Pentraxin 3 in primary percutaneous coronary intervention for ST elevation myocardial infarction is associated with early irreversible myocardial damage : Kinetic profile, relationship to interleukin 6 and infarct size.

BACKGROUND: The inflammatory marker long pentraxin 3 (PTX3) has been shown to be a strong predictor of 30-day and one-year mortality after acute myocardial infarction. The aim of this study was to evaluate the kinetic profile of PTX3 and its relationship with interleukin 6 (IL-6), high-sensitive C-reactive protein (hs-CRP) and infarct size. METHODS: PTX3, IL-6 and hs-CRP were measured at predefined time points, at baseline (before percutaneous coronary intervention (PCI)), at 12 and 72 hours after PCI in 161 patients with first-time ST elevation myocardial infarction (STEMI). RESULTS: PTX3 and IL-6 levels increased in the early phase, followed by a gradual decrease between 12 and 72 hours. There were statistically significant correlations between PTX3 and IL-6 in general, for all time points and for changes over time (0-72 hours). In a linear mixed model, PTX3 predicted IL-6 (p < 0.001). PTX3 is also correlated with hs-CRP in general, and at each time point post PCI, except at baseline. PTX3, IL-6 and hs-CRP were all significantly correlated with infarct size in general, and at the peak time point for maximum troponin I. In addition, there was a modest correlation between IL-6 levels at baseline and infarct size at 72 hours after PCI (ρ = 0.23, p = 0.006). CONCLUSIONS: PTX3 had a similar kinetic profile to IL-6, with an early increase and decline, and was statistically significantly correlated with markers of infarct size in STEMI patients post primary PCI. Baseline levels of IL-6 only predicted infarct size at 72 hours post PCI.

Oral 2-oleyl glyceryl ether improves glucose tolerance in mice through the GPR119 receptor.

The intestinal G protein-coupled receptor GPR119 is a novel metabolic target involving glucagon-like peptide-1 (GLP-1)-derived insulin-regulated glucose homeostasis. Endogenous and diet-derived lipids, including N-acylethanolamines and 2-monoacylglycerols (2-MAG) activate GPR119. The purpose of this work is to evaluate whether 2-oleoyl glycerol (2-OG) improves glucose tolerance through GPR119, using wild type (WT) and GPR 119 knock out (KO) mice. We here show that GPR119 is essential for 2-OG-mediated release of GLP-1 and CCK from GLUTag cells, since a GPR119 specific antagonist completely abolished the hormone release. Similarly, in isolated primary colonic crypt cultures from WT mice, GPR119 was required for 2-OG-stimulated GLP-1 release while there was no response in crypts from KO mice. In vivo, gavage with 2-oleyl glyceryl ether ((2-OG ether), a stable 2-OG analog with a potency of 5.3 µM for GPR119 with respect to cAMP formation as compared to 2.3 µM for 2-OG), significantly (P < 0.05) improved glucose clearance in WT littermates, but not in GPR119 KO mice. Finally, deletion of GPR119 in mice resulted in lower glucagon levels, whereas the levels of insulin and GIP were unchanged. In the present study we show that 2-OG stimulates GLP-1 secretion through GPR119 activation in vitro, and that fat-derived 2-MAGs are potent candidates for mediating fat-induced GLP-1 release through GPR119 in vivo. © 2016 BioFactors, 42(6):665-673, 2016.

Investigations of the human endocannabinoid system in two subcutaneous adipose tissue depots in lean subjects and in obese subjects before and after weight loss.

CONTEXT: Endocannabinoids (ECs) have a role in obesity by affecting appetite and through peripheral effects. Obesity is associated with a dysregulation of the endocannabinoid system (ECS). OBJECTIVE: We aimed to determine the ECS in subcutaneous adipose tissue (AT) in obese subject and investigate the influence of diet-induced weight loss on this system. DESIGN: The obese study participants underwent a 12 weeks diet regimen resulting in 10-12% weight loss. All study participants underwent fasting blood samples and AT biopsies from abdomen and gluteal region, the obese subjects both before and after weight loss. SETTING AND PARTICIPANTS: A total of 21 healthy obese individuals (10 men/11 women, age 39.5 ± 1.6 years, body mass index (BMI): 37.5 ± 0.8 kg m(-2)) and 21 age- and gender-matched lean subjects (BMI: 23.8 ± 0.4 kg m(-2)) were studied. MAIN OUTCOME MEASURES: The activity of ECS in AT was determined by measuring arachidonoyl glycerol (2-AG) and N-arachidonoylethanolamine/anandamide in AT by mass spectrometry and gene expressions of enzymes and receptors involved in the ECS. RESULTS: The EC, 2-AG was reduced in obese individuals in the gluteal AT depot (P<0.01). Moreover, 2-AG increased in both depots in the obese subjects following weight loss (P<0.05). The gene expression of the CB1 was either not affected by the obese state (in the gluteal AT depot) or reduced (in the abdominal depot, P<0.05) and significantly affected by weight loss. The expression of the degrading enzymes FAAH, FAAH2, MGL and MGL2 was differently affected by obesity, AT depot and weight loss. CONCLUSION: We found reduced levels of 2-AG in subcutaneous AT in obesity, which increased after weight loss. In abdominal AT, the low CB1 expression was normalised after weight loss, whereas in gluteal AT the CB1 expression was reduced after weight loss. These findings support the concept of a dysregulated ECS in AT in association with obesity.

International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB1 and CB2.

There are at least two types of cannabinoid receptors (CB(1) and CB(2)). Ligands activating these G protein-coupled receptors (GPCRs) include the phytocannabinoid Δ(9)-tetrahydrocannabinol, numerous synthetic compounds, and endogenous compounds known as endocannabinoids. Cannabinoid receptor antagonists have also been developed. Some of these ligands activate or block one type of cannabinoid receptor more potently than the other type. This review summarizes current data indicating the extent to which cannabinoid receptor ligands undergo orthosteric or allosteric interactions with non-CB(1), non-CB(2) established GPCRs, deorphanized receptors such as GPR55, ligand-gated ion channels, transient receptor potential (TRP) channels, and other ion channels or peroxisome proliferator-activated nuclear receptors. From these data, it is clear that some ligands that interact similarly with CB(1) and/or CB(2) receptors are likely to display significantly different pharmacological profiles. The review also lists some criteria that any novel "CB(3)" cannabinoid receptor or channel should fulfil and concludes that these criteria are not currently met by any non-CB(1), non-CB(2) pharmacological receptor or channel. However, it does identify certain pharmacological targets that should be investigated further as potential CB(3) receptors or channels. These include TRP vanilloid 1, which possibly functions as an ionotropic cannabinoid receptor under physiological and/or pathological conditions, and some deorphanized GPCRs. Also discussed are 1) the ability of CB(1) receptors to form heteromeric complexes with certain other GPCRs, 2) phylogenetic relationships that exist between CB(1)/CB(2) receptors and other GPCRs, 3) evidence for the existence of several as-yet-uncharacterized non-CB(1), non-CB(2) cannabinoid receptors; and 4) current cannabinoid receptor nomenclature.

High-sensitive C-reactive protein is associated with reduced lung function in young adults.

Systemic inflammation has been associated with reduced lung function. However, data on the interrelationships between lung function and inflammation are sparse, and it is not clear if low-grade inflammation leads to reduced lung function. Associations between high-sensitive C-reactive protein (CRP) and spirometric lung function were assessed in a population-based cohort of approximately 1,000 Danes aged 20 yrs. In males, the average decline in forced expiratory volume in one second (FEV(1)) in the highest CRP quintile was 23 mL.yr(-1) versus 1.6 mL.yr(-1) in the lowest quintile. In females, the average decline was 6.2 mL.yr(-1) in the highest CRP quintile versus an increase of 1.8 mL.yr(-1) in the lowest CRP quintile. In a multiple regression analysis adjusted for sex, body mass index, cardiorespiratory fitness, smoking, asthma, airway hyperresponsiveness and serum eosinophil cationic protein, higher levels of CRP at age 20 yrs were associated with a greater reduction in both FEV(1) and forced vital capacity between ages 20 and 29 yrs. The findings show that higher levels of C-reactive protein in young adults are associated with subsequent decline in lung function, suggesting that low-grade systemic inflammation in young adulthood may lead to impaired lung function independently of the effects of smoking, obesity, cardiorespiratory fitness, asthma and eosinophilic inflammation.

Dynamic changes of the endogenous cannabinoid and opioid mesocorticolimbic systems during adolescence: THC effects.

Adolescence is a critical phase of active brain development often characterized by the initiation of marijuana (Cannabis sativa) use. Limited information is known regarding the endogenous cannabinoid system of the adolescent brain as well as related neurotransmitters that appear sensitive to cannabis exposure. We recently observed that adult rats pre-exposed to Delta-9-tetrahydrocannabinol (THC) during adolescence self-administered higher amounts of heroin and had selective impairments of the enkephalin opioid system within the nucleus accumbens (NAc) implicated in reward-related behavior. To explore the ontogeny of the cannabinoid and opioid neuronal systems in association with adolescence THC exposure, rats were examined at different adolescent stages during an intermittent THC paradigm (1.5 mg/kg i.p. every third day) from postnatal days (PNDs) 28-49. Rat brains were examined 24 h after injection at PND 29 (early adolescence), PND 38 (mid adolescence) and PND 50 (late adolescence) and analyzed for endocannabinoids (anandamide and 2-arachidonoylglycerol), Met-enkephalin, cannabinoid CB(1) receptors and micro opioid receptors (microOR) in the NAc, caudate-putamen and prefrontal cortex (PFC). Of the markers studied, the endocannabinoid levels had the most robust alterations throughout adolescence and were specific to the PFC and NAc. Normal correlations between anandamide and 2-arachidonoylglycerol concentrations in the NAc (positive) and PFC (negative) were reversed by THC. Other significant THC-induced effects were confined to the NAc - increased anandamide, decreased Met-enkephalin and decreased microORs. These findings emphasize the dynamic nature of the mesocorticolimbic endocannabinoid system during adolescence and the selective mesocorticolimbic disturbance as a consequence of adolescent cannabis exposure.

Endocannabinoids and nutrition.

The endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are bioactive lipids derived from the n-6 family of polyunsaturated fatty acids that are essential fatty acids. Symptoms of essential fatty acid deficiency in rats - growth retardation, scaly skin, and increased transepidermal water loss - can mainly be attributed to lack of linoleic acid as a structural element of the epidermis. Arachidonic acid, however, also serve essential functions, particularly in cellular signalling via its precursor role for numerous oxygenated derivatives such as prostaglandins, leukotrienes, hepoxilins and other eicosanoids. Furthermore, arachidonic acid is also a structural part of endocannabinoids that have signalling functions in relation to modulation of neurotransmitter release, which might involve physiological and pathophysiological phenomena such as regulation of appetite, energy metabolism, pain perception, memory and learning. Furthermore, along with AEA formation other acylethanolamides are always formed - e.g., oleoylethanolamide (OEA), that can inhibit food intake, and palmitoylethanolamide, that is anti-inflammatory - possibly through activation of peroxisome proliferator activated receptor alpha (PPAR alpha) and/or GPR119. As all these unsaturated fatty acids are ingested daily in smaller or larger amounts, one can ask whether different dietary fats can affect the levels of these fatty acids in the tissues and thereby the quantitative formation of these bioactive signalling molecules. Generally, in vivo arachidonic-acid-derived eicosanoid production can be increased and decreased by prolonged feeding with pharmacological levels of arachidonic acid and long-chain (n-3) fatty acids (fish oil), respectively. Changes in levels of these two fatty acids within the traditional human diet hardly affects the eicosanoid production, however. Moreover, preliminary data suggest that dietary intake of arachidonic acid and fish oil also doesn't easily affect endocannabinoid formation; however, dietary fat in terms of saturated, polyunsaturated and monounsaturated seems to affect tissue levels of AEA, 2-AG and OEA.

No morphine sparing effect of ketamine added to morphine for patient-controlled intravenous analgesia after uterine artery embolization.

BACKGROUND: Pain following embolization of the uterine arteries (UAEs) is variable and may be very severe requiring large doses of parenteral opioids for relief. The present study tested the hypothesis that the addition of ketamine to i.v. patient-controlled morphine reduces the amount of morphine required for pain-control during the first 24 h after UAE embolization. METHODS: Fifty-six patients undergoing UAE embolization for treatment of symptomatic uterine leiomyomata were randomized to receive either 2 mg/ml of morphine (Control group, n=30) or 2 mg/ml of both morphine and ketamine (Ketamine group, n=26) by i.v. patient-controlled analgesia (IV-PCA). Pump settings were bolus dose 1 ml, lockout 10 min, no background infusion. In addition, all patients received diclofenac and acetaminophen for pain relief. Pain scores, morphine consumption and adverse events like nausea, vomiting, itching, visual disturbances, anxiety, dreaming and hallucinations, if any, were recorded for 24 h after embolization. RESULTS: The mean +/- SD 24-h consumption of patient-controlled morphine was 38.3 +/- 21.0 mg in the Ketamine group vs. 33.3 +/- 18.3 mg in the Control group (NS). The difference between the means was 5.0 mg (95% confidence interval: -5.7; 15.6). One patient in the Ketamine group vs. none in the Control group experienced auditory hallucinations. CONCLUSION: Studying an unselected group of patients undergoing embolization of the UAEs for treatment of symptomatic uterine leiomyomata under conditions of basal analgesia with acetaminophen and diclofenac, we failed to demonstrate any morphine-sparing effect of IV-PCA ketamine and morphine compared with IV-PCA morphine alone.

Fish oil in various doses or flax oil in pregnancy and timing of spontaneous delivery: a randomised controlled trial.

OBJECTIVES: To test the earlier suggested hypothesis that intake of long-chain n-3 fatty acids from fish oil may delay the timing of spontaneous delivery and to test if alpha-linolenic acid, provided as flax oil capsules, shows the same effect. DESIGN: Randomised controlled trial including women reporting low dietary fish intake. The women were allocated in the proportions of 1:1:1:1:1:1:2 into six treatment groups and a control group, respectively, from week 17-27 of gestation. The treatment groups received fish oil, in various doses, or flax oil, and the control group did not receive any treatment. SETTING: The Danish National Birth Cohort. SAMPLE: A total of 3098 women allocated into six treatment groups and one control group. METHODS: The six intervention groups were offered fish oil capsules in doses of 0.1, 0.3, 0.7, 1.4 and 2.8 g of eicosapentaenoic acid and docosahexaenoic acid per day or 2.2 g of alpha-linolenic acid (ALA) per day from week 17-27 of gestation until delivery. MAIN OUTCOME MEASURES: Timing of spontaneous delivery. RESULTS: No differences in timing of spontaneous delivery was detected in the fish oil groups or the flax oil group, compared with the control group. The difference in timing of spontaneous delivery in the group receiving the highest fish oil dose compared with the control group was 0.8 days (95% CI: -2.3 to 1.0). Only a minority of the women in the intervention groups took capsules until delivery. CONCLUSION: Possible explanations for these findings include no true effect of n-3 fatty acids on spontaneous delivery or a quick-acting effect not detectable in this trial.

Effects of sucking acidic candies on saliva in unilaterally irradiated pharyngeal cancer patients.

Patients who have received radiation therapy on the head and neck area often use acidic candies to relieve symptoms of dry mouth. Therefore, the aim of this study was to determine the erosive potential in relation to teeth of an acidic candy in 10 such patients. The patients sucked the candy while their whole saliva was collected into a closed system at different times: baseline, candy-stimulated, and post-stimulated. The erosive potential of the candy was evaluated from candy-induced changes in saliva degree of saturation with respect to hydroxyapatite (HAp). Previously published normative values were used for comparison. The results showed that saliva became significantly more undersaturated with respect to HAp in irradiated patients, and failed to return to baseline values during the post-stimulatory period, which it normally does in healthy individuals. Thus, prevention of dental breakdown in these patients should involve counseling regarding choice of stimulant for dry mouth relief.

Preoperative radiotherapy for esophageal carcinoma.

BACKGROUND: The existing randomized evidence has failed to conclusively demonstrate the benefit or otherwise of preoperative radiotherapy in treating patients with potentially resectable esophageal carcinoma. OBJECTIVES: This meta-analysis aimed to assess whether there is benefit from adding radiotherapy prior to surgery and whether or not any pre-defined patient subgroups benefit more or less from preoperative radiotherapy SEARCH STRATEGY: MEDLINE and CancerLit searches were supplemented by information from trial registers and by hand searching relevant meeting proceedings and by discussion with relevant trialists, organisations and industry. The search strategy was run again in MEDLINE, EMBASE and the Cochrane Library on 30th April 2001, two years after original publication. No new trials were found. The search strategy was re-run August 2002 and August 2003 on MEDLINE, EMBASE , CancerLit and The Cochrane Library, and July 2004 and 2005 on MEDLINE, EMBASE and the Cochrane Library. No new relevant trials were identified on any of these occasions. SELECTION CRITERIA: Trials were eligible for inclusion in this meta-analysis provided they randomized patients with potentially resectable carcinoma of the esophagus (of any histological type) to receive radiotherapy or no radiotherapy prior to surgery. Trials must have used a randomization method which precluded prior knowledge of treatment assignment and completed accrual by December 1993, to ensure sufficient follow-up by the time of the first analysis (September 1995). DATA COLLECTION AND ANALYSIS: A quantitative meta-analysis using updated data from individual patients from all properly randomized trials (published or unpublished) comprising 1147 patients (971 deaths) from five randomized trials. This approach was used to assess whether preoperative radiotherapy improves overall survival and whether it is differentially effective in patients defined by age, sex and tumour location. MAIN RESULTS: With a median follow-up of 9 years, in a group patients with mostly squamous carcinomas, the hazard ratio (HR) of 0.89 (95% CI 0.78-1.01) suggests an overall reduction in the risk of death of 11% and an absolute survival benefit of 3% at 2 years and 4% at 5 years. This result is not conventionally statistically significant (p=0.062). No clear differences in the size of the effect by sex, age or tumor location were apparent. AUTHORS' CONCLUSIONS: Based on existing trials, there was no clear evidence that preoperative radiotherapy improves the survival of patients with potentially resectable esophageal cancer. These results indicate that if such preoperative radiotherapy regimens do improve survival, then the effect is likely to be modest with an absolute improvement in survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients (90% power, 5% significance level) would be needed to reliably detect such an improvement (from 15 to 20%).

Soft tissue sarcomas of the head and neck: a single-centre experience.

OBJECTIVE: The aim of this study was to report our experience with malignant and borderline soft tissue tumours (STS) of the head and neck region in the period 1977-2000. DESIGN: Retrospective case study including new evaluation of histological specimens. SETTING: Tertiary centre, single centre. PARTICIPANTS: Review of patient's records and new evaluation of pathological specimens were made for 66 patients. After evaluation only 36 patients (26 men and 10 women) still met present criteria for a STS in head and neck in adults. RESULTS: The original histological diagnosis was changed in 27 (41%) of the 66 patients with a primary diagnosis of sarcoma. After review the most common histological diagnoses were leiomyosarcoma (5) and rhabdomyosarcoma (5). Overall 5-year survival rate was 60%. Overall 5-year disease-free survival rate was 44%. The study showed that both tumour grade and surgical margin had a statistically significant impact on survival. No relation was found between survival and tumour size or age. CONCLUSION: The grave prognosis especially for high-grade tumours emphasizes the need for improved treatment strategies. Furthermore, conclusions from older studies concerning prognosis may be obsolete as approximately 40% of tumours previously diagnosed as sarcomas may be invalid by present day standards.

Efficacy of A-line AEP Monitor as a tool for predicting acceptable tracheal intubation conditions during sevoflurane anaesthesia.

BACKGROUND: It is essential for the clinical anaesthetist to know whether patients are sufficiently anaesthetized to tolerate direct laryngoscopy and endotracheal intubation. Because of the lack of an accurate objective method to determine the level of general anaesthesia, under- or overdosing of anaesthetics may occur. Auditory evoked potential (AEP) is one of several physiological parameters under investigation. We aimed to determine the clinically required depth of anaesthesia, measured by the A-line AEP Monitor and expressed as A-Line ARX Index (AAI) for 90% probability of acceptable conditions for endotracheal intubation. METHODS: We studied 108 patients anaesthetized by mask with increasing concentration of sevoflurane in 30% oxygen and 70% nitrous oxide. Fentanyl 1.5 microg kg(-1) and glycopyrrolate 0.2 mg were administered intravenously immediately before starting induction of anaesthesia. The monitor was programmed to give an alarm at AAI 10, 15, 20, 25 or 30 according to randomization. When the alarm sounded, the end-expiratory sevoflurane concentration was registered and endotracheal intubation was attempted. Intubation conditions were assessed by an observer blinded to the AAI. RESULTS: At AAI 10 we found acceptable conditions in 91% (confidence interval [CI 72-99%]) of patients. The prediction probability value P(K) of AAI was 0.69 (CI 0.59-0.79) and the P(K) of end-expiratory sevoflurane concentration was 0.93 (CI 0.87-0.99). ED(90) (the AAI with a 90% probability of acceptable intubation conditions) was calculated as 8.5 (CI 0-17.5). CONCLUSIONS: AAI indicates the depth of anaesthesia necessary for acceptable endotracheal intubation conditions. Under the conditions of the present study, end-expiratory sevoflurane concentration was a better predictor and may turn out to be more useful in the clinical setting.

Efficacy of the A-line AEP monitor as a tool for predicting successful insertion of a laryngeal mask during sevoflurane anesthesia.

BACKGROUND: The use of clinical signs for assessing depth of anesthesia is unreliable during periods with little noxious stimulation. A patient may appear adequately anesthetized at one moment at a given level of stimulation, but may later, when facing other more intense stimuli, show signs of insufficient anesthesia. In order to prevent under- or overdosing of anesthetics, an anesthesia depth monitor that is able to predict responses to noxious stimulation would therefore be useful. Auditory evoked potentials (AEP) is one of several physiological parameters under investigation. The method has been improved by rapid extraction and conversion of the AEP curve into an index (A-Line ARX Index = AAI). We aimed to determine the clinically required depth of anesthesia, measured by the A-line AEP Monitor, for at least 90% probability of acceptable insertion conditions for a laryngeal mask airway (LMA). METHODS: We studied 112 patients anesthetized by mask with increasing concentration of sevoflurane in oxygen. The monitor was programmed to give an alarm at AAI between 15 and 40 according to randomization. When the alarm sounded, the end-expiratory sevoflurane concentration was recorded and the LMA inserted. Insertion conditions were assessed by an observer blinded to the AAI. RESULTS: The ED(95) and prediction probability (P(K)) for AAI were 14.5 (CI 7.4-21.6) and 0.76 (0.66-0.86), respectively, while the ED(95) and P(K) for expiratory sevoflurane concentration were 4.36% (CI 3.73-4.98) and 0.95 (0.91-0.99). CONCLUSIONS: AAI indicates the level of depth of anesthesia necessary for acceptable laryngeal mask insertion conditions. End-expiratory sevoflurane concentration was the better predictor.

Secular trends in physical fitness and obesity in Danish 9-year-old girls and boys: Odense School Child Study and Danish substudy of the European Youth Heart Study.

INTRODUCTION: Low physical fitness and obesity have been shown to be associated with cardiovascular disease (CVD) risk. Obesity is on the increase in many countries, but little is known about physical fitness trends. Monitoring of changes in fitness and obesity in the population is important for preventive strategies, and the aim of this study was to analyse the secular trends in fitness and body composition in Danish children. MATERIALS AND METHODS: Two representative population studies were conducted 12 years apart on 9-year-old children in the same location: the Odense School Child Study in 1985-86 and the European Youth Heart Study in 1997-98. In both studies, physical fitness was determined by a maximal cycle ergometer test, and obesity was assessed by skinfolds. RESULTS: Boys had a lower physical fitness and were fatter in 1997-98 than in 1985-86. In addition, an increased polarization is emerging, with the difference between the fit and the unfit and the difference between the lean and the fat being greater in 1997-98 than in 1985-86. In girls, a similar polarization was found, but no overall change in fitness or obesity. CONCLUSION: The negative trend and increased polarization for physical fitness and obesity in Danish children suggest a future generation with a higher degree of CVD risk.

Biological cardiovascular risk factors cluster in Danish children and adolescents: the European Youth Heart Study.

BACKGROUND: The aim of this study was to determine whether the number of participants with multiple coronary heart disease (CHD) risk factors exceeded the number expected from a random distribution. METHODS: A cross-sectional study of 1020 randomly selected boys and girls, 9 and 15 years old, was conducted. Risk factors were total cholesterol, HDL-cholesterol, triglyceride, serum insulin, and blood pressure. Physical fitness was assessed from a maximal cycle test and body fat from the sum of four skinfolds. Risk factors selected in the analysis were those related to the metabolic syndrome. RESULTS: More participants than expected had four or five CHD risk factors. Four risk factors were found in 3.03 (95% confidence interval (CI): 2.24-4.10) times as many participants as expected from a random distribution and five risk factors were found in 8.70 (95% CI: 4.35-17.4) times as many participants as expected. Fifty (5.4%) had four or five risk factors and in these individuals physical fitness was 1.2 standard deviation (SD) lower and body mass index (BMI) 1.6 SD higher than mean values for the population. CONCLUSION: Clustering of risk factors for the metabolic syndrome was found in children and adolescents. Low levels of physical fitness and raised BMI in these individuals indicate that lifestyle factors such as physical activity and diet may influence the development of these unhealthy risk profiles.

Growth hormone-mediated breakdown of body fat: effects of GH on lipases in adipose tissue and skeletal muscle of old rats fed different diets.

Lipid storage and breakdown is mainly controlled by lipoprotein lipase and hormone-sensitive lipase. The aim of this work was to elucidate whether growth hormone mediated loss of adipose tissue involves a concerted action on tissue lipases, and to what degree such events are modulated by dietary regimen. Twelve-month-old rats fed first a high-fat diet or a low-fat diet for 14 weeks were injected with saline or growth hormone (4 mg/kg/d) for four days or three weeks in different combinations with either high- or low-fat diets. In adipose tissue, growth hormone generally inhibited lipoprotein lipase and also attenuated the inhibiting effect of insulin on hormone-sensitive lipase activity. Growth hormone treatment combined with restricted high-fat feeding reduced the activity of both lipases in adipose tissue and stimulated hormone-sensitive lipase in muscle. Generally, plasma levels of free fatty acids, glycerol and cholesterol were reduced by growth hormone, and in combination with restricted high-fat feeding, triglyceride levels improved too. We conclude that growth hormone inhibits lipid storage in adipose tissue by reducing both lipoprotein lipase activity and insulin's inhibitory action on hormone-sensitive lipase. We also propose that growth hormone's effects on tissue lipases and blood lipids are modulated by dietary regimen.

Effect of sevoflurane on the mid-latency auditory evoked potentials measured by a new fast extracting monitor.

BACKGROUND: Mid-latency auditory evoked potentials (MLAEP) are widely suppressed during general anesthesia and may therefore be useful for assessment of the depth of anesthesia. However, interpretation of amplitudes and latencies in the AEP signal is time consuming. A new monitor (A-line) that quantifies the MLAEP into an index has therefore been developed. The present study aimed to assess the precision of a prototype of the new monitor and to test the hypothesis that the depth of anesthesia index shows a graded response with changing steady-state end-expiratory concentrations of sevoflurane. METHODS: We studied 10 ASA physical status I or II patients undergoing elective hysterectomy under combined epidural and general anesthesia by sevoflurane. Baseline auditory evoked potentials were recorded in the conscious patient immediately before induction of general anesthesia. Depth of anesthesia indices were recorded before anesthesia and at decreasing end-expiratory steady-state sevoflurane concentrations of 2.0%, 1.5%, 1.0% and 0.5%. All indices were recorded in duplicate 6 s apart. By use of an autoregressive model with exogenous input (ARX-model), the monitor extracted the AEP within 6 s. The depth of anesthesia AEP index calculated in this way was defined as the A-line ARX index (AAI). RESULTS: Approximately 95% of the differences between repeated recordings were 5 AAI-units or less. A wide interindividual variation was observed at each observation point. AAI at 1%, 1.5% and 2% end-expiratory concentration was significantly less than the baseline AAI obtained before induction of anesthesia (P < 0.001). AAI did not change significantly in the 1-2% concentration range. CONCLUSION: The new monitor was precise. Attenuation of the A-line ARX-index (AAI) for mid-latency auditory evoked potentials (MLAEP) during general anesthesia was profound. However, the monitor did not show a graded response with changing end-expiratory steady-state concentrations of sevoflurane.

Effect of delayed supine positioning after induction of spinal anaesthesia for caesarean section.

BACKGROUND: The study tested the hypothesis that the incidence of hypotension during spinal anaesthesia for caesarean section is less in parturients who remain in the sitting position for 3 min compared with parturients who are placed in the modified supine position immediately after induction of spinal anesthesia. METHODS: Spinal anaesthesia was induced with the woman in the sitting position using 2.8 ml hyperbaric bupivacaine 0.5% at the L(3-4) or L(2-3) interspace. Ninety-eight patients scheduled for elective caesarean section under spinal anaesthesia were randomised to assume the supine position on an operating table tilted 10 degrees to the left (modified supine position) immediately after spinal injection (group 0, n=52) or to remain in the sitting position for 3 min before they also assumed the modified supine position (group 3, n=46). Isotonic saline 2-300 ml was given intravenously over 15 min before spinal injection followed by 15 ml/kg over 15-20 min after induction of spinal anaesthesia. If the systolic blood pressure decreased to less than 70% of baseline or to less than 100 mmHg or if there was any complaint of nausea, ephedrine was given in 5 mg boluses intravenously every 2 min. RESULTS: The blood pressure decreased significantly in both groups following spinal injection (P<0.001). Blood pressure variations over time differed significantly between the two groups (P<0.05). However, the incidence of maternal hypotension before delivery was similar in the two groups. The difference was caused by the time to the blood pressure nadir being significantly shorter in group 0 compared with group 3 (9.1+/-4.5 min vs. 11.7+/-3.7 min, P<0.01). Similar numbers of patients received rescue with ephedrine before delivery: 35 (67%) in group 0 vs. 26 (57%) in group 3 (NS). The mean total dose of ephedrine before delivery was 10.9 mg in group 0 vs. 9.2 mg in group 3 (NS). There were no differences in neonatal outcome between the two groups. CONCLUSION: At elective caesarean section, a 3-min delay before supine positioning does not influence the incidence of maternal hypotension after induction of spinal anaesthesia in the sitting position with 2.8 ml of bupivacaine 0.5% with 8% dextrose.