Darbo tikslas – nustatyti dažniausių alerginių ligų ir joms būdingų simptomų paplitimą bei jo kaitą (1994-2002 m.) tarp skirtingo amžiaus Kauno miesto vaikų. Uždaviniai: 1. Ištirti bronchų astmos ir jai būdingų simptomų paplitimą ir kaitą tarp 6–7 ir 13–14 metų amžiaus vaikų. 2. Ištirti alerginio rinito ir jam būdingų simptomų paplitimą ir kaitą tarp 6–7 ir 13–14 metų amžiaus vaikų. 3. Ištirti atopinio dermatito ir jam būdingų simptomų paplitimą ir kaitą tarp 6–7 ir 13–14 metų amžiaus vaikų. 4. Nustatyti alerginių ligų derinių paplitimą bei kaitą skirtingose vaikų amžiaus grupėse. 5. Įvertinti bronchų astmos, alerginio rinito ir atopinio dermatito paplitimo priklausomybę nuo aplinkos veiksnių. / The aim of the study To assess the changes in prevalence of asthma, allergic rhinitis, atopic dermatitis and their symptoms in 6-7 and 13-14 years old children in Kaunas. Objectives of the study: 1. To examine the changes in the prevalence of asthma and its symptoms in 6-7 and 13-14 years old children. 2. To examine the changes in the prevalence of allergic rhinitis and its symptoms in 6-7 and 13-14 years old children. 3. To examine the changes in the prevalence of atopic dermatitis and its symptoms in 6-7 and 13-14 years old children. 4. To assess the changes in the prevalence of allergic diseases combinations in different age-groups in children. 5. To measure environmental risk factors‘ impact on the prevalence of asthma, allergic rhinits and atopic dermatitis.

Oral tolerance is the state of immunologic non-responsiveness that is established following oral antigen consumption. Failures of oral tolerance can result in food allergy. The mechanisms regulating oral tolerance are not well understood, but similar mechanisms may control tolerance to foods and commensal microbes in the intestine. The specific roles of many pattern recognition receptors (PRRs) and innate cells have not been examined in the context of oral tolerance. Mast cells are innate sentinel cells positioned at mucosal surfaces, and have been identified as key regulators of peripheral tolerance to allografts. Toll-like receptor 2 (TLR2) is a PRR involved in bacterial responses and the regulation of intestinal inflammation. We evaluated the impact of mast cells, TLR2, immunoglobulin E (IgE)-mediated mast cell activation, TLR2 activation, and histamine receptor blockade in the development of oral tolerance in mice. Models of tolerance to ovalbumin, peanut butter, and cow’s milk were established. Oral tolerance was assessed in wild type, TLR2-deficient, or mast cell-deficient mice and was measured primarily by analysis of antigen-specific antibody levels after a systemic antigen challenge. The development of antigen-specific Tregs was also assessed. We observed that neither mast cells nor TLR2 were necessary for oral tolerance induction. Moreover, IgE-mediated mast cell activation and antihistamine treatment did not significantly alter oral tolerance induction. TLR2 activators, notably Pam3CSK4, were administered orally concurrent with food antigen and were found to impair oral tolerance to a later systemic antigen challenge. When Pam3CSK4 was administered as an oral adjuvant with ovalbumin, a profound selective enhancement of the IgA response to oral challenge was observed. These results highlight an important differential regulation of oral tolerance by TLR2. Oral TLR2 activation selectively promotes IgA responses to antigen upon repeated oral challenge but prevents the maintenance of oral tolerance upon a systemic challenge. Taken together these results suggest that mast cells are not essential regulators of oral tolerance, but TLR2 is involved in regulating IgA and IgE responses during oral and systemic challenges. These findings inform mechanisms of commensal tolerance and have implications for the potential therapeutic manipulation of oral tolerance to foods.

Environmental factors more often is thought to have influence in determining children’s health and development. Prevalence of allergic diseases over the last decades is increasing, especially in Western Europe. Despite lots of performed surveys it is still unclear why the prevalence of food allergy is mounting. Incidence of food allergy is age dependent and usually manifest as one of the first forms of allergy. It is considered as the first step of „atopic march“. To accurately assess the occurrence of possible risk factors for a disease that can start already in infancy and may resolve by school age, a prospective birth cohort with regular follow-up of participating children and families provides the best possible study design. EuroPrevall birth cohort study, in which participated Vilnius University, was the first in the world investigation specially created just for evaluation of food allergy. During in this dissertation presented project for the first time real prevalence of food hypersensitivity and allergy in infants and small children in Lithuania have been determined, the most common food allergens were assessed and changes in prevalence of sensitization to them during first 30 months of life were analysed, also the role of possible determinants for the development of food allergies, such as genetic background, maternal diet during pregnancy and breastfeeding, way of birth, infections, medicines, psycho-social and environmental factors, were examined and different... [to full text] / Svarbus vaidmuo, nulemiantis vaikų sveikatą ir vystymąsi, vis dažniau priskiriamas vaiką supančiai aplinkai. Sergamumas alerginėmis ligomis sparčiai didėja, o pastaraisiais dešimtmečiais jis itin išaugo, ypač Vakarų Europoje. Nepaisant daugelio atliktų tyrimų, vis dar lieka neaišku, kodėl alerginių ligų paplitimas nuolat didėja. Alergijos maistui paplitimas įvairiose amžiaus grupėse skiriasi ir yra viena iš anksčiausiai pasireiškiančių alergijos formų. Manoma, kad ji gali būti pirmasis „atopinio maršo“ žingsnis. Norint tiksliai įvertinti galimų rizikos veiksnių įtaką ligos atsiradimui, kuri gali prasidėti jau kūdikystėje ir išnykti iki mokyklinio amžiaus, tinkamiausias tyrimo metodas yra prospektyvinis naujagimių kohortos tyrimas su reguliaria į tyrimą įtrauktų vaikų ir jų šeimų stebėsena. EuroPrevall naujagimių kohorta - tai pirmasis pasaulyje tyrimas, kuriame dalyvavo ir Vilniaus Universitetas, specialiai suformuotas tik alergijos maistui ištyrimui. Šio disertacijoje pateikiamo tyrimo metu Lietuvoje pirmąkart ištirtas padidėjusio jautrumo maistui ir alergijos maistui paplitimas tarp mažų vaikų ir nustatyti dažniausiai alergiją sukeliantys maisto produktai ir sensibilizacijos maisto alergenams kaita pirmaisiais 30 gyvenimo mėnesiais, taip pat išanalizuoti tėvų ir kūdikių rizikos veiksniai, tokie kaip genetinis pagrindas, mamos mityba nėštumo metu ir žindant, gimdymo būdas, infekcijos, vartoti medikamentai, psicho-socialiniai ir aplinkos faktoriai, įtakojantys alergijos... [toliau žr. visą tekstą]

No description available.

Šiame darbe nagrinėjama, kokią reikšmę turi žiedadulkių sklaida meteorologiniams veiksniams. Darbui pasiekti išsikeltas tikslas Darbo tikslas – įvertinti žiedadulkių pernašą ir nustatyti žiedadulkių kiekį ore lemiančius meteorologinius veiksnius. Uždaviniai: remiantis Šiaulių miesto aeropalinologinių ir oro masių trajektorijų duomenimis, išanalizuoti žiedadulkių tolimosios pernašos mechanizmą. Pagal atmosferos modelių rezultatus nustatyti kritulių, oro temperatūros, vėjo greičio, santykinino drėgnumo įtaką žiedadulkių gausai ore. Įvertinti žiedadulkių sklaidą leminačius veiksnius ir išskirti žiedadulkių sklaidos dėsningumus. Atgalinių masių trajektorijų analizė parodė, kad 2004-2013 m. augalų žydėjimo metu vyravo šiaurės vakarinė oro pernaša. Oro masės atslinkdavo iš Europos 1 regiono.Tyriamųjų medžių paplitimas šaiaurės vakarų Europoje turi įtakos žiedadulkių atnešimui prieš ir po barstymo sezono. Žiedadulkių prieš žiedadulkių barstymo sezono buvo daugiausiai iš 1 regiono.Žiedadulkių po žiedadulkių barstymo sezono taip pat buvo daugiausiai iš 1 regiono. Visų tiriamųjų šešių augalų genčių tuopos, pušies, lazdyno, alksnio beržo ir ąžuolo žiedadulkių sezonu 2004 - 2013 metais dažniausiai pūtė vakarų (V) krypties vėjas. 2004 – 2013 laikotarpyje nustatyta, kad mažiausi koreliacijos koeficientai gauti lyginant tarp meteorologinių veiksnių (kritulių, vėjo greičio) ir žiedadulkių koncentracijos. Išsiaiškinta, kad tiriamuoju atveju didžiausi koreliacijos koeficientai gauti tarp... [toliau žr. visą tekstą] / This analysis examines the significance of pollen dissemination for meteorological factors. Things to do to achieve its goals. The goal - to assess pollen transfer and determine the amount of pollen in the air leading to meteorological factors. Objectives: Based on the city of Siauliai aeropalinologinių air mass trajectory data to analyze pollen carryover mechanism. According to the results of atmospheric models to determine rainfall, air temperature, wind speed, relative humidity influence to the abundance of pollen in the air. To evaluate the spread of pollen influencing factors and exclude pollen dispersion patterns. The callback trajectory analysis showed that for 2004-2013. flowering time was dominated by north west air Carryover. Air masses came from the first european region. Study of the prevalence of trees in northwestern Europe has shown that it affects pollen fetch before and after the application season. Pollen before the pollen season has been spreading mainly in Region 1. After spreading pollen pollen season was also the most in Region 1. From all six subjects plants: genus poplar, pine, hazel, alder, birch and oak pollen in season 2004 - 2013 was mostly blowing west (W) direction wind. In 2004 - 2013 period was found that the lowest correlation coefficients was obtained by comparing to meteorological factors (rainfall, wind speed) and the pollen concentration. It has shown that during the event the highest correlation coefficients were obtained between... [to full text]

This thesis explores 5C dietary-restricted college students’ reiteration of a “lack of [food] options” in the dining hall and at on-campus, institutionally-sponsored events of particularly Scripps College. Given that Scripps specifically has in the past responded to dietary-restricted student needs, and that it offers an admittedly broad variety of foods for a college dining hall, dietary-restricted students’ dissatisfaction with “food options” presents an interesting problem. Situated within broader Claremont College community discussions, this ethnographic work hopes to better understand not just what students want, but what they need to socially and culturally sustain themselves while dwelling in the residential 5C community. I argue that when my dietary- and non-dietary-restricted interlocutors narrate their desire for, request, and provide food options, they are engaging in efforts to facilitate access to membership and participation in all aspects of the “residential college experience.” In the spirit of interlocutors’ enduring determination to exist in a space of possibility with regard to their identities and the necessary food options that could exist, this thesis also contains Scripps-specific suggestions to better include those with dietary restrictions in the Scripps College residential community.

Baigiamojo darbo tikslas: išanalizuoti kačių astmos pasireiškimo dažnumą, ligos atsiradimo priežastis, dažniausiai taikomas diagnostines priemones ir gydymą. Apibūdinimas: kačių astma – tai galimai alerginės kilmės susirgimas, kurio metu atsiranda kvėpavimo takų uždegimas, padidėjusi gleivių sekrecija, spontaniška bronchokonstrikcija ir kvėpavimo takų remodeliacijos. Šie pokyčiai sukelia kosulį, dusulį, švokštimą ir kvėpavimo nepakankamumą. Dažniausiai praktikoje susiduriama su diagnostikos problematika. Baigiamojo darbo metodikos: tyrimas buvo atliekamas 2013 metais, jame dalyvavo 9 astma sergančios katės ir 5 sveikos katės. Buvo atlikta kačių, įtariamų sergant astma, šeimininkų apklausa, kurios metu vertinami galimai astmos pasireiškimui turėję įtakos veiksniai. Tuomet atliekamos kitos diagnostinės procedūros, kurių metu gaunama diagnozė, patvirtinanti kačių astmą ir skiriamas tolimesnis gydymas. Pagrindiniai tiriamojo darbo rezultatai ir išvados: kačių astma nėra dažnai pasitaikanti kvėpavimo takų liga. Tarp astma sergančių kačių nėra ženklių lyties skirtumų, 56 % sirgusiųjų sudarė patelės, o patinai – 44 %. Astma dažniau pasireiškė katėms, kurių amžius svyravo nuo 1 iki 5 metų (45 %) ir toms, kurios buvo negrynaveislės (45 %). Apklausos metu nustatyti pagrindiniai potencialūs astmą sukeliantys veiksniai, t.y. šeimininkų rūkymas (12 %), parfumuotų valiklių (12 %), oro gaiviklių bei dezodorantų (12 %) naudojimas katės gyvenamojoje aplinkoje. Astmos diagnostikoje takyti... [toliau žr. visą tekstą] / The aim: to analyze the manifestation frequency of feline asthma, diagnostic methods, treatment and identify the factors, which have influence in manifestation of this disease. Description: feline asthma has an allergic etiology. The hallmark features include airway inflammation, mucus hypersecretion, spontaneous bronchoconstriction and airway remodeling. These changes lead to clinical signs of cough, dyspnea, wheeze and respiratory distress. The diagnosis of asthma can be complicated, because there are no single test for diagnose feline asthma. Methodology: the study was carried out in a small animal clinic X in 2013 year. 9 asthmatic cats and 5 healthy cats were included in this study. There was composed questionnaire form for the owners, whose cats were possibly asthmatic. All the received material was used for statistic analysis about the factors, which had more impact in causing asthma. The other diagnostic manipulations were performed to get this certain diagnosis and find the best treatment options. There were reviewed epidemiology, clinical manifestations, patogenesis and factors, which influence asthma, blood results, diagnosis and treatment of feline asthma. Results and conclusions: feline asthma is not common respiratory disease in cats. The study revealed that there is no clear sex predilection (females – 56 % and males – 44 %). Middle-aged cats (1 to 5 years) were seen more affected (45 %). 45 % of the cats were mixed breed. The main asthma predisposing factors... [to full text]

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.

[Truncated abstract] The dramatic increase in the expression of allergic diseases such as asthma and allergy over the last 20-30 years has highlighted the urgent need to identify causative factors. It was hypothesised that direct immune interactions between mother and fetus contribute to the cytokine milieu of pregnancy, thus influencing immune maturation after birth. Further it was speculated that the cytokine responses produced as a result of maternalfetal interactions are Th-2 skewed in women allergic disease, which programmes their offspring towards developing an allergic phenotype after birth. To test this hypothesis a cohort of 169 pregnant women were recruited at 20 weeks gestation and defined as allergic or non-allergic based on both clinical history and skin prick test sensitisation. These women and their infants were followed up throughout pregnancy (20 weeks, 30 weeks, 36 weeks gestation and 6 weeks post-partum) and up to 2.5 years of age. Mixed lymphocyte reactions (MLR) were used to measure maternal cytokine (IL-6, IL-10, IL-13 and IFN-) and lymphoproliferative responses to fetal alloantigens at each pregnancy time-point. Human leukocyte antigen (HLA) typing of mothers and infants were performed to assess the effect of HLA mismatch on maternal MLR responses to their fetus. After delivery, mononuclear cells (MNC) were isolated from cord blood (CB) and stimulated with allergens, mitogen and toll-like receptor (TLR) ligands. .... As IL-6 also participates in adaptive immunity by promoting Th-2 differentiation it is proposed that the production of IL-6 as a results of maternal encounters with paternal antigens during pregnancy, contribute to the Th-2 skewed responses observed universally in most infants at birth. Associations between maternal-fetal interaction and clinical outcomes in infancy: Although clinical signs of allergy in infancy were not the main outcome measure of this thesis, there were interesting, yet complex relationships between the production of these maternal cytokines towards the fetus and allergic disease at infant follow-ups. Increased maternal IFN-¿ to fetal alloantigen was associated with asthma at 2.5 years and a trend towards recurrent wheeze at 12 months. In contrast decreased maternal IL-13 production was associated with IgE mediated food allergy at 12 months. Adjusting for maternal allergy and other potential confounders including infant gender, method of delivery, HLA mismatch, and paternal allergy did not account for these relationships. Further follow-ups of these infants are required to determine if these relationship last in to early childhood. In conclusion, the findings of this thesis provides further support for the hypothesis that immune responses at birth are programmed prenatally, and that this programming has implications later in life. Importantly, the placenta is the immunologically active interface between mother and fetus during pregnancy. Therefore it is emphasised that there is a crucial need for future research to focus on early immune programming at the placental level before the aetiological pathways of immune mediated diseases can be fully elucidated.