Analgesia for adenotonsillectomy in children: a comparison of morphine, ketamine and tramadol

Background : Establishment of good analgesia is of major concern in the postoperative period following adenotonsillectomy. The aim of this study was to compare the effects of ketamine, morphine and tramadol on postoperative pain after adenotonsillectomy in children. Methods : Sixty children (age 5–12 years) scheduled for adenotonsillectomy were randomized into four groups to receive intravenously (i.v.) either 0.5 mg·kg^?1 ketamine hydrochloride (K), 0.1 mg·kg^?1 morphine hydrochloride (M), 1.5 mg·kg^?1 tramadol hydrochloride (T) or normal saline (S) in a volume of 4 ml during induction. After tracheal intubation 10 μg·kg^?1·min^?1 ketamine hydrochloride in group K and 0.6 ml·kg^?1·h^?1 saline i.v. in groups M, K and S were infused peroperatively. Postoperative analgesic requirements and side‐effects were recorded. Pain was assessed by the Numeric Rating Scale (NRS) and the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) scores. Results : Heart rate increased significantly peroperatively only in group K. NRS at first and fifth minute in group M and at first minute in group T and K and CHEOPS score at first, fifth, 15th and 60th min in group M were found to be significantly lower than in the control group. The time to first analgesic requirement was significantly longer in group M compared with ketamine and the control group. Six children in group M, nine in group T, 11 in group K and 15 in group S needed additional analgesics. Conclusions : Morphine hydrochloride 0.1 mg·kg^?1 i.v. administered during induction of anaesthesia provides efficient pain relief in children undergoing adenotonsillectomy.     

Managing sedation withdrawal in children who undergo prolonged PICU admission after discharge to the ward

Children who undergo a prolonged stay within the intensive care unit require adequate sedation and analgesia. During the recovery phase there will need to be a period of sedation withdrawal to prevent occurrence of an abstinence syndrome. We present a strategy developed within our hospital for managing this process which uses the resource of the Pain Service, along with guidelines to help prevent the development of withdrawal, and a plan for managing any signs of abstinence which occur.     

The slow component of V̇O2 kinetics in very heavy and fatiguing square-wave exercise

We hypothesized that oxygen consumption (O₂) rises incrementally in very heavy and fatiguing exercise where the slow component gain increases with higher work rates. Eight trained males completed a graded exercise test and bouts of square-wave cycle ergometry at 40% and 60% of the difference between the estimated lactate threshold (LT) and O_2peak (designated 40%D and 60%D). Exhaled gases were collected and analyzed every breath using models that allowed for a linear slow component or a slow component with one or more exponential increments. All subjects were able to complete 30 min at 40%D but not at 60%D. The slow component was generally best fit with two increments at 40%D and two or three increments at 60%D. In further (<Emphasis Type=Italic>, our results question the reliability of determining parameters of multiple slow component increments when repeated bouts are averaged together. This study demonstrates that O₂ can continue to rise incrementally beyond the onset of the slow component in very heavy and fatiguing exercise. These results support the concept of a recurring mechanism underlying the slow component of O₂ kinetics during square-wave exercise and suggest that the dynamics (time of onset, rate of development, magnitude) of this mechanism may vary from day to day.     

Reproducibility of the heart rate variability responses to graded lower body negative pressure

The reproducibility of heart rate variability (HRV) measures during graded lower body negative pressure (LBNP) have not been studied in sufficient detail. Active college age men (n=14) underwent an orientation exposure and two trials of graded LBNP to presyncope or –100 mmHg, separated by 1 week. Heart rate, stroke volume (impedance cardiography), blood pressure (Finapres), and forearm blood flow were assessed, as was HRV in both time and frequency domains. The trial-to-trial responses to LBNP common to all subjects (LBNP–60 mmHg and at test termination) showed parallel changes, suggesting similar responses between both trials. Good reproducibility estimates were found for the resting HRV data (lowest: R=0.62 for low frequency/high frequency ratio; highest: R=0.94 for standard deviation of normal R-R intervals). During LBNP, reproducibility estimates varied but were generally similar to that seen at rest. At test termination, they were unacceptably low (R<0.41) for the HRV data assessed in the frequency domain and expressed in absolute units. LBNP tolerance was lower in the first trial [LBNP tolerance index: 404 (21) versus 437 (15) mmHg min^–1; P<0.05] but the intraclass correlation coefficient was high (R=0.87). These data suggest that (1) HRV responses to submaximal LBNP up to –60 mmHg are consistent across trials, (2) the considerable variability seen in the HRV parameters at maximal LBNP can be reduced by expressing these data in either the time domain or using normalized units in the frequency domain, and (3) cardiovascular responses to sub- and maximal LBNP are reproducible. Data are presented as mean (SEM) unless otherwise stated.     

Oral administration of a mite allergen expressed by zucchini yellow mosaic virus in cucurbit species downregulates allergen-induced airway inflammation and IgE synthesis

BACKGROUND: Sublingual-swallow immunotherapy in house dust mite-related asthma has a good safety profile and improves respiratory function and bronchial hyperreactivity. Zucchini yellow mosaic virus (ZYMV) is envisaged as a promising viral vector for expressing large quantity of foreign proteins in cucurbit species. OBJECTIVE: We sought to investigate whether oral feeding of dust mite allergen expressed by ZYMV in a cucurbit species can suppress allergen-induced inflammation and IgE synthesis. METHODS: An infectious plant virus clone, p35SZYMV2-26, that contains the full-length cDNA to the genomic RNA of a Taiwan isolate of ZYMV, driven by the cauliflower mosaic virus 35S promoter, was engineered as an in vivo viral vector to express Dermatophagoides pteronyssinus group 5 allergen (Der p 5) in cucurbit species. Female BALB/c mice were intraperitoneally sensitized with Escherichia coli bacteria-expressed Der p 5 and orally treated with the virus-expressed Der p 5 (vDer p 5) extracted from the recombinant virus-infected squash plants. Der p 5-specific immunoglobulins were measured by ELISA, and bronchoalveolar lavage assays were used to measure airway inflammation. RESULTS: Infectivity assays and immunoblotting revealed that large quantities of free-form vDer p 5 are produced in the recombinant virus-infected squash plants. The recombinant virus carried and expressed the Der p 5 allergen in squash plants for at least 1 year after numerous passages. In animal tests, squash extract containing vDer p 5 inhibited Der p 5-specific IgE synthesis and airway inflammation. CONCLUSION: Our results suggest that oral feeding with allergen produced by the plant viral vector provides a novel approach for the therapy of allergic asthma.     

Sitting and standing tolerance in patients with chronic back pain: comparison between physician prediction and covert observation

OBJECTIVES: To measure covertly observed continuous sitting and standing tolerance in patients with chronic back pain and to compare observations to physician predictions. DESIGN: Blinded, prospective, cohort study. SETTING: Ambulatory referral centers, both public and private, at 5 major medical centers in the eastern United States. PARTICIPANTS: All volunteers (N=154; 64.0% women, mean age, 48.7y; 16.8% had active lawsuits) with diagnosis codes of the International Classification of Diseases, 9th Revision consistent with thoracic and/or lumbosacral back pain were selected from a cohort of 651 outpatients with chronic pain enrolled in the Multiperspective Multidimensional Pain Assessment Protocol (MMPAP). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Continuous sitting and standing tolerance was measured by (1). covert observation of subjects during the MMPAP trial and (2). blinded expert physician prediction based on complete history and physical examination. RESULTS: Most (124/154, 80.5%) subjects stood for 30 minutes or more and most (124/154, 80.5%) sat for 60 minutes or more. Overall, physicians underpredicted the ability to sit 60 minutes or more and to stand 30 minutes or more. Physician prediction showed poor correlation to covert observation for sitting tolerance (kappa=-.061, P=.221) and standing tolerance (kappa=-.021, P=.727). CONCLUSIONS: The majority of this sample demonstrated the ability to sit continuously 60 minutes or more and to stand continuously 30 minutes or more while being covertly observed. Expert physician prediction showed poor correlation to covertly observed sitting and standing tolerances, raising doubt about the validity of using physician evaluation to establish work restrictions in patients with chronic back pain. These findings are preliminary, follow only a brief period of covert observation, and indicate the need for further research in this area.     

No influence of high- and low-carbohydrate diet on the oral glucose tolerance test in pregnancy

OBJECTIVE: Our objective was to determine the influence of the carbohydrate content of the diet preceding the oral glucose tolerance test (OGTT) in pregnancy on the test results and to evaluate the necessity of the recommended preparatory high-carbohydrate diet. STUDY DESIGN: Thirty-four women from our outpatient clinic were enrolled in this prospective study. After giving informed consent, each women underwent a 90-min lesson (supervised by a dietary assistant) covering the carbohydrate, protein and fat content of different foods. Women were then randomized and in a crossover design started a diet with either a low or a high carbohydrate content. We were aiming at a carbohydrate intake of 40% in the low-carbohydrate week (LCH) and 50% in the high-carbohydrate week (HCH). Compliance was monitored by a detailed food diary which the women kept and which included the weight of the foods they consumed. RESULTS: The actual dietary intakes as calculated from the food diaries showed that the mean caloric intake was 1801 +/- 314 kcal in the LCH and 2118 +/- 312 kcal in the HCH week (<0.001). During the LCH diet, CH intake was 39 +/- 6.1% and 49 +/- 6.6% in the HCH week (P < 0.001). The carbohydrate intake per kilogram bodyweight was 30 +/- 5.3 kcal vs. 35 +/- 5.2 kcal (P < 0.001). The number of patients diagnosed with gestational diabetes was two in the LCH and three in the HCH week (not significant). The sum of the OGTT values (fasting, 1 h and 2 h) after the LCH was 18.9 +/- 2.1 mmol/l vs. 18.8 +/- 2.1 mmol/l after the HCH (P = 0.51). No differences could be found in both groups regarding the fasting, 1-h, or 2-h glucose values. Including patients with a CH difference of at least 5%, 10%, and 15% carbohydrate between the weeks, we still did not observe any differences in the OGTT sum. We also looked at a possible influence of the CH content of the diet on the day before the test and of the last meal before the OGTT results and observed there was none. CONCLUSION: This is the first study which has observed the influence of the previous day's meal on the test results. We conclude from our results that the carbohydrate percentage of the preparatory diet did not influence the results of an OGTT, even when we increased the difference in carbohydrate intake stepwise up to 15%. This might indicate that a preparatory diet before the OGTT is not necessary for women with normal nutritional behavior.     

A new buprenorphine analogy, thenorphine, inhibits morphine-induced behavioral sensitization in mice

AIM: To investigate effects of thenorphine, a new compound of partial agonist of μ-opioid receptor, on the loco-motor activity and the behavioral sensitization to morphine in mice. METHODS: Locomotor activity was observed after administration of thenorphine or co-administration of thenorphine and morphine in mice. Mice were induced behavioral sensitization to morphine by intraperitoneal injection of 20 mg/kg morphine once daily for 7 d. Thenorphine was co-administrated with morphine to observe the effects of thenorphine on the development, transfer and expression of morphine-induced behavioral sensitization. RESULTS: A single dose of thenorphine (0.0625, 0.25, and 1.0 mg/kg) could dose-dependently inhibit the locomotor activity in mice (P<0.05), repeated administrations of thenorphine, however, were not able to induce locomotor sensitization, but induced tolerance. Pretreatment with thenorphine 30 min prior to morphine effectively inhibited the psychomotor effect of morphine in mice (P<0.01). Co-adminis     

Effect of Momordica charantia on lipid profile and oral glucose tolerance in diabetic rats

In this study, the methanol extract of Momordica charantia fruit extract was administered to diabetic rats to assess the long term effect of the extract on the lipid profile and the oral glucose tolerance test. Treatment for 30 days showed a significant decrease in triglyceride, low density lipoprotein and a significant increase in high density lipoprotein level. A significant effect on oral glucose tolerance was also noted. Chronic administration showed an improvement in the oral glucose tolerance curve. The effect was more pronounced when the test was done in rats fed the extract on the day of the test compared with tests done in rats which were not fed the extract on the same day.     

Identification of an HLA-A*0201 cytotoxic T lymphocyte epitope specific to the endothelial antigen Tie-2

Tie-2 stabilises pericyte-endothelial interactions during angiogenesis and is highly expressed on endothelium during several diseases, including arthritis, age-related macular degeneration and cancer. A vaccine that targets endothelium overexpressing Tie-2 may result in vessel damage and stimulate an inflammatory cascade resulting in disease regression. We have identified a region unique to Tie-2 (amino acids 1-196) that is homologous in humans and mice. Using computer algorithms, several HLA-A*0201 epitopes that are identical in mice and humans were predicted within this region; however, binding assays showed that the majority of these epitopes were of low affinity. Modification of the anchor residues of 4 epitopes enhanced HLA binding. These epitopes were incorporated by site-directed mutagenesis into a Tie-2 DNA construct. Immunisation of HLA*0201 transgenic mice with one of the modified Tie-2 constructs stimulated CTLs that recognised both wild-type and modified peptide-pulsed target cells. In contrast, no CTLs were generated in mice immunised with wild-type Tie-2 construct, demonstrating that the modified epitope was necessary in the generation of CTLs. Moreover, CTLs from mice immunised with the modified construct killed HLA-A*0201 endothelial cells overexpressing Tie-2. Our study demonstrates that it is possible to break tolerance to the endothelial antigen Tie-2, suggesting that it may be feasible to design a vaccine to activate CTLs to kill endothelial cells overexpressing Tie-2.