Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor transcription factor t... more Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor transcription factor that has an important role in controlling cardiac metabolic gene expression. We determined whether mice lacking PPARα (PPARα (−/−) mice) have alterations in cardiac energy metabolism. Rates of palmitate oxidation were significantly decreased in isolated working hearts from PPARα (−/−) hearts compared with hearts from age-matched wild type mice (PPARα (+/+) mice), (62 ± 12versus 154 ± 65 nmol/g dry weight/min, respectively,p < 0.05). This was compensated for by significant increases in the rates of glucose oxidation and glycolysis. The decreased fatty acid oxidation in PPARα (−/−) hearts was associated with increased levels of cardiac malonyl-CoA compared with PPARα (+/+) hearts (15.15 ± 1.63 versus 7.37 ± 1.31 nmol/g, dry weight, respectively, p < 0.05). Since malonyl-CoA is an important regulator of cardiac fatty acid oxidation, we also determined if the enzymes that control malony...
The number of elderly patients presenting for anaesthesia and surgery has increased exponentially... more The number of elderly patients presenting for anaesthesia and surgery has increased exponentially in recent years. Regional anaesthesia is frequently used in elderly patients undergoing surgery. Although the type of anaesthesia (general versus regional anaesthesia) has no substantial effect on perioperative morbidity and mortality in any age group; it intuitively makes sense that elderly patients would benefit from regional anaesthesia because they remain minimally sedated throughout the procedures and awaken with excellent postoperative pain control. However, a multitude of factors influence the outcome, such as the type, duration and invasiveness of the operation, co-existing medical and mental status of the patient and the skill and expertise of the anaesthesiologist and surgeon. These factors make it difficult to decide if and when one technique is equivocally better than another. Thus, it is more important to optimise the overall management of the patient during the perioperati...
Results: In normal fetuses, it was possible to identify the respective position of the inferior v... more Results: In normal fetuses, it was possible to identify the respective position of the inferior vena cava and the descending aorta in all cases. In the 3 cases with left atrial isomerism, it was possible to identify the azygos continuation adjacent to the descending aorta and the abnormal stomach position. In no case could the multiple spleens be identified. In the 3 cases with right atrial isomerism, it was possible to identify the abnormal central position of the inferior vena cava and the displacement of the stomach to the left. The abnormal liver morphology consistent with left and right isomerism could be identified in 5/6 cases. Discussion: Identification of fetal situs has so far been carried out by assessing the position of the abdominal vessels on an axial view of the fetal abdomen. Using the coronal plane of the fetal trunk from three-dimensional volumes, it was possible to identify visceral anatomic patterns consistent with a diagnosis of situs solitus or ambiguous (left or right isomerim) independently from the type of congenital heart disease present. This may be of help in difficult cases to tag the type of cardiosplenic syndrome.
The number of elderly patients presenting for anaesthesia and surgery has increased exponentially... more The number of elderly patients presenting for anaesthesia and surgery has increased exponentially in recent years. Regional anaesthesia is frequently used in elderly patients undergoing surgery. Although the type of anaesthesia (general versus regional anaesthesia) has no substantial effect on perioperative morbidity and mortality in any age group; it intuitively makes sense that elderly patients would benefit from regional anaesthesia because they remain minimally sedated throughout the procedures and awaken with excellent postoperative pain control. However, a multitude of factors influence the outcome, such as the type, duration and invasiveness of the operation, co-existing medical and mental status of the patient and the skill and expertise of the anaesthesiologist and surgeon. These factors make it difficult to decide if and when one technique is equivocally better than another. Thus, it is more important to optimise the overall management of the patient during the perioperati...
We designed this study to determine the threshold current for nerve stimulation of an insulated n... more We designed this study to determine the threshold current for nerve stimulation of an insulated needle in the epidural space. The intended dermatome was identified using the bony landmarks of the spine. An 18-gauge insulated Tuohy needle was inserted perpendicularly to the skin and advanced until "loss of resistance" was felt. A nerve stimulator was then connected to the insulated needle. Twenty patients were studied using an insulated Tuohy needle and one patient was studied using a noninsulated Tuohy needle. Muscle twitch was elicited with a current of 11.1 +/- 3.1 mA (mean +/- sd) in all patients in which an insulated needle was used. Muscle twitches were within 2 myotomes of the intended level (based on bony landmarks). Muscle twitch was not elicited with a noninsulated needle. After catheter threading, positive stimulation tests were elicited via epidural catheters in all patients (4.9 +/- 2.3 mA). Postoperative radiograph confirmed all catheter placements within 2 my...
A small volume of local anesthetic or normal saline abolishes the muscle twitch induced by a 1ow ... more A small volume of local anesthetic or normal saline abolishes the muscle twitch induced by a 1ow current (0.5 mA) during electrolocation. This study examines the hypothesis that the mechanism of this phenomenon is primarily the electrophysiologic effect of the injectate on the electrical current density at the needle tip. Five pigs were studied. An insulated Tuohy needle was inserted in each pig toward the left and right brachial plexuses and the left and right femoral nerves. The needle was advanced until corresponding motor responses were observed at each site, using a current of 0.5 mA. The effect of injecting 1 mL each of normal saline and 5% dextrose in water (NS and D5W) on muscle twitch was investigated at all 20 needle insertion sites. Changes in the conductive area induced by the injectates were also demonstrated using gel electrophoresis. In all cases, the muscle twitches were abolished immediately after the injection of NS and recovered instantaneously after a subsequent injection of D5W. The electrical resistance between the needle and the ground electrodes decreased instantly after the NS injection. The resistance not only recovered but also increased after the injection of D5W. In the gel electrophoresis experiment, the results demonstrated that the expanded conductive area induced by the saline column surrounding the insulated needle was similar to that observed with the uninsulated needle. The injection of a conducting solution (i.e., NS) rendered the current that was previously sufficient to elicit a motor response (0.5 mA) ineffective. The most likely reason for this change is that the conductive area surrounding the stimulating needle expanded after the injection and dispersion of the conducting solution (i.e., NS), thereby reducing the current density at the target nerve. This effect can be reversed by injecting a nonconducting solution (i.e., D5W) via the stimulating needle.
Muscle twitches elicited with electrical stimulation (6-17 mA) during epidural insertion indicate... more Muscle twitches elicited with electrical stimulation (6-17 mA) during epidural insertion indicate correct epidural needle placement while muscle twitches at a lower current (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1 mA) may indicate intrathecal needle placement. This study examined whether applying continuous electrical stimulation at 6 mA could indicate needle entry into the epidural space without inadvertently penetrating the intrathecal space. After institutional review board (IRB) approval, 10 pediatric patients scheduled for lumbar puncture were studied. Following sedation with propofol, an insulated 24-gauge Pajunck unipolar needle was inserted through an 18-gauge introducer needle placed at the L4-5 interspace. The needle was first connected to a nerve stimulator (6 mA) and advanced. At the first sign of muscle twitching, needle advancement was stopped and the threshold current for motor activity was determined. The current was then turned off, the stylet was removed and the needle checked for cerebrospinal fluid (CSF). If CSF was not present, the needle was advanced into the intrathecal space (as confirmed by the presence of CSF). Ten pediatric patients (ASA II or III) aged 7.8 +/- 4.3 years (2.8-16.0 years) were studied. All patients had two distinguishable threshold currents as the needle advanced. The mean threshold current to elicit muscle twitch in the presumed epidural space was 3.84 +/- 0.99 mA. CSF was not present in any of the patients at this location. The mean threshold current in the intrathecal space was 0.77 +/- 0.32 mA. The average estimated distance from the first threshold location to the intrathecal space was 3 mm. All muscle twitches were at the L3-5 myotomes. Nine muscle twitches were unilateral and one was bilateral. Monitoring with an insulated needle with electrical stimulation at 6 mA may prevent unintentional placement of epidural needles into the intrathecal space.
A prospective observational case series of children receiving light general anesthesia for magnet... more A prospective observational case series of children receiving light general anesthesia for magnetic resonance imaging (MRI) was performed. Our purpose was to examine the merit of anesthesia and recovery/discharge times of combined remifentanil and propofol total intravenous anesthesia (TIVA) in spontaneously breathing children. After IRB approval and informed consent, 56 patients receiving Remi/Propofol TIVA (Remifentanil 10 microg.ml(-1) Propofol 10 mg.ml(-1)) were observed. Blood pressure, respiratory rate, endtidal CO(2) (P(E)CO(2)), oxygen saturation and temperature were recorded at the start and finish of anesthesia. In addition, induction and recovery times were noted. Recovery time was from scan completion until discharge from the initial recovery area. Discharge time was from scan completion to discharge home. Fifty-six patients received Remi/Propofol TIVA. The mean Remi/Propofol recovery and discharge times were 8.9 and 28.2 min, respectively. There was a statistically significant decrease in respiratory rate and increase in CO(2) from the start to the end of the procedure. During the scan, seven patients moved. One patient experienced postprocedure nausea and or vomiting. The combination of remifentanil and propofol for TIVA may be an effective method of light general anesthesia in pediatric patients undergoing MRI.
Providing effective analgesia is challenging for correction of idiopathic scoliosis, as nonsteroi... more Providing effective analgesia is challenging for correction of idiopathic scoliosis, as nonsteroidal anti-inflammatory drugs and epidural anesthesia are controversial and large-dose opioids can cause significant side effects. Perioperative adjuvant low-dose ketamine has been shown to provide good supplementary analgesia as well as to potentially spare opioid consumption. Ketamine may also improve early ease of mobility without addition of any noticeable adverse effects. This case describes the combined use of a continuous low-dose ketamine infusion and patient-controlled analgesia (PCA) morphine for postoperative analgesia in an adolescent girl undergoing posterior spinal instrumentation and correction of scoliosis. The patient had excellent postoperative analgesia and was able to participate in early rehabilitation. The opioid-sparing effect of ketamine was not demonstrated in this case. Further study of continuous low-dose ketamine infusions in this patient population would be beneficial to provide more evaluation of the efficacy and tolerability of ketamine and of its opioid-sparing potential.
Nutrition, Metabolism and Cardiovascular Diseases, 2009
Several working definitions of metabolic syndrome have been proposed for clinical use. However, i... more Several working definitions of metabolic syndrome have been proposed for clinical use. However, individuals can be discordantly classified as having or not having metabolic syndrome depending on the choice of one or another definition. This study compared the cardiovascular risk profile of subjects concordantly and discordantly diagnosed by the criteria of the National Cholesterol Education Program (NCEP) and the criteria of the International Diabetes Federation (IDF). Nine hundred and twenty-nine non-diabetic adult subjects belonging to a cross-sectional population-based study in Gran Canaria island (Spain) were assessed. Participants completed a questionnaire and underwent physical examination, fasting blood analyses, and a standardized oral glucose tolerance test. Two hundred and four subjects (22%) had metabolic syndrome according to both definitions, 31 (3.3%) only by the IDF criteria, and 5 (0.5%) only by the NCEP criteria. Participants fulfilling both proposals showed more adverse age and sex-adjusted measures of BMI, waist, HDL cholesterol, triglycerides, post-load glucose, HOMA-IR and plasminogen inhibitor activator-1 (PAI-1) than individuals exclusively satisfying the IDF criteria. Moreover, in contrast to subjects meeting both criteria, those that fulfilled only the IDF criteria had levels of BMI, waist, total and HDL cholesterol, post-load glucose, glycated HbA1c, C-reactive protein, PAI-1 and fibrinogen not significantly different from those observed in subjects without metabolic syndrome. The IDF definition identifies a surplus of individuals whose cardiovascular risk profile, particularly regarding to some non-traditional cardiovascular risk factors, is less adverse than that observed in subjects also diagnosed by the NCEP definition.
Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor transcription factor t... more Peroxisome proliferator-activated receptor α (PPARα) is a nuclear receptor transcription factor that has an important role in controlling cardiac metabolic gene expression. We determined whether mice lacking PPARα (PPARα (−/−) mice) have alterations in cardiac energy metabolism. Rates of palmitate oxidation were significantly decreased in isolated working hearts from PPARα (−/−) hearts compared with hearts from age-matched wild type mice (PPARα (+/+) mice), (62 ± 12versus 154 ± 65 nmol/g dry weight/min, respectively,p < 0.05). This was compensated for by significant increases in the rates of glucose oxidation and glycolysis. The decreased fatty acid oxidation in PPARα (−/−) hearts was associated with increased levels of cardiac malonyl-CoA compared with PPARα (+/+) hearts (15.15 ± 1.63 versus 7.37 ± 1.31 nmol/g, dry weight, respectively, p < 0.05). Since malonyl-CoA is an important regulator of cardiac fatty acid oxidation, we also determined if the enzymes that control malony...
The number of elderly patients presenting for anaesthesia and surgery has increased exponentially... more The number of elderly patients presenting for anaesthesia and surgery has increased exponentially in recent years. Regional anaesthesia is frequently used in elderly patients undergoing surgery. Although the type of anaesthesia (general versus regional anaesthesia) has no substantial effect on perioperative morbidity and mortality in any age group; it intuitively makes sense that elderly patients would benefit from regional anaesthesia because they remain minimally sedated throughout the procedures and awaken with excellent postoperative pain control. However, a multitude of factors influence the outcome, such as the type, duration and invasiveness of the operation, co-existing medical and mental status of the patient and the skill and expertise of the anaesthesiologist and surgeon. These factors make it difficult to decide if and when one technique is equivocally better than another. Thus, it is more important to optimise the overall management of the patient during the perioperati...
Results: In normal fetuses, it was possible to identify the respective position of the inferior v... more Results: In normal fetuses, it was possible to identify the respective position of the inferior vena cava and the descending aorta in all cases. In the 3 cases with left atrial isomerism, it was possible to identify the azygos continuation adjacent to the descending aorta and the abnormal stomach position. In no case could the multiple spleens be identified. In the 3 cases with right atrial isomerism, it was possible to identify the abnormal central position of the inferior vena cava and the displacement of the stomach to the left. The abnormal liver morphology consistent with left and right isomerism could be identified in 5/6 cases. Discussion: Identification of fetal situs has so far been carried out by assessing the position of the abdominal vessels on an axial view of the fetal abdomen. Using the coronal plane of the fetal trunk from three-dimensional volumes, it was possible to identify visceral anatomic patterns consistent with a diagnosis of situs solitus or ambiguous (left or right isomerim) independently from the type of congenital heart disease present. This may be of help in difficult cases to tag the type of cardiosplenic syndrome.
The number of elderly patients presenting for anaesthesia and surgery has increased exponentially... more The number of elderly patients presenting for anaesthesia and surgery has increased exponentially in recent years. Regional anaesthesia is frequently used in elderly patients undergoing surgery. Although the type of anaesthesia (general versus regional anaesthesia) has no substantial effect on perioperative morbidity and mortality in any age group; it intuitively makes sense that elderly patients would benefit from regional anaesthesia because they remain minimally sedated throughout the procedures and awaken with excellent postoperative pain control. However, a multitude of factors influence the outcome, such as the type, duration and invasiveness of the operation, co-existing medical and mental status of the patient and the skill and expertise of the anaesthesiologist and surgeon. These factors make it difficult to decide if and when one technique is equivocally better than another. Thus, it is more important to optimise the overall management of the patient during the perioperati...
We designed this study to determine the threshold current for nerve stimulation of an insulated n... more We designed this study to determine the threshold current for nerve stimulation of an insulated needle in the epidural space. The intended dermatome was identified using the bony landmarks of the spine. An 18-gauge insulated Tuohy needle was inserted perpendicularly to the skin and advanced until "loss of resistance" was felt. A nerve stimulator was then connected to the insulated needle. Twenty patients were studied using an insulated Tuohy needle and one patient was studied using a noninsulated Tuohy needle. Muscle twitch was elicited with a current of 11.1 +/- 3.1 mA (mean +/- sd) in all patients in which an insulated needle was used. Muscle twitches were within 2 myotomes of the intended level (based on bony landmarks). Muscle twitch was not elicited with a noninsulated needle. After catheter threading, positive stimulation tests were elicited via epidural catheters in all patients (4.9 +/- 2.3 mA). Postoperative radiograph confirmed all catheter placements within 2 my...
A small volume of local anesthetic or normal saline abolishes the muscle twitch induced by a 1ow ... more A small volume of local anesthetic or normal saline abolishes the muscle twitch induced by a 1ow current (0.5 mA) during electrolocation. This study examines the hypothesis that the mechanism of this phenomenon is primarily the electrophysiologic effect of the injectate on the electrical current density at the needle tip. Five pigs were studied. An insulated Tuohy needle was inserted in each pig toward the left and right brachial plexuses and the left and right femoral nerves. The needle was advanced until corresponding motor responses were observed at each site, using a current of 0.5 mA. The effect of injecting 1 mL each of normal saline and 5% dextrose in water (NS and D5W) on muscle twitch was investigated at all 20 needle insertion sites. Changes in the conductive area induced by the injectates were also demonstrated using gel electrophoresis. In all cases, the muscle twitches were abolished immediately after the injection of NS and recovered instantaneously after a subsequent injection of D5W. The electrical resistance between the needle and the ground electrodes decreased instantly after the NS injection. The resistance not only recovered but also increased after the injection of D5W. In the gel electrophoresis experiment, the results demonstrated that the expanded conductive area induced by the saline column surrounding the insulated needle was similar to that observed with the uninsulated needle. The injection of a conducting solution (i.e., NS) rendered the current that was previously sufficient to elicit a motor response (0.5 mA) ineffective. The most likely reason for this change is that the conductive area surrounding the stimulating needle expanded after the injection and dispersion of the conducting solution (i.e., NS), thereby reducing the current density at the target nerve. This effect can be reversed by injecting a nonconducting solution (i.e., D5W) via the stimulating needle.
Muscle twitches elicited with electrical stimulation (6-17 mA) during epidural insertion indicate... more Muscle twitches elicited with electrical stimulation (6-17 mA) during epidural insertion indicate correct epidural needle placement while muscle twitches at a lower current (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;1 mA) may indicate intrathecal needle placement. This study examined whether applying continuous electrical stimulation at 6 mA could indicate needle entry into the epidural space without inadvertently penetrating the intrathecal space. After institutional review board (IRB) approval, 10 pediatric patients scheduled for lumbar puncture were studied. Following sedation with propofol, an insulated 24-gauge Pajunck unipolar needle was inserted through an 18-gauge introducer needle placed at the L4-5 interspace. The needle was first connected to a nerve stimulator (6 mA) and advanced. At the first sign of muscle twitching, needle advancement was stopped and the threshold current for motor activity was determined. The current was then turned off, the stylet was removed and the needle checked for cerebrospinal fluid (CSF). If CSF was not present, the needle was advanced into the intrathecal space (as confirmed by the presence of CSF). Ten pediatric patients (ASA II or III) aged 7.8 +/- 4.3 years (2.8-16.0 years) were studied. All patients had two distinguishable threshold currents as the needle advanced. The mean threshold current to elicit muscle twitch in the presumed epidural space was 3.84 +/- 0.99 mA. CSF was not present in any of the patients at this location. The mean threshold current in the intrathecal space was 0.77 +/- 0.32 mA. The average estimated distance from the first threshold location to the intrathecal space was 3 mm. All muscle twitches were at the L3-5 myotomes. Nine muscle twitches were unilateral and one was bilateral. Monitoring with an insulated needle with electrical stimulation at 6 mA may prevent unintentional placement of epidural needles into the intrathecal space.
A prospective observational case series of children receiving light general anesthesia for magnet... more A prospective observational case series of children receiving light general anesthesia for magnetic resonance imaging (MRI) was performed. Our purpose was to examine the merit of anesthesia and recovery/discharge times of combined remifentanil and propofol total intravenous anesthesia (TIVA) in spontaneously breathing children. After IRB approval and informed consent, 56 patients receiving Remi/Propofol TIVA (Remifentanil 10 microg.ml(-1) Propofol 10 mg.ml(-1)) were observed. Blood pressure, respiratory rate, endtidal CO(2) (P(E)CO(2)), oxygen saturation and temperature were recorded at the start and finish of anesthesia. In addition, induction and recovery times were noted. Recovery time was from scan completion until discharge from the initial recovery area. Discharge time was from scan completion to discharge home. Fifty-six patients received Remi/Propofol TIVA. The mean Remi/Propofol recovery and discharge times were 8.9 and 28.2 min, respectively. There was a statistically significant decrease in respiratory rate and increase in CO(2) from the start to the end of the procedure. During the scan, seven patients moved. One patient experienced postprocedure nausea and or vomiting. The combination of remifentanil and propofol for TIVA may be an effective method of light general anesthesia in pediatric patients undergoing MRI.
Providing effective analgesia is challenging for correction of idiopathic scoliosis, as nonsteroi... more Providing effective analgesia is challenging for correction of idiopathic scoliosis, as nonsteroidal anti-inflammatory drugs and epidural anesthesia are controversial and large-dose opioids can cause significant side effects. Perioperative adjuvant low-dose ketamine has been shown to provide good supplementary analgesia as well as to potentially spare opioid consumption. Ketamine may also improve early ease of mobility without addition of any noticeable adverse effects. This case describes the combined use of a continuous low-dose ketamine infusion and patient-controlled analgesia (PCA) morphine for postoperative analgesia in an adolescent girl undergoing posterior spinal instrumentation and correction of scoliosis. The patient had excellent postoperative analgesia and was able to participate in early rehabilitation. The opioid-sparing effect of ketamine was not demonstrated in this case. Further study of continuous low-dose ketamine infusions in this patient population would be beneficial to provide more evaluation of the efficacy and tolerability of ketamine and of its opioid-sparing potential.
Nutrition, Metabolism and Cardiovascular Diseases, 2009
Several working definitions of metabolic syndrome have been proposed for clinical use. However, i... more Several working definitions of metabolic syndrome have been proposed for clinical use. However, individuals can be discordantly classified as having or not having metabolic syndrome depending on the choice of one or another definition. This study compared the cardiovascular risk profile of subjects concordantly and discordantly diagnosed by the criteria of the National Cholesterol Education Program (NCEP) and the criteria of the International Diabetes Federation (IDF). Nine hundred and twenty-nine non-diabetic adult subjects belonging to a cross-sectional population-based study in Gran Canaria island (Spain) were assessed. Participants completed a questionnaire and underwent physical examination, fasting blood analyses, and a standardized oral glucose tolerance test. Two hundred and four subjects (22%) had metabolic syndrome according to both definitions, 31 (3.3%) only by the IDF criteria, and 5 (0.5%) only by the NCEP criteria. Participants fulfilling both proposals showed more adverse age and sex-adjusted measures of BMI, waist, HDL cholesterol, triglycerides, post-load glucose, HOMA-IR and plasminogen inhibitor activator-1 (PAI-1) than individuals exclusively satisfying the IDF criteria. Moreover, in contrast to subjects meeting both criteria, those that fulfilled only the IDF criteria had levels of BMI, waist, total and HDL cholesterol, post-load glucose, glycated HbA1c, C-reactive protein, PAI-1 and fibrinogen not significantly different from those observed in subjects without metabolic syndrome. The IDF definition identifies a surplus of individuals whose cardiovascular risk profile, particularly regarding to some non-traditional cardiovascular risk factors, is less adverse than that observed in subjects also diagnosed by the NCEP definition.
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Papers by Alese Wagner