Short-term fasting lowers glucagon levels under euglycemic and hypoglycemic conditions in healthy humans.

Fasting is associated with increased susceptibility to hypoglycemia in people with type 1 diabetes, thereby making it a significant health risk. To date, the relationship between fasting and insulin-induced hypoglycemia has not been well characterized, so our objective was to determine whether insulin-independent factors, such as counterregulatory hormone responses, are adversely impacted by fasting in healthy control individuals. Counterregulatory responses to insulin-induced hypoglycemia were measured in 12 healthy people during 2 metabolic studies. During one study, participants ate breakfast and lunch, after which they underwent a 2-hour bout of insulin-induced hypoglycemia (FED). During the other study, participants remained fasted prior to hypoglycemia (FAST). As expected, hepatic glycogen concentrations were lower in FAST, and associated with diminished peak glucagon levels and reduced endogenous glucose production (EGP) during hypoglycemia. Accompanying lower EGP in FAST was a reduction in peripheral glucose utilization, and a resultant reduction in the amount of exogenous glucose required to maintain glycemia. These data suggest that whereas a fasting-induced lowering of glucose utilization could potentially delay the onset of insulin-induced hypoglycemia, subsequent reductions in glucagon levels and EGP are likely to encumber recovery from it. As a result of this diminished metabolic flexibility in response to fasting, susceptibility to hypoglycemia could be enhanced in patients with type 1 diabetes under similar conditions.

A Brain-Melanocortin-Vagus Axis Mediates Adipose Tissue Expansion Independently of Energy Intake.

The melanocortin system is a brain circuit that influences energy balance by regulating energy intake and expenditure. In addition, the brain-melanocortin system controls adipose tissue metabolism to optimize fuel mobilization and storage. Specifically, increased brain-melanocortin signaling or negative energy balance promotes lipid mobilization by increasing sympathetic nervous system input to adipose tissue. In contrast, calorie-independent mechanisms favoring energy storage are less understood. Here, we demonstrate that reduction of brain-melanocortin signaling actively promotes fat mass gain by activating the lipogenic program and adipocyte and endothelial cell proliferation in white fat depots independently of caloric intake via efferent nerve fibers conveyed by the common hepatic branch of the vagus nerve. Those vagally regulated obesogenic signals also contribute to the fat mass gain following chronic high-fat diet feeding. These data reveal a physiological mechanism whereby the brain controls energy stores that may contribute to increased susceptibility to obesity.

A randomized-controlled, double-blind study to evaluate the efficacy of caudal midazolam, ketamine and neostigmine as adjuvants to bupivacaine on postoperative analgesic in children undergoing lower abdominal surgery.

• Background: Caudal epidural is the most commonly used technique for the management of postoperative pain in children. The aim of the present study was to assess and compare the efficacy of caudal bupivacaine as a postoperative analgesic alone or combined with midazolam, ketamine, and neostigmine in pediatric patients undergoing lower abdominal surgery. METHODS: Eighty pediatric patients categorized under the American Society of Anesthesiologists Physical Status I and II Classification System, who have been scheduled to undergo lower abdominal surgery were randomly designated into four groups to receive caudal block with either 1 ml/kg of 0.25% caudal bupivacaine for group B, 1 ml/kg of 0.25% caudal bupivacaine mixed with 2 µg/kg neostigmine for group BN, 1 ml/kg of 0.25% caudal bupivacaine mixed with 0.5 mg/kg ketamine for group BK or 1 ml/kg of 0.25% caudal bupivacaine mixed with 50 mcg/kg midazolam for group BM. Postoperative analgesia was examined by a blinded anesthetist utilizing a Revised Faces Pain Scale.Consumption of the total amount of rescue analgesic each 24 h, postoperative time to requirement of the first dose and any adverse effects were noted. RESULTS: The four groups were comparable as regards age, sex, weight, duration of surgery, heart rate, blood pressure and the time from induction of anesthesia to response to voice. The Revised Faces Pain Scale was 2.6±1.5 in group BN, 3.1±1.8 in group BM, 4.4±2.4 in group BK, and 5.6±1.3 in group B (p=0.005). Postoperative duration of analgesia was 433±68 min, 769±118 min, 1097±126 min and 1254±176 min in groups B, BK, BM and BN respectively (P=0.001). The dose of rescue analgesic within 24 h in group B was significantly higher than those of the other three groups (P<0.05). CONCLUSION: Addition of either neostigmine, midazolam, or ketamine to caudal bupivacaine extended analgesia time and decreased rescue analgesic compared to bupivacaine alone in children who underwent lower abdominal surgery.

Biochemical surrogate markers of hemolysis do not correlate with directly measured erythrocyte survival in sickle cell anemia.

Hemolysis is a key feature of sickle cell anemia (HbSS). Direct quantitation of hemolysis could be used as an objective outcome in clinical trials of new therapeutics for HbSS and would also enable better human studies of the pathogenesis of complications of HbSS that are ostensibly hemolysis-related, such as pulmonary hypertension. However, contemporary human studies in HbSS have used only surrogate markers of hemolysis rather than direct measurements of RBC survival. We directly quantified hemolysis in HbSS by measuring survival of an age cohort of RBCs labeled with a stable isotope, administered orally as 15 N-glycine, a metabolic precursor of heme. The atomic excess of 15 N in heme extracted from blood was monitored by mass spectrometry over time. We performed 13 labeling experiments in 11 individuals with HbSS. Mean RBC survival was 31.9 days (range 14.1-53.6). Both HbF level, a known determinant of hemolysis, and absolute reticulocyte count (ARC), an index of the marrow's response to hemolysis, correlated with directly measured RBC survival (r = 0.61, P < 0.002; r = -0.84, P < 0.001). However, commonly used biochemical surrogates of hemolysis (LDH, AST, bilirubin, and plasma free hemoglobin) did not correlate with directly measured RBC survival. These biochemical surrogates should be interpreted cautiously, at best, in clinical trials and human physiologic studies in HbSS. ARC was the best correlate of total hemolysis, but only 70% of the variation in RBC survival was reflected in this marker. If greater accuracy is required in human studies, 15 N-glycine RBC labeling can directly and accurately quantify hemolysis. Am. J. Hematol. 91:1195-1201, 2016. © 2016 Wiley Periodicals, Inc.

Connectivity of pacemaker neurons in the neonatal rat superficial dorsal horn.

Pacemaker neurons with an intrinsic ability to generate rhythmic burst-firing have been characterized in lamina I of the neonatal spinal cord, where they are innervated by high-threshold sensory afferents. However, little is known about the output of these pacemakers, as the neuronal populations that are targeted by pacemaker axons have yet to be identified. The present study combines patch-clamp recordings in the intact neonatal rat spinal cord with tract-tracing to demonstrate that lamina I pacemaker neurons contact multiple spinal motor pathways during early life. Retrograde labeling of premotor interneurons with the trans-synaptic pseudorabies virus PRV-152 revealed the presence of burst-firing in PRV-infected lamina I neurons, thereby confirming that pacemakers are synaptically coupled to motor networks in the spinal ventral horn. Notably, two classes of pacemakers could be distinguished in lamina I based on cell size and the pattern of their axonal projections. Whereas small pacemaker neurons possessed ramified axons that contacted ipsilateral motor circuits, large pacemaker neurons had unbranched axons that crossed the midline and ascended rostrally in the contralateral white matter. Recordings from identified spino-parabrachial and spino-periaqueductal gray neurons indicated the presence of pacemaker activity within neonatal lamina I projection neurons. Overall, these results show that lamina I pacemakers are positioned to regulate both the level of activity in developing motor circuits and the ascending flow of nociceptive information to the brain, thus highlighting a potential role for pacemaker activity in the maturation of pain and sensorimotor networks in the central nervous system.

Application of the upper lip catch test for airway evaluation in edentulous patients: An observational study.

BACKGROUND: Application of upper lip catch test (ULCT) for airway evaluation in edentulous patients. METHODS: This research is an evaluation of a clinical diagnostic test in edentulous patients prior to operation. Five hundred eighty eight edentulous patients in a referral university hospital, between March 2008 and June 2011 scheduled for elective surgery under general anesthesia were enrolled. Those unable to open the mouth and those with pharyngo-laryngeal pathology were excluded. ULCT was assessed and compared with Cormack-Lehane grading as a gold standard for airway evaluation. RESULTS: A high negative predictive value of 99.4% was a notable finding for the ULCT. The results also showed a high specificity (89.4%), high sensitivity (75.0%) and a high accuracy (89.3%) in a comparatively higher range for the ULCT. CONCLUSION: The ULCT proved to be a useful predictor for airway assessment in edentulous patients in this setting. Further studies are needed to reconfirm its validity in other ethnic groups.

Diagnostic value of the upper lip bite test in predicting difficulty in intubation with head and neck landmarks obtained from lateral neck X-ray.

BACKGROUND: Unanticipated difficult tracheal intubation remains a primary concern of anaesthesiologists and upper lip bite test (ULBT) is one of the assessments used in predicting difficult intubation. In this study, we aimed to check the utility of lateral neck X-ray measurements in improving the diagnostic value of the ULBT. METHODS: In a prospective study conducted from January 2007 until December 2010, we recorded personal and demographic data of 4500 patients who entered the study and subjected them to standard lateral neck radiography. Before the induction of anaesthesia, clinical examination and ULBT results were recorded and during induction of anaesthesia laryngoscopic grading was evaluated and recorded in questionnaires. All the compiled data were analysed by SPSS 14.0 (SPSS Inc., Chicago, IL, USA) software. Diagnostic value for each test was calculated and compared. RESULTS: Negative predictive values (NPVs) were high in all tests. ULBT had the highest specificity and NPV compared with the other tests. The positive predictive value for all the tests had been low, but marginally high in the ULBT. CONCLUSION: Although all the tests used had relatively acceptable predictive values, combination of tests appeared to be more predictive. Highest sensitivities were observed with ULBT, mandibulohyoid distance and thyromental distance respectively. Use of radiological parameters may not be suitable as screening tools, but may help in anticipating and preparing for a difficult scenario.

Anesthetic techniques for fetal surgery: effects of maternal anesthesia on intraoperative fetal outcomes in a sheep model.

BACKGROUND: Use of high-dose inhalational anesthesia during open fetal surgery may induce maternal-fetal hemodynamic instability and fetal myocardial depression. The authors' preliminary human retrospective study demonstrated less fetal bradycardia and left ventricular systolic dysfunction with lower dose desflurane supplemented with propofol and remifentanil IV anesthesia (SIVA). In this animal study, the authors compare maternal-fetal effects of high-dose desflurane anesthesia (HD-DES) and SIVA. METHODS: Of 26 instrumented midgestational ewes, data from 11 animals exposed to both SIVA and HD-DES in random sequences and six animals exposed to HD-DES while maternal normotension was maintained were analyzed. Maternal electroencephalography was used to guide comparable depths of anesthesia in both techniques. Hemodynamic parameters, blood gas, and fetal cardiac function from echocardiography were recorded. RESULTS: Compared with SIVA, HD-DES resulted in significant maternal hypotension (mean arterial pressure difference, 19.53 mmHg; 95% CI, 17.6-21.4; P < 0.0001), fetal acidosis (pH 7.11 vs. 7.24 at 150 min, P < 0.001), and decreased uterine blood flow. In the HD-DES group with maternal normotension, uterine blood flow still declined and fetal acidosis persisted, with no statistically significant difference from the group exposed to HD-DES that had maternal hypotension. There was no statistically significant difference in fetal cardiac function. CONCLUSION: In sheep, SIVA affects maternal hemodynamics less and provides better fetal acid/base status than high-dose desflurane. Fetal echocardiography did not reflect myocardial dysfunction in this model.

Comparing the effect of using atracourium and cis-atracourium as adjuvant agents to the local anesthetic substance on peribulbar-induced akinesia.

Peribulbar anesthesia is widely applied in cataract surgeries. The aim of this study was comparing the effect of using Atracourium, cis-Atracourium, and placebo as adjuvant agents to the local anesthetic substance on peribulbar-induced akinesia in cataract surgeries. The study was double-blind randomized clinical trial, among the patients candidate for the cataract surgery who were hospitalized in ocular surgery ward in Farabi Hospital between 2006 and 2007. 90 patients were subcategorized into 3 groups randomly. Group I received a mixture (8 ml) containing equal parts of Marcaine 0.5%, Lidocaine 2% and Hyaluronidase 90 IU plus 0.5 ml normal saline; group II received the mixture (8 ml) plus 0.5 ml Atracourium 5 mg, and group III received the mixture (8 ml) plus 0.5 ml cis-Atracurium with the help of peribulbar blockage technique. The score of akinesia were evaluated in the 1st, 3rd, 5th, 10th minutes after administration of the medications. 10 minute after drug administration, 25 (92.6%) reached the total akinesia with Atracourium, 23 (85.2%) with cis-Atracourium, and 23 (85.2%) with the placebo (P>0.05). Addition of low-dose Atracourium and cis-Atracourium to the anesthetic drug is recommended in order to accelerate the onset of akinesia resulted by the peribulbar block, and in order to enhance the quality of akinesia especially when Hyaloronidaze is not added.

Comparing the efficacy of prophylactic p6 acupressure, ondansetron, metoclopramide and placebo in the prevention of vomiting and nausea after strabismus surgery.

To compare the efficacy of acupressure wrist bands, ondansetron, metoclopramide and placebo in the prevention of vomiting and nausea after strabismus surgery. Two hundred patients, ASA physical status I or II, aged between 10 and 60 years, undergoing strabismus surgery in Farabi Hospital in 2007-2008 years, were included in this randomized, prospective, double-blind and placebo-controlled study. Group I was the Control, group II received metoclopramide 0.2 mg/kg, group III received ondansetron 0.15 mg/kg iv just before induction, in Group IV acupressure wristbands were applied at the P6 points. Acupressure wrist bands were placed inappropriately in Groups I, II and III. The acupressure wrist bands were applied 30 min prior to the induction of anesthesia and removed six hours after surgery. Postoperative nausea and vomiting (PONV) was evaluated within 0-2 hours and 2-24 hours after surgery by a blinded observer. Results were analyzed by X(2) test. A P value of < 0.05 was taken as significant. The incidence of PONV was not significantly different in acupressure, metoclopramide and ondansetron during the 24 hours. Acupressure at P6 causes a significant reduction in the incidence of PONV 24 hours after strabismus surgery as well as metoclopramide 0.2 mg/kg and ondansetron 0.15 mg/kg iv for patients aged 10 or more.

Oral contrast for abdominal computed tomography in children: the effects on gastric fluid volume.

BACKGROUND: Oral enteric contrast medium (ECM) is frequently administered to achieve visualization of the gastrointestinal tract during abdominal evaluation with computed tomography (CT). Administering oral ECM less than 2 hours before sedation/anesthesia violates the nothing-by-mouth guidelines and in theory may increase the risk of aspiration pneumonia. In this study we measured the residual gastric fluid when using a protocol in which ECM is administered up to 1 hour before anesthesia/sedation. We hypothesized that patients receiving ECM 1 hour before anesthesia/sedation would have residual gastric fluid volume (GFV) >0.4 mL/kg. METHODS: Anesthesia and radiology reports, CT images, and department incident reports were reviewed between January 2005 and June 2009 for all patients who required sedation/anesthesia for abdominal CT. For each patient, the volume of contrast or stomach fluid was calculated using a region of interest outlining the stomach portion containing high-attenuation fluid and low-attenuation of other gastric contents. Information obtained from anesthesia/sedation reports included demographic characteristics, presenting pathology, drugs used for anesthesia/sedation induction and maintenance, airway interventions, method for securing endotracheal tube, and complications related to ECM administration, including oxygen desaturation, vomiting, coughing, bronchospasm, laryngospasm, and aspiration. RESULTS: We identified 365 patients (mean age = 32 months; range = 0.66 to 211.10 months) who received oral/IV contrast material before anesthesia/sedation for abdominal CT and 47 patients (mean age = 52 months; range = 0.63 to 215.84 months) who received only IV contrast material and followed the traditional fast. For those who received oral contrast, the mean contrast volume administered was 18.10 mL/kg (range = 1.5 to 82.76 mL/kg). The median GVF 1 hour after completing the oral contrast was significantly higher than that in patients who received only IV contrast (0.38 mL/kg vs. 0.15 mL/kg, P = 0.0049). GFV exceeded 0.4 mL/kg in 189 patients (178 of 365 [49%] in the oral contrast group vs. 11 of 47 [23%] in the IV contrast group) (χ(2) = 10.7874, P = 0.0010). Among those who received oral contrast, 207 patients had general anesthesia and 158 patients had deep sedation. Two cases of vomiting were reported in the general anesthesia group with no evidence of pulmonary aspiration identified. CONCLUSION: For children receiving an abdominal CT, the residual GFV exceeded 0.4 mL/kg in 49% (178/365) of those who received oral ECM up to 1 hour before anesthesia/sedation in comparison with 23% (11/47) of those who received IV-only contrast.

Acupressure using ondansetron versus metoclopramide on reduction of postoperative nausea and vomiting after strabismus surgery.

OBJECTIVE: To compare the clinical efficacy of acupressure with treatment induced by ondansetron and metoclopramide on reduction of the severity of postoperative nausea and vomiting (PONV) after strabismus surgery. METHODS: There were 200 patients with ASA classes I-II, ages 10 to 60 years old, who underwent strabismus surgery that were included in this randomized, prospective, double-blind, placebo-controlled trial. Group I was the control, group II received metoclopramide 0.2 mg/kg, and group III received ondansetron 0.15 mg/kg intravenously immediately prior to anesthesia induction. In Group IV, acupressure wristbands were applied at the P6 points. Acupressure wrist bands were not placed appropriately for subjects of groups I-III. The acupressure wrist bands were applied 30 minutes before anesthesia induction and removed six hours after surgery completion. Anesthesia was standardized. PONV was evaluated within 0 - 2 hours and 2 - 24 hours after surgery by a blinded observer. Results were analyzed by the Chi-square or Fisher exact test. A P value of <0.05 was considered significant. RESULTS: The incidence of PONV was not significantly different among acupressure, metoclopramide and ondansetron groups during 24 hours. Also, the severity of PONV was not significantly different between acupressure, metoclopramide, and ondansetron in the recovery and ward. CONCLUSION: Acupressure at the P6 point causes a significant reduction in the incidence and severity of PONV 24 hours after strabismus surgery as well as metoclopramide (0.2 mg/kg) and ondansetron (0.15 mg/kg) intravenous for patients aged 10 or older. (Irct ID: IRCT138807152556N1).

Upper lip bite test as a predictor of difficult mask ventilation: a prospective study.

BACKGROUND: Oxygenation and ventilation by means of bag-mask and ambubag play a significant role in maintaining an optimal oxygen saturation of blood and hence the essence of life itself. Predicting difficulty in mask ventilation is again of paramount importance at the time of induction of anesthesia, and in emergency situations. In this study we aimed at evaluating factors that could help in predicting the difficulty of bag-mask ventilation. METHODS: In a prospective study, 200 patients were allocated into two groups, 100 each. First group with a ULBT class I, and the other group with ULBT class II and III. Factors such as height, weight, gender, past history of snoring, neck circumference, Mallampati class, sternomental and thyromental distances were then evaluated in each of the patients in the two groups in order to arrive at their impact on the incidence of difficult mask ventilation. Data were analyzed using Chi-square, student t-test and Fisher's exact tests depending upon the situation. A p < 0.05 was considered to be statistically significant. RESULTS: The results revealed that negative predictive value (NPV) of ULBT class, history of snoring and neck circumference were 86%, 83%, 81%, respectively. A combination of these three predictors had an NPV of 95%. CONCLUSION: ULBT class alone was of value in predicting difficulty in mask ventilation, but a combination of the three tests significantly improved the predictive value.

Evaluation of pediatric CPR course on knowledge of pediatric residents--before and after ACLS course.

An evaluation was conducted on the knowledge gained by pediatric residents on CPR, before and after a PALS (Pediatric Advanced Cardiac Life Support) course. Following an examination of all pediatric residents at Tehran University of Medical Sciences, they were divided into two groups: non-trained (Group 1) and a group scheduled to undergone training (Group 2). A course on ACLS was conducted. Examination were performed before and after the ACLS course. The mean of the examination prior to the course in Group 1 and 2 was low, reflecting no significant differences between the Groups. Examination after the ACLS course showed a statistically significant improvement in Group 2 (P < or = 0.05). It is concluded that knowledge of pediatric residents was low before ACLS course and enhanced after the course.

Outcome of lupus nephritis in Iranian children: prognostic significance of certain features.

The objective of this study was to determine the clinical and histopathological features and outcome of children with lupus nephritis (LN). Of 84 children with systemic lupus erythematosus (SLE), we retrospectively studied 58 children (69%) under 15 years of age with biopsy-proven LN who had been followed between October 1989 and January 2005. The mean age at diagnosis or initial referral was 10.6 +/- 2.25 years, and the mean follow-up was 5.3 +/- 4.1 years. Class IV LN was observed in 34 (58.6%) patients. The 5-year patient and renal survival rates were 82.5 and 78.5%, respectively, in the total group, and 75 and 85.8%, respectively, in patients with Class IV LN. No independent predictor of unfavorable outcome, including renal histology, was detected by multivariate analysis. The mid-term patient and the renal survival rates of Iranian children with biopsy-proven LN are high. Within 5 years of follow-up, renal histology was not a predictor for survival.