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Inflammatory mammary carcinoma (IMC) is a rare disease with a poor prognosis and one affecting dogs. Inflammatory breast carcinoma (IBC) is a subtype of malignant breast cancer in humans with a high degree of malignancy and a similarly poor prognosis. Since the clinical symptoms and prognoses of both are similar, canine IMC has been considered as a model of human IBC. In this study, we newly established a stable IMC-derived cell line from a patient at the Yamaguchi University Animal Medical Center in Japan.

Awake craniotomy is becoming more popular as a neurosurgical technique that allows for increased tumor resection and decreased postoperative neurologic morbidity. This technique, however, presents many challenges to both the neurosurgeon and anesthetist. An ASA class II, 37-year-old man with recurrent oligodendroglioma presented for repeated craniotomy. Prior craniotomy under general anesthesia resulted in residual neurologic deficits. An awake craniotomy was planned to allow for intraoperative testing for maximum tumor resection and avoidance of neurologic morbidity. The patient was sedated with propofol, and bupivacaine was infiltrated for placement of Mayfield tongs and skin incision. Following exposure of brain tissue, propofol infusion was discontinued to allow for patient cooperation during the procedure. Speech, motor, and sensory testing occurred during tumor resection until resection stopped after onset of weakness in the right arm. The propofol infusion was resumed while the cranium was closed and Mayfield tongs removed. The patient was awake, alert, oriented, and able to move all extremities but had residual weakness in the right forearm. Awake craniotomy requires appropriate patient selection, knowledge of the surgeon's skill, and a thorough anesthesia plan. This case report discusses the clinical and anesthetic management for awake craniotomy and reviews the literature. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) involves progressive motor neuron loss, leading to paralysis and death typically within 3-5 years of diagnosis. Dysfunctional astrocytes may contribute to disease and glial cell line-derived neurotrophic factor (GDNF) can be protective. Here we show that human neural progenitor cells transduced with GDNF (CNS10-NPC-GDNF) differentiated to astrocytes protected spinal motor neurons and were safe in animal models. CNS10-NPC-GDNF were transplanted unilaterally into the lumbar spinal cord of 18 ALS participants in a phase 1/2a study (NCT02943850). The primary endpoint of safety at 1 year was met, with no negative effect of the transplant on motor function in the treated leg compared with the untreated leg. Tissue analysis of 13 participants who died of disease progression showed graft survival and GDNF production. Benign neuromas near delivery sites were common incidental findings at post-mortem. This study shows that one administration of engineered neural progenitors can provide new support cells and GDNF delivery to the ALS patient spinal cord for up to 42 months post-transplantation., (© 2022. The Author(s).)

Purpose: Spontaneous postural sway during quiet standing has been considered a simple output error of postural control. However, as postural sway and inherent body orientation evoke compensatory activity of the plantar flexors, they might contribute to blood circulation under gravitational stress via the muscle pump. Hence, the present study employed an external support device to attenuate the plantar flexor activity in supported standing (SS), to experimentally identify its physiological impact on blood circulation., Methods: Eight healthy young subjects performed two 5-min quiet standing trials (i.e., normal standing (NS) and SS), and the beat-to-beat interval (RRI) and blood pressure (BP) were compared between trials. We confirmed that postural sway and corresponding plantar flexor activity, quantified by the anteroposterior displacement of the foot center of pressure and lower back position with respect to the wall, and by the amplitude of electromyography and mechanomyography, respectively, were attenuated in SS, while mean body orientation angle and relative position of the BP sensor were comparable to NS., Results: The 5-min averages of diastolic BP and mean arterial pressure during SS were significantly higher than during NS, while RRI and systolic BP did not change. These could be interpreted as an increase in peripheral vascular resistance; meanwhile, in NS, this effect was replaced by the muscle pump of the plantar flexors., Conclusion: The muscle contractions related to spontaneous postural sway and body orientation produce substantial physiological impact on blood circulation during quiet standing.

We herein report a 50-year-old Chinese woman with Hb Phnom Penh (α117Phe-Ile-α118Thr) showing high or reasonable HbA1c values depending on the type of high-performance liquid chromatography (HPLC) system. A high HbA1c value of 7.5% (HPLC assay: G9) and a reasonable HbA1c value of 5.2% (assay unknown) were observed. Therefore, the patient was refereed to our hospital; the oral glucose tolerance test showed normal glucose tolerance. The HbA1c values measured by an enzymatic assay, immunoassay, and affinity assay, as well as most HPLC assays were within the reference range, whereas those measured by the Tosoh HPLC systems were high.

Blonanserin differs from other antipsychotic drugs, such as risperidone and olanzapine, and exhibits a higher affinity for dopamine-D 2/3 receptors than for serotonin 5-HT 2A receptors. We investigated the involvement of dopamine-D 3 receptors in the effect of blonanserin on the social deficit observed in an animal model of schizophrenia and sought to elucidate the molecular mechanism underlying its action. Mice received phencyclidine (PCP: 10 mg/kg/day, s.c.), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, once a day for 14 consecutive days. We then evaluated the sociability, using a social interaction test, and the expression of GluN1 subunit, an essential subunit of the NMDA receptors, in these mice. Blonanserin significantly ameliorated the PCP-induced social deficit, whereas olanzapine and haloperidol did not. This effect of blonanserin was antagonized by 7-OH-DPAT, a dopamine-D 3 receptor agonist, and SCH23390, a dopamine-D 1 receptor antagonist. However, the ameliorating effect of blonanserin was not inhibited by DOI, a serotonin 5-HT 2A receptor agonist. The PCP-induced social deficit was also ameliorated by U99194, a dopamine-D 3 receptor antagonist and SKF38393, a dopamine-D 1 receptor agonist, being effects antagonized by 7-OH-DPAT or SCH23390. Blonanserin significantly inhibited the decrease in the phosphorylation levels of GluN1 at Ser 897 by protein kinase A (PKA) in the prefrontal cortex (PFC) in PCPadministered mice. These results suggest that activation of NMDA receptors due to Ser 897 -phosphorylation of GluN1 subunit, which is a step linked to dopamine-D 1 receptor-PKA signaling through dopamine-D 3 receptor antagonism in the PFC, is required for the ameliorating effect of blonanserin on the PCP-induced social deficit. These findings also provide in vivo evidence that blonanserin antagonism of the dopamine-D 3 receptors may be useful as a novel treatment strategy and that the dopamine-D 3 receptors can be a novel therapeutic target molecule for the social deficit observed in schizophrenia., (Copyright © 2019. Published by Elsevier Ltd.)

Canagliflozin has a robust inhibitory effect on sodium glucose transporter (SGLT)-2 and a mild inhibitory effect on SGLT1. The main purpose of this study was to investigate the effect of canagliflozin on circulating active glucagon-like peptide 1 (GLP-1) levels in patients with type 2 diabetes. Patients were randomly divided into a control group (n =15) and a canagliflozin-treated group (n =15). After hospitalization, the canagliflozin-treated group took 100 mg/day canagliflozin for the entire study, and after 3 days both groups took 20 mg/day teneligliptin for an additional 3 days. In a meal test, canagliflozin significantly decreased the area under curve (AUC) (0-120 min) for plasma glucose (PG) after 3 days when compared with that at baseline, and addition of teneligliptin to the canagliflozin-treated group further decreased it. A significant decrease in the AUC (0-120 min) for serum insulin by canagliflozin was obtained, but the addition of teneligliptin elevated the AUC, and thus abolished the significant difference from baseline. A significant increase in the AUC (0-120 min) of plasma active GLP-1 by canagliflozin-treatment compared with that at baseline was observed, and the addition of teneligliptin resulted in a further increase. However, canagliflozin-treatment did not change the AUC (0-120 min) of plasma active glucose-dependent insulinotropic peptide (GIP). In conclusions, canagliflozin-administration before meals decreased PG and serum insulin, and increased plasma active GLP-1 levels in patients with type 2 diabetes. Canagliflozin did not greatly influence plasma active GIP levels.

Background: Betatrophin is a hormone mainly secreted by the liver that influences lipid metabolisms. The main purposes of this study were to investigate the effect of canagliflozin (a sodium glucose transporter 2 inhibitor) on circulating betatrophin levels, and to investigate the correlation of various markers associated with glucose and lipid metabolisms with betatrophin in patients with poorly controlled type 2 diabetes., Methods: Patients were randomly divided into a control group (n = 15) and a canagliflozin-treated group (n = 15). After hospitalization, the canagliflozin-treated group took 100 mg/day of canagliflozin for 3 days. Blood tests were performed at baseline and after 3 days of treatment., Results: Canagliflozin treatment for 3 days did not significantly change fasting and postprandial serum betatrophin levels. On the other hand, betatrophin levels had a significant positive correlation with hemoglobin A1c, fasting plasma glucose, and high-density lipoprotein cholesterol levels at baseline., Conclusions: The current study suggests that short-term treatment by canagliflozin does not influence circulating betatrophin levels, and that betatrophin is positively associated with markers of glycemic control and high-density lipoprotein cholesterol in patients with poorly controlled type 2 diabetes., Competing Interests: The authors have no conflicts of interest to disclose.

Background: The goal of the current study was to investigate the long-term effects (after 3 years or more) of alogliptin on glycemic control in Japanese patients with type 2 diabetes., Methods: We retrospectively studied the effect of alogliptin on glycemic control in the patients with type 2 diabetes who had participated in our previous 3-month study and who continued to take alogliptin for at least 36 months., Results: The mean duration of alogliptin treatment was 42.8 ± 2.2 months. In all 39 patients, a significant reduction in hemoglobin A1c (HbA1c) levels was noted between the baseline and final visit: 7.8±0.6% to 7.2±1.0% (P = 0.0001). A significant reduction in HbA1c levels was found in a subgroup of patients who did not change their anti-diabetic drugs or did decrease the dose of their sulfonylureas (SUs) or did change to a lower strength repaglinide (n = 32): 7.7±0.6% to 7.2±1.0% (P = 0.0005). A significant decrease in low-density lipoprotein cholesterol (LDL-C) levels was observed in all of the patients that had LDL-C levels determined (P = 0.0406) (n = 37), and in a subgroup of patients who had not taken either statins, fibrates, or pioglitazone, or who had taken one or more of these drugs but the doses were not changed during the observation period (P = 0.0250) (n = 27)., Conclusion: The current study found that alogliptin performed well for glycemic control when evaluated by HbA1c levels in a long-term observation period exceeding 3 years in Japanese patients with type 2 diabetes. Alogliptin may also decrease circulating LDL-C levels with long-term use.

The synthesis of 2-aminobenzenesulfonamide-containing cyclononyne (ABSACN), starting from 2-nitrobenzenesulfonamide and but-2-yne-1,4-diol via Mitsunobu and Nicholas reactions, is described for the development of an adjustable alkyne reagent in click reactions. In a strain-promoted azide-alkyne cycloaddition (SPAAC) reaction, the reactivity of the alkyne is controlled by introducing various N-functionalities. The structure-reactivity relationship is found to be influenced by a transannular hydrogen bond between amino and sulfonyl groups.

Objective: The main purpose of this study was to investigate the association of serum SerpinB1 levels and various parameters in patients with type 2 diabetes. The effect of canagliflozin (a sodium glucose cotransporter 2 (SGLT2) inhibitor), which can decrease circulating insulin levels, on serum SerpinB1 levels was also investigated. A recent study suggests that the serum levels of SerpinB1, also known as monocyte neutrophil elastase inhibitor, increase with insulin resistance, may have a protective effect for pancreatic β cells, and may decrease insulin resistance., Research Design and Methods: The study included 30 patients with type 2 diabetes hospitalized for glycemic control and 10 control subjects., Results: SerpinB1 levels were significantly higher in patients with type 2 diabetes, compared with that in heathy control subjects (10.01±3.59 vs 5.69±1.64 ng/mL, p<0.0001). Serum SerpinB1 levels had a significant negative correlation with low-density lipoprotein cholesterol (LDL-C) (p=0.0123). Serum SerpinB1 levels had a significant positive association or trend toward a positive association with age and with hemoglobin A1c (HbA1c), and significant negative association with LDL-C levels in some multiple regression analysis models. Patients treated with statins had a tendency toward higher serum SerpinB1 levels, compared with those patients not treated with statins. During a 3-day observation period both with and without canagliflozin treatment, the serum SerpinB1 levels did not change., Conclusions: Serum SerpinB1 levels are elevated in patients with type 2 diabetes compared with that in healthy subjects and are negatively correlated with serum LDL-C., Competing Interests: Conflicts of Interest: None declared.

Study Objective: To compare three different video laryngoscope devices (VL) to standard direct laryngoscopy (DL) for tracheal intubation of obese patients undergoing bariatric surgery., Hypothesis: VL (vs DL) would reduce the time required to achieve successful tracheal intubation and improve the glottic view., Design: Prospective, randomized and controlled., Setting: Preoperative/operating rooms and postanesthesia care unit., Patients: One hundred twenty-one obese patients (ASA physical status I-III), aged 18 to 80 years, body mass index (BMI) >30 kg/m(2) undergoing elective bariatric surgery., Intervention: Patients were prospectively randomized assigned to one of 4 different airway devices for tracheal intubation: standard Macintosh (Mac) blade (DL); Video-Mac VL; Glide Scope VL; or McGrath VL., Measurements: After performing a preoperative airway evaluation, patients underwent a standardized induction sequence. The glottic view was graded using the Cormack Lehane and percentage of glottic opening (POGO) scoring systems at the time of tracheal intubation. Times from the blade entering the patient's mouth to obtaining a glottic view, placement of the tracheal tube, and confirmation of an end-tidal CO2 waveform were recorded. In addition, intubation attempts, adjuvant airway devices, hemodynamic changes, adverse events, and any airway-related trauma were recorded., Main Results: All three VL devices provided improved glottic views compared to standard DL (p < 0.05). Video-Mac VL and McGrath also significantly reduced the time required to obtain the glottic view. Video-Mac VL significantly reduced the time required for successful placement of the tracheal tube (vs DL and the others VL device groups). The Video-Mac and GlideScope required fewer intubation attempts (P< .05) and less frequent use of ancillary intubating devices compared to DL and the McGrath VL., Conclusion: Video-Mac and GlideScope required fewer intubation attempts than standard DL and the McGrath device. The Video-Mac also significantly reduced the time needed to secure the airway and improved the glottic view compared to standard DL., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Study Objective: To compare the C-MAC video laryngoscope to the standard flexible fiberoptic scope (FFS) with an eye piece (but without a camera or a video screen) for intubation of patients undergoing cervical spine surgery with manual inline stabilization. The primary end point was the time to achieve successful tracheal intubation. Secondary end points included glottic view at intubation and number of intubation attempts., Design: Prospective, randomized, single-blinded study., Setting: Cedars Sinai Medical Center in Los Angeles, CA., Patients: One hundred forty patients (American Society of Anaesthesiologists physical status I-III), aged 18 to 80years undergoing elective cervical spine surgery., Intervention: Patients were prospectively randomized to undergo tracheal intubation using either an FFS (n=70) or the C-MAC video laryngoscope (n=70)., Measurements: After performing a preoperative airway evaluation, patients underwent a standardized induction sequence. The glottic view was assessed at the time of tracheal tube placement using the Cormack-Lehane and percentage of glottic opening scoring systems. In addition, the time required for successful insertion of the tracheal tube, number of intubation attempts to secure the airway, the need for adjuvant airway devices, hemodynamic changes, adverse events, and any airway-related trauma were recorded., Main Results: The glottic view at the time of intubation did not differ significantly with the 2 devices; however, the C-MAC facilitated more rapid tracheal intubation compared with the FFS (P=.001). The peak heart rate response following insertion of the tracheal tube was also reduced (P=.004) in the C-MAC (vs FFS) group., Conclusion: The C-MAC may offer an advantage over the FFS with respect to the time required to obtain glottic view and successful placement of the tracheal tube in patients requiring cervical spine immobilization., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Unlabelled: The elevation of serum plant sterols in addition to serum LDL-cholesterol (LDL-C) is one of the important risk factors for coronary heart disease. We investigated how to alterations of serum hepatic synthesised cholesterol and plant sterols levels, clinical markers for inflammation and oxidative stress after combination therapy with ezetimibe, an inhibitor of cholesterol transporter in the small intestinal colon, and statin drugs in type 2 diabetic patients. Studies were conducted in 28 patients with type 2 diabetes mellitus complicated with dyslipidemia. Patients were divided into 3 groups as follows: the 1st group is 7 patients treated with 10mg ezetimibe sequent on pretreatment with mild statin drug (MS+E group), and the 2nd group is 7 patients treated with 10mg ezetimibe sequent on pretreatment with strong statin drug (SS+E group), and then the 3rd group is 14 patients treated with 10mg ezetimibe alone without pretreatment with any statin drugs (naïve E group). In addition to various metabolic markers, serum plant sterols such as sitosterol and campesterol, and hepatic synthesised cholesterol such as lathosterol were measured by the gas liquid chromatography. Serum highly sensitive CRP (hsCRP) as an inflammation marker, and then malonyldealdehyde (MDA) and carbonyl-modified protein (CMP) as an oxidative stress were assayed by the conventional method, respectively. Fasting plasma glucose and serum glucosylated HbA1c (JDS value) did not show any significant changes after administration of ezetimibe in whole groups. Serum LDL-C was reduced significantly and serum triglyceride exhibited a tendency of reduction in whole groups. Serum sitosterol and campesterol were decreased significantly, while serum lathosterol was increased significantly or markedly in whole patients and also in each group. There were no significant changes in serum hsCRP in whole groups. Both serum MDA and CMP revealed significant or marked reductions in each group., Conclusions: The present investigation suggests that the combination therapy of the ezetimibe and statin drugs is potential to remarkably reduce serum LDL-C, plant sterols, MDA and CMP, and therefore might lead to prevent atherosclerosis., (Copyright © 2014 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

The main purpose of the current study was to investigate the effect of a combination of alogliptin [a dipeptydil peptidase (DPP)-4 inhibitor] and lansoprazole [a proton pump inhibitor (PPI)] compared with alogliptin mono-therapy on glycemic control in patients with type 2 diabetes. This study was a multicenter randomized open-label study. One hundred type 2 diabetic patients were randomly assigned to either the alogliptin with lansoprazole group or the alogliptin mono-therapy group. After 3 months of treatment, the changes in hemoglobin (Hb)A1c, fasting plasma glucose (FPG), serum gastrin, homeostasis model assessment (HOMA)-β, and HOMA-insulin resistance (IR) were evaluated. A significant decrease in HbA1c and FPG, and a significant increase in HOMA-β were observed in both groups (all with P <0.0001). However, there were no significant differences in changes in HbA1c, FPG, or HOMA-β before and after therapy between the combination and alogliptin mono-therapy group (P =0.2945, P =0.1901, P =0.3042, respectively). There was a significant elevation of serum gastrin in the combination group compared with the alogliptin mono-therapy group (P =0.0004). This study showed that, although combination therapy with alogliptin and lansoprazole more effectively elevated serum gastrin levels compared with alogliptin mono-therapy, the effect of the combination therapy on glycemic control was equal to that of alogliptin mono-therapy during a 3-month study period.

Objective: To examine involvement of oxidative stress in the pathogenesis and vascular complications of diabetes., Methods: This cross sectional study was conducted at the Joint Laboratory Office (JLO), Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan from April 2010 to December 2011. Fasting glucose, glycosylated hemoglobin (HbA1c), serum lipids, urinary albumin excretion (UAE), ankle brachial index and pulse wave velocity were measured in 51 patients with type 2 diabetes and 20 healthy controls. The fundus oculi and Achilles` tendon reflex were also examined in the patients. Oxidative stress was measured by a reactive oxygen metabolites (ROM) test and antioxidant potency was evaluated by a biological antioxidant potential (BAP) test in the Free Radical Analytical System (FRAS)-4. Superoxide dismutase (SOD) activity was assayed using electron spin resonance (ESR)., Results: Diabetic patients tended to have increased ROM compared with healthy subjects, and ROM showed a marked increase with progression of diabetic retinopathy. A significant reduction of BAP was found in patients who were smokers, and BAP was significantly negatively correlated with UAE (p=0.029). Serum SOD activity significantly decreased with progression of diabetic retinopathy (p=0.017)., Conclusion: The FRAS-4 measurements showed that increased oxidative stress and decreased antioxidative potency are linked to deteriorated blood glucose control, heavy smoking, and progression of retinopathy and nephropathy in patients with type 2 diabetes.

Background: There is still controversy regarding the optimal strategy for managing postoperative nausea and vomiting (PONV) in high-risk surgical populations. Although acustimulation at the P6 acupoint has been demonstrated to be effective in preventing PONV, the effect of this nonpharmacologic therapy on the patient's recovery with respect to resumption of normal activities of daily living has not been previously assessed when it is used as part of a multimodal antiemetic regimen. Therefore, we designed this randomized, sham-controlled, and double-blind study to assess the efficacy of a disposable acupressure device (Pressure Right®; Pressure Point Inc., Grand Rapids, MI) on the incidence of emetic episodes and quality of recovery when used in combination with ondansetron and dexamethasone for antiemetic prophylaxis., Methods: One hundred ASA physical status I and II patients undergoing major laparoscopic procedures were randomly assigned to either a control group (n = 50) receiving a "sham" acustimulation device or an acupressure group (n = 50) receiving a disposable Pressure Right device placed bilaterally at the P6 point 30 to 60 minutes before induction of anesthesia. All patients received a standardized general anesthetic. A combination of ondansetron, 4 mg IV, and dexamethasone, 4 mg IV, was administered during surgery for antiemetic prophylaxis in both study groups. The incidence of nausea and vomiting and the need for "rescue" antiemetic therapy were assessed at specific time intervals for up to 72 hours after surgery. The recovery profiles and quality of recovery questionnaires were evaluated at 48 hours and 72 hours after surgery. Patient satisfaction with the management of their PONV was assessed at the end of the 72-hour study period., Results: The 2 study groups did not differ in their demographic characteristics or risk factors for PONV. The incidence of vomiting at 24 hours was significantly decreased in the acupressure group (10% vs 26%, P = 0.04, 95% confidence interval for absolute risk reduction 1%-31%). The overall incidence of vomiting from 0 to 72 hours after surgery was also significantly decreased from 30% to 12% in the acupressure group (P = 0.03, 95% confidence interval 2%-33%). Furthermore, adjunctive use of the acupressure device seemed to enhance patient satisfaction with their PONV management and quality of recovery at 48 hours after surgery. However, the recovery times to hospital discharge, resumption of normal physical activities, and return to work did not differ significantly between the 2 study groups., Conclusion: Use of the Pressure Right acupressure device in combination with antiemetic drugs provided a reduction in the incidence of vomiting from 0 to 72 hours after surgery with an associated improvement in patient satisfaction with their PONV management. However, recovery and outcome variables failed to demonstrate any improvement with the addition of the acupressure device.

Dipeptidyl peptidase 4 (DPP-4) inhibitors is a new class of antihyperglycemic agents that is now available for the treatment of type 2 diabetes. We investigated the relationship between the baseline serum level of soluble CD 26/DPP-4 and the response to treatment with sitagliptin, a DPP-4 inhibitor, over 24 weeks in patients who had type 2 diabetes inadequately controlled by metformin and/or sulfonylurea therapy. We studied 52 consecutive patients with type 2 diabetes who had poor glycemic control despite treatment with metformin and/or sulfonylurea. All patients were given 50 mg/day of sitagliptin and were followed at monthly intervals for 24 weeks. Treatment with sitagliptin decreased significantly hemoglobin A1c (HbA1c) from 7.91 ± 1.08% at baseline to 6.96 ± 1.18% at 8 weeks, 7.04 ± 0.77% at 16 weeks, and 7.08 ± 0.80% at 24 weeks. The baseline serum level of sCD26 was correlated positively with HbA1c at both 16 weeks and 24 weeks. Furthermore, the serum sCD26 level at baseline was also correlated positively with the changes from baseline of HbA1c at 16 and 24 weeks (r = 0.318, P = 0.0296 and r = 0.516, P = 0.0003, respectively). In a multivariate logistic regression model that explained 56.1% (R(2) = 0.561) of the variation of the changes from baseline of HbA1c at 24 weeks, the baseline HbA1c (β = -0.638, P < 0.001) and serum sCD26 (β = 0.357, P = 0.041) were independent determinants of the change of HbA1c at 24 weeks. In conclusions, a higher serum level of sCD26 is associated with a worse response to sitagliptin in patients with type 2 diabetes controlled inadequately by metformin and/or sulfonylurea therapy., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Objective: Various adipocytokines are closely associated with both obesity and insulin resistance. We investigated how body fat weight (BFW) and body fat ratio (BFR) affected serum adipocytokines in patients with type 2 diabetes mellitus., Methods: Studies were conducted in type 2 diabetic patients (n = 41) and age-matched healthy subjects (n = 18). BFW and BFR were determined using a high-frequency bioelectric impedance method. We measured the adipocytokines such as leptin, adiponectin, and tumor necrosis factor (TNF)-α in serum., Results: BFW and BFR showed significant positive correlations with BMI and serum leptin concentrations in diabetic patients. A significant positive correlation was found between BFW and serum FFA. Multivariate analysis identified only BMI a significant independent determinant of BFW. Stepwise analysis disclosed a significant positive correlation between HOMA-R and serum leptin., Conclusions: In diabetic patients, accumulation of body fat may increase serum leptin and FFA, which in turn would contribute to insulin resistance., (© Crown Copyright 2011 Published by Elsevier Ltd on behalf of Asia Oceania Assoc. for the Study of Obesity. All rights reserved.)

Background: Nonsteroidal antiinflammatory drugs have become increasingly popular as part of multimodal analgesic regimens for pain management in the ambulatory setting. We designed this randomized, double-blind, placebo-controlled study to evaluate the effect of postoperative administration of either a nonselective nonsteroidal antiinflammatory drug (ibuprofen) or the cyclooxygenase-2 selective inhibitor (celecoxib when administered as part of a multimodal analgesic regimen) on the severity of pain, the need for rescue analgesics, and clinically relevant patient outcomes after ambulatory surgery. The primary end point was the time to resumption of normal activities of daily living., Methods: One hundred eighty patients undergoing outpatient surgery were randomly assigned to 1 of 3 treatment groups: group 1 (control) received either 2 placebo capsules (matching celecoxib) or 1 placebo tablet (matching ibuprofen) in the recovery room and 1 placebo tablet at bedtime on the day of surgery, followed by 1 placebo capsule or tablet 3 times a day for 3 days after discharge; group 2 (celecoxib) received celecoxib 400 mg (2 capsules) orally in the recovery room and 1 placebo capsule and tablet at bedtime on the day of surgery, followed by celecoxib 200 mg (1 capsule) twice a day + placebo capsule every day at bedtime for 3 days after surgery; or group 3 (ibuprofen) received ibuprofen 400 mg (1 tablet) orally in the recovery room and 400 mg orally at bedtime on the day of surgery, followed by 400 mg orally 3 times a day for 3 days after surgery. Recovery times, postoperative pain scores, and the need for rescue analgesics were recorded before discharge. Follow-up evaluations were performed at 24 hours, 48 hours, 72 hours, 7 days, and 30 days after surgery to assess postdischarge pain, analgesic requirements, resumption of normal activities, opioid-related side effects, as well as quality of recovery and patient satisfaction with their postoperative pain management using a 5-point verbal rating scale., Results: The 3 groups did not differ with respect to their demographic characteristics. Compared with the placebo treatment, both celecoxib and ibuprofen significantly decreased the need for rescue analgesic medication after discharge (P < 0.05). The effect sizes (celecoxib and ibuprofen versus control group) were 0.73 to 1 and 0.3 to 0.8, respectively. Quality of recovery scores and patient satisfaction with their postoperative pain management were also improved in the celecoxib and ibuprofen groups compared with the control group (P < 0.05, effect size [vs control group] = 0.67). The incidence of postoperative constipation was significantly higher in the control group (28%) compared with the celecoxib (5%) and ibuprofen (7%) groups, respectively (P < 0.05). Both active treatments were well tolerated in the postdischarge period. However, the time to resumption of normal activities of daily living was similar among the 3 groups., Conclusions: Both ibuprofen (1200 mg/d) and celecoxib (400 mg/d) significantly decreased the need for rescue analgesic medication in the early postdischarge period, leading to an improvement in the quality of recovery and patient satisfaction with their pain management after outpatient surgery.

The main purpose of this study was to investigate whether treatment with long-acting insulin once a day or short-acting insulin three times before each meal daily has a stronger antioxidative effect in patients with type 2 diabetes. These patients had not been treated previously with insulin and were hospitalized for initiation of glycemic control by insulin injection. The patients (n=43) were assigned consecutively and alternately to a group treated with insulin aspart injection three times daily just before each meal and a group treated with insulin detemir injection once daily before bedtime. The results showed that insulin aspart three times a day produced a greater improvement in plasma glucose, and particularly in mean postprandial plasma glucose, compared with insulin detemir once a day (p = 0.0006 for comparison of changes between the two insulin treatments). The amount of insulin needed to approach the target levels of plasma glucose was larger in the insulin aspart group (26.0 ± 10.7 U/day vs. 13.7 ± 4.9 U/day; p < 0.0001). However, only insulin detemir significantly decreased oxidative stress evaluated based on the level of urinary 8-iso-prostaglandin F2α (p = 0.0079), although the mechanisms are not fully evident.

An increase of serum ferritin, an indicator of body iron store, is associated with insulin resistance and with an increased risk of type 2 diabetes in the general population. A low serum adiponectin is also associated with insulin resistance. Recently, hepcidin was identified as a regulator of iron metabolism. We investigated whether serum adiponectin was associated with serum ferritin or prohepcidin, a precursor of hepcidin, in healthy subjects and patients with type 2 diabetes. We studied 65 healthy subjects and 104 patients with type 2 diabetes. A serum ferritin concentration ≥ 300 ng/ml for men or ≥ 150 ng/ml for women was defined as hyperferritinemia. Serum ferritin was significantly higher and serum prohepcidin was significantly lower in diabetic patients than in control subjects. Serum total and high molecular weight (HMW) adiponectin correlated negatively with serum ferritin in control subjects or diabetic patients, while serum total and HMW adiponectin correlated positively with serum prohepcidin in diabetic patients, but not in control subjects. Serum total and HMW adiponectin were lower in patients with hyperferritinemia than in those without it. In conclusion, serum ferritin was increased in type 2 diabetic patients, while serum prohepcidin was decreased. A high serum ferritin was associated with insulin resistance, and with low serum total and HMW adiponectin in patients with type 2 diabetes., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: There is controversy regarding the relative perioperative benefits of desflurane versus sevoflurane when used for maintenance of anesthesia in the ambulatory setting. Although studies have consistently demonstrated a faster emergence with desflurane (versus sevoflurane), the impact of this difference on the later recovery end points has not been definitively established. Furthermore, the effect of desflurane (versus sevoflurane) on the incidence of coughing is also controversial., Methods: We randomized 130 outpatients undergoing superficial surgical procedures requiring general anesthesia to one of two maintenance anesthetic treatment groups. All patients were induced with propofol, 2 mg/kg IV, and after placement of a laryngeal mask airway, anesthesia was maintained with either sevoflurane 1%-3% or desflurane 3%-8% in an air/oxygen mixture. The inspired concentration of the volatile anesthetic was varied to maintain hemodynamic stability and a Bispectral Index value of 50-60. Analgesia was provided with local anesthetic infiltration and ketorolac (30 mg IV). Antiemetic prophylaxis consisted of a combination of ondansetron (4 mg), dexamethasone (4 mg), and metoclopramide (10 mg) at the end of surgery. Assessments included recovery times to eye opening, response to commands, orientation, fast-track score of 14, first oral intake, sitting, standing, ambulating unassisted, and actual discharge. Patient satisfaction with anesthesia, the ability to resume normal activities on the first postoperative day, adverse side effects (e.g., coughing, purposeful movement, oxygen desaturation <90%, sore throat, postoperative nausea, and vomiting), and the requirement for postoperative analgesic and antiemetic drugs were recorded in the early postoperative period and during the initial 24-h period after discharge., Results: The two study groups had comparable demographic characteristics. Although the overall incidence of coughing during the perioperative period was higher in the desflurane group (60% versus 32% in the sevoflurane group, P < 0.05), the incidences of coughing during the actual administration of the volatile anesthetics (i.e., the maintenance period) did not differ between the two groups. Emergence from anesthesia was more rapid after desflurane; however, all patients achieved fast-track recovery criteria (fast-track score >or=12) before leaving the operating room. Finally, the time to discharge home (90 +/- 31 min in sevoflurane and 98 +/- 35 min in desflurane, respectively) and the percentage of patients able to resume normal activities on the first postoperative day (sevoflurane 48% and desflurane 60%) did not differ significantly between the two anesthetic groups., Conclusions: Use of desflurane for maintenance of anesthesia was associated with a faster emergence and a higher incidence of coughing. Despite the faster initial recovery with desflurane, no significant differences were found between the two volatile anesthetics in the later recovery period. Both volatile anesthetics should be available for ambulatory anesthesia.

Based on comparative studies in patients receiving emetogenic chemotherapy, it has been suggested that granisetron would be more effective than ondansetron for the prevention of postdischarge nausea and vomiting (PDNV). However, there have been no direct comparisons of these two popular 5-HT3 antagonists with respect to PDNV and quality of recovery. We designed this randomized, double-blind study to compare the antiemetic efficacy of oral granisetron (1 mg) to a standard IV dose of ondansetron (4 mg) when administered for antiemetic prophylaxis as part of a multimodal regimen in a laparoscopic surgical population. A total of 220 patients undergoing laparoscopic surgery with a standardized general anesthetic technique were enrolled in this prospective study at two major medical centers. Patients were randomly assigned to one of two prophylactic treatment groups: the control (ondansetron) group received an oral placebo 1 h before surgery and ondansetron, 4 mg IV, at the end of the surgery, and the granisetron group received granisetron, 1 mg per os, 1 h before surgery, and normal saline, 2 mL IV, at the end of the surgery. The early recovery profiles, requirement for rescue antiemetics, incidence of PDNV, and the side effects were recorded over the 48 h study period. In addition, nausea scores were assessed using an 11-point verbal rating scale at specific intervals in the postoperative period. The quality of recovery and patient satisfaction scores were recorded at 48 h after surgery. The demographic characteristics were similar in the two prophylaxis treatment groups, as well as the recovery times to patient orientation, oral intake, and hospital discharge. The incidences of PDNV, requirements for rescue antiemetics, and quality of recovery did not differ between the two study groups. The antiemetic drug acquisition costs to achieve comparable patient satisfaction with ondansetron and granisetron were US 25.65 dollars and 47.05 dollars, respectively. Therefore, ondansetron (4 mg IV) was more cost-effective than granisetron (1 mg per os) for routine antiemetic prophylaxis as part of a multimodal regimen in patients undergoing either outpatient or inpatient laparoscopic surgery.

Cerebral monitoring indices are associated with a large degree of inter-patient variability and electrical signal interference during surgery. We designed this clinical study to test the hypothesis that use of the spectral entropy (Entropy) module is associated with less frequent intraoperative interference with the displayed indices than the bispectral index (BIS) monitor when used during general anesthesia with propofol and desflurane. Thirty consenting patients scheduled for major laparoscopic surgery procedures were enrolled in this prospective study. The elapsed time to obtain a baseline index value was recorded, as well as the simultaneous state entropy (SE), response entropy (RE), and BIS values at specific time intervals during the induction, maintenance, and emergence periods in patients administered a standardized general anesthetic technique. During the maintenance period, the changes in these indices were evaluated after a bolus dose of propofol (20 mg IV) and a 2% increase or decrease in the inspired concentration of desflurane. As expected, the baseline SE values were less than the RE and BIS values (88 +/- 2 versus 96 +/- 3 and 96 +/- 4, respectively). However, the SE and RE values correlated with the BIS value during the induction (r = 0.77 and 0.78, respectively) and emergence (r = 0.86 and 0.91, respectively) periods. The area under the receiver operating characteristic curve for detection of consciousness also indicated a similar performance of the SE (0.93 +/- 0.04) relative to the RE (0.98 +/- 0.04) and BIS (0.97 +/- 0.04). During the maintenance period, the responses to changes in propofol and desflurane concentrations were consistent with all three indices. Finally, the entropy indices were less interfered with by the electrocautery unit during the operation (12% versus 62% for the BIS monitor). Because the average selling prices of the Entropy and BIS disposable electrode strips (14.25 dollars versus 14.95 dollars USD, respectively) are comparable, we conclude that the Entropy module is a cost-equivalent alternative to the BIS monitor.

Unlabelled: Non-opioid analgesics have become increasingly popular as part of a multimodal regimen for pain management in the ambulatory setting. We designed this randomized, double-blind, placebo-controlled study to evaluate the effect of perioperative administration of the cyclooxygenase-2 inhibitor rofecoxib on patient outcome after inguinal herniorrhaphy procedures. Sixty consenting outpatients undergoing elective hernia repair surgery were randomly assigned to one of two treatment groups: control (vitamin C, 500 mg) or rofecoxib (rofecoxib, 50 mg). The first oral dose of the study medication was administered 30-40 min before entering the operating room, and a second dose of the same medication was given on the morning of the first postoperative day. Recovery times, postoperative pain scores, the need for "rescue" analgesics, and side effects were recorded at 1- to 10-min intervals before discharge from the recovery room. Follow-up evaluations were performed at 36 h, 7 days, and 14 days after surgery to assess postdischarge pain, analgesic requirements, resumption of normal activities, as well as patient satisfaction with their postoperative pain management. Rofecoxib significantly decreased the early recovery times, leading to an earlier discharge home after surgery (88 +/- 30 vs 126 +/- 44 min, P < 0.05). When compared with the control group, the patients' median [range] quality of recovery score was also significantly higher in the rofecoxib group (18 [14-18] vs 16 [13-18], P < 0.05). In the predischarge period, a significantly larger percentage of patients required rescue pain medications in the control group (67% vs 37% in the rofecoxib group, P < 0.05). At the 36-h follow-up assessment, rofecoxib-treated patients reported significantly reduced oral analgesic requirements (0 [0-20] vs 9 [1-33] pills, P < 0.05) and lower maximal pain scores, resulting in improved patient satisfaction with their postoperative pain management (3 [1-4] vs 2 [0-3], P < 0.05). However, there were no differences in the times required to resume their activities of daily living. In conclusion, perioperative rofecoxib, 50 mg per os, significantly decreased postoperative pain and the need for analgesic rescue medication, leading to a faster and improved quality of recovery after outpatient hernia surgery. However, perioperative use of rofecoxib failed to improve recovery end points in the postdischarge period., Implications: Rofecoxib (50 mg per os), given before and after surgery, was effective in improving postoperative pain management, as well as the speed and quality of recovery after outpatient inguinal herniorrhaphy. However, it failed to accelerate the postdischarge resumption of normal activities of daily living.

Unlabelled: There is controversy regarding the optimal technique for maintaining hemodynamic stability during anesthesia. We designed this prospective, randomized, double-blinded study to test the hypothesis that the technique used for maintaining hemodynamic stability during general anesthesia can influence recovery after ambulatory surgery. Forty-five healthy consenting women undergoing gynecologic laparoscopy procedures were randomly assigned to 1 of 3 treatment groups: Group 1 (control, n = 15) received normal saline 5 mL and 1 mL, followed by a saline infusion at a rate of 0.005 mL x kg(-1) x min(-1); Group 2 (n = 15) received esmolol 50 mg and saline 1 mL, followed by an esmolol infusion 5 microg x kg(-1) x min(-1); and Group 3 (n = 15) received esmolol 50 mg and nicardipine 1 mg, followed by an esmolol infusion 5 microg x kg(-1) x min(-1). The study drugs were administered after the induction of anesthesia with fentanyl 1.5 microg/kg, and propofol 2 mg/kg I.V. Tracheal intubation was facilitated with vecuronium 0.12 mg/kg I.V. Anesthesia was initially maintained with desflurane 2% end-tidal and N(2)O 67% in oxygen in all 3 groups. During surgery, the mean arterial blood pressure (MAP) was maintained within +/-15% of the baseline value by varying the study drug infusion rate and the inspired concentration of desflurane. In addition to MAP and heart rate values, electroencephalogram bispectral index values were recorded throughout the perioperative period. Recovery times and postoperative side effects were assessed. Compared with the control group, adjunctive use of esmolol and nicardipine attenuated the increase in heart rate (in Group 2) and MAP (in Group 3) after tracheal intubation. Furthermore, the use of an esmolol infusion as an adjunct to desflurane to control the acute autonomic responses during the maintenance period significantly decreased emergence times (4 +/- 2 versus 7 +/- 4 min), decreased the need for postoperative opioid analgesics (43% versus 80%), and reduced the time to discharge (209 +/- 89 versus 269 +/- 100 min). We conclude that the adjunctive use of esmolol alone or in combination with nicardipine during the induction of anesthesia reduced the hemodynamic response to tracheal intubation. Furthermore, use of an esmolol infusion as an adjuvant to desflurane-N(2)O anesthesia for controlling the acute hemodynamic responses during the maintenance period improved the recovery profile after outpatient laparoscopic surgery., Implications: The adjunctive use of the beta-adrenergic blocker esmolol to control the acute sympathetic responses during desflurane-based anesthesia provided a more rapid awakening from anesthesia, reduced the postoperative opioid analgesic requirement, and decreased the time to discharge home after ambulatory laparoscopic surgery.

Study Objective: To evaluate the effect of different maintenance boluses of a short-acting nondepolarizing neuromuscular blocking drug on its spontaneous recovery profile during anesthesia., Design: Prospective, randomized, double-blind, dose-ranging study., Setting: University-based medical center., Patients: 69 ASA physical status I and II consenting adult outpatients undergoing general anesthesia with an anticipated duration of at least 2 hours., Interventions: Patients were randomized to one of three study groups. Following induction of anesthesia with propofol and fentanyl, rapacuronium 1.5 mg x kg(-1) intravenously (i.v.), was administered to facilitate tracheal intubation. Anesthesia was maintained with desflurane 4% end-tidal in combination with nitrous oxide 67% in oxygen. When the first twitch (T(1)) in the train-of-four (TOF) returned to 25% of its baseline value, a maintenance dose of rapacuronium 0.25 mg x kg(-1) i.v. (Group 1), 0.5 mg. kg(-1) i.v. (Group 2), or 0.75 mg. kg(-1) i.v. (Group 3) was administered. The time course of neuromuscular block was monitored at the wrist using standard electromyography., Measurements and Main Results: The times for recovery of the T(1) to 25% of the baseline value following different maintenance doses of rapacuronium were only 6.3 +/- 2.2, 7.5 +/- 2.3, and 9.6 +/- 2.5 minutes, in Groups 1, 2 and 3, respectively. However, the times for the TOF ratio to return to 0.7 were 44 +/- 15, 53 +/- 20, and 66 +/- 30 minutes in Groups 1, 2, and 3, respectively. Although recovery times were significantly longer after rapacuronium 0.75 mg x kg(-1) i.v. (Group 3), there were no significant differences in any of the recovery variables between Groups 1 and 2., Conclusions: Spontaneous recovery of the T(1) to 25% of the baseline value occurred 6 to 10 minutes after a maintenance bolus dose of rapacuronium 0.25 to 0.75 mg x kg(-1) i.v. However, recovery to a TOF>0.7 required 44 to 66 minutes during desflurane anesthesia., (Copyright 2002 by Elsevier Science Inc.)

Unlabelled: We evaluated the cognitive recovery profiles in elderly patients after general anesthesia with desflurane or sevoflurane. After IRB approval, 70 ASA physical status I-III consenting elderly patients (> or =65 yr old) undergoing total knee or hip replacement procedures were randomly assigned to one of two general anesthetic groups. Propofol and fentanyl were administered for induction of anesthesia, followed by either desflurane 2%-4% or sevoflurane 1%-1.5% with nitrous oxide 65% in oxygen. The desflurane (2.5 +/- 0.6 MAC. h) and sevoflurane (2.7 +/- 0.5 MAC. h) concentrations were adjusted to maintain comparable depths of hypnosis using the electroencephalogram bispectral index monitor. The Mini-Mental State (MMS) test was used to assess cognitive function preoperatively and postoperatively at 1, 3, 6, and 24-h intervals. The use of desflurane was associated with a more rapid emergence from anesthesia (6.3 +/- 2.4 min versus 8.0 +/- 2.8 min) and a shorter length of stay in the postanesthesia care unit (213 +/- 66 min versus 241 +/- 87 min). However, there were no significant differences between the Desflurane and the Sevoflurane groups when the MMS scores were compared preoperatively, and postoperatively at 1, 3, 6, and 24 h. Compared with the preoperative (baseline) MMS scores, the values were significantly decreased at 1 h postoperatively (27.8 +/- 1.7 versus 29.5 +/- 0.5 in the Desflurane group, and 27.4 +/- 1.7 versus 29.2 +/- 1.0 in the Sevoflurane group, respectively). However, the MMS scores returned to preoperative baseline levels within 6 h after surgery. At 1 h and 3 h after surgery, 51% and 11% (versus 57% and 9%) of patients in the Desflurane (versus Sevoflurane) Group experienced cognitive impairment. In conclusion, desflurane is associated with a faster early recovery than sevoflurane after general anesthesia in elderly patients. However, recovery of cognitive function was similar after desflurane and sevoflurane-based anesthesia., Implications: Desflurane was associated with a faster early recovery than sevoflurane after general anesthesia in elderly patients. However, recovery of cognitive function was similar with both volatile anesthetics.

Unlabelled: Dolasetron (12.5 mg IV) is effective in both preventing and treating postoperative nausea and vomiting (PONV) after ambulatory surgery. However, the optimal timing of dolasetron administration and its effect on the patient's quality of life after discharge have not been established. One-hundred-five healthy, consenting women undergoing gynecologic laparoscopic procedures with a standardized general anesthetic technique were enrolled in this randomized, double-blinded study. Group 1 received dolasetron 12.5 mg IV 10-15 min before the induction of anesthesia; Group 2 received dolasetron 12.5 mg IV at the end of the laparoscopy (79 +/- 48 min later than Group 1); and Group 3 received dolasetron 12.5 mg IV at the end of anesthesia (93 +/- 52 min later than Group 1). The incidence of PONV, complete responses (defined as no emetic episodes and no rescue medication within the 24-h period after anesthesia), recovery profiles, and patient satisfaction were recorded. In the postanesthesia care unit and during the 24-h follow-up period, the incidence of nausea and vomiting, as well as the need for rescue antiemetics, did not differ significantly among the three groups. The percentages of patients with complete responses to the study drug within the first postoperative 24 h were also similar in all three groups (55%, 59%, and 52% for Groups 1, 2, and 3, respectively). The early and intermediate recovery profiles, including resumption of a normal diet and patient satisfaction with the control of PONV, were not different among the three study groups. Dolasetron 12.5 mg IV administered before the induction of anesthesia is as effective as dolasetron given at the end of laparoscopy or at the end of anesthesia in preventing PONV after outpatient laparoscopy., Implications: The timing of dolasetron administration appears to have little effect on its efficacy when administered as a prophylactic antiemetic in the ambulatory setting.