RESUMEN
The potential to replace shark-derived squalene in vaccine adjuvant applications with synthetic squalene/poly(isoprene) oligomers, synthesized by the controlled oligomerization of isoprene is demonstrated. Following on from our previous work regarding the synthesis of poly(isoprene) oligomers, we demonstrate the ability to tune the molecular weight of the synthetic poly(isoprene) material beyond that of natural squalene, while retaining a final backbone structure that contained a minimum of 75% of 1,4 addition product and an acceptable polydispersity. The synthesis was successfully scaled from the 2 g to the 40 g scale both in the bulk (i.e., solvent free) and with the aid of additional solvent by utilizing catalytic chain transfer polymerization (CCTP) as the control method, such that the target molecular weight, acceptable dispersity levels, and the desired level of 1,4 addition in the backbone structure and an acceptable yield (â¼60%) are achieved. Moreover, the stability and in vitro bioactivity of nanoemulsion adjuvant formulations manufactured with the synthetic poly(isoprene) material are evaluated in comparison to emulsions made with shark-derived squalene. Emulsions containing the synthetic poly(isoprene) achieved smaller particle size and equivalent or enhanced bioactivity (stimulation of cytokine production in human whole blood) compared to corresponding shark squalene emulsions. However, as opposed to the shark squalene-based emulsions, the poly(isoprene) emulsions demonstrated reduced long-term size stability and induced hemolysis at high concentrations. Finally, we demonstrate that the synthetic oligomeric poly(isoprene) material could successfully be hydrogenated such that >95% of the double bonds were successfully removed to give a representative poly(isoprene)-derived squalane mimic.
Asunto(s)
Adyuvantes Inmunológicos/química , Butadienos/química , Hemiterpenos/química , Pentanos/química , Escualeno/análogos & derivados , Escualeno/química , Vacunas/química , Química Farmacéutica/métodos , Estabilidad de Medicamentos , Emulsiones/química , Tamaño de la Partícula , PolimerizacionRESUMEN
Hypercalcemia is a common but challenging disorder. It results from PTH-dependent or independent increased bone resorption, increased vitamin D-dependent absorption, or as a result of various drugs and substances. Outpatient hypercalcemia is most commonly caused by primary hyperparathyroidism while malignancy accounts for most inpatient disease. Treatment includes adequate hydration, intravenous bisphosphonates, and occasionally calcitonin as a temporizing measure. Treating the underlying cause, such as employing chemotherapy for malignancy or parathyroidectomy for hyperparathyroidism, is also essential.
Asunto(s)
Calcio/metabolismo , Hipercalcemia/diagnóstico , Hipercalcemia/terapia , Diagnóstico Diferencial , Difosfonatos/uso terapéutico , Homeostasis , Humanos , Hipercalcemia/etiología , Hipercalcemia/fisiopatología , Hiperparatiroidismo/etiología , Hiperparatiroidismo/fisiopatología , Hiperparatiroidismo/cirugía , ParatiroidectomíaRESUMEN
Sustainable and biobased surfactants are required for a wide range of everyday applications. Key drivers are cost, activity and efficiency of production. Polycondensation is an excellent route to build surfactant chains from bio-sourced monomers, but this typically requires high processing temperatures (≥200 °C) to remove the condensate and to lower viscosity of the polymer melt. In addition, high temperatures also increase the degree of branching and cause discolouration through the degradation of sensitive co-initiators and monomers. Here we report the synthesis of novel surface-active polymers from temperature sensitive renewable building blocks such as dicarboxylic acids, polyols (d-sorbitol) and fatty acids. We demonstrate that the products have the potential to be key components in renewable surfactant design, but only if the syntheses are optimised to ensure linear chains with hydrophilic character. The choice of catalyst is key to this control and we have assessed three different approaches. Additionally, we also demonstrate that use of supercritical carbon dioxide (scCO2) can dramatically improve conversion by reducing reaction viscosity, lowering reaction temperature, and driving condensate removal. We also evaluate the performance of the new biobased surfactants, focussing upon surface tension, and critical micelle concentration.
RESUMEN
Hürthle cell, a rare form of thyroid carcinoma, has been reported only five times in patients with Grave's Disease. We present a case report and comprehensive review of the literature. Surgery should be considered in patients with both Graves' Disease and an expanding goiter. Initial high-dose radioiodine should be administered post-operatively in patients with Hürthle cell carcinoma. Serum thyroglobulin and 18-FDG total body PET imaging may be valuable in discovering residual or recurrent disease.
Asunto(s)
Adenoma Oxifílico/complicaciones , Enfermedad de Graves/complicaciones , Neoplasias de la Tiroides/complicaciones , Adenoma Oxifílico/diagnóstico , Adenoma Oxifílico/terapia , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/terapiaRESUMEN
BACKGROUND: Distal pancreatectomy (DP) is carried out for resection of lesions in the body and tail of the pancreas. DP may lead to both insulin and glucagon deficiency, which may worsen diabetes mellitus and render patients more vulnerable to severe hypoglycemia. Maintaining glycemic control can be challenging after DP, and no guidelines have been established for clinicians. The objective of this study was to investigate postoperative glycemic control and insulin dose among patients after DP. METHODS: The medical records from 82 eligible adult patients after DP between 2013 and 2014 were reviewed retrospectively. RESULTS: Twenty-one (25.6%) patients had pre-existing diabetes. The average length of stay was 5.8 ± 2.6 days. The average resected volume was 193 ± 313 cm3. Of 2124 blood glucose (BG) values, only 0.3% were <70 mg/dL (3.9 mmol/L); 45% were 140-180 mg/dL (7.8-10.0 mmol/L); and 14% were >180 mg/dL. Postoperatively, insulin was the most common agent prescribed for glycemic control. Among those who received insulin, 86.8% used rapid-acting correction insulin, 4.4% prandial insulin, and 8.8% long-acting insulin. On postoperative day 1 through 6 and on the day before hospital discharge, <30% of patients received insulin, and a total daily dose (TDD) of <0.10 units/kg was frequently needed for glycemic control. At discharge, 35.3% of patients with pre-existing diabetes improved; 23.2% required diabetic medications, of whom 50% took insulin. Only 2 patients without pre-existing diabetes required medications. CONCLUSION: Postoperative BG levels were relatively well controlled. The majority of BG levels were in the optimal range, and the incidence of hypoglycemia or clinically significant hypoglycemia was minimal with our current regimen. Postoperative patients required small TDD of insulin for glycemic control. Our data suggested that 0.05-0.20 units/kg was an appropriate dose range for postoperative glycemic control among the vulnerable population. Our findings provide guidance for clinicians to dose insulin safely for postoperative patients with DP in a hospital setting.
Asunto(s)
Diabetes Mellitus/cirugía , Hipoglucemia/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Pancreatectomía/efectos adversos , Complicaciones Posoperatorias/tratamiento farmacológico , Adulto , Anciano , Glucemia/efectos de los fármacos , Diabetes Mellitus/sangre , Femenino , Glucagón/sangre , Humanos , Hipoglucemia/etiología , Insulina/sangre , Tiempo de Internación , Masculino , Persona de Mediana Edad , Páncreas/cirugía , Pancreatectomía/métodos , Alta del Paciente , Complicaciones Posoperatorias/etiología , Periodo Posoperatorio , Estudios RetrospectivosRESUMEN
PURPOSE: The purpose of the study was to determine the prevalence of undiagnosed diabetes mellitus (DM) and prediabetes (pre-DM) in acute stroke patients, to evaluate recommendations of diabetes treatment and follow-up care in a hospital setting, and to examine 1-year readmission rates based on admission A1C measure. METHODS: This retrospective study comprised 200 patients randomly selected from 1095 patients admitted with an acute stroke and an A1C measurement during admission. DM and pre-DM prevalence levels were determined per A1C level. Recommendations for diabetes treatment during and after hospitalization were assessed; charts were reviewed for readmission. RESULTS: Among 200 patients, 43% had known DM, and 0.5% had pre-DM. Among 113 patients without history of DM or pre-DM, 61.9% had A1C 5.7% to 6.4% (39-46 mmol/mol), and 8.8% had A1C ≥6.5% (48 mmol/mol). None of the newly diagnosed pre-DM and 60% of newly diagnosed DM were documented. Only 7 of newly diagnosed DM or pre-DM patients received diabetes education. For patients with known DM and A1C ≥7.0% (53 mmol/mol), 40.5% registered no change of diabetic regimen. Few patients were recommended for diabetes follow-up care. Patients with A1C ≥6.5% or <5.7% were more likely to be readmitted for any reason within 1 year (33.3% and 31.6%, respectively) than patients with A1C levels of 5.7% to 6.4% (16.5%). CONCLUSIONS: The majority of acutely admitted stroke patients without known DM or pre-DM had A1C ≥5.7%. Newly diagnosed DM or pre-DM patients received inadequate diabetes education and follow-up care. These findings provide significant opportunities for improving acute stroke management.
Asunto(s)
Diagnóstico Tardío/efectos adversos , Diabetes Mellitus Tipo 2/diagnóstico , Educación del Paciente como Asunto/estadística & datos numéricos , Estado Prediabético/diagnóstico , Accidente Cerebrovascular/etiología , Enfermedad Aguda , Anciano , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Hemoglobina Glucada/análisis , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Estado Prediabético/sangre , Estado Prediabético/complicaciones , Estudios Retrospectivos , Accidente Cerebrovascular/sangreRESUMEN
This study was undertaken to evaluate the effectiveness of a new neuromotor behavioural assessment in identifying preterm infants whose development was potentially at risk as a result of their early birth and immediate postnatal experiences. All infants born at less than 30 weeks gestation or who weighed less than 1000g at birth and cared for in the Mater Hospital's Neonatal Intensive Care Unit in Brisbane over a two year period were included in the study. Infants were assessed in their third week of life and again at 36 weeks gestational equivalent age, or prior to discharge, whichever occurred sooner. Results indicate that the assessment is effective in differentiating those infants who suffered from adverse neonatal events from those who did not, when assessed between 30 and 36 weeks gestational equivalent age. The assessment did not prove useful for infants of less than 30 or greater than 36 weeks gestational equivalent age.
RESUMEN
Primary thyroid lymphoma is a rare form of non-Hodgkin's lymphoma that typically presents as a rapidly enlarging goiter in patients with a history of autoimmune thyroid disease. We present the evaluation, pitfalls in diagnosis, and treatment of a 49-year-old woman with diffuse large B-cell primary thyroid lymphoma presenting with airway obstruction.