- Long-term improvement in glucose control and counterregulation by islet transplantation for type 1 diabetes. [JOURNAL ARTICLE]
- J Clin Endocrinol Metab 2016 Aug 29.:jc20161649.
Islet transplantation has been shown to improve glucose counterregulation and hypoglycemia symptom recognition in patients with type 1 diabetes (T1D) complicated by severe hypoglycemia episodes and symptom unawareness, but long-term data are lacking.To assess the long-term durability of glucose counterregulation and hypoglycemia symptom responses 18 months after intrahepatic islet transplantation, and associated measures of glycemic control during a 24 month follow-up period.Ten patients with T1D disease duration ∼27 years were studied longitudinally before and 6 and 18 months post-transplant in the Clinical & Translational Research Center of the University of Pennsylvania, and compared to 10 nondiabetic control subjects.All 10 patients underwent intrahepatic islet transplantation according to the CIT07 protocol at the Hospital of the University of Pennsylvania.Counterregulatory hormone, endogenous glucose production, and autonomic symptom responses derived from stepped hyperinsulinemic-hypoglycemic and paired hyperinsulinemic-euglycemic clamps with infusion of 6,6-(2)H2-glucose.Near-normal glycemia (HbA1c ≤6.5%; time 70 - 180 mg/dl ≥95%) was maintained for 24 months in all patients with one returning to low-dose insulin therapy. In response to insulin-induced hypoglycemia, glucagon secretion was incompletely restored at 6 and 18 months, epinephrine was improved at 6 and normalized at 18 months, and endogenous glucose production and symptoms, absent before, were normalized at 6 and 18 months post-transplant.In patients with T1D experiencing problematic hypoglycemia, intrahepatic islet transplantation can lead to long-term improvement of glucose counterregulation and hypoglycemia symptom recognition, physiologic effects that likely contribute to glycemic stability post-transplant.
- Formation of core-shell Au@Ag nanorods induced by catecholamines: A comparative study and an analytical application. [Journal Article]
- Anal Chim Acta 2016 Sep 14.:185-94.
Gold nanorods (AuNRs) stabilized by cetyltrimethylammonium bromide (CTAB) were synthesized and an interaction of catecholamines (CAs) with silver ions in the presence of the obtained AuNRs was studied. The reaction results into formation of core-shell Au@Ag nanorods (Au@AgNRs) and leads to a hypsochromic shift of the long-wave surface plasmon resonance (SPR) band in the absorption spectrum of AuNRs. The influence of a CA structure, excess of CTAB, interaction time, pH, concentration of AuNRs, silver ions and CAs on this interaction was studied. Based on correlation of the NRs spectral characteristics with the concentration of CAs, a method for spectrophotometric determination of dobutamine, epinephrine, norepinephrine and dopamine with detection limits 27, 18, 16 and 13 μg L(-1), respectively, has been developed. The method can be applied to the analysis of medicines.
- A prospective multicenter study of submucosal injection to improve endoscopic snare papillectomy for ampullary adenoma. [JOURNAL ARTICLE]
- Gastrointest Endosc 2016 Aug 23.
Whether or not submucosal injection of a diluted epinephrine solution should be used to lift ampullary tumors during endoscopic snare papillectomy is unclear. This study aimed to investigate the clinical efficacy of a simple snaring method versus submucosal injection for papillectomy.A prospective multicenter study was performed at four tertiary referral centers. Patients with papillary lesions were randomized to undergo either simple snare papillectomy (SSP) or submucosal injection papillectomy (SIP) using 1:10,000 diluted epinephrine. The main outcome measures were complete resection rate and post-papillectomy adverse events.A total of 50 patients with biopsy-proven papillary adenomas were enrolled. Complete resection rates in SSP and SIP groups were 80.8% (21/26) and 50.0% (12/24), respectively (p=0.02). However, tumor persistence at 1 month (15.4% vs. 8.3%, p=0.62) and recurrence at 12 months (12.0% vs. 9.5%, p=0.58) did not differ despite initial difference in the prevalence of a positive resection margin. The mean tumor size was 12 mm in SSP group and 9.29 mm in SIP group. Post-papillectomy bleeding developed in 42.3% (11/26) and 45.8% (11/24) of patients, respectively (p=0.80). Delayed bleeding (>12 h) occurred in 27.3% (3/11) and 36.4% (4/11) of patients, respectively (p=0.50). Post-procedure pancreatitis occurred in 15.4% (4/26) and 25% (6/24) of patients, respectively (p=0.49). Pancreatitis severity did not differ between the groups, and there were no procedure-related mortalities.Although the recurrence rate was similar between the SSP and SIP groups, SIP showed no advantage over SSP in terms of achieving complete resection or decreasing the frequency of post-papillectomy adverse events, such as bleeding. SSP may thus be a simpler and primarily recommendable technique.
- Continuous cold exposure induces an anti-inflammatory response in mesenteric adipose tissue associated with catecholamine production and thermogenin expression in rats. [Journal Article]
- Endocr Regul 2016 Jul; 50(3):137-44.
Continuous exposure to cold leads to an activation of adaptive thermogenesis in the brown adipose tissue and induction of brown/beige cell phenotype in the white adipose tissue. Thermogenic response is associated with alternatively activated macrophages producing catecholamines, which subsequently activate the uncoupling protein 1 (UCP-1). The aim of this work was to elucidate the effect of cold exposure on catecholamine and immune responses associated with adipocyte browning in the mesenteric adipose tissue (mWAT) of rat.The rats were exposed to continuous cold (4 °C) for 1 or 7 days. Catecholamines production and gene expressions of inflammatory and other factors, related to adipocyte "browning", were analyzed in the homogenized mWAT samples using 2-CAT ELISA kits.Cold exposure induced a sympathetic response in the mWAT, evidenced by the tyrosine hydroxylase (TH) protein level rise. Induction of non-sympathetical catecholamine production was observed 7 days after cold exposure by elevated TH and phenylethanolamine-N-methyltransferase (PNMT) expression, leading to an increased epinephrine levels. Cold exposure for 7 days stimulated the infiltration of macrophages, evaluated by F4/80 and CD68 expressions, and expression of anti-inflammatory mediators, while pro-inflammatory cytokines were inhibited. Anti- inflammatory response, accompanied by de novo catecholamine production and up-regulation of β3-adrenergic receptors, led to the stimulation of UCP-1 and PGC1α expression, suggesting a cold-induced "browning" of the mWAT, mediated by alternatively activated macrophages.The present data indicate that prolonged cold exposure may induce anti-inflammatory response in mWAT associated with induction of UCP-1 expression. Although functional thermogenesis in the mWAT is most likely redundant, a highly efficient dissipation of energy by UCP1 may affect the energy homeostasis in this visceral fat.
- Harmful effect of epinephrine on postreperfusion syndrome in an elderly liver transplantation recipient with sigmoid ventricular septum: A case report. [Journal Article]
- Medicine (Baltimore) 2016 Aug; 95(34):e4394.
As a common morphological change of aging heart, sigmoid ventricular septum is frequently found during routine preoperative evaluation, but often disregarded because of its little clinical importance. However, in this report, we describe a 70-year old patient with sigmoid ventricular septum who developed severe hemodynamic deterioration during liver transplantation because of its unique morphology of heart.During the course of reperfusion of the graft, patient's hemodynamics were closely monitored using transesophageal echocardiography.Immediately after graft reperfusion, epinephrine was given as a treatment of choice for postreperfusion syndrome. Surprisingly, however, hemodynamic derangement persisted and became even worse. Intraoperative transesophageal echocardiography revealed left ventricular outflow tract obstruction resulting from systolic anterior motion of the mitral valve leaflet. Therefore, the patient was treated with phenylephrine and fluid bolus under the guidance of transesophageal echocardiography.As more elderly recipient present for liver transplantation surgery nowadays, left ventricular outflow tract obstruction should always be considered as a possible cause for hemodynamic instability during reperfusion period. In addition, transesophageal echocardiography is a useful tool for both diagnosis of hemodynamic derangement and guidance for appropriate management during liver transplantation surgery.
- Cuffed endotracheal tubes in neonates and infants undergoing cardiac surgery are not associated with airway complications. [Journal Article]
- J Clin Anesth 2016 Sep.:422-7.
To determine the incidence of postoperative airway complications in infants <5kg in weight undergoing cardiac surgery intubated with Microcuff (Kimberley-Clark, Roswell, GA) endotracheal tubes (ETTs).Retrospective review of infants weighing <5.0 kg with congenital heart disease (CHD) presenting for cardiac surgery.Single-center, tertiary pediatric cardiac critical care unit at a university hospital.A total of 208 infants weighing <5 kg underwent cardiac surgery for CHD from 2008 to 2013.Intubation with Microcuff (Kimberley-Clark) ETTs.Retrospective review of infants weighing <5.0 kg with CHD presenting for cardiac surgery to a single-center tertiary care university hospital.Perioperative data were collected. Primary outcome was development of tracheal stenosis and/or reintubation for stridor. Stridor was defined as mild (≤2 doses of racemic epinephrine), moderate (>2 doses of racemic epinephrine), or severe (requiring reintubation). Secondary outcomes were variables possibly contributing to postextubation stridor. Infants with a tracheostomy, airway anomalies, and death prior to initial extubation were excluded. Logistic regression analysis was performed to evaluate the association between clinical risk factors and the incidence of postextubation stridor.A total of 208 infants weighing <5 kg underwent cardiac surgery for CHD from 2008 to 2013; 12 subjects were excluded for death prior to initial extubation. No infant developed tracheal stenosis. The incidence of any stridor was 20.9% (95% confidence interval, 15.8%-27.1%) with severe stridor in 2 cases (1%). Age at surgery, weight, duration of intubation, dexamethasone use, and ETT size were not significantly associated with postextubation stridor. Presence of a comorbidity was significantly associated with stridor (P=.01).Microcuff ETTs in infants <5.0 kg in weight undergoing cardiac surgery are associated with a low incidence of severe postextubation stridor. Because cuffed ETTs allow for improved control of ventilation/oxygenation and decreased risk of aspiration, they should be considered for use in this high-risk population. Larger studies are needed to confirm these results.
- Prevention of anaphylaxis: the role of the epinephrine auto-injector. [REVIEW, JOURNAL ARTICLE]
- Am J Med 2016 Aug 20.
Anaphylaxis is a life-threatening condition, with at-risk individuals remaining at chronic high risk of recurrence. Anaphylaxis is frequently underrecognized and undertreated by healthcare providers. The first-line pharmacologic intervention for anaphylaxis is epinephrine, and guidelines uniformly agree that its prompt administration is vital to prevent progression, improve patient outcomes, and reduce hospitalizations and fatalities. Importantly, healthcare costs potentially associated with failure to provide epinephrine (hospitalizations and emergency department visits) generally exceed those of its provision. At-risk patients are prescribed epinephrine auto-injectors to facilitate timely administration in the event of an anaphylactic episode. Despite guideline recommendations that patients carry two auto-injectors at all times, a significant proportion of patients fail to do so, with cost of medicine cited as one reason for this lack of adherence. With the rise of high-deductible healthcare plans, patient adherence to recommendations may be further impacted by increased cost sharing. The recognition and classification of epinephrine as a preventive medicine by both the US Preventive Services Task Force and insurers could increase patient access, improve outcomes, and save lives.
- Dexamethasone and Clonidine, but not Epinephrine, Prolong Duration of Ropivacaine Brachial Plexus Blocks, Cross-Sectional Analysis in Outpatient Surgery Setting. [JOURNAL ARTICLE]
- Pain Med 2016 Aug 22.
The primary aim of this study is to determine the effect of adding dexamethasone, clonidine or both with and without epinephrine to ropivacaine and bupivacaine brachial plexus blocks.Observational study of prospectively collected data SETTING: Single academic outpatient surgery center METHODS: We evaluated 5,515 patient entries who received brachial plexus block (BPB). Multiple, rescue, unsuccessful, and distal nerve blocks of the upper extremity were excluded. The duration was calculated from the time the block was performed until the resolution of the block by patient report. Block durations were compared using Analysis of Variance.After exclusions, 3,706 nerve blocks were analyzed. The median concentration of ropivacaine used was 0.5%. Both clonidine and dexamethasone significantly increased block duration by 1.1 and 3.0 hours, respectively. Combining clonidine and dexamethasone with ropivacaine increased block duration by 6.2 hours (p<0.001) when compared to ropivacaine alone. Dexamethasone and Clonidine increased block duration by 5.2 hours (p<0.001) when compared to clonidine alone and by 3.2 hours (p<0.001) compared to dexamethasone alone. The addition of epinephrine to any of the adjuvants made no statistically significant difference to the duration of action except when it was added to dexamethasone.For brachial plexus blocks, epinephrine did not affect the duration of analgesia when added to ropivacaine. Epinephrine did not enhance the observed increase of block duration induced by clonidine or the combination of clonidine and dexamethasone. The most block duration enhancement was observed when combination of clonidine and dexamethasone were added to ropivacaine.
- Evaluation of the anti-fatigue effects of a traditional herbal drug, Gongjin-dan, under insufficient sleep conditions: study protocol for a randomised controlled trial. [Journal Article]
- Trials 2016.:418.
Many herbal medicines are traditionally used as anti-fatigue agents in east Asian countries; however, there is a dearth of clinical evidence supporting the anti-fatigue effects of such medicines and their mechanisms. This study is a feasibility trial to assess the clinical efficacy of Gongjin-dan (GJD) and verify its mechanisms by exploring fatigue outcomes, including endocrine and immunological biomarkers in humans.To investigate the anti-fatigue effects of GJD and the mechanism underlying these effects, a randomised, double-blind, placebo-controlled crossover clinical trial was designed. Participants (24 healthy male volunteers) will be hospitalised for 4 days (3 nights), during which acute fatigue and stress conditions will be induced by sleep deprivation, and GJD or a placebo will be administered (twice daily). The primary outcome will be changes in serum cortisol levels, measured in the morning, as an objective biomarker of sleep deprivation-induced fatigue and stress. The secondary outcomes will include: the Fatigue Severity Scale; the Brief Fatigue Inventory, and the Leeds Sleep Evaluation Questionnaire scores; levels of salivary cortisol, epinephrine, norepinephrine, oxidative stress-related biomarkers, homocysteine, and immunological factors; and heart rate variability. After a washout period of more than 4 weeks, a second treatment phase will commence in which participants who were previously administered the placebo will receive the drug and vice versa, following the same treatment regime as in the first phase.This study protocol provides a unique opportunity to enhance our understanding of fatigue and the effects of GJD on fatigue in terms of endocrine and immunological mechanisms by validating the study design and determining feasibility. Findings from this trial will help researchers to design a pilot or definitive clinical trial of traditional herbal medicine for chronic fatigue.Korean National Clinical Trial Registry CRIS; KCT0001681 , registered on 29 October 2015.
- Impact of monitoring endotracheal tube cuff leak pressure on postextubation stridor in children. [JOURNAL ARTICLE]
- J Crit Care 2016 Jul 9.:173-177.
To determine if implementing a protocol maintaining an air leak when using cuffed endotracheal tubes (ETT) throughout the course of mechanical ventilation (MV) in children would decrease the rate of postextubation stridor (PES).All children requiring MV through a cuffed ETT were included, except those with (1) upper airway anomaly, (2) died while on MV, (3) received tracheostomy before extubation, and (4) transferred before extubation. We implemented a protocol limiting the volume of air instilled into the cuff, allowing an air leak by 25 cm H2O pressure or by peak inspiratory pressure, whichever was higher. Monitoring occurred every 6 hours, adjusting cuff volumes if necessary. Patients receiving nebulized racemic epinephrine within 24 hours of extubation for upper airway obstruction were defined as having PES.At baseline, 110 patients received cuffed ETTs. The proportion of patients who had an air leak at the time of extubation was 47.3%, and that who developed PES was 21.8%. During the intervention, 101 patients received cuffed ETTs. Most (72.3%) had an air leak at the time of extubation (P< .01), and 9.9% developed PES, a 54.6% relative decrease (relative risk, 0.45; 95% confidence interval, 0.22-0.90; P= .018).Maintaining an appropriate air leak throughout the course of MV using cuffed ETT decreases the rate of PES in children.