Michael Irwin | University of California, Los Angeles (original) (raw)

Papers by Michael Irwin

BMC Gastroenterology, 2013

Background: Intestinal ischemia-reperfusion injury (IRI) can occur in clinical scenarios such as ... more Background: Intestinal ischemia-reperfusion injury (IRI) can occur in clinical scenarios such as organ transplantation, trauma and cardio-pulmonary bypass, as well as in neonatal necrotizing enterocolitis or persistent ductus arteriosus. Pharmacological protection by pretreating ("preconditioning") with opioids attenuates IRI in a number of organs. Remifentanil appears particularly attractive for this purpose because of its ultra-short duration of action and favorable safety profile. To date, little is known about opioid preconditioning of the intestine.

Biological Research For Nursing, 2013

Objectives: Researchers have proposed biological (inflammation) and psychological (depression) fa... more Objectives: Researchers have proposed biological (inflammation) and psychological (depression) factors as potential mechanisms for poorer outcomes and readmissions in heart failure (HF) patients. However, studies investigating the link between inflammation and depressive symptoms in these patients are few. We examined the relationships between levels of the inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, and soluble tumor necrosis factor receptor 2 (sTNR2) and depressive symptoms in HF outpatients. Method: 55 patients (74.5% men; 60% Whites; mean age 71.6 + 11.3 years) with New York Heart Association Class II, III, or IV HF (49%, 47%, and 4%, respectively) and mean ejection fraction (EF) 29.9 + 7.1% completed the Patient Health Questionnaire (PHQ)-9 as a measure of depressive symptoms. We also obtained height, weight, and CRP, IL-6, and sTNFR2 levels. We used multivariate regressions to assess the predictive value of PHQ-9 scores on each inflammatory marker. Results: 22 (40%) participants reported depressive symptoms (PHQ-9 score ≥ 5). After controlling for age, gender, body mass index, HF etiology, EF, and statin use, we found significant relationships between levels of both sTNFR2 (b ¼ .35, p ¼ .01) and IL-6 (b ¼ .30, p ¼ .04), but not CRP (b ¼ À.96, p ¼ .52), and depression scores. Conclusion: Our findings add to a growing body of evidence supporting the proposition that heightened inflammation explains the effect depression has on HF. Health care providers should screen for depression in HF patients, as they may be at higher risk of augmented inflammation and poor outcomes.

Biological Psychiatry, 2002

Alcoholic patients show prominent disturbances of sleep electroencephalograms (EEGs) with a marke... more Alcoholic patients show prominent disturbances of sleep electroencephalograms (EEGs) with a marked loss of slow wave sleep that is even more profound in African American alcoholics as compared to European Americans. Using partial sleep deprivation, this study examined the extent to which abnormal sleep is reversible in alcoholic subjects. In a sample stratified on ethnicity, polysomnographic and spectral sleep EEG measures were compared in male primary alcoholic in patients (n=46) and age-matched comparison controls (n=32) at baseline-and recovery sleep following a night of partial sleep deprivation. As compared to controls, alcoholic patients showed a loss of slow wave sleep and more spectral power in beta frequencies. Following sleep deprivation, slow wave sleep and delta power differentially changed between the groups. European American controls showed increases of slow wave sleep that were more robust than responses found in African American controls, whereas both alcoholic groups failed to show increases of slow wave sleep from baseline to recovery. Spectral EEG analyses revealed similar results; sleep deprivation induced significant increases of delta power during NREM-1 in the controls, but not in the alcoholics. Alcohol dependence compromises the augmentation of slow wave sleep and delta power seen in healthy adults following sleep deprivation. The differential effect of alcoholism on sleep stage physiology suggests a defect in the regulation or plasticity of slow wave sleep with implications for theories linking sleep depth to morbidity and outcome in alcoholics.

Behavioral Sleep Medicine, 2014

The purpose of this research was to evaluate the factor structure of the Pittsburgh Sleep Quality... more The purpose of this research was to evaluate the factor structure of the Pittsburgh Sleep Quality Index (PSQI) in rheumatoid arthritis (RA). The sample included 107 patients with RA, 88 females and seven males, with an average age of 56.09 years, recruited from the greater Southern California area. Confirmatory factor analysis evaluated single, two-and three-factor models. The single factor solution yielded a poor fit to the data. While the three-factor solution had the best fit, the two-factor solution, comprised of sleep efficiency and perceived sleep quality factors, was optimal because it had very good fit, and acceptable reliability for its individual factors. Clinical indices were consistently correlated with the sleep quality factor, but not with the sleep efficiency factor.

The effects of selective cyclooxygenase-2 (COX-2) inhibitors in biological functions are frequent... more The effects of selective cyclooxygenase-2 (COX-2) inhibitors in biological functions are frequently investigated in animal models. However, there is little data on their analgesic efficacy in experimental animals. This study aimed to determine whether oral gavage of 5 mg/kg valdecoxib in mice is active as an analgesic at this dose and whether it is associated with therapeutic blood levels. A nonselective COX inhibitor, ketorolac, was also investigated for comparison. A total of 106 C57 BL/6N mice were administered a single oral dose of 5 mg/kg of valdecoxib, ketorolac or placebo. The antinociceptive effects of both drugs were tested using hot-plate and formalin tests. For the hot-plate test, reaction time (latency) of the mouse before jumping was recorded. The total time that the mouse spent on licking/biting the injected paw (with dilute formalin) was recorded in the formalin test. Apart from the behavioral tests, plasma concentrations of the drugs at this dose were also determined. Mice were fed with 5 mg/kg of either valdecoxib or ketorolac. Blood samples were collected between 1 and 9 h postingestion. Valdecoxib and ketorolac concentration in the plasma was determined by high performance liquid chromatography with ultraviolet detection (HPLC-UV). Effective antinociception was observed for both drugs in the hot-plate test from 75 min to 2 h after oral dosing. Also, both drug treatments showed a significantly reduced nociceptive response in the second phase in the formalin test (20-30 min after injection). Both valdecoxib and ketorolac showed plasma concentrations comparable to the therapeutic concentrations in humans. A single oral dose of valdecoxib or ketorolac (5 mg/kg) is able to produce a therapeutic analgesic effect in mice.

BACKGROUND: 15-F2t-isoprostane (IsoP), a marker of reactive oxygen species-induced oxidative stre... more BACKGROUND: 15-F2t-isoprostane (IsoP), a marker of reactive oxygen species-induced oxidative stress, is increased after myocardial ischemia and reperfusion. It exerts deleterious effects on postischemic myocardium accompanied with increased release of endothelin-1 ...

A 60-year-old man with a history of oesophagectomy for carcinoma presented with worsening dysphag... more A 60-year-old man with a history of oesophagectomy for carcinoma presented with worsening dysphagia, dyspnoea and tachypnoea secondary to oesophageal stricture and tumour invasion of the trachea causing a "ball-valve" obstruction. The patient required placement of a T-Y tracheobronchial stent to relieve the airway obstruction and was successfully managed using sevoflurane for gaseous induction followed by maintenance with propofol total intravenous anaesthesia.

Preconditioning with remifentanil confers cardioprotection. Since Ca(2+) overload is a precipitat... more Preconditioning with remifentanil confers cardioprotection. Since Ca(2+) overload is a precipitating factor of injury, we determined the effects of remefentanil on intracellular Ca(2+) ([Ca(2+)](i)) and its transients induced by electrical stimulation and caffeine, which reflects Ca(2+) handling by Ca(2+) handling proteins, in rat ventricular myocytes. Freshly isolated adult male Sprague-Dawley rat myocytes were loaded with Fura-2/AM and [Ca](i) was determined by spectrofluorometry. Remifentanil at 0.1 - 1000 microg/L was administered. Ten minutes after administration, either 0.2 Hz electrical stimulation was applied or 10 mmol/L caffeine was added. The [Ca(2+)](i), and the amplitude, time resting and 50% decay (t(50)) of both transients induced by electrical stimulation (E [Ca(2+)](i)) and caffeine (C [Ca(2+)](i)) were determined. Remifentanil (0.1 - 1000.0 microg/L) decreased the [Ca(2+)](i) in a dose-dependent manner. It also decreased the amplitude of both transients dose-dependently. Furthermore, it increased the time to peak and t(50) of both transients dose-dependently. Remifentanil reduced the [Ca(2+)](i) and suppressed the transients induced by electrical stimulation and caffeine in rat ventricular myocytes.

* Department of Anesthesiology, The University of Hong Kong, Hong Kong SAR, China,† Research Cent... more * Department of Anesthesiology, The University of Hong Kong, Hong Kong SAR, China,† Research Centre of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, Hong Kong SAR, China, and‡ Department of Pharmacology and Pharmacy, The ...

Many patients with neuromuscular disorders develop progressive scoliosis and require corrective s... more Many patients with neuromuscular disorders develop progressive scoliosis and require corrective surgery. We present a patient with hereditary motor and sensory neuropathies who developed severe hypotension during corrective surgery for thoracolumbar scoliosis. The haemodynamic disturbance was probably secondary to thoracic hyperlordosis and the knee-chest position and was aggravated by surgical manipulation. This may be prevented by tailored preoperative evaluation of different patient prone position supports and frames in order to select that which causes least cardiovascular and respiratory disturbance. This patient also developed severely deranged liver function postoperatively and the possible aetiology is discussed.

A patient underwent major spinal surgery, twice within a 3 week period. On the first occasion his... more A patient underwent major spinal surgery, twice within a 3 week period. On the first occasion his post-operative pain was managed by conventional morphine patient-controlled analgesia (PCA). After the second procedure his pain was managed by a patient-controlled computer-assisted titration of alfentanil. This provided the opportunity to compare the efficacy of these two drug regimens in the same subject. The results showed comparable quality of analgesia and sedation and similar effects on respiration. However, the patient expressed a preference for morphine PCA.

BMC Gastroenterology, 2013

Background: Intestinal ischemia-reperfusion injury (IRI) can occur in clinical scenarios such as ... more Background: Intestinal ischemia-reperfusion injury (IRI) can occur in clinical scenarios such as organ transplantation, trauma and cardio-pulmonary bypass, as well as in neonatal necrotizing enterocolitis or persistent ductus arteriosus. Pharmacological protection by pretreating ("preconditioning") with opioids attenuates IRI in a number of organs. Remifentanil appears particularly attractive for this purpose because of its ultra-short duration of action and favorable safety profile. To date, little is known about opioid preconditioning of the intestine.

Biological Research For Nursing, 2013

Objectives: Researchers have proposed biological (inflammation) and psychological (depression) fa... more Objectives: Researchers have proposed biological (inflammation) and psychological (depression) factors as potential mechanisms for poorer outcomes and readmissions in heart failure (HF) patients. However, studies investigating the link between inflammation and depressive symptoms in these patients are few. We examined the relationships between levels of the inflammatory markers C-reactive protein (CRP), interleukin (IL)-6, and soluble tumor necrosis factor receptor 2 (sTNR2) and depressive symptoms in HF outpatients. Method: 55 patients (74.5% men; 60% Whites; mean age 71.6 + 11.3 years) with New York Heart Association Class II, III, or IV HF (49%, 47%, and 4%, respectively) and mean ejection fraction (EF) 29.9 + 7.1% completed the Patient Health Questionnaire (PHQ)-9 as a measure of depressive symptoms. We also obtained height, weight, and CRP, IL-6, and sTNFR2 levels. We used multivariate regressions to assess the predictive value of PHQ-9 scores on each inflammatory marker. Results: 22 (40%) participants reported depressive symptoms (PHQ-9 score ≥ 5). After controlling for age, gender, body mass index, HF etiology, EF, and statin use, we found significant relationships between levels of both sTNFR2 (b ¼ .35, p ¼ .01) and IL-6 (b ¼ .30, p ¼ .04), but not CRP (b ¼ À.96, p ¼ .52), and depression scores. Conclusion: Our findings add to a growing body of evidence supporting the proposition that heightened inflammation explains the effect depression has on HF. Health care providers should screen for depression in HF patients, as they may be at higher risk of augmented inflammation and poor outcomes.

Biological Psychiatry, 2002

Alcoholic patients show prominent disturbances of sleep electroencephalograms (EEGs) with a marke... more Alcoholic patients show prominent disturbances of sleep electroencephalograms (EEGs) with a marked loss of slow wave sleep that is even more profound in African American alcoholics as compared to European Americans. Using partial sleep deprivation, this study examined the extent to which abnormal sleep is reversible in alcoholic subjects. In a sample stratified on ethnicity, polysomnographic and spectral sleep EEG measures were compared in male primary alcoholic in patients (n=46) and age-matched comparison controls (n=32) at baseline-and recovery sleep following a night of partial sleep deprivation. As compared to controls, alcoholic patients showed a loss of slow wave sleep and more spectral power in beta frequencies. Following sleep deprivation, slow wave sleep and delta power differentially changed between the groups. European American controls showed increases of slow wave sleep that were more robust than responses found in African American controls, whereas both alcoholic groups failed to show increases of slow wave sleep from baseline to recovery. Spectral EEG analyses revealed similar results; sleep deprivation induced significant increases of delta power during NREM-1 in the controls, but not in the alcoholics. Alcohol dependence compromises the augmentation of slow wave sleep and delta power seen in healthy adults following sleep deprivation. The differential effect of alcoholism on sleep stage physiology suggests a defect in the regulation or plasticity of slow wave sleep with implications for theories linking sleep depth to morbidity and outcome in alcoholics.

Behavioral Sleep Medicine, 2014

The purpose of this research was to evaluate the factor structure of the Pittsburgh Sleep Quality... more The purpose of this research was to evaluate the factor structure of the Pittsburgh Sleep Quality Index (PSQI) in rheumatoid arthritis (RA). The sample included 107 patients with RA, 88 females and seven males, with an average age of 56.09 years, recruited from the greater Southern California area. Confirmatory factor analysis evaluated single, two-and three-factor models. The single factor solution yielded a poor fit to the data. While the three-factor solution had the best fit, the two-factor solution, comprised of sleep efficiency and perceived sleep quality factors, was optimal because it had very good fit, and acceptable reliability for its individual factors. Clinical indices were consistently correlated with the sleep quality factor, but not with the sleep efficiency factor.

The effects of selective cyclooxygenase-2 (COX-2) inhibitors in biological functions are frequent... more The effects of selective cyclooxygenase-2 (COX-2) inhibitors in biological functions are frequently investigated in animal models. However, there is little data on their analgesic efficacy in experimental animals. This study aimed to determine whether oral gavage of 5 mg/kg valdecoxib in mice is active as an analgesic at this dose and whether it is associated with therapeutic blood levels. A nonselective COX inhibitor, ketorolac, was also investigated for comparison. A total of 106 C57 BL/6N mice were administered a single oral dose of 5 mg/kg of valdecoxib, ketorolac or placebo. The antinociceptive effects of both drugs were tested using hot-plate and formalin tests. For the hot-plate test, reaction time (latency) of the mouse before jumping was recorded. The total time that the mouse spent on licking/biting the injected paw (with dilute formalin) was recorded in the formalin test. Apart from the behavioral tests, plasma concentrations of the drugs at this dose were also determined. Mice were fed with 5 mg/kg of either valdecoxib or ketorolac. Blood samples were collected between 1 and 9 h postingestion. Valdecoxib and ketorolac concentration in the plasma was determined by high performance liquid chromatography with ultraviolet detection (HPLC-UV). Effective antinociception was observed for both drugs in the hot-plate test from 75 min to 2 h after oral dosing. Also, both drug treatments showed a significantly reduced nociceptive response in the second phase in the formalin test (20-30 min after injection). Both valdecoxib and ketorolac showed plasma concentrations comparable to the therapeutic concentrations in humans. A single oral dose of valdecoxib or ketorolac (5 mg/kg) is able to produce a therapeutic analgesic effect in mice.

BACKGROUND: 15-F2t-isoprostane (IsoP), a marker of reactive oxygen species-induced oxidative stre... more BACKGROUND: 15-F2t-isoprostane (IsoP), a marker of reactive oxygen species-induced oxidative stress, is increased after myocardial ischemia and reperfusion. It exerts deleterious effects on postischemic myocardium accompanied with increased release of endothelin-1 ...

A 60-year-old man with a history of oesophagectomy for carcinoma presented with worsening dysphag... more A 60-year-old man with a history of oesophagectomy for carcinoma presented with worsening dysphagia, dyspnoea and tachypnoea secondary to oesophageal stricture and tumour invasion of the trachea causing a "ball-valve" obstruction. The patient required placement of a T-Y tracheobronchial stent to relieve the airway obstruction and was successfully managed using sevoflurane for gaseous induction followed by maintenance with propofol total intravenous anaesthesia.

Preconditioning with remifentanil confers cardioprotection. Since Ca(2+) overload is a precipitat... more Preconditioning with remifentanil confers cardioprotection. Since Ca(2+) overload is a precipitating factor of injury, we determined the effects of remefentanil on intracellular Ca(2+) ([Ca(2+)](i)) and its transients induced by electrical stimulation and caffeine, which reflects Ca(2+) handling by Ca(2+) handling proteins, in rat ventricular myocytes. Freshly isolated adult male Sprague-Dawley rat myocytes were loaded with Fura-2/AM and [Ca](i) was determined by spectrofluorometry. Remifentanil at 0.1 - 1000 microg/L was administered. Ten minutes after administration, either 0.2 Hz electrical stimulation was applied or 10 mmol/L caffeine was added. The [Ca(2+)](i), and the amplitude, time resting and 50% decay (t(50)) of both transients induced by electrical stimulation (E [Ca(2+)](i)) and caffeine (C [Ca(2+)](i)) were determined. Remifentanil (0.1 - 1000.0 microg/L) decreased the [Ca(2+)](i) in a dose-dependent manner. It also decreased the amplitude of both transients dose-dependently. Furthermore, it increased the time to peak and t(50) of both transients dose-dependently. Remifentanil reduced the [Ca(2+)](i) and suppressed the transients induced by electrical stimulation and caffeine in rat ventricular myocytes.

* Department of Anesthesiology, The University of Hong Kong, Hong Kong SAR, China,† Research Cent... more * Department of Anesthesiology, The University of Hong Kong, Hong Kong SAR, China,† Research Centre of Heart, Brain, Hormone and Healthy Aging, The University of Hong Kong, Hong Kong SAR, China, and‡ Department of Pharmacology and Pharmacy, The ...

Many patients with neuromuscular disorders develop progressive scoliosis and require corrective s... more Many patients with neuromuscular disorders develop progressive scoliosis and require corrective surgery. We present a patient with hereditary motor and sensory neuropathies who developed severe hypotension during corrective surgery for thoracolumbar scoliosis. The haemodynamic disturbance was probably secondary to thoracic hyperlordosis and the knee-chest position and was aggravated by surgical manipulation. This may be prevented by tailored preoperative evaluation of different patient prone position supports and frames in order to select that which causes least cardiovascular and respiratory disturbance. This patient also developed severely deranged liver function postoperatively and the possible aetiology is discussed.

A patient underwent major spinal surgery, twice within a 3 week period. On the first occasion his... more A patient underwent major spinal surgery, twice within a 3 week period. On the first occasion his post-operative pain was managed by conventional morphine patient-controlled analgesia (PCA). After the second procedure his pain was managed by a patient-controlled computer-assisted titration of alfentanil. This provided the opportunity to compare the efficacy of these two drug regimens in the same subject. The results showed comparable quality of analgesia and sedation and similar effects on respiration. However, the patient expressed a preference for morphine PCA.