Class of 2013 Abstract / Specific Aims: Trace elements such as manganese are added into parenteral nutrition formulations to prevent or treat trace elements deficiencies. Excessive amounts of certain trace elements added to parenteral nutritional formulations can cause potential adverse effects. The purpose of this study was to evaluate whole-blood manganese concentrations obtained in patients prescribed parenteral nutrition for more than 30 days. The manganese concentrations obtained were evaluated based on the duration and amount of manganese prescribed in the parenteral nutritional formulations.. Methods: In this IRB approved project, adult patients prescribed parenteral nutrition for at least 30 consecutive days at an academic medical center or through the outpatient healthcare system between January 2007 and December 2011 were evaluated. Subjects were excluded if no manganese concentrations were obtained while parenteral nutrition was prescribed. Manganese concentrations were grouped by duration that trace elements were added to parenteral nutrition formulations as < 30 days, 30-90 days, 90-365 days, and >365 days. A fifth group of manganese concentrations were evaluated if they were obtained when manganese was not added to the parenteral nutritional formulation for at least 90 days. Data collected included demographic information, reason for initiation and discontinuation of parenteral nutrition, reason for long-term parenteral nutrition, duration of parenteral nutrition, duration and timing of other nutrient sources, amount prescribed and timing of trace elements, trace element concentrations, and documentation of potential manganese toxicity in medical records. A normal manganese concentration was defined as 4.2 to 16.5 mcg/L. Main Results: A total of 27 subjects who were prescribed long-term parenteral nutrition were evaluated. Subjects had a median age of 54 years and range of 18 to 71 years. The majority of subjects (53%) were initially prescribed parenteral nutrition for enteric fistula or malabsorption issues while 27% of subjects were classified as have short gut. A total of 41 manganese concentrations were reported with a median value of 20.1 mcg/L and range of 9.1 to 49.9 mcg/L. The percentage of abnormally high manganese concentrations was 0% at 0-30 days, 63% at 30-90 days, 83% at 90-365 days, and 100% at >365 days of parenteral nutrition with manganese added through a multitrace element solution. In subjects who had received parenteral nutrition for at least 90 days without manganese, abnormal manganese concentrations reported rate was 28%. The rate of abnormal manganese concentrations was significant different between 0-30 days compared to 90-365 days (p = 0.015) and > 365 days (p =0.09) of multi-trace element added to parenteral nutrition. The median number of days between the initial day of parenteral nutition and day managanese concentration checked was 131 days and ranged from 0 to 849 days. Conclusion: The majority of commercially available trace element solutions contain approximately 500% per mL of the recommended daily supplementation amount. In 27 subjects who received long-term parenteral nutrition, the risk of hypermanganesemia was significantly associated with durations of parenteral nutrition that contained multi-trace element solutions for more than 90 days.

Orientadores: Antonio Fernando Ribeiro, José Roberto Negrão Nogueira / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-28T09:12:18Z (GMT). No. of bitstreams: 1 Hortencio_TaisDaieneRusso_D.pdf: 2122387 bytes, checksum: 6b337a8713273a2fcc11dbc17230038f (MD5) Previous issue date: 2015 / Resumo: Introdução O desenvolvimento da nutrição parenteral (NP) na década de 1960 e sua subsequente utilização na prática clínica tem tido um enorme impacto sobre os pacientes com numerosas doenças para as quais a nutrição foi impossível por outra via. Mas, esta nova tecnologia tem riscos associados, incluindo o desenvolvimento de distúrbios metabólicos, superalimentação e complicações infecciosas. Método Foram realizados dois estudos. O primeiro estudo teve como objetivo avaliar, em uma coorte histórica de pacientes pediátricos no Brasil que receberam NP individualizada e exclusiva, a prevalência de hipofosfatemia, hipocalemia e hipomagnesemia em até 48 horas antes do início da infusão de NP (P1), do 1° ao 4° dia (P2); 5° ao 7° dia (P3) e, investigar se a infusão de caloria e proteína e também a desnutrição foram relacionadas com esses distúrbios. O segundo estudo foi feito no Canadá. Trata-se de um estudo retrospectivo e multicêntrico, avaliando pacientes sob nutrição parenteral domiciliar (NPD), prospectivamente inseridos no Home Parenteral Nutrition Registry (HPN Registry) nos períodos: 2005-2008 ou 2011-2014. Mudanças na demografia, indicações para NPD, prescrição, avaliação nutricional, acesso vascular e número de infecção de cateter por 1000 dias de cateter foram avaliados. Resultados A desnutrição esteve presente em 32,8% dos 119 pacientes avaliados no primeiro estudo, 66,4% estavam em unidade de terapia intensiva pediátrica (UTI Ped), 13,5% morreram. O período de maior prevalência de distúrbios minerais foi o P1 54 (45,3%), no P2 = 35 (31,8%), no P3 = 4 (3,57%). Hipocalemia esteve relacionada à desnutrição OR 2,79 (95% CI 1,09-7,14) p = 0,045. Nos primeiros sete dias, foram infundidas calorias inferior à quantidade recomendada pelas recomendações atuais em até 84,9% dos pacientes e proteína adequada em até 75,7%. Proteína infundida acima da recomendação nos primeiros quatro dias foi relacionada com hypomagnesaemia OR: 5,66 (IC 95% 1,24 - 25,79) p = 0,033. No estudo canadense, comparando os períodos 2011-2014 com 2005-2008, as indicações para a NPD mudaram significativamente com o aumento da proporção de pacientes com câncer (37,9% versus 16,7%) e diminuição da síndrome do intestino curto (32% versus 65,5%). A taxa de infecção de cateter diminuiu de 1,58 para 0,97 por 1.000 dias de cateter; o uso de cateter tunelizado diminuiu de 64,3% para 38,0% e a proporção de cateteres centrais de inserção periférica (PICC) aumentou de 21,6% para 52,9%. Além disso, houve uma redução no número e dias de internações relacionadas à NPD, e mudanças na prescrição de energia, proteína e oligoelementos. Conclusão Hipofosfatemia, hipocalemia e hipomagnesemia foram eventos frequentes, sendo a individualização ferramenta primordial para gerenciá-los. Pacientes desnutridos tiveram maior chance de desenvolver hipocalemia e os que receberam proteína acima da recomendação tiveram mais chances de desenvolver hipomagnesemia. Os resultados sugerem uma mudança no perfil demográfico e acesso venoso no Canadá, com melhora na infecção de cateter, hospitalizações relacionadas à NPD, e prescrições / Abstract: Introduction: The development of parenteral nutrition (PN) in the 1960s and its subsequent use in clinical practice has had a huge impact on patients with numerous diseases for which nutrition was impossible by other route. But, this new technology has associated risks, including the development of metabolic disorders, overfeeding, and infectious complications. Methods We conducted two studies The first study aims to evaluate in a historical cohort of pediatric patients, the prevalence of hypophosphatemia, hypokalemia and hypomagnesaemia until 48th hours before beginning PN infusion (P1), from 1st¿4th day (P2); 5th¿7th day (P3) of PN infusion and, investigate if malnutrition, calories, and proteins infusion were correlated to these disorders. In Canada, a retrospective study evaluating patients who were prospectively entered in the registry either in 2005¿2008 or in 2011¿2014 was done. Changes in patient demography, indications for Home Parenteral Nutricion (HPN), regimen, nutritional assessment, vascular access, and number of line sepsis per 1000 catheter days were evaluated. Results Malnutrition was present 32.8% of 119 patients participants from the first study, 66.4% were in pediatric intensive care unit (PICU), 13.5% died. The P1 was the period of highest prevalence mineral disorders 54 (45.3%), P2 had 35 (31.8%) and, P3=4 (3.57%). Hypokalemia events were related to malnutrition OR 2.79 (95% CI 1.09-7.14) p = 0.045. In the first seven days, infused calories were below the amount recommended by current guidelines in up to 84.9% of patients and protein infused was adequate in up to 75.7%. Protein infused above recommendation was related to hypomagnesaemia OR: 5,66 (95% CI 1,24 ¿ 25,79) p=0,033. In 2011¿2014 compared with 2005¿2008, indications for HPN changed significantly with an increased proportion of patients with cancer (37.9% versus 16.7%) and decreased short bowel syndrome (32% versus 65.5%). The line sepsis rate decreased from 1.58 to 0.97 per 1,000 catheter days; tunnelled catheters decreased as the most frequently chosen vascular access method from 64.3% to 38.0% and the proportion of peripherally inserted central catheters (PICC) increased from 21.6% to 52.9%. In addition, there was a reduction in number, and days of hospitalizations related to HPN, and changes in the prescription of energy, proteins, and trace elements were noted. Conclusion Hypophosphatemia, hypokalemia and hypomagnesemia were frequent events, being individualization primary tool to manage them. Malnourished patients were more likely to develop hypokalemia, and patients receiving protein above the recommendation were more likely to develop hypomagnesemia. Results suggest a shift in patient demography and line access in Canada, with improvement in line sepsis, hospitalizations and HPN prescriptions / Doutorado / Saude da Criança e do Adolescente / Doutora em Ciências

Thesis (M.S.)--University of Michigan, 1982.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted. Includes summaries in Swedish and Chinese. Includes bibliographical references.

Thesis (M.S.)--University of Michigan, 1982.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted. Includes summaries in Swedish and Chinese. Includes bibliographical references.

Total parenteral nutrition (TPN) provides an experimental situation where adequate nutrition is provided intravenously, bypassing the gastrointestinal tract. Under these conditions the importance of orally ingested nutrients in the control of gastric and pancreatic endocrine secretion can be assessed. The objectives of this thesis were two-fold. First, to examine the effects of TPN on the enteroinsular axis component of insulin secretion. Second, to study the importance of orally ingested nutrients in the regulation of gastric hormone secretion using the TPN rat model. In order to carry out these objectives, techniques for TPN and enteral feeding (TEN) of the rat were first developed. A dietary regimen for use in TPN and TEN rats was formulated from commercially-available, human TPN components. Under most circumstances, the TPN/TEN regimen met or exceeded the nutritional requirements for growing rats, as determined by the National Research Council (1978). Hematological analysis revealed few side effects of — intravenous or intragastric feeding. Parenterally and enterally-fed animals demonstrated comparable weight gain to that of a control group (ORAL) fed a rat chow (#5012, Ralston Purina) diet ad libitum. In addition, both TPN and TEN animals appeared healthy after the 7-day infusion period. These studies indicated that the infusion formulation was suitable for chronic intravenous and intragastric feeding. In the first series of experiments, the effects of TPN and TEN on the hormonal component of the enteroinsular axis were studied. TPN animals exhibited hyperinsulinemia and mild hyperglycemia. Conversely, TEN animals exhibited normal plasma glucose and immunoreactive insulin (IRI) concentrations. These data suggested that enterally delivered nutrients were assimilated with greater efficiency than intravenously administered nutrients. It was hypothesized that gut factors normally released by oral food intake facilitated the disposal of nutrients by hepatic and/or peripheral tissues. During the infusion period, TPN animals exhibited chronically depressed circulating IR-gastric inhibitory polypeptide (GIP) levels, in contrast to TEN animals where IR-GIP was elevated. Seven days of TPN or TEN resulted in no change in fasting plasma IRI or IR-GIP levels. However, an exaggerated insulin response to an oral glucose challenge (OGC) occurred after TPN, while the glucose response was reduced. The insulin response from the perfused pancreata of TPN animals to a GIP gradient was 20% and 40% greater than from ORAL and TEN pancreata respectively. Shorter periods of TPN (3 and 5-day periods) indicated that the hypersensitivity of the pancreas to GIP was a progressive condition, increasing with longer periods of infusion. Immunocytochemical and morphometric analysis revealed no differences in the jejunal GLP-cell population after chronic (7-day) intravenous or intragastric feeding. In addition, these routes of feeding had no effect on pancreatic islet area or endocrine cell composition of the islets. Based on these results, it was hypothesized that the increased B-cell sensitivity to GIP may have been causally related to the exposure of the pancreas to chronically low plasma GIP levels during the infusion period. To further test this hypothesis, chronically depressed plasma GIP levels, observed during TPN, were elevated by exogenous GIP infusion to levels seen in TEN rats. Chronic GIP —treatment in TPN animals (TPN-GIP) resulted in normalization of the insulin response to an OGC and in the in vitro insulin response of the isolated pancreas to GIP. These data were taken as further evidence that B-cell sensitivity to GIP was affected by ambient plasma GIP levels, and it was hypothesized that changes in sensitivity may be mediated by alteration at the receptor or post-receptor level. The effect of TPN on nutrient and neuronally mediated insulin release was also investigated. During TPN, metabolites and neuronal elements provided the main stimulus for insulin release, since hormonal components of the enteroinsular axis remained inactive. The present experiments indicated that the B-cell was hypersensitive to glucose, vagal stimulation and the cholinergic agonist methacholine, but normally sensitive to vasoactive intestinal polypeptide (VIP) and the insulinotropic amino acid arginine. These results indicated that TPN was associated with an increased B-cell sensitivity to specific hormonal, nutritive and neuronal stimuli. It was hypothesized that an increased B-cell sensitivity to these specific stimuli contributed to hyperinsulinemia observed in TPN animals during the infusion period, and to the exaggerated insulin response observed after an oral glucose challenge. Total parenteral nutrition also provided an experimental situation in which to study the importance of gastric nutrients in the regulation of Gl-hormone secretion. TPN resulted in a rapid and progressive depletion of circulating gastrin levels. G-cell secretory activity in vivo under basal and stimulatory conditions was also reduced by TPN. This condition persisted in vitro in the isolated stomach. The antral G-cell population was shown to decrease progressively with longer TPN periods, but G-cell hypoplasia and reductions in antral gastrin content were less dramatic than reductions in G-cell secretory activity. It was hypothesized that reductions in G-cell secretory activity were in part causally related to antral G-cell hypoplasia. The present data further suggested, however, that mechanisms which control synthesis and/or secretion within G-cells may have also been impaired, since various stimulants of gastrin release could not reverse gastrin hyposecretion observed during basal periods. Gastrin hyposecretion also could not be reversed by chronic bombesin administration, but was reversed by a 6-day period of oral — refeeding, indicating that the presence of nutrients in the gastric lumen was the primary regulator of tissue gastrin levels and G-cell secretory activity. The gastric D-cell was much less affected by the absence of nutrients in the gastric lumen than was the G-cell, and antral somatostatin hypersecretion may have contributed to G-cell hyposecretion. The experiments presented in this thesis indicated that total parenteral nutrition had marked effects on both B- and G-cell secretory activity. These studies clearly demonstrated the importance of enteral feeding in the maintenance of normal pancreatic and gastrointestinal endocrine secretion. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

Orientador: Gabriel Hessel / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T12:37:09Z (GMT). No. of bitstreams: 1 Freitas_RenataGermanoBorgesdeOliveiraNascimento_M.pdf: 1569637 bytes, checksum: b72c8890e15da5747d9f2995f98d2fda (MD5) Previous issue date: 2014 / Resumo: O objetivo geral do estudo foi avaliar o estado nutricional e suas relações com a atividade inflamatória e a prescrição da nutrição parenteral (NP) de pacientes internados em um hospital terciário em uso de NP. Métodos: A pesquisa foi longitudinal e desenvolvida em 3 capítulos. A coleta de dados foi realizada durante as primeiras 72 horas, no 7º e 14º dia de uso da NP entre os adultos (2 primeiros capítulos). Entre os pacientes pediátricos, foram computados os dados de 24 horas anteriores às individualizações da NP (capítulo 3). Os exames laboratoriais realizados foram: albumina, proteína C reativa (PCR), pré-albumina, colesterol total, HDL, triglicerídeos (TGL) e creatinina, glutationa peroxidase (GPx), sódio, potássio, cálcio iônico, cloreto, magnésio e fósforo inorgânico. A avaliação da gravidade foi determinada pelo cálculo do escore de Acute Physiologic and Chronic Health Evaluation (APACHE II) e Sequential Organ Failure Assessment (SOFA). Com os dados do peso e da altura, foi calculado o Índice de Massa Corporal (IMC) e com a circunferência braquial (CB) e a prega cutânea tricipital (PCT), foram calculados as medidas derivadas: circunferência muscular do braço (CMB), área muscular braquial corrigida (AMBc) e área adiposa braquial (AAB). A prescrição energética dos pacientes foi realizada de acordo com a ESPEN (2009), e ASPEN (2002) para adultos e segundo a ASPEN (2010) e a ESPGHAN (2005) para os pediátricos. Foi comparada a recomendação calórica das fórmulas Harris Benedict (HB) e ESPEN 2009. Resultados: Entres os 88 pacientes avaliados, apesar da maioria ter sido classificada como normoponderal pelo IMC (55,36%), a depleção de massa magra foi predominante segundo AMBc (93,33%) e CMB (62,5%). Os níveis da PCR estavam elevados e albumina, pré-albumina e GPx, baixos. Ao longo do estudo a pré-albumina aumentou (p=0.0261). Houve diferença entre as fórmulas (25kcal/kg/dia) e HB (p?0,0001). Entre os 53 pacientes da unidade de terapia intensiva (UTI), 20 (37,74%) foram a óbito. Foi encontrada diferença significativa do SOFA com o desfecho e uma tendência inversamente proporcional do IMC com o óbito. Foi encontrada correlação negativa e forte entre o SOFA e a pré-albumina (r = -0.64; p = 0.05). Com relação aos 12 pacientes pediátricos (49 individualizações), a maioria foi classificada com desnutrição. Observou-se que 74/254 (29,2%) dos exames bioquímicos demandaram NP individualizada por motivos indubitáveis. Conclusões: O IMC parece estar relacionado com a inflamação. Os valores baixos de pré-albumina e albumina indicam desnutrição e/ou processo inflamatório. A aplicação da fórmula (25kcal/kg/dia), já padronizada, contribuiu com a melhora do estado nutricional, evidenciado pelos valores de pré-albumina. Entre os pacientes da UTI, o SOFA foi um bom instrumento para avaliação prognóstica. A albumina foi um marcador para desnutrição. É possível que o IMC seja um parâmetro para avaliação prognóstica do paciente. Entre os pediátricos, o estado nutricional dos pacientes foi considerado crítico, na maioria dos casos. Desta forma, a individualização realizada no início da NP para a adequação energética proteica é essencial. Além disto, a NP individualizada foi indispensável em, no mínimo, 29,2% das NP, para correção das alterações dos exames bioquímicos / Abstract: This study aimed to evaluate the nutritional state and its relationships with inflammatory activity and parenteral nutrition (PN) prescription of patients using PN hospitalized in a tertiary hospital. Methods: The research was longitudinal and developed in three chapters. The data collection was performed during the first 72 hours, on the 7th and 14th days using PN in adults (two first chapters). The data from pediatric patients were computed 24 hours before PN individualizations (chapter 3). The following laboratory examinations were performed: albumin, reactive C-protein (RCP), prealbumin, total cholesterol, HDL, triglycerides (TGL) and creatinine, glutathione peroxidase (GPx), sodium, potassium, ionized calcium, chloride, magnesium, inorganic phosphorus. The evaluation of severity was determined by the calculation of the score of Acute Physiologic and Chronic Health Evaluation (APACHE II) and Sequential Organ Failure Assessment (SOFA). The body mass index (BMI) was calculated using weight and height, and using brachial circumference (BC) and triceps skinfold thickeness (TST), the following derived measurements were calculated: mid arm muscle circumference (MAMC), corrected arm muscle area (CAMA) and arm fat area (AFA). The energy requirement of patients was performed according to the ESPEN (2009) and ASPEN (2002) for adults, and the ASPEN (2010) and ESPGHAN (2005) for pediatric patients. The calorie recommendation of the formulas Harris Benedict (HB) and ESPEN 2009 were compared. Results: Among the 88 evaluated patients, although most of them has been classified as normoponderal by the BMI (55.36%), malnutrition was prevalent according to AMBc (93.33%) and CMB (62.5%). While the PCR levels were elevated, albumin, prealbumin and GPx levels were low. During the study, prealbumin increased (p=0.0261). There was difference between the formulas (25kcal/kg/day) and HB (p?0.0001). Amont the 53 patients in the intensive therapy unit (ITU), 20 (37.74%) died. It was found a significant difference of SOFA with outcome, and a inversely proportional trend of BMI with death. There was a negative and strong correlation between SOFA and prealbumin (r = -0.64; p = 0.05). Most of the 12 pediatric patients (49 individualizations) were classified as having malnutrition. It was observed that 74/254 (29.2%) of biochemical examinations demanded individualized PN due to indubitable reasons. Conclusions: BMI seems to be related to inflammation. The low values of prealbumin and albumin indicate malnutrition and/or inflammatory process. The application of the already standardized formula (25kcal/kg/day) contributed to an improvement in the nutritional state, evidenced by prealbumin values. SOFA was a good instrument for prognostic evaluation in patients in the ITU. Albumin was a marker of malnutrition. It is possible that the BMI is a parameter for prognostic evaluation of patients. The nutritional state of most pediatric patients was considered critical. Thus, the individualization performed in the beginning of the PN for energy protein adequacy is essential. In addition, the individualized PN was indispensable in at least 29.2% of PN, for correction of alterations of biochemical examinations / Mestrado / Saude da Criança e do Adolescente / Mestra em Ciências

No description available.

The aim of this research was to formulate, characterise and assess the feasibility of a novel drug delivery system known as the in situ gelling matrix (ISGM) where a hydrophilic polymer is suspended in a non-aqueous solvent that converts into a gel when injected subcutaneously or intramuscularly thus giving a controlled release matrix for a drug. Although the concept has been patented with claims that this kind of drug delivery is achievable in theory for a wide variety of candidate substances, actual formulation studies for making a commercially viable product for this technology are completely lacking in practice. The research embodied in this thesis addresses this lack. Initial studies involved conducting a biocompatibility study using the HET-CAM (hens egg test - chorioallantoic membrane) test on a range of possible ingredients for the delivery system. The materials deemed biocompatible were then carried through to a screening process where the physical stability of the hydrophilic polymers in non-aqueous solvents was monitored. It was found that the hydrophilic polymers tested sedimented rapidly in the non-aqueous solvents indicating such a system was not physically stable. Consequently, density-inducing or viscosity-inducing agents were added to the non-aqueous solvents to retard the sedimentation rate. The addition of polycarbophil, a viscosity-inducing agent, clearly increased the viscosity of the system. However, undesirable formation of polycarbophil globules occurred during the manufacturing process, which caused batch-to-batch variations in the viscosity of the continuous phase. Various manufacturing methods were tested before arriving at the optimum procedure to prevent globule formation using a high speed dispersion tool. A final physical sedimentation analysis of candidate continuous phases and hydrophilic polymers was conducted for determining the ideal combination of ingredients to use in the system. These investigations finally led to the adoption of an optimum mix of components consisting of 10% (w/w) hydroxypropyl methylcellulose (HPMC) (the hydrophilic polymer) suspended in a continuous phase of propylene glycol (the non-aqueous solvent) containing 0.67% (w/w) polycarbophil (the viscosity inducing agent). Using this mix of components, the in situ gelling matrix system was then subjected to various characterisation studies including infrared (IR), differential scanning calorimetry (DSC), ultraviolet-visible (UV-Vis) spectrophotometry and redispersion studies. The chemical stability of the hydrophilic polymer and the continuous phase (the non-aqueous solvent and polycarbophil) was monitored and were found to be chemically stable over a 9 month period. The feasibility of the in situ gelling matrix technology as a controlled release device was assessed using the drug propranolol. In vitro drug release studies were conducted using a custom-built dissolution apparatus. The effect of various parameters such as the concentration of the hydrophilic gelling agent on the drug release rate was investigated. Increasing the concentration of the gelling agent in the formulation resulted in a slower rate of release. The drug release data were modelled using the Higuchi relationship and a power law relationship to compare the effects of the various parameters on the release rate Stability studies on the drug in the in situ gelling matrix system were carried out by storing samples in accelerated ageing conditions of 40 C / 75% relative humidity for 4 weeks. During this time, the samples were analysed each week by high performance liquid chromatography (HPLC). These demonstrated that no apparent drug degradation had occurred over the 4-week period. This indicates that the drug propranolol in the in situ gelling matrix system is stable under ambient conditions for at least 4 weeks. The results of this study demonstrated that the in situ gelling matrix technology is potentially viable as a drug delivery system and provide a practical methodology for the commercial development of such systems.