiais para sua realização e apresenta limitações em crianças de baixa idade e em pacientes anafiláticos. Assim, há necessidade de métodos diagnósticos alternativos, entre eles o estabelecimento de pontos de corte de concentrações de IgE sérica específica para leite de vaca, que permitam o diagnóstico mesmo sem a realização do TPODCPC. O objetivo deste estudo foi estabelecer uma concentração discriminante de IgE sérica específica para leite de vaca e suas frações protéicas para o diagnóstico de alergia à proteína do leite de vaca (APLV) e avaliar se há diferentes concentrações discriminantes de IgE específica para este alérgeno no grupo de pacientes com anafilaxia. Realizou-se um estudo de coorte histórica incluindo pacientes com APLV e grupo controle composto por pacientes com suspeita não confirmada de APLV. Para estes objetivos, foram construídas curvas ROC para os seguintes alérgenos: leite de vaca, caseína, a- lactoalbumina e b-lactoglobulina. Os níveis de IgE específica foram avaliados posteriormente, em separado, nos pacientes com anafilaxia. Foram incluídos 123 pacientes (1,3M:1F mediana = 1,91 anos, com idade de 3,5 meses a 13,21 anos) com diagnóstico confirmado de APLV através de TPODCPC (n=26), presença de anafilaxia à proteína do leite de vaca (n=46) ou história clínica fortemente sugestiva de APLV associada à pesquisa positiva de IgE específica através de teste cutâneo (n=51). Entre os 65 pacientes com anafilaxia, 19 confirmaram o diagnóstico posteriormente, através de testes de provocação. O grupo controle foi composto por 61 pacientes (1M:1,1F) com idade variando entre 0,66 e 16,7 anos (mediana= 6,83 anos). A metodologia adotada para estabelecimento dos pontos de corte foi a construção de curva ROC e posterior cálculo dos valores preditivos positivos e negativos. Os pontos de corte obtidos considerando-se uma especificidade de 98% e um valor preditivo positivo acima de 95% foram: 3,06 kU/L para o leite de vaca, 2,06 kU/L para a- lactoalbumina, 1,85 kU/L para b-lactoglobulina e 1,47 kU/L para caseína. O valor de IgE específica para leite de vaca revelou-se com maior capacidade discriminante que os encontrados para as frações, tornando estes últimos dispensáveis. Com relação à anafilaxia, a curva ROC construída a partir de uma análise comparativa entre pacientes com e sem esta manifestação, indicou um ponto de corte elevado de 39kU/L, tornando impossível sua utilização na prática clínica. O presente estudo mostrou que um ponto de corte de IgE específica para leite de vaca é suficiente para o diagnóstico de APLV, não sendo necessária a avaliação das frações protéicas. Na presença de anafilaxia desencadeada pelo leite de vaca não há necessidade da utilização de pontos de corte de IgE específica, sendo os dados clínicos e a sensibilização ao leite suficientes para o diagnóstico de APLV. / Cow\'s milk proteins are the main allergens related to food allergy in children and the diagnosis include the double blind placebo controlled food challenge (DBPCFC). Although this test presents accuracy, it involves risks, it is necessary special conditions and it presents limitations in infants and anaphylactic patients. It is necessary other diagnostic methods, among them the cut off values for IgE specific for milk to allow the cow\'s milk allergy (CMA) diagnosis without the need to perform the DBPCFC. The objective of this study was to establish a discriminating concentration of specific IgE to cow\'s milk and its proteins fractions for the diagnosis of allergy to CMA and to assess if there are different discriminating concentrations of specific IgE to this allergen in the group of patients with anaphylaxis. It was carried out a historical cohort study including patients with CMA and the control group was composed by patients with excluded CMA suspicion. To obtain the cutoff points for diagnosis of CMA , ROC curves were constructed for the following allergens: cow\'s milk, casein, a-lactalbumin and a b-lactoglobulin. The levels of specific IgE were later evaluated, separately, in patients with anaphylaxis. The study included 123 patients (1.3 M: 1F median = 1.91 years, ranging from 3.5 months to 13.21 years) with confirmed diagnosis of CMPA through DBPCFC (n = 26), the presence of anaphylaxis triggered by cow\'s milk protein (n = 46) or strongly suggestive clinical history associated with positive specific IgE through skin test (n = 51). Among the 65 patients with anaphylaxis, 19 confirmed the diagnosis through challenge tests . The control group was consisted of 61 patients (1M: 1.1 F) with ages ranging between 0.66 and 16.7 years (mean 6.86, median = 6.83 years). The methodology to stablish the cutoff was the construction of a ROC curve and subsequent calculation of positive and negative predictive value. The cutoff points obtained considering a 98% specificity and positive predictive value above 95% were: 3.06 kU / L for cow\'s milk, 2.06 kU/ L for/ a-lactalbumin, 1.85 kU/ L for/ b-lactoglobulin and 1.47 kU / L for casein. The value of specific IgE to cow\'s milk showed better discriminant capacity than those found for the fractions, being these last values dispensable. In relation to anaphylaxis, the ROC curve constructed from a comparative analysis between patients with and without this manifestation indicated a very high cutoff of 39kU/L, being without value for the clinical practice. This study showed that the cut off point detected for hole cows milk was enough for CMA diagnosis, without necessity of the milk fractions evaluation. In the presence of cows milk anaphylaxis, it is not necessary the IgE specific cut off value, being the clinical data and the sensitization to cows milk enough for the CMA diagnosis.

As proteínas do leite de vaca são os principais alérgenos relacionados à alergia alimentar em crianças e o diagnóstico inclui a realização do teste de provocação oral duplo cego placebo controlado (TPODCPC). Apesar da acurácia, este teste envolve riscos, necessita condições especiais para sua realização e apresenta limitações em crianças de baixa idade e em pacientes anafiláticos. Assim, há necessidade de métodos diagnósticos alternativos, entre eles o estabelecimento de pontos de corte de concentrações de IgE sérica específica para leite de vaca, que permitam o diagnóstico mesmo sem a realização do TPODCPC. O objetivo deste estudo foi estabelecer uma concentração discriminante de IgE sérica específica para leite de vaca e suas frações protéicas para o diagnóstico de alergia à proteína do leite de vaca (APLV) e avaliar se há diferentes concentrações discriminantes de IgE específica para este alérgeno no grupo de pacientes com anafilaxia. Realizou-se um estudo de coorte histórica incluindo pacientes com APLV e grupo controle composto por pacientes com suspeita não confirmada de APLV. Para estes objetivos, foram construídas curvas ROC para os seguintes alérgenos: leite de vaca, caseína, a- lactoalbumina e b-lactoglobulina. Os níveis de IgE específica foram avaliados posteriormente, em separado, nos pacientes com anafilaxia. Foram incluídos 123 pacientes (1,3M:1F mediana = 1,91 anos, com idade de 3,5 meses a 13,21 anos) com diagnóstico confirmado de APLV através de TPODCPC (n=26), presença de anafilaxia à proteína do leite de vaca (n=46) ou história clínica fortemente sugestiva de APLV associada à pesquisa positiva de IgE específica através de teste cutâneo (n=51). Entre os 65 pacientes com anafilaxia, 19 confirmaram o diagnóstico posteriormente, através de testes de provocação. O grupo controle foi composto por 61 pacientes (1M:1,1F) com idade variando entre 0,66 e 16,7 anos (mediana= 6,83 anos). A metodologia adotada para estabelecimento dos pontos de corte foi a construção de curva ROC e posterior cálculo dos valores preditivos positivos e negativos. Os pontos de corte obtidos considerando-se uma especificidade de 98% e um valor preditivo positivo acima de 95% foram: 3,06 kU/L para o leite de vaca, 2,06 kU/L para a- lactoalbumina, 1,85 kU/L para b-lactoglobulina e 1,47 kU/L para caseína. O valor de IgE específica para leite de vaca revelou-se com maior capacidade discriminante que os encontrados para as frações, tornando estes últimos dispensáveis. Com relação à anafilaxia, a curva ROC construída a partir de uma análise comparativa entre pacientes com e sem esta manifestação, indicou um ponto de corte elevado de 39kU/L, tornando impossível sua utilização na prática clínica. O presente estudo mostrou que um ponto de corte de IgE específica para leite de vaca é suficiente para o diagnóstico de APLV, não sendo necessária a avaliação das frações protéicas. Na presença de anafilaxia desencadeada pelo leite de vaca não há necessidade da utilização de pontos de corte de IgE específica, sendo os dados clínicos e a sensibilização ao leite suficientes para o diagnóstico de APLV. / Cow\'s milk proteins are the main allergens related to food allergy in children and the diagnosis include the double blind placebo controlled food challenge (DBPCFC). Although this test presents accuracy, it involves risks, it is necessary special conditions and it presents limitations in infants and anaphylactic patients. It is necessary other diagnostic methods, among them the cut off values for IgE specific for milk to allow the cow\'s milk allergy (CMA) diagnosis without the need to perform the DBPCFC. The objective of this study was to establish a discriminating concentration of specific IgE to cow\'s milk and its proteins fractions for the diagnosis of allergy to CMA and to assess if there are different discriminating concentrations of specific IgE to this allergen in the group of patients with anaphylaxis. It was carried out a historical cohort study including patients with CMA and the control group was composed by patients with excluded CMA suspicion. To obtain the cutoff points for diagnosis of CMA , ROC curves were constructed for the following allergens: cow\'s milk, casein, a-lactalbumin and a b-lactoglobulin. The levels of specific IgE were later evaluated, separately, in patients with anaphylaxis. The study included 123 patients (1.3 M: 1F median = 1.91 years, ranging from 3.5 months to 13.21 years) with confirmed diagnosis of CMPA through DBPCFC (n = 26), the presence of anaphylaxis triggered by cow\'s milk protein (n = 46) or strongly suggestive clinical history associated with positive specific IgE through skin test (n = 51). Among the 65 patients with anaphylaxis, 19 confirmed the diagnosis through challenge tests . The control group was consisted of 61 patients (1M: 1.1 F) with ages ranging between 0.66 and 16.7 years (mean 6.86, median = 6.83 years). The methodology to stablish the cutoff was the construction of a ROC curve and subsequent calculation of positive and negative predictive value. The cutoff points obtained considering a 98% specificity and positive predictive value above 95% were: 3.06 kU / L for cow\'s milk, 2.06 kU/ L for/ a-lactalbumin, 1.85 kU/ L for/ b-lactoglobulin and 1.47 kU / L for casein. The value of specific IgE to cow\'s milk showed better discriminant capacity than those found for the fractions, being these last values dispensable. In relation to anaphylaxis, the ROC curve constructed from a comparative analysis between patients with and without this manifestation indicated a very high cutoff of 39kU/L, being without value for the clinical practice. This study showed that the cut off point detected for hole cows milk was enough for CMA diagnosis, without necessity of the milk fractions evaluation. In the presence of cows milk anaphylaxis, it is not necessary the IgE specific cut off value, being the clinical data and the sensitization to cows milk enough for the CMA diagnosis.

Orientador: Jorge Luís Ferreira Abrão / Banca: Inês Amosso Dolci / Banca: Diana Pancini de Sá Antunes Ribeiro / Resumo: A maternidade é conhecida como um momento sublime na vida da mulher, mesmo em meio às transformações ocorridas no mundo contemporâneo, essa visão idealizada da maternidade é composta de fatores: sociais, culturais e históricos. A psicanálise também contribuiu na construção desta visão, tanto para uma responsabilização das mães pela estruturação psíquica das crianças, quanto para a naturalização da maternidade caracterizado-a como própria da feminilidade. Porém, inúmeros autores apontam para as dificuldades e pressões vivenciadas pelas mães da gestação ao pós-parto na relação com seu bebê, pois a vivência da maternidade sempre vem acompanhada de sentimentos conflitantes, ou seja, ambivalências. A literatura aponta também que a ambivalência se torna mais intensa quando o encontro com o bebê real é marcado por uma doença. No caso do presente trabalho, estudamos os efeitos da alergia à proteína do leite de vaca (APLV), na relação mãe-bebê, uma vez que essa doença, que vem ganhando importância no contexto pediátrico, apresenta uma particularidade: ao atingir o bebê em aleitamento, quem realiza uma dieta livre de qualquer produto lácteo é a mãe; devido à essa particularidade acreditamos que essa doença ao atingir bebês cria uma condição especial ao desenvolvimento da relação mãe-bebê. Com o objetivo de compreender as manifestações do sentimento de ambivalência em mães de bebês com a referida alergia realizamos uma investigação qualitativa psicanalítica, tendo como ponto de partida um estudo sobre os cuidados maternos ao longo da história, seguido de revisão... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Motherhood is known as a sublime moment in the life of a woman, even with the changes in the contemporary world, this idealized vision of motherhood is composed by some factors: social, cultural and historical. Psychoanalysis has also contributed in building this vision, not only the responsibility of these mothers for the psychic structure of these children, but also for the naturalization of motherhood characterized it as their own femininity. However, many authors pointed out the difficulties and pressures experienced by the these mothers from pregnancy to post partum relate to their babies, because the experience of motherhood always comes along with a conflicted feelings, and this is called ambivalence. The literature also indicates that ambivalence becomes more intense when the encounter with the real baby is marked by a disease. In the present work, we studied the effects of allergy to the protein in cow's milk (APLV) in mother-infant relationship, once that this disease which has become importance in the pediatric context ,it shows an particularity: when it get to the baby who is breastfeeding, who carries on a free diet of any dairy product is the mother because of this particularity we believe that whenever this disease reaches the baby it creates a special condition between the development of mother-infant relationship. In order to understand the manifestations of ambivalence feelings in mothers who have allergic babies , we carried out a qualitative investigation of psychoanalysis, and as a starting... (Complete abstract click electronic access below) / Mestre

Abstract Food hypersensitivities are becoming increasingly common worldwide. Previous studies indicate that cell mediated immunity has a role in delayed paediatric gastrointestinal food hypersensitivities, but the exact pathogenetic mechanisms are unknown. Cytotoxic activation of T-lymphocytes is known to play an important role in the pathogenesis of celiac disease (CD). The pathogenetic mechanisms of cow's milk protein sensitive enteropathy (CMSE) are largely unknown. CMSE is a non-IgE related type of food hypersensitivity with variable gastrointestinal symptoms but no visible mucosal abnormalities on light microscopy. The diagnosis is based on an open or blinded elimination/challenge test, as the endoscopic, histological and laboratory findings are generally non-specific. This thesis aims to characterize the role of lymphocyte cytotoxicity in the pathogenesis and diagnosis of CMSE in preschool and school aged children, including comparison with CD where the pathogenetic significance of cytotoxicity is well established. The study cohort consisted of 151 children, including 57 with untreated CMSE, 18 with treated CMSE, 24 with CD, and 52 controls. Using immunohistochemistry, the mucosal expressions of cytotoxic T cell-restricted intracellular antigen type 1 (TIA-1), perforin, granzyme A and B were analysed in the duodenal bulb and descending duodenum. Intraepithelial T-lymphocytes were labelled with CD3, alpha/beta and gamma/delta T cell receptor antigens. To determine the rates of overall and epithelial apoptosis as well as proliferation, the immunohistochemical TUNEL technique, M30 and Ki-67 antibodies were used. Serum levels of granzymes, CD30 and soluble Fas were studied using ELISA method. The number of intraepithelial lymphocytes with TIA-1, perforin and granzyme A containing granules was increased in CMSE. This increase was related to antigen challenge and not a constitutional abnormality. The cytotoxic reaction in CMSE differed from that in CD by being of lesser magnitude, concerning predominantly the descending duodenum and not showing signs of cytotoxicity related epithelial destruction. The serum levels of GrA, GrB and CD30 were increased in both CMSE and CD, correlating with the number of duodenal CD3+, alpha/beta and gamma/delta+ intraepithelial lymphocytes. The results strongly support the role of cell-mediated immunity in the pathogenesis of CMSE. Mucosal cytotoxic activation seems to be manifested by the release of cytoxicity related proteins in serum. This provides a new approach to the monitoring of intestinal immune activation which could help in diagnosis and in objectively monitored treatment response.

This diploma thesis deals with the evaluation of clinical manifestations in infants with allergic colitis and their overall nutritional status, anthropometry, blood count and antibodies against cow's milk proteins. Allergic colitis is one of the most common manifestations of infant allergy to cow`s milk protein with gastrointestinal involvement. The theoretical part summarizes the anthropometric evaluation of growth and development, infant nutrition, the most important laboratory indicators of nutritional status. The part is generally devoted to food allergies, mainly allergy to cow's milk protein. The practical part deals with the evaluation of a sample of examined patients in gastroenterology outpatient clinics and nutritional outpatient clinic of the Department of Pediatrics and Adolescent Medicine of the 1st Faculty of Medicine, Charles University and General Hospital in Prague. The observed group of infants with allergic colitis includes infants exclusively breastfed, breastfed by a mother following a non-dairy diet, infants on an extensive hydrolyzate or on an amino acid formula. The main goal of the diploma thesis was to trace the most common clinical manifestations and whether there are any changes in their nutritional status during the disease and its treatment. A total of 45 randomly...