No description available.

No description available.

The purpose of this study was to determine the safety and pharmacokinetic profile of firocoxib in healthy neonatal foals. Foals are more sensitive to the side effects of nonsteroidal anti-inflammatory drugs, (NSAIDs), particularly due to immature renal clearance mechanisms and ulcerogenic effects on gastric mucosa. Firocoxib, a novel second generation NSAID, is reported to have reduced side effects due to its COX-2 selectivity. The pharmacokinetic profile of firocoxib in neonates has not been established, making reliable dosing difficult. We hypothesized that firocoxib given per os at the labeled dose to neonatal foals would be absorbed and not be associated with clinically significant adverse events. Seven healthy American Quarter Horse foals of mixed gender were administered 0.1mg/kg firocoxib orally q24h for nine consecutive days, commencing at 36h of age. Blood samples were collected for firocoxib analysis using high pressure liquid chromatography with fluorescence detection at 0 (dose #1 only), 0.25, 0.5, 1, 2, 4, 8, 16 and 24 hours after doses #1, 5 and 9. For all other doses (2, 3, 4, 6, 7 and 8) blood was collected immediately prior to the next dose (24 hour trough). Elimination samples (36, 48, 72, 96, 120 and 144 hours) were collected after dose #9. Safety was assessed via physical examinations, changes in body weight, gastroscopy, complete blood count, serum biochemistry and urinalysis. Firocoxib was rapidly absorbed following oral administration with minimal accumulation after repeat dosing. After the initial dose, an average peak serum concentration (Cmax) of 89.50 ° 53.36 ng/mL (mean ° SD) was achieved (Tmax) in 0.54 ° 0.65 hours. Steady state was obtained after approximately 4 doses and the average maximum concentration (Cavg) in serum was 39.1 ° 8.4 ng/mL. After the final dose, the mean terminal half-life (T½?») was 10.46 ° 4.97 hours. Firocoxib was not detected in plasma 72 hours after the final dose (<2ng/mL). Bioavailability could not be determined as currently, there is no accompanying intravenous dose of firocoxib for this age group to permit the calculation. No significant abnormalities were noted on blood work, urinalysis or gastroscopy. This study demonstrated that firocoxib is absorbed after oral administration in neonatal foals with no observable adverse effects after multiple doses. / Master of Science

Pneumocystis carinii is an opportunistic fungal pathogen that causes lifethreatening pneumonia in immunocompromised individuals. Infants appear to be particularly susceptible to Pneumocystis (PC) pulmonary infections. The higher incidence of PC as well as other pulmonary infections among infants is likely due to an immature immune system. The neonatal lung environment is deficient immunologically in preterm as well as term infants (1, 2). Decreased phagocytic capacity of macrophages in newborns may increase the risk of infection from inhaled pathogens (1, 2). We have previously demonstrated that there is approximately a 3-week delay in the clearance of PC organisms from pup mouse lungs compared to adults. Herein, we demonstrate that there is also a 1-week delay in the infiltration of AMs in pup compared to adult PC-infected mice. We go on to show that there is a delay in pup versus adult lung macrophage phenotypic expression and cytokine production in response to PC organisms. We demonstrated that pup AMs are competent to produce cytokine in response to LPS and that stimulation with zymosan generates cytokine production in pup AMs that is comparable to adult cytokine production. These data indicate that pup lung macrophages are specifically poorly responsive to PC organisms and likely require exogenous stimulation to mount a significant immune response and expedite clearance of the organism. We go on to show that heat-killed Escheriae coli improves cytokine response, cellular infiltration and reduces organism burden in PC-infected pup mice. The clinically relevant cytokine, GM-CSF, has been used to improve the clearance of several pulmonary infections, including PC in adult animal models. We show that monotherapy with GM-CSF is insufficient to improve PC clearance in pup mice; however, when combined with TMP/SMX it improves PC clearance and maintains a reduced PC burden following discontinuation of therapy. Furthermore, we have shown that GM-CSF improves the ability of human infant lung macrophages to phagocytose PC organsms without generating an increased inflammatory response. These data suggest that combination therapy with TMP/SMX and GM-CSF may be a viable treatment option for infants failing or intolerant to standard therapy.

Thesis advisor: Cherie McGill / Thesis advisor: Marius Stan / Seriously ill newborns are a part of a recent bioethical phenomenon that emerged during the late 1970s. With the rise of new, innovative medical technology, doctors can keep these seriously ill newborns alive, but at monumental financial and psychological costs. This thesis utilizes several economic and ethical frameworks to contextualize these newborns within our healthcare system. After all, our healthcare resources are limited. We must therefore discern between the continuation of an infant’s treatment and conversely, the withdrawal of treatment. / Thesis (BA) — Boston College, 2017. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Departmental Honors. / Discipline: Philosophy.

Pensando nas falhas de transferência de imunidade passiva e nos prejuízos gerados para a equideocultura, este projeto visou avaliar a suplementação com levedura viva, Saccharomyces cerevisiae vivas na dieta de éguas no terço final da gestação sobre a transferência de imunidade passiva, através da avaliação do colostro, concentração de imunoglobulina, perfil celular e composição e desenvolvimento do sistema imune dos potros. O experimento foi conduzido nas dependências do Laboratório de Pesquisa em Saúde Digestiva e Desempenho de Equinos (LabEqui), FMVZ/USP no Campus Fernando Costa em Pirassununga/SP. Foram utilizadas dezesseis éguas prenhes sem raça definida, com idade média de 90&#177;7 meses, mantidas em piquetes sem acesso a gramíneas durante todo o período experimental. A dieta foi formulada para atender a exigência da categoria de acordo com NRC 2007, foi composta de feno de gramínea e concentrado, água e sal mineral ad libitum. As mesmas foram divididas em dois grupos de oito animais cada, 1) grupo controle: feno de Tifton 85 e concentrado comercial sem suplementação, 2) grupo suplementado: feno de Tifton 85 e ração comercial com suplementação de Actisaf HR Plus Sc 47&reg; - 10 g/animal/dia. O delineamento foi inteiramente casualizado (DIC), com medidas repetidas no tempo. Foi observado efeito para células mononucleares no colostro no grupo suplementado (P=0,05) e para células polinucleares para grupo controle (P=0,05). Pode-se concluir que suplementação com levedura viva Saccharomyces cerevisae na dieta de éguas no terço final da gestação, melhora a qualidade do colostro no que se refere ao perfil celular porém não melhora a transferência de imunidade passiva dos potros. / Considering the failures of passive immunity transfer and losses generated for equideoculture, this project aimed to evaluate the live yeast supplement Saccharomyces cerevisiae in the diet of mares in the final third of gestation on the transference of passive immunity through the evaluation of colostrum , immunoglobulin concentration, cellular profile and composition and development of the immune system of foals. The experiment was conducted at the Laboratory of Research on Digestive Health and Performance of Equines (LabEqui), FMVZ / USP at the Fernando Costa Campus in Pirassununga / SP. Sixteen pregnant mares were used, with mean age of 90 &#177; 7 months, kept in pickets without access to grasses throughout the experimental period. The diet was formulated to meet the requirement of the category according to NRC 2007, was composed of grass hay and concentrate, water and mineral salt ad libitum. They were divided in two groups of eight animals each, 1) control group: Tifton 85 hay and commercial concentrate without supplementation, 2) supplemented group: Tifton 85 hay and commercial feed with Actisaf HR Plus Sc 47&reg;-10 supplementation g / animal / day. A completely randomized (DIC) design, with measures repeated over time was considered in the model. There was observed a statistical effect of supplementation (P = 0.05) over mononuclear cells in colostrum and for polynuclear cells (P = 0.05). It can be concluded that supplementation with live yeast Saccharomyces cerevisae in the diet of mares in the final third of gestation may improve quality of colostrum with respect to the cellular profile, but does not improve the transference of passive immunity of the colts.

Bubble CPAP (BCPAP) is used in the neonatal intensive care unit (NICU) as a form of non-invasive ventilation and is commonly employed in neonates demonstrating respiratory distress. BCPAP may be used to avoid the need for intubation and mechanical ventilation thereby reducing lung injury and other morbidities as well as decrease hospital stay. PURPOSE: The purpose of this study is to retrospectively investigate the length of stay on bubble CPAP (BCPAP) considering gestational age, birth weight, and surfactant delivery in the neonatal population born at an urban tertiary high load level three (NICU). METHODS: A retrospective study using existing data from an urban tertiary high load level three NICU was completed. DATA ANALYSIS: Data analysis was performed using SPSS 16.0. Descriptive statistics were run for each variable. Contingency tables were run to determine if gestational age at birth, birth weight, and length of time on BCPAP had significance compared to surfactant delivery. Intercorrelations were run to determine if gestational age at birth, birth weight, and length of time on BCPAP had an effect on each other. Davis conventions were used to analyze the results. RESULTS: Descriptive statistics indicated the mean gestational age at birth to be 32.263 weeks, SD = +2.978, mean neonatal weight to be 1.899 kg, SD = +0.728, and mean length of time on BCPAP to be 124.430 hours, SD = +185.474. Contingency statistics showed a substantial association (reta = 0.562) between the gestational age at birth and surfactant delivery, a very strong association (reta = 1.000) between the birth weight and surfactant delivery, and a very strong association (reta = 0.914) between the length of time the neonate was on BCPAP and surfactant delivery. Pearson product-moment correlation coefficients showed gestational age at birth had a very strong positive association with birth weight (r = 0.811, p < 0.01) and a moderate negative association with length of time on BCPAP (r = -0.439, p < 0.01). Intercorrelations also showed birth weight had a moderate negative association with length of time on BCPAP (r = -0.306, p < 0.01). CONCLUSIONS: The neonate was less likely to receive surfactant if, their gestational age was older at birth, they had a heavier birth weight, and their length of time on BCPCP was shorter. The data also demonstrated that the older the neonate’s gestational age at birth and the heavier the neonatal birth weight equated to a shorter length of time on BCPAP. Lastly the data demonstrated that the heavier the neonate’s birth weight, the shorter length of time on BCPAP.

Hyperglycaemia is a common condition in the very low birth weight infant and is linked to mortality and increased risks of morbidities such as sepsis and retinopathy of prematurity. The preterm neonate is in a state of transition from complete dependence on the mother to physiological independence. Many metabolic regulation systems are under-developed, attenuating the natural metabolic hormonal control response. Tight regulation of glucose levels can significantly reduce the negative outcomes associated with hyperglycaemia, but achieving it remains clinically elusive for the neonate. Glucose control in adult critical care is a highly researched topic, and several studies have demonstrated significantly improved outcomes with protocols that modulate the insulin and/or nutrition inputs into the patient. Despite the potential, no standard protocol exists for neonates. Glucose restriction is often used as a treatment for neonatal hyperglycaemia, however this deprives the infant of much needed energy for growth. Limited trials of insulin infusions have been reported, based on fixed protocols or ad-hoc clinical decisions that do not objectively account for an individual patient's metabolic state. Model-based methods can deliver control that is patient-specific and adaptive to handle highly dynamic patients. A physiological model of the glucose-insulin regulatory system is presented in this thesis, adapted from adult critical care. This model has three compartments for glucose utilisation, effective interstitial insulin and its transport, and insulin kinetics in blood plasma, with emphasis on clinical applicability. The predictive control for the model is driven by the patient-specific and time-varying insulin sensitivity parameter. A novel integral-based parameter identification enables fast and accurate real-time model adaptation to individual patients and patient condition. Validation on retrospective clinical data demonstrated the model's ability to capture the major dynamics of the glucose-insulin system in the critically ill neonate. Model fit and prediction performance analysis resulted in a similar level of performance as adult intensive care models and thus suitable for model-based targeted control. Comparison of insulin sensitivity profiles with adult critical care patients highlighted the glycaemic control problem as one of managing inter- and intra-patient variability. Stochastic models and time-series methods for forecasting future insulin sensitivity are presented in this thesis. These methods can deliver probability intervals to support clinical control interventions. The risk of adverse glycaemic outcomes given observed variability from cohort-specific and patient-specific forecasting methods can be quantified to inform clinical staff. Hypoglycaemia can thus be further avoided with the probability interval guided intervention assessments. Simulation studies of clinical control trials on `virtual patients' derived from retrospective clinical data provided a framework to optimise control protocol design in-silico. Comparisons with retrospective control showed substantial improvements in glycaemia within the target 4 - 7 mmol/L range by optimising the infusions of insulin. The simulation environment allowed experimentation with controller parameters to arrive at a protocol that operates within the constraints imposed by the clinically fragile state of the preterm infant. The resulting control system was piloted in seven 12-24 hour clinical trials at the Christchurch Women's Neonatal Department. Glucose levels were tightly controlled in all cases over a trial cohort that represented a wide range of patient conditions and severity of illness. Model predictive performance agreed with simulation results and the stochastic model forecast bounds maintained patient safety. Overall, the research presented takes model-based neonatal glycaemic control from concept to proof-of-concept clinical pilot trials. The thesis develops the full range of models, tools and methods to optimise the protocol design and problem solution. This research thus provides a template for model-based glycaemic control development in general that could be extended to other glycaemic control and similar problems.

No description available.

Substance use during pregnancy can adversely affect both health and social outcomes for the infant and the mother. Many practices related to the care of infants with prenatal substance exposure are not consistent from one facility to another and have been developed on an anecdotal basis rather than based on empirical research. A replication study of a 2002 national practice survey is being planned that will describe some of the practices related to daily care, discharge planning, and community support for this group of infants and their caregivers. In this thesis, I present the findings of a pilot study that was conducted as a prelude to this larger national study. A summary of a literature review of recent survey research is presented along with a description of the process of revising a previously developed instrument to survey the practices used when caring for infants with prenatal drug and alcohol exposure and their mothers in the hospital setting. Content validity of this revised instrument was established with the support of a content expert group and the revised instrument was pilot tested with a small sample of nurses who practice in hospitals that will not be eligible for the national study. The findings from this pilot study will guide the research team in developing and conducting the national survey. / Graduate / 0539 / 0380 / 0573