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Biomedical subjects

L J Roberts

Publications and source records attributed to L J Roberts.

At least 19 recordsLinked to original sources
PubMed2003

Are anaesthetists prone to suicide? A review of rates and risk factors.

Suicide represents a major source of mortality in Western countries. There is an emerging literature about suicide and the medical profession. The suicide of an anaesthetist represents a catastrophic event, with painful consequences for family, colleagues and the community at large. This review will examine the literature regarding suicide amongst anaesthetists and trainees in the field. It is presented in three sections. First, it provides an overview of existing epidemiological data, comparing rates in the general population, the medical profession, in general, and in anaesthesia, in particular. Second, risk factors that may account for differences in rates will be discussed. Finally, a series of recommendations has been formulated.

Adult↗
PubMed2003

Acrania.

Explore the source record for details and available documents.

Abnormalities, Multiple↗
PubMed2002

Career choice influences in Australian anaesthetists.

All female members and a randomly selected group of male members of the Australian Society of Anaesthetists (n = 488) were surveyed by questionnaire as part of a broader study of gender issues in anaesthesia. This paper reports on reasons for career choice and the importance of role models. Responses were received from 199 women and 98 men (60.9% of those surveyed), representing all States and one Territory. Most males (95.9%) and a majority of females (55.7%) worked full-time. Reasons for career choice varied with gender, with a significantly greater proportion of women (39.7%) than men (8.7%) choosing anaesthesia because of controllable hours, particularly the ability to work part-time. Experiences in anaesthesia during internship and residency were important for 19.1% of women and 14.1% of men, although very few mentioned undergraduate exposure. Other important factors in career choice were the application of physiology and pharmacology in patient care, practical and procedural aspects of practice, and chance. A majority of women (56%) and men (55%) named specific role models who were influential and encouraging in their choice. These results are similar to those of other studies.

Adult↗
PubMed2002

Plasma F2-isoprostane levels are elevated in chronic hemodialysis patients.

AIMS: Cardiovascular mortality has been reported to be 10- to 20-fold higher in chronic dialysis patients than in the age-matched general population. It has been suggested that increased oxidant stress and resulting vascular wall injury due to uremia and the hemodialysis procedure may be one of the mechanisms predisposing to these cardiovascular complications. Further, hemodialysis membrane bioincompatibility can contribute to increased oxidative stress and prevalence of inflammation. MATERIALS: We studied 18 chronic hemodialysis (CHD) patients (age 62.8 +/- 14.7 years, 39% male, 61% African-American, 44% insulin-dependent diabetic, 61% smokers, 61% with documented coronary artery disease) during hemodialysis with 2 membranes with different flux and complement activating properties. METHODS: We have measured free and phospholipid-bound F2-isoprostane (F2-IsoP) levels, a sensitive marker of oxidative stress, in CHD patients and compared them to levels in healthy subjects. We have also examined the acute effects of the hemodialysis procedure using both biocompatible and bioincompatible membranes on F2-IsoP levels. RESULTS: The results indicated that, compared to controls, both free (96.2 +/- 48.8 pg/ml versus 37.6 +/- 17.2 pg/ml) and bound F2-IsoP (220.4 +/- 154.8 pg/ml versus 146.8 +/- 58.4 pg/ml) levels were significantly higher (p < 0.05 for both). There was a statistically significant decrease in free F2-IsoP concentrations at 15 and 30 minutes of HD, which rebounded to baseline levels at the completion of the procedure. There were no significant differences in F2-IsoP concentrations between the 2 study dialyzers at any time point. Age, smoking status, diabetes mellitus and presence of cardiovascular disease were also not correlated with F2-IsoP levels in this patient population. There was a significant association between predialysis F2-IsoP and C-reactive protein concentrations. CONCLUSION: Using a sensitive and specific assay for the measurement of F2-IsoP, we demonstrated that CHD patients are under increased oxidative stress. During a single hemodialysis treatment, the hemodialysis membrane appears to have no discernable effect on oxidative stress status. Measurement of F2-isoprostanes may be a useful biomarker of oxidative stress status as well as in developing new therapeutic strategies to ameliorate inflammatory and oxidative injury in this patient population.

Aged↗
PubMed2001

Measurement of F(2)-isoprostanes unveils profound oxidative stress in aged rats.

Free radicals have been theorized to play a causative role in the normal aging process. To date, methods used to detect oxidative stress in aged experimental animals have only detected 2- to 3-fold differences or less between young and aged animals. Measurement of F(2)-isoprostanes has emerged as probably the most reliable approach to assess oxidative stress status in vivo. Therefore, we measured levels of F(2)-isoprostanes free in plasma and levels esterified in plasma lipids in young rats (3-4 months of age) and aged rats (22-24 months of age). Plasma concentrations of free F(2)-isoprostanes were increased dramatically by a mean of 20.3-fold (range 4.3 to 42.9-fold) and levels esterified in plasma lipids were also strikingly increased by a mean of 29.9-fold (range 15.8 to 50.0-fold). These findings unveil profound oxidative stress in aged rats which adds considerable support for the free radical theory of aging.

Aging↗
PubMed2001

Interactions between apolipoprotein E gene and dietary alpha-tocopherol influence cerebral oxidative damage in aged mice.

Cerebral oxidative damage is a feature of aging and is increased in a number of neurodegenerative diseases. We pursued the gene-environment interaction of lack of apolipoprotein E (apoE) and modulation of dietary alpha-tocopherol on cerebral oxidative damage in aged male and female mice by quantifying the major isomers of cerebral isoprostanes, derived from arachidonic acid (AA) oxidation, and neuroprostanes, derived from docosahexaenoic acid (DHA) oxidation. Mice fed alpha-tocopherol-deficient, normal, or -supplemented diet had undetectable, 4486 +/- 215, or 6406 +/- 254 ng of alpha-tocopherol per gram of brain tissue (p < 0.0001), respectively. Two factors, male gender and lack of apoE, combined to increase cerebral AA oxidation by 28%, whereas three factors, male gender, lack of apoE, and deficiency in alpha-tocopherol, combined to increase cerebral DHA oxidation by 81%. alpha-Tocopherol supplementation decreased cerebral isoprostanes but not neuroprostanes and enhanced DHA, but not AA, endoperoxide reduction in vivo and in vitro. These results demonstrated that the interaction of gender, inherited susceptibilities, and dietary alpha-tocopherol contributed differently to oxidative damage to cerebral AA and DHA in aged mice.

Administration, Oral↗
PubMed2001

Formation of highly reactive gamma-ketoaldehydes (neuroketals) as products of the neuroprostane pathway.

Neuroprostanes are prostaglandin-like compounds produced by free radical-induced peroxidation of docosahexaenoic acid, which is highly enriched in the brain. We previously described the formation of highly reactive gamma-ketoaldehydes (isoketals) as products of the isoprostane pathway of free radical-induced peroxidation of arachidonic acid. We therefore explored whether isoketal-like compounds (neuroketals) are also formed via the neuroprostane pathway. Utilizing mass spectrometric analyses, neuroketals were found to be formed in abundance in vitro during oxidation of docosahexaenoic acid and were formed in greater abundance than isoketals during co-oxidation of docosahexaenoic and arachidonic acid. Neuroketals were shown to rapidly adduct to lysine, forming lactam and Schiff base adducts. Neuroketal lysyl-lactam protein adducts were detected in nonoxidized rat brain synaptosomes at a level of 0.09 ng/mg of protein, which increased 19-fold following oxidation in vitro. Neuroketal lysyl-lactam protein adducts were also detected in vivo in normal human brain at a level of 9.9 +/- 3.7 ng/g of brain tissue. These studies identify a new class of highly reactive molecules that may participate in the formation of protein adducts and protein-protein cross-links in neurodegenerative diseases and contribute to the injurious effects of other oxidative pathologies in the brain.

Animals↗
PubMed2001

Characterization of the lysyl adducts of prostaglandin H-synthases that are derived from oxygenation of arachidonic acid.

These investigations characterize the covalent binding of reactive products of prostaglandin H-synthases (PGHSs) to the enzyme and to other molecules. The intermediate product of oxygenation of arachidonic acid by the PGHSs, prostaglandin (PG) H2, undergoes rearrangement to the highly reactive gamma-keto aldehydes, levuglandin (LG) E2 and D2. We previously have demonstrated that LGE2 reacts with the epsilon-amine of lysine to form both the lysyl-levuglandin Shiff base and the pyrrole-derived lysyl-levuglandin lactam adducts. We now demonstrate that these lysyl-levuglandin adducts are formed on the PGHSs following the oxygenation of arachidonic acid; after reduction of the putative Schiff base, proteolytic digestion of the enzyme, and isolation of the adducted amino acid residues, these adducts were identified by liquid chromatography-tandem mass spectrometry. The reactivity of the LGs is reflected by the finding that virtually all of the LG predicted to be formed from PGH2 can be accounted for as adducts of the PGH-synthase and that oxygenation of arachidonic acid by PGH-synthases also leads to the formation of adducts of other proteins present in the reaction solution. The reactivity of the PGH-synthase adducts themselves is demonstrated by the formation of intermolecular cross-links.

Animals↗
PubMed2001

Brain regional quantification of F-ring and D-/E-ring isoprostanes and neuroprostanes in Alzheimer's disease.

Isoprostanes (IsoP) are produced exclusively from free radical damage to arachidonic acid, a fatty acid that is evenly distributed throughout white matter and gray matter, whereas neuroprostanes (NPs) are generated analogously from docosahexaenoic acid (DHA), a fatty acid enriched in gray matter where it is concentrated in neurons. IsoP and NPs derive from endoperoxide intermediates that isomerize to D/E-ring forms or that are reduced to F-ring compounds. We quantified F-ring and D/E-ring IsoP and NPs in temporal and parietal cortex, hippocampus, and cerebellum of nine definite Alzheimer's disease (AD) patients and 11 age-matched controls. Total NP levels (F-ring plus D/E-ring), but not total IsoP, were significantly greater in AD than controls (P: < 0.0001); only cerebral regions in AD patients had NPs greater than controls (P: < 0.05). The F-ring to D/E-ring ratio for NPs, but not IsoP, was 40 to 70% lower in all brain regions of AD patients compared to controls (P: < 0.005). These data extend results from in situ techniques, that have localized reactive products of lipid peroxidation primarily to neurons, by quantifying significantly greater free radical damage to the DHA-containing compartments in cerebrum in AD patients than controls, and suggest that one mechanism of increased oxidative stress may be diminished reducing capacity in DHA-containing compartments.

Alleles↗
PubMed2001

Assessment of oxidant stress in allergic asthma by measurement of the major urinary metabolite of F2-isoprostane, 15-F2t-IsoP (8-iso-PGF2alpha).

Asthma is a chronic inflammatory disease of the airways which may involve an oxidant injury to the lung. Assessment of oxidant stress is difficult in vivo, but measurement of F2-isoprostanes (F2-IsoPs), free radical-catalysed products of arachidonic acid, appears to offer a reliable approach for quantitative measurement of oxidative stress status in vivo. We have recently developed a mass spectrometric assay for 2,3-dinor-5,6-dihydro-15-F2t-IsoP (15-F2t-IsoP-M), the major urinary metabolite of the F2-IsoP, 15-F2t-IsoP (8-iso-PGF2a). Measurement of the urinary excretion of this metabolite offers a reliable index of oxidative stress status in vivo that has advantages over measuring unmetabolized F2-IsoPs in urine and plasma. To assess the occurrence of oxidative stress in patients with atopic asthma following allergen exposure in vivo by measuring the urinary excretion of 15-F2t-IsoP-M. Analysis of 15-F2t-IsoP-M by GC-NICI-MS in nine mild atopic asthmatics following inhaled allergen provocation and four asthmatic subjects after inhaled challenge with methacholine. Urinary excretion of 15-F2t-IsoP-M increased at 2 h after allergen challenge and remained significantly elevated in all urine collections during the subsequent 8-h period of the study compared to the baseline value (ANOVA, and Student-Newman-Keuls multiple comparisons test). No increase in the urinary excretion of 15-F2t-IsoP-M occurred after inhalation of methacholine. Allergen challenge causes an oxidant injury in human atopic asthmatics. 15-F2t-IsoP-M is a valuable marker of oxidant stress in vivo.

Allergens↗
PubMed2001

Enhanced hippocampal F2-isoprostane formation following kainate-induced seizures.

We attempted to obtain evidence for the occurrence of oxidant injury following seizure activity by measuring hippocampal F2-isoprostanes (F2-IsoPs), a reliable marker of free radical-induced lipid peroxidation. Formation of F2-IsoPs esterified in hippocampal phospholipids was correlated with hippocampal neuronal loss and mitochondrial aconitase inactivation, a marker of superoxide production in the kainate model. F2-IsoPs were measured in microdissected hippocampal CA1, CA3 and dentate gyrus (DG) regions at various times following kainate administration. Kainate produced a large increase in F2-IsoP levels in the highly vulnerable CA3 region 16 h post injection. The CA1 region showed small, but statistically insignificant increases in F2-IsoP levels. Interestingly, the DG, a region resistant to kainate-induced neuronal death also showed marked (2.5-5-fold) increases in F2-IsoP levels 8, 16, and 24 h post injection. The increases in F2-Isop levels in CA3 and DG were accompanied by inactivation of mitochondrial aconitase in these regions. This marked subregion-specific increase in F2-Isop following kainate administration suggests that oxidative lipid damage results from seizure activity and may play an important role in seizure-induced death of vulnerable neurons.

Aconitate Hydratase↗
PubMed2001

Increase in plasma esterified F2-isoprostanes following intravenous iron infusion in patients on hemodialysis.

BACKGROUND: In epoetin-treated dialysis patients, currently iron is administered by the intravenous route to maintain optimum erythropoiesis. However, rapid infusion of iron in excess of transferrin binding capacity can lead to the availability of unbound iron that can theoretically catalyze peroxidation of lipids, such as low-density lipoprotein (LDL), which when oxidatively modified is proinflammatory and promotes atherogenesis. METHODS: To address this issue, our study used one of the most specific measures of lipid peroxidation available, namely gas chromatography/mass spectometry (GC/MS) analysis of F2-isoprostanes. Using a prospective design, blood samples were collected 15 minutes before (pre) and 30 minutes after (post) a one-hour infusion of 700 mg bolus of intravenous iron in 22 adult home-hemodialysis patients on a non-hemodialysis day. RESULTS: With iron-dextran infusion, serum iron markedly increased (mean +/- SE, 42 +/- 4 vs. 311 +/- 92 microg/dL, P < 0.0001) and exceeded the transferrin saturation of 100% in 22 out of 22 patients (pre 23 +/- 3 vs. post 165 +/- 8%, P < 0.0001). Plasma concentrations of free F2-isoprostanes did not change significantly following infusion of iron (pre 40 +/- 5 vs. post 39 +/- 6 pg/mL). However, levels of F2-isoprostanes esterified in plasma lipoproteins increased significantly in the postinfusion samples (pre 199 +/- 19 vs. post 233 +/- 25 pg/mL, P < 0.004). Pre-infusion levels of serum iron correlated directly with pre-infusion levels of esterified F2-isoprostanes (r = 0.56, P = 0.008), which persisted in the postinfusion period (r = 0.43, P = 0.04). However, there was no correlation between esterified F2-isoprostanes and serum ferritin levels. In the last four patients in whom blood samples were collected five hours after the intravenous iron infusion, there were further increases in esterified F2-isoprostanes that very closely correlated with postinfusion serum iron levels (r = 0.99, P = 0.013). In a control study, the in vitro addition of iron dextran to blood samples did not increase free or esterified F2-isoprostanes, suggesting that the increase in esterified F2-isoprostanes seen in vivo after iron infusion in patients is not due to a procedural artifact. CONCLUSION: Collectively our data suggest that high levels of serum iron appearing soon after a large bolus of iron infusion is associated with significant, albeit modest, increases in levels of F2-isoprostanes esterified in plasma lipoproteins that tended to increase with time. Although it is uncertain whether this degree of lipid peroxidation may have deleterious effects, it may be sagacious to explore whether this can be prevented by slow infusion of frequent smaller doses of iron and, if necessary, along with administration of antioxidants.

Adult↗
PubMed2001

Outcome of intrathecal opioids in chronic non-cancer pain.

Eighty-eight patients (58 women and 30 men; mean age 53.4 years) with chronic non-cancer pain present on average for 9.8 years were evaluated following treatment with intrathecal opioids for an average duration of 36.2 months. Outcome measures were global pain relief, physical activity levels, medication consumption, work status, intrathecal opioid side-effects, proportion of patients who ceased therapy and patient satisfaction. The most common diagnosis in this group was lumbar spinal or radicular pain after failed spinal surgery (n= 55, 63%). At the time of follow-up, mean pain relief was 60% with 74% of patients (36 of 49) reporting increased activity levels. Oral medication intake was significantly reduced (Medication Quantification Scale Score prior to implantation 31.0+/-2.6 and at follow-up 12.7+/-1.4; n= 48; p< 0.0001). These gains were not accompanied by a change in work status (43 of 50 working age patients not working at follow-up). There were frequent reports of opioid side-effects, including sexual dysfunction and menstrual disturbance. Technical complications occurred with the drug administration device, most often catheter related, requiring at least one further surgical procedure in 32 patients (40%). Patient satisfaction with intrathecal opioids was high, with 45 of 51 (88%) reporting satisfaction. Mean intrathecal morphine dose increased from 9.95+/-1.49 mg/day (mean+/-SEM) at 6 months to 15.26+/-2.52 mg/day 36 months after initiation of therapy. Drug administration systems were permanently removed in five patients (6%). Intrathecal opioid therapy appears to have a place in the management of chronic non-cancer pain. Therapy does not seem to be significantly inhibited by the development of tolerance.

Activities of Daily Living↗
PubMed2001

Supplementation with vitamin E but not with vitamin C lowers lipid peroxidation in vivo in mildly hypercholesterolemic men.

Although the use of vitamin E supplements has been associated with a reduction in coronary events, assumed to be due to lowered lipid peroxidation, there are no previous long-term clinical trials into the effects of vitamin C or E supplementation on lipid peroxidation in vivo. Here, we have studied the long-term effects of vitamins C and E on plasma F2-isoprostanes, a widely used marker of lipid peroxidation in vivo. As a study cohort, a subset of the "Antioxidant Supplementation in Atherosclerosis Prevention" (ASAP) study was used. ASAP is a double-masked placebo-controlled randomized clinical trial to study the long-term effect of vitamin C (500 mg of slow release ascorbate daily), vitamin E (200 mg of D-alpha-tocopheryl acetate daily), both vitamins (CellaVie), or placebo on lipid peroxidation, atherosclerotic progression, blood pressure and myocardial infarction (n = 520 at baseline). Lipid peroxidation measurements were carried out in 100 consecutive men at entry and repeated at 12 months. The plasma F2-isoprostane concentration was lowered by 17.3% (95% CI 3.9-30.8%) in the vitamin E group (p = 0.006 for the change, as compared with the placebo group). On the contrary, vitamin C had no significant effect on plasma F2-isoprostanes as compared with the placebo group. There was also no interaction in the effect between these vitamins. In conclusion, long-term oral supplementation of clinically healthy, but hypercholesterolemic men, who have normal vitamin C and E levels with a reasonable dose of vitamin E lowers lipid peroxidation in vivo, but a relatively high dose of vitamin C does not. This observation may provide a mechanism for the observed ability of vitamin E supplements to prevent atherosclerosis.

Aged↗
PubMed2001

2,3-Dinor-5,6-dihydro-15-F(2t)-isoprostane: a bioactive prostanoid metabolite.

15-F(2t)-isoprostane (15-F(2t)-IsoP), also termed 8-isoprostaglandin F(2alpha), is one of a series of prostanoids formed by free radical-mediated peroxidation of arachidonic acid and exerts potent biological actions such as vasoconstriction. We recently demonstrated that 15-F(2t)-IsoP is metabolized in humans to a major metabolite, 2,3-dinor-5,6-dihydro-15-F(2t)-IsoP (15-F(2t)-IsoP-M). 15-F(2t)-IsoP-M can also potentially be formed as a product of free radical-induced oxidation of the low abundance fatty acid gamma-linolenic acid. We confirmed that 15-F(2t)-IsoP-M is generated during oxidation of gamma-linolenic acid and explored whether it may exhibit biological activity. 15-F(2t)-IsoP-M caused marked constriction of porcine surface retinal and intraparenchymal brain microvessels, comparable to that observed with 15-F(2t)-IsoP. These effects were associated with increased thromboxane A(2) (TXA(2)) formation and were virtually abolished by TXA(2)-synthase and -receptor inhibitors (CGS-12970 and L-670596). Vasoconstriction induced by either 15-F(2t)-IsoP or 15-F(2t)-IsoP-M on perfused ocular choroid was also abrogated by TXA(2)-synthase inhibition as well as by removal of endothelium. Similar to 15-F(2t)-IsoP, 15-F(2t)-IsoP-M evoked vasoconstriction and TXA(2) generation by activating Ca(2+) influx from nonvoltage-gated channels (SK&F96365 sensitive) in the retina and from both nonvoltage- and N-type voltage-gated Ca(2+) channels (omega-conotoxin MVIIA sensitive), respectively, in brain endothelial and astroglial cells; smooth muscle cells were unresponsive to both agents. Cross-desensitization experiments further suggest that 15-F(2t)-IsoP and 15-F(2t)-IsoP-M act on the same receptor mechanism. Findings reveal a novel concept by which a beta-oxidation metabolite of 15-F(2t)-IsoP that can also be formed by nonenzymatic oxidation of gamma-linolenic acid is equivalently bioactive to 15-F(2t)-IsoP and may prolong the vascular actions of F(2)-IsoPs.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗