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1.
Surgery ; 167(4): 757-764, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32061400

RESUMEN

BACKGROUND: Although preoperative administration of high-dose glucocorticoid may lead to improved recovery after operative procedures, this regimen has not been examined in patients undergoing abdominal wall reconstruction for repair of large ventral hernias. The aim of the current trial was to examine the effects of preoperative, single high-dose glucocorticoid on recovery after abdominal wall reconstruction. METHOD: Forty patients undergoing abdominal wall reconstruction for repair of ventral incisional hernias with a horizontal fascial defect >10 cm were randomized to intravenous administration of either 125 mg methylprednisolone or placebo at the induction of anesthesia. The primary endpoint was pain in the supine position as assessed by a numeric rating scale of 0 to 10 at rest at 8 am on the first postoperative day. Secondary outcomes included postoperative pain during activity, nausea, fatigue, inflammatory response (measured by plasma levels of C-reactive protein), duration of stay, and 30-day complications or readmissions. RESULTS: There was no difference in pain at rest on the first postoperative day (methylprednisolone mean 1.7 vs placebo 2.2, P > .95), whereas patients in the methylprednisolone group reported less pain during activity (mean 3.0 vs 5.0; P = .011) and during coughing (3.4 vs 5.9; P = .010). There were no differences between the 2 groups regarding postoperative fatigue or nausea. Postoperative levels of C-reactive protein were less in the methylprednisolone group (P = .039). CONCLUSION: A single-shot, high-dose methylprednisolone before abdominal wall reconstruction for a large incisional hernia decreased early postoperative pain and attenuated the inflammatory response.


Asunto(s)
Pared Abdominal/cirugía , Hernia Incisional/cirugía , Metilprednisolona/uso terapéutico , Procedimientos de Cirugía Plástica/métodos , Complicaciones Posoperatorias/prevención & control , Anciano , Proteína C-Reactiva/análisis , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Premedicación
2.
Naunyn Schmiedebergs Arch Pharmacol ; 392(10): 1285-1292, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31187186

RESUMEN

Amitriptyline poisoning (AT) is a common poisoning, and AT possess the ability to promote life-threatening complications by its main action on the central nervous and cardiovascular systems. The pharmacokinetic properties might be altered at toxic levels compared to therapeutic levels. The effect of coated activated charcoal hemoperfusion (CAC-HP) on the accumulation of AT and its active metabolite nortriptyline (NT) in various tissues was studied in a non-blinded randomized controlled animal trial including 14 female Danish Land Race piglets. All piglets were poisoned with amitriptyline 7.5 mg/kg infused in 20 min, followed by orally instilled activated charcoal at 30 min after infusion cessation. The intervention group received 4 h of CAC-HP followed by a 1-h redistribution phase. At study cessation, the piglets were euthanized, and within 20 min, vitreous fluid, liver tissue, ventricle and septum of the heart, diaphragm and lipoic and brain tissues were collected. AT and NT tissue concentrations were quantified by UHPLC-MS/MS. A 4-h treatment with CAC-HP did not affect the tissue accumulation of AT in the selected organs when tested by Mann-Whitney U test (p values between 0.44 and 0.73). For NT concentrations, p values were between 0.13 and 1.00. Although not significant, an interesting finding was that data showed a tendency of increased tissue accumulation of AT and NT in the CAC-HP group compared with the control group. Coated activated charcoal hemoperfusion does not significantly alter the tissue concentration of AT and NT in the AT-poisoned piglet.


Asunto(s)
Amitriptilina , Antidepresivos Tricíclicos , Antídotos , Carbón Orgánico , Animales , Femenino , Amitriptilina/farmacocinética , Amitriptilina/envenenamiento , Antidepresivos Tricíclicos/farmacocinética , Antidepresivos Tricíclicos/envenenamiento , Antídotos/envenenamiento , Carbón Orgánico/farmacología , Cromatografía Líquida de Alta Presión , Modelos Animales de Enfermedad , Hemoperfusión/métodos , Nortriptilina/farmacocinética , Porcinos , Espectrometría de Masas en Tándem , Distribución Tisular
3.
Basic Clin Pharmacol Toxicol ; 122(4): 442-447, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29117643

RESUMEN

Coated activated charcoal haemoperfusion (CAC-HP) does not reduce the plasma concentration in amitriptyline (AT)-poisoned pigs. The aim of this non-blinded, randomized, controlled animal trial was to determine if CAC-HP reduces the pathological ECG changes caused by AT poisoning. Fourteen female Danish Landrace pigs (mean weight 27.7 kg, range 20-35 kg (CAC-HP) and 24.4 kg, range 18-30 kg (control group, CG), n = 7 in each group) were included. After randomization, the pigs were anaesthetized and intravenously poisoned with AT. The intervention group underwent 4 hr of CAC-HP plus standard care (oral activated charcoal). Intervention was compared to standard care alone. From each pig, a 12-lead ECG and haemodynamic variables were obtained at baseline, at full AT loading dose, before and during CAC-HP. Baseline ECG variables (RR, PR, QRS, QTc, QTp, QTe, TpTe and TpTe/QT) for lead II, v2 and v5 were not significantly different (F = 0.035-0.297, p-values 0.421-0.919). Differences within groups over time and between groups were tested by anova repeated measures. For all variables, the time-plus-group level of significance revealed a p-value > 0.05. Severe cardiovascular arrhythmias occurred in both groups with 3 in the CAC-HP group versus 1 incident with premature death in the CG. The attenuating effect of CAC-HP to orally instilled activated charcoal alone on AT-induced ECG alterations did not differ significantly. We conclude that the use of modern CAC-HP as an adjunctive treatment modality in AT-poisoned pigs is inadequate.


Asunto(s)
Amitriptilina/envenenamiento , Antidepresivos Tricíclicos/envenenamiento , Sobredosis de Droga/terapia , Hemoperfusión/métodos , Intoxicación/terapia , Administración Oral , Amitriptilina/sangre , Animales , Antidepresivos Tricíclicos/sangre , Arritmias Cardíacas/sangre , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/terapia , Carbón Orgánico/química , Carbón Orgánico/uso terapéutico , Terapia Combinada/métodos , Modelos Animales de Enfermedad , Sobredosis de Droga/sangre , Sobredosis de Droga/diagnóstico , Sobredosis de Droga/etiología , Electrocardiografía/métodos , Femenino , Humanos , Intoxicación/sangre , Intoxicación/diagnóstico , Intoxicación/etiología , Sus scrofa , Resultado del Tratamiento
4.
Dan Med J ; 64(9)2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28874242

RESUMEN

INTRODUCTION: High-dose recombinant human erythropoietin (rhEpo) has been shown to improve cognitive performance in both healthy volunteers and in patients suffering from diseases affecting the brain. The aim of this study was to examine whether administration of low-dose and even micro-dose rhEpo improves cognitive performance in healthy volunteers. METHODS: We enrolled 25 healthy volunteers in a double-blind, randomised, placebo-controlled study to receive either low-dose rhEpo (n = 8, 60 IU/kg/week), micro-dose rhEpo (n = 9, 20 IU/kg/week), or saline (n = 8) for four weeks. Two cognitive performance-tests, the Raven Standard Progressive Matrices (Raven) and the Number Finder (NUFI), were performed during the first and last day of the study period. Semi-structured interviews were conducted weekly and were coded according to a scale. RESULTS: Subjects receiving micro-dose rhEpo improved significantly measured by the Raven score (p = 0.04), and subjects receiving low-dose rhEpo treatment improved significantly measured by the NUFI score (p = 0.047), whereas no improvement was found in experienced cognitive performance in any of the groups. We found no significant difference in either Raven, NUFI or self-reported results between the groups. CONCLUSIONS: In this small study, we found no significant effect of low-dose or micro-dose rhEpo on visual attention, cognitive performance in complex cognitive tasks or self-experienced cognitive performance compared with placebo. FUNDING: The Aase and Ejnar Danielsen's Foundation. Danish Ministry of Science, Innovation and Higher Education. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03093506.


Asunto(s)
Cognición/efectos de los fármacos , Eritropoyetina/administración & dosificación , Proteínas Recombinantes/administración & dosificación , Adulto , Trastornos del Conocimiento/tratamiento farmacológico , Método Doble Ciego , Femenino , Voluntarios Sanos , Humanos , Masculino , Adulto Joven
5.
Neurochem Res ; 42(6): 1583-1588, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28058526

RESUMEN

Citrate is key constituent of the tricarboxylic acid (TCA) cycle, serves as substrate for fatty acid and sterol biosynthesis, and functions as a key regulator of intermediary energy metabolism. Ursula Sonnewald had initiated studies using for the first time both proton- and 13C-NMR to investigate metabolic processes in cultured neurons and astrocytes resulting in the important observation that citrate was specifically synthesized in and released from astrocytes in large amounts which is in keeping with the high concentration found in the CSF. The aim of this review is to highlight the possible roles of citrate in physiological and pathophysiological processes in the CNS. An interesting feature of citrate is its ability to chelate Ca2+, Mg2+ and Zn2+and thereby playing a pivotal role as an endogenous modulator of glutamate receptors and in particular the NMDA subtypes of these receptors in the CNS. Besides its presence in cerebrospinal fluid (CSF) citrate is also found in high amounts in prostate fluid reaching concentrations as high as 180 mM and here Zn2+ seems also to play an important role, which makes prostate cells interesting for comparison of features of citrate and Zn2+ between these cells and cells in the CNS.


Asunto(s)
Astrocitos/metabolismo , Sistema Nervioso Central/metabolismo , Ácido Cítrico/metabolismo , Neuronas/metabolismo , Animales , Humanos , Magnesio/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Zinc/metabolismo
6.
Basic Clin Pharmacol Toxicol ; 120(5): 491-497, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27863000

RESUMEN

Coated activated charcoal haemoperfusion (CAC-HP) is a well-known treatment modality. Case reports have revealed conflicting results about the efficacy of CAC-HP in the treatment of amitriptyline (AT) poisoning, and no randomized clinical trials have been identified in the literature. This study aimed at quantifying the efficacy of modern CAC-HP as an adjunctive treatment of AT intoxication compared with standard care alone. Fourteen female Danish landrace pigs were randomized to either standard care or standard care plus 4 hr of CAC-HP. The pigs were anaesthetized, and vital parameters were continuously recorded. Amitriptyline infusion (7.5 mg/kg) was completed in 20 min. Thirty minutes after AT infusion, activated charcoal was instilled orally in both groups. In the intervention group, CAC-HP was initiated 60 min. after AT infusion. Blood and urine samples were collected as were vital parameters at specific time intervals. The protocol was approved by the Danish Experimental Animal Expectorate and complied with the NIH guide for care and use of laboratory animals. Data were managed according to the ARRIVE guidelines. No statistical significant differences between intervention and control groups were found when analysing for differences in AT levels in plasma at any time-point. Furthermore, significant differences between the control and intervention groups in regard to vital parameters could not be found either. In our animal model, the addition of CAC-HP did not improve the clearance of AT compared with standard treatment alone. We suggest that the effect of modern CAC-HP as a treatment modality in AT-poisoned human patients may be inadequate.


Asunto(s)
Amitriptilina/envenenamiento , Antídotos/administración & dosificación , Carbón Orgánico/administración & dosificación , Hemoperfusión/métodos , Amitriptilina/farmacocinética , Animales , Antidepresivos Tricíclicos/farmacocinética , Antidepresivos Tricíclicos/envenenamiento , Femenino , Hemodinámica/efectos de los fármacos , Distribución Aleatoria , Porcinos , Factores de Tiempo , Resultado del Tratamiento
7.
Dan Med J ; 63(8)2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27477797

RESUMEN

INTRODUCTION: Preoperative administration of high-dose glucocorticoid leads to improved recovery and decreased length of stay after abdominal surgery. Even so, studies on administration of glucocorticoids for patients undergoing abdominal wall reconstruction (AWR) for giant ventral hernia repair are lacking, perhaps due to a fear of impaired wound healing. We hypothesised that patients undergoing AWR would benefit from preoperative glucocorticoids and aimed at examining this in a randomised controlled trial. METHODS: A total of 40 patients scheduled to undergo AWR for ventral hernias with a fascial defect exceeding 10 cm will be randomised for intravenous administration of either 125 mg methylprednisolone or saline at the induction of anaesthesia. The primary endpoint is pain at rest on the first post-operative day. Patients will be followed until 30 days post-operatively, and secondary outcomes include subjective measures, wound complications and analysis of blood and wound fluids. CONCLUSIONS: This is the first trial on the effect of preoperative glucocorticoid administration in patients undergoing AWR. Due to long post-operative stays and a high rate of post-operative complications, this patient group can potentially benefit much from any post-operative optimisation. Furthermore, insight into any impact of glucocorticoids on wound healing in hernia patients may provide important information. FUNDING: none. TRIAL REGISTRATION: This study was registered with Clinicaltrials.gov (NCT02594241) and Eudra-CT (2015-004916-39).


Asunto(s)
Pared Abdominal/cirugía , Abdominoplastia/métodos , Glucocorticoides/administración & dosificación , Herniorrafia/métodos , Complicaciones Posoperatorias/prevención & control , Cuidados Preoperatorios/métodos , Mallas Quirúrgicas , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Estudios de Seguimiento , Hernia Ventral/cirugía , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Cicatrización de Heridas/efectos de los fármacos
8.
Annu Int Conf IEEE Eng Med Biol Soc ; 2016: 2712-2716, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28324969

RESUMEN

Traditionally, measurements of the oxygen saturation (SpO2) has been confound to the extremities. In this study, we therefore investigated the possibility for reliable estimation of clinically relevant SpO2 levels from photoplethysmography (PPG) obtained on the sternum of patients with obstructive airway diseases. We initiated the study with a calibration of a prototype sternal PPG sensor. In accordance with the ISO 80601-2-61:2011 guidelines, the calibration was conducted as a controlled desaturation study. We obtained a calibration accuracy of 1.75% which is well within the clinically and commercially accepted range. We then compared the SpO2 levels simultaneously obtained from the sternal PPGs and a commercially available finger pulse oximeter on 28 admitted patients with either asthma or Chronic Obstructive Pulmonary Disease (COPD). The Pearson correlation between the SpO2 levels estimated from the two body locations was found to be 0.89 (p<;0.05) and the mean system bias was only 0.052% with upper and lower limits of agreement of 2.5% and -2.4%, respectively. This finding is very promising for the future design of new sternum based patch technologies that might be able to provide continuous estimates of the SpO2 levels on critically or chronically ill patients.


Asunto(s)
Fotopletismografía/métodos , Enfermedad Pulmonar Obstructiva Crónica , Esternón , Dedos , Humanos , Oximetría , Oxígeno
9.
Annu Int Conf IEEE Eng Med Biol Soc ; 2016: 2725-2728, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28268883

RESUMEN

Calculation of long-term quasi-continuous oxygen saturation (SpO2) levels is highly relevant for critically ill patients. The purpose of this study is therefore to conduct a preliminary investigation of the clinical reliability of long-term photoplethysmography (PPG) recordings obtained from the sternum of patients admitted to the hospital with obstructive lung diseases. Due to the lack of a gold standard reference that is suitable for long-term monitoring without interfering with the patient's activity level, we extracted reliable segments based on knowledge from the basic pulse oximeter theory as well as knowledge about the inherent physiological regulation of the SpO2 levels. We included 15 admitted patients who were monitored with a prototype of a sternal PPG sensor for approximately 20 hours. On average, we found that clinically reliable SpO2 levels could be calculated for 58% of the recording time. Furthermore, the average and standard deviation of the longest period of time with unreliable data was only 23.6 ± 19.38 minutes. This indicates a high potential for quasi-continuous calculation of SpO2 levels from sternal PPGs in many different clinical applications in the future.


Asunto(s)
Enfermedades Pulmonares Obstructivas/diagnóstico , Monitoreo Fisiológico , Oximetría , Fotopletismografía , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados
10.
J Sports Sci ; 33(6): 570-8, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25259652

RESUMEN

The present investigation was performed to elucidate if the non-erythropoietic ergogenic effect of a recombinant erythropoietin treatment results in an impact on skeletal muscle mitochondrial and whole body fatty acid oxidation capacity during exercise, myoglobin concentration and angiogenesis. Recombinant erythropoietin was administered by subcutaneous injections (5000 IU) in six healthy male volunteers (aged 21 ± 2 years; fat mass 18.5 ± 2.3%) over 8 weeks. The participants performed two graded cycle ergometer exercise tests before and after the intervention where VO2max and maximal fat oxidation were measured. Biopsies of the vastus lateralis muscle were obtained before and after the intervention. Recombinant erythropoietin treatment increased mitochondrial O2 flux during ADP stimulated state 3 respiration in the presence of complex I and II substrates (malate, glutamate, pyruvate, succinate) with additional electron input from ß-oxidation (octanoylcarnitine) (from 60 ± 13 to 87 ± 24 pmol · s(-1) · mg(-1) P < 0.01). ß-hydroxy-acyl-CoA-dehydrogenase activity was higher after treatment (P < 0.05), whereas citrate synthase activity also tended to increase (P = 0.06). Total myoglobin increased by 16.5% (P < 0.05). Capillaries per muscle area tended to increase (P = 0.07), whereas capillaries per fibre as well as the total expression of vascular endothelial growth factor remained unchanged. Whole body maximal fat oxidation was not increased after treatment. Eight weeks of recombinant erythropoietin treatment increases mitochondrial fatty acid oxidation capacity and myoglobin concentration without any effect on whole body maximal fat oxidation.


Asunto(s)
Eritropoyetina/administración & dosificación , Ejercicio Físico/fisiología , Hematínicos/administración & dosificación , Metabolismo de los Lípidos , Mitocondrias Musculares/metabolismo , Citrato (si)-Sintasa/metabolismo , Enoil-CoA Hidratasa/metabolismo , Hematócrito , Humanos , Inyecciones Subcutáneas , Masculino , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/metabolismo , Mioglobina/metabolismo , Neovascularización Fisiológica , Oxidación-Reducción , Consumo de Oxígeno , Proteínas Recombinantes/administración & dosificación , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto Joven
11.
Artículo en Inglés | MEDLINE | ID: mdl-26737798

RESUMEN

The respiratory rate (RR) is a clinically important vital sign and is a frequently used parameter in the general hospital wards. In current clinical practice, the monitoring of the RR is by manual count of the chest movement for one minute. This paper addresses a new approach where the respiratory rate is extracted using photoplethysmography (PPG) on the chest bone (sternum). Sternal PPG signals were acquired from 10 healthy subjects resting in a supine position. As reference signals, finger PPG, electrocardiogram (ECG), and capnography were simultaneously recorded during spontaneous and paced breathing. The sternal PPG signals were then compared with the reference signals in terms of Bland-Altman analysis, the power spectrum analysis and the magnitude squared coherence. The Bland-Altman analysis showed an average bias of 0.21 breaths/min between RR extracted from sternal PPG and capnography. The respiratory power content at the sternum was 78.8 (38) % in terms of the median and (the interquartile range). The cardiac content was 19 (18.4) % within the cardiac region. The results from the magnitude squared coherence analysis was 0.97 (0.09) in the respiratory region (6 to 27 breaths/min) and 0.98 (0.01) in the cardiac pulse region (30-120 beats/min). This preliminary study demonstrates the possibility of monitoring the RR from sternal PPG on a healthy group of subjects during rest.


Asunto(s)
Fotopletismografía/métodos , Frecuencia Respiratoria/fisiología , Procesamiento de Señales Asistido por Computador , Esternón/fisiología , Humanos
12.
Artículo en Inglés | MEDLINE | ID: mdl-25570719

RESUMEN

The heart rate variability (HRV) is a commonly used method to quantify the sympathetic and the parasympathetic modulation of the heart rate. HRV is mainly conducted on electrocardiograms (ECG). However, the use of photo-plethysmography (PPG) as a marker of the autonomic tone is emerging. In this study we investigated the feasibility of deriving pulse rate variability (PRV) using PPG signals recorded by a reflectance PPG sensor attached to the chest bone (sternum) and comparing it to HRV. The recordings were conducted on 9 healthy subjects being in a relaxed supine position and under forced respiration, where the subjects were asked to breathe following a visual scale with a rate of 27 breaths/min. HRV parameters such as the mean intervals (meanNN), the standard deviation of intervals (SDNN), the root mean square of difference of successive intervals (RMSSD), and the proportion of intervals differing more than 50 ms (pNN50) were calculated from the R peak-to-R peak (R-R) and pulse-to-pulse (P-P) intervals. In the frequency domain the low and high frequency ratio of the power spectral density (LF/HF) was also computed. The Pearson correlation coefficient showed significant correlation for all the parameters (r > 0.95 with p < 0.001) and the Bland-Altmann analysis showed close agreement between the two methods for all the parameters during resting and forced respiration condition. Thus, PRV analysis using sternal PPG can be an alternative to HRV analysis on healthy subjects at.


Asunto(s)
Voluntarios Sanos , Frecuencia Cardíaca/fisiología , Esternón/fisiología , Adulto , Electrocardiografía , Femenino , Humanos , Masculino , Fotopletismografía , Procesamiento de Señales Asistido por Computador , Factores de Tiempo
13.
Anesthesiol Res Pract ; 2012: 647258, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22988456

RESUMEN

Background. The prone position is applied to facilitate surgery of the back and to improve oxygenation in the respirator-treated patient. In particular, with positive pressure ventilation the prone position reduces venous return to the heart and in turn cardiac output (CO) with consequences for cerebral blood flow. We tested in healthy subjects the hypothesis that rotating the head in the prone position reduces cerebral blood flow. Methods. Mean arterial blood pressure (MAP), stroke volume (SV), and CO were determined, together with the middle cerebral artery mean blood velocity (MCA V(mean)) and jugular vein diameters bilaterally in 22 healthy subjects in the prone position with the head centered, respectively, rotated sideways, with and without positive pressure breathing (10 cmH(2)O). Results. The prone position reduced SV (by 5.4 ± 1.5%; P < 0.05) and CO (by 2.3 ± 1.9 %), and slightly increased MAP (from 78 ± 3 to 80 ± 2 mmHg) as well as bilateral jugular vein diameters, leaving MCA V(mean) unchanged. Positive pressure breathing in the prone position increased MAP (by 3.6 ± 0.8 mmHg) but further reduced SV and CO (by 9.3 ± 1.3 % and 7.2 ± 2.4 % below baseline) while MCA V(mean) was maintained. The head-rotated prone position with positive pressure breathing augmented MAP further (87 ± 2 mmHg) but not CO, narrowed both jugular vein diameters, and reduced MCA V(mean) (by 8.6 ± 3.2 %). Conclusion. During positive pressure breathing the prone position with sideways rotated head reduces MCA V(mean) ~10% in spite of an elevated MAP. Prone positioning with rotated head affects both CBF and cerebrovenous drainage indicating that optimal brain perfusion requires head centering.

14.
Neurochem Res ; 37(12): 2767-75, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23011203

RESUMEN

Structure activity relationship (SAR) analyses of pharmacological data of compounds constitute an important part of the discovery process in the design of new drug candidates with improved pharmacological properties. In particular G-Protein Coupled Receptors (GPCRs) associated with the cAMP second messenger systems G(s) and G(i) have constituted one of the most widely used basis for pharmacological in vitro assays for assessing functional receptor effects. Such assays are based on Radio Immuno Assay (RIA) analysis to measure the cellular cAMP concentration as readout of receptor activation. It appears, however, to be a common practice to omit the use of cAMP standard curves to transform the measured signals (cpm or cps) into cAMP concentrations on which estimations of potencies (EC(50) values) and efficacies (E(MAX) values) in G(s) and G(i) coupled receptor stimulation are based. Such practice may lead to significant errors as compounds mediating their effects via G(s) coupled receptors may appear more potent and efficacious than they actually are. Contrary, compounds mediating their effects via G(i) coupled receptors may appear less potent and efficacious than they are in reality. Potency rank orders will therefore change considerably, when estimations are based on incorrect calculation of the original experimental results. Thus, the only correct way to calculate effect data on which to base E(MAX) and EC(50) estimations is to use cAMP concentrations derived from transformation of the measured signals (cpm or cps) using cAMP standard curves. The present work outlines the mathematical procedures by which such transformations are to be performed.


Asunto(s)
Receptores Acoplados a Proteínas G/metabolismo , Algoritmos , AMP Cíclico/metabolismo , Células HEK293 , Humanos , Ligandos , Radioinmunoensayo
15.
Reg Anesth Pain Med ; 37(5): 502-7, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22705951

RESUMEN

BACKGROUND AND OBJECTIVES: Open inguinal hernia repair in adults is considered a minor surgical procedure but can be associated with significant pain. We aimed to evaluate acute postoperative pain management in male adults randomized to receive an ultrasound-guided ilioinguinal and iliohypogastric nerve block administered before surgery, in addition to a standard analgesic regimen. METHODS: Sixty patients were included in this randomized, controlled, and double-blind study. Patients were randomized to the administration of a block with 20 mL bupivacaine 0.5% or a placebo block with 20 mL saline. The primary outcome measure was pain at mobilization in the postanesthesia care unit (PACU). Pain at rest, dermatomal anesthesia, time spent in the PACU/ward, opioid consumption, postoperative vomiting and nausea, ability to perform activities of daily living, and perceived ill health status were secondary outcomes. RESULTS: A significant reduction in pain scores at mobilization (P<0.001) and rest (P < 0.005) was recorded in the bupivacaine group upon arrival in the PACU and again after 30 minutes. Pain at rest was similarly reduced in the bupivacaine group at the time of discharge (P < 0.017). There were significantly fewer patients (P < 0.05) with severe (numerical rating scale >5) and moderate (numerical rating scale >3) pain at mobilization and rest, respectively. Opioid consumption and time spent in the PACU were not significantly different between groups. CONCLUSIONS: Ultrasound-guided blocks of the ilioinguinal and iliohypogastric nerves resulted in a statistically significant and clinically relevant reduction in postoperative pain in the PACU both at mobilization and at rest.


Asunto(s)
Hernia Inguinal/cirugía , Herniorrafia/métodos , Bloqueo Nervioso/métodos , Dolor Postoperatorio/prevención & control , Ultrasonografía Intervencional/métodos , Adulto , Anciano , Bupivacaína/administración & dosificación , Método Doble Ciego , Femenino , Hernia Inguinal/epidemiología , Herniorrafia/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/epidemiología , Dolor Postoperatorio/etiología
16.
Front Physiol ; 3: 50, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22419911

RESUMEN

Erythropoietin (Epo) treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo) treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over 8 weeks with oral iron (100 mg) supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis before and after rhEpo treatment. OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate, and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS) was assessed by addition of an uncoupler. rhEpo treatment increased OXPHOS (from 92 ± 5 to 113 ± 7 pmol·s(-1)·mg(-1)) and ETS (107 ± 4 to 143 ± 14 pmol·s(-1)·mg(-1), p < 0.05), demonstrating that Epo treatment induces an upregulation of OXPHOS and ETS in human skeletal muscle.

17.
IEEE Trans Biomed Circuits Syst ; 6(1): 45-53, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23852744

RESUMEN

We report the development of an Electronic Patch for wearable health monitoring. The Electronic Patch is a new health monitoring system incorporating biomedical sensors, microelectronics, radio frequency (RF) communication, and a battery embedded in a 3-dimensional hydrocolloid polymer. In this paper the Electronic Patch is demonstrated with a new optical biomedical sensor for reflectance pulse oximetry so that the Electronic Patch in this case can measure the pulse and the oxygen saturation. The reflectance pulse oximetry solution is based on a recently developed annular backside silicon photodiode to enable low power consumption by the light emitting components. The Electronic Patch has a disposable part of soft adhesive hydrocolloid polymer and a reusable part of hard polylaurinlactam. The disposable part contains the battery. The reusable part contains the reflectance pulse oximetry sensor and microelectronics. The reusable part is 'clicked' into the disposable part when the patch is prepared for use. The patch has a size of 88 mm by 60 mm and a thickness of 5 mm.


Asunto(s)
Electrónica Médica/instrumentación , Monitoreo Fisiológico/instrumentación , Oximetría , Algoritmos , Suministros de Energía Eléctrica , Equipos y Suministros Eléctricos , Diseño de Equipo , Humanos , Oximetría/instrumentación , Oximetría/métodos , Reproducibilidad de los Resultados , Procesamiento de Señales Asistido por Computador
18.
Reg Anesth Pain Med ; 36(6): 568-71, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22005660

RESUMEN

BACKGROUND AND OBJECTIVES: Transversus abdominis plane (TAP) blocks have been shown to reduce postoperative pain after various abdominal surgical procedures in several studies. The motor nerves of the abdominal wall are located in the same plane as the sensory nerves affected by the TAP block. The aim of this study was to examine whether the application of an ultrasound-guided TAP block would affect the muscles of the anterior abdominal wall with respect to their function as accessory respiratory muscles and hence pulmonary function. METHODS: Twelve healthy male volunteers were included in a randomized, double-blind, crossover study. Primary outcome measure was change in forced expiratory volume in 1 sec (FEV1) after the bilateral dual injection of either 4 × 15 mL of 0.25% bupivacaine or saline. Secondary outcome measures included forced vital capacity, maximum expiratory pressure, and a number of frontal abdominal quadrants anesthetized. RESULTS: Change in FEV1 following the administration of bupivacaine showed a mean increase of 15 (SEM, 45.5) mL compared with the saline block, which showed a mean increase in FEV1 of 34 (SEM, 57.4) mL (P = 0.62). Similar results were obtained for forced vital capacity and maximum expiratory pressure. Abdominal quadrants were inconsistently anesthetized following administration of bupivacaine blocks. CONCLUSIONS: The administration of ultrasound-guided bilateral dual TAP blocks does not result in clinically relevant or statistically significant changes in the pulmonary function in healthy male subjects.


Asunto(s)
Pared Abdominal/fisiología , Volumen Espiratorio Forzado/fisiología , Bloqueo Nervioso/métodos , Adolescente , Adulto , Estudios Cruzados , Método Doble Ciego , Humanos , Masculino , Dimensión del Dolor/métodos , Proyectos Piloto , Pruebas de Función Respiratoria/métodos , Adulto Joven
19.
Dan Med Bull ; 58(6): A4221, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21651873

RESUMEN

INTRODUCTION: Studies have shown that early warning score systems can identify in-patients at high risk of catastrophic deterioration and this may possibly be used for an emergency department (ED) triage. Bispebjerg Hospital has introduced a multidisciplinary team (MT) in the ED activated by the Bispebjerg Early Warning Score (BEWS). The BEWS is calculated on the basis of respiratory frequency, pulse, systolic blood pressure, temperature and level of consciousness. The aim of this study is to evaluate the ability of the BEWS to identify critically ill patients in the ED and to examine the feasibility of using the BEWS to activate an MT response. MATERIAL AND METHODS: This study is based on an evaluation of retrospective data from a random sample of 300 emergency patients. On the basis of documented vital signs, a BEWS was calculated retrospectively. The primary end points were admission to an intensive care unit (ICU) and death within 48 hours of arrival at the ED. This study was registered at clinicaltrials.gov (NCT01243021). RESULTS: A BEWS ≥ 5 is associated with a significantly increased risk of ICU admission within 48 hours of arrival (relative risk (RR) 4.1; 95% confidence interval (CI) 1.5-10.9) and death within 48 hours of arrival (RR 20.3; 95% CI 6.9-60.1). The sensitivity of the BEWS in identifying patients who were admitted to the ICU or who died within 48 hours of arrival was 63%. The positive predictive value of the BEWS was 16% and the negative predictive value 98% for identification of patients who were admitted to the ICU or who died within 48 hours of arrival. CONCLUSION: The BEWS is a simple scoring system based on readily available vital signs. It is a sensitive tool for detecting critically ill patients and may be used for ED triage and activation of an MT response.


Asunto(s)
Enfermedad Crítica , Diagnóstico Precoz , Servicio de Urgencia en Hospital , Unidades de Cuidados Intensivos/organización & administración , Personal de Enfermería en Hospital/organización & administración , Triaje/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Intervalos de Confianza , Sistemas de Apoyo a Decisiones Clínicas , Urgencias Médicas , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Riesgo , Medición de Riesgo/métodos , Sensibilidad y Especificidad , Factores de Tiempo , Adulto Joven
20.
Dan Med Bull ; 58(6): A4294, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21651880

RESUMEN

INTRODUCTION: Bispebjerg Hospital has introduced a triage system at the Emergency Department (ED) based on "primary criteria" and a physiological scoring system named the Bispebjerg Early Warning Score (BEWS). A BEWS is calculated on the basis of five vital signs which are accessible bedside. Patients who have a "primary criterion" or a BEWS ≥ 5 are presumed to be critically ill or severely injured and should be received by a multidisciplinary team, termed the Emergency Call (EC) and Trauma Call (TC), respectively. The aim of this study was to examine compliance with this triage system at Bispebjerg Hospital. MATERIAL AND METHODS: Retrospective evaluation of the triage of a random sample of 300 ED patients. ED medical charts were searched for "primary criteria", documentation of vital signs and a BEWS score. If a BEWS score had not been calculated, this was done retrospectively by the author. An evaluation was made to determine whether ECs or TCs had been correctly activated. RESULTS: In 47 patients, all five vital signs for calculation of a BEWS had been documented. A BEWS had been calculated in 22 patients. Nine patients had a TC activation criterion, and in all these cases a TC was activated. A total of 48 patients had an EC activation criterion, but an EC had only been activated in 24 patients. Among the 24 patients for whom an EC had not been activated, eight had a "primary criterion" and 16 patients had a retrospective BEWS ≥ 5. CONCLUSION: The triage system is not being used systematically and documentation of vital signs is insufficient at Bispebjerg Hospital. As a consequence, many patients who are presumed to be critically ill are not allocated to an EC. Initiatives have been taken to raise compliance with the system.


Asunto(s)
Enfermedad Crítica/epidemiología , Adhesión a Directriz/estadística & datos numéricos , Índices de Gravedad del Trauma , Triaje/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Sistemas de Apoyo a Decisiones Clínicas , Dinamarca , Diagnóstico Precoz , Servicio de Urgencia en Hospital/organización & administración , Servicio de Urgencia en Hospital/normas , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Adhesión a Directriz/tendencias , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico , Estudios Retrospectivos , Factores de Tiempo , Centros Traumatológicos , Triaje/organización & administración , Triaje/normas , Signos Vitales , Adulto Joven
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