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Biomedical subjects

M J Burns

Publications and source records attributed to M J Burns.

At least 19 recordsLinked to original sources
PubMed2003

QTL analysis of an intervarietal set of substitution lines in Brassica napus: (i) Seed oil content and fatty acid composition.

Backcross breeding with marker-assisted selection was used to construct an intervarietal set of part chromosome substitution lines in Brassica napus, formed from a cross between two winter varieties of oilseed rape: Tapidor and Victor. A total of 22 lines from this substitution library were examined over a 3-year period, in a total of nine field trials, for seed oil fatty acid composition and seed oil content. Trialing of the substitution lines gave evidence for the existence of 13 quantitative trait loci (QTL). All 13 QTL affected fatty acid composition of the seed, and were distributed among linkage groups 1, 3, 6, 7, 8, 11, 13, 14, 18, and 19. Seven of these QTL, on linkage groups 3, 6, 8, 13, 14, 18, and 19, also affected total seed oil content. The positions of these QTL are compared to those in the published literature and with respect to erucic acid QTL previously identified in a backcross population of the same cross. The substitution line approach gives increased precision and sensitivity for QTL mapping compared to other methods.

Brassica napus↗
PubMed2001

Pentobarbital for severe gamma-butyrolactone withdrawal.

STUDY OBJECTIVE: Gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL) have become popular drugs of abuse. Acute overdose with either agent results in a well-recognized syndrome of central nervous system and respiratory depression. Recently, a withdrawal syndrome has been described for GHB. We report a severe form of GBL withdrawal, characterized by delirium, psychosis, autonomic instability, and resistance to benzodiazepine therapy. METHODS: We performed a chart review of consecutive admissions for GBL withdrawal in a regional toxicology treatment center. RESULTS: During a 6-month period, 5 patients presented with severe withdrawal attributed to abrupt GBL discontinuation. Patients manifested tachycardia, hypertension, paranoid delusions, hallucinations, and rapid fluctuations in sensorium. Test results for ethanol and routine drugs of abuse were negative. Initial treatment with high doses of lorazepam proved ineffective. Pentobarbital was then administered, resulting in excellent control of behavioral, autonomic, and psychiatric symptoms and in rapid reduction or avoidance of benzodiazepines. Median hospital stay was 5 days. No patient had respiratory depression or required mechanical ventilation. Patients were discharged on tapering doses of benzodiazepines or pentobarbital and were free of psychotic symptoms at follow-up. CONCLUSION: GBL discontinuation can result in severe withdrawal, necessitating ICU admission. Pentobarbital may be more effective than benzodiazepines at controlling delirium in patients with abnormal vital signs, paranoid delusions, and hallucinations as a result of GBL withdrawal.

4-Butyrolactone↗
PubMed2001

The pharmacology and toxicology of atypical antipsychotic agents.

Recently, atypical antipsychotic agents have largely replaced traditional agents as first-line drugs for the treatment of schizophrenia. It is likely that atypical agents will soon account for the majority of poisonings from antipsychotic agents that present to health care facilities in the US. This article reviews the pharmacodynamics, pharmacokinetics, and toxicology of atypical antipsychotic drugs, chiefly clozapine, risperidone, olanzapine, and quetiapine. A descriptive summary of the human overdose experience with these agents is provided. Adverse effect and drug interaction data are reviewed. Based on the available pharmacodynamic, pharmacokinetic, and human overdose data, recommendations on management are provided.

Antipsychotic Agents↗
PubMed2001

Phentolamine reduces myocardial injury and mortality in a rat model of phenylpropanolamine poisoning.

BACKGROUND: Phenylpropanolamine produces dose-related, life-threatening cardiovascular, and central nervous toxicity from alpha-adrenergic overstimulation. Although some recommend the alpha-adrenergic antagonist, phentolamine, as treatment for such toxicity, its therapeutic efficacy has not been previously studied. We sought to determine if pretreatment with phentolamine could reduce acute myocardial injury and mortality in rats administered an overdose of phenylpropanolamine. METHODS: In the mortality arm of the study, 28 unanesthetized, male Wistar rats (14 animals per group) were randomized to receive an intraperitoneal injection of phentolamine (3 mg/kg) or an equal volume of normal saline diluent (control group). Twenty-five minutes later, all rats received an intraperitoneal injection of phenylpropanolamine (150 mg/kg). Mortality was compared at 24 hours. In the myocardial injury arm of the study, 20 unanesthetized rats (10 per group) were randomized to receive an intraperitoneal injection of phentolamine (3 mg/kg) or normal saline (control group). Twenty-five minutes later, all rats received an intraperitoneal injection of phenylpropanolamine (75 mg/kg). Seventy-two hours after phenylpropanolamine administration, all surviving animals were sacrificed and transverse sections of their hearts were graded histologically for injury by a blinded cardiac pathologist. RESULTS: Twelve rats died within 6 hours of phenylpropanolamine administration. Mortality was significantly lower in the phentolamine-pretreated rats (2/14; 14%) as compared to the control group (10/14; 71%; p = 0.006). The degree of myocardial injury was significantly lower in the phentolamine-pretreated rats (0) as compared to the control group (1.4 +/- 1.6; p = 0.012). CONCLUSION: In this rat model, phentolamine pretreatment prevented acute myocardial injury and significantly reduced lethality from an intraperitoneal phenylpropanolamine overdose.

Adrenergic alpha-Agonists↗
PubMed2001

Reversal of severe methanol-induced visual impairment: no evidence of retinal toxicity due to fomepizole.

CASE REPORT: We report a case of methanol poisoning exhibiting complete recovery from severe visual impairment following treatment with ethanol, fomepizole, and hemodialysis. An adult male presented with central blindness after ingesting methanol. Initial visual acuity was <20/800 (finger counting at 1-2 feet) with retinal edema on fundoscopy, arterial pH 7.19, methanol 97 mg/dL (30 mmol/L), formate 14.3 mmol/L, and ethanol undetectable. The patient was treated with ethanol, then fomepizole intravenously (15, 10, then 5 mg/kg), and hemodialysis. Methanol metabolism was effectively blocked by fomepizole even after ethanol had been eliminated, and the patient recovered 20/20 vision by day 14 with normal fundoscopy. This case report confirms highly efficient inhibition of alcohol dehydrogenase by fomepizole, as well as demonstrate the safety of fomepizole in a patient already exhibiting end-organ retinal toxicity. The potential for fomepizole to inhibit retinol dehydrogenase, an isoenzyme of alcohol dehydrogenase essential to vision, did not appear to be clinically significant in this symptomatic methanol-poisoned patient.

Adult↗
PubMed2001

In vivo observation of cavitation and embolism repair using magnetic resonance imaging.

Magnetic resonance imaging (MRI) was used to noninvasively monitor the status of individual xylem vessels in the stem of an intact, transpiring grape (Vitis vinifera) plant over a period of approximately 40 h. Proton density-weighted MRI was used to visualize the distribution of mobile water in the stem and individual xylem vessels were scored as either water or gas filled (i.e. embolized). The number of water-filled vessels decreased during the first 24 h of the experiment, indicating that approximately 10 vessels had cavitated during this time. Leaf water potentials decreased from -1.25 to -2.1 MPa during the same period. Watering increased leaf water potentials to -0.25 MPa and prevented any further cavitation. Refilling of xylem vessels occurred as soon as the lights were switched off, with the majority of vessels becoming refilled with water during the first 2 to 3 h in darkness. These measurements demonstrate that MRI can be used to monitor the functional status of individual xylem vessels, providing the first method to study the process of cavitation and embolism repair in intact plants.

Magnetic Resonance Imaging↗
PubMed2001

Core rewarming via warm lavage liquid ventilation in a swine model of hypothermia-associated ventricular fibrillation.

OBJECTIVES: To determine whether warm lavage liquid ventilation (LV) would provide rapid cardiopulmonary rewarming in swine with severe hypothermia and ventricular fibrillation. METHODS: Intubated common swine (n = 3; mean +/- SEM weight 26+/-1.2 kg) were cooled to a mean aortic temperature of 26.4+/-0.9 degrees C. Ventricular fibrillation was induced by transthoracic electrical shock. Rewarming was initiated by continuous endotracheal instillation of warm (44 degrees C) pre-oxygenated, perfluorocarbon liquid at 5 mL/kg/min. Endotracheal instillation of perfluorocarbon occurred while standard gas ventilation continued. Manual chest compressions were performed throughout the 30-minute rewarming process. Outcome measures were the absolute and relative rates of change of all temperatures. RESULTS: After 30 minutes of warm lavage LV, the mean aortic and pulmonary artery temperatures increased by 6.6+/-0.6 degrees C, respectively. Esophageal, nasal, and rectal temperatures did not change significantly. In one animal, normal sinus rhythm spontaneously returned after 16 minutes of rewarming. CONCLUSIONS: During cardiac arrest, warm lavage liquid ventilation may produce rapid cardiopulmonary rewarming.

Analysis of Variance↗
PubMed2001

Depression, service utilization, and treatment costs among Medicare elderly: gender differences.

OBJECTIVE: To compare gender differences in mood disorders, service utilization, and health care costs among a random sample of Medicare elderly beneficiaries of Tennessee. DATA SOURCES: Medicare expenditure data from a 5% random sample of Tennessee Medicare beneficiaries (n = 35,673) were examined for 1991-1993. The physician reimbursement files provided data relative to ICD-9 diagnostic codes, physician visits, and the cost of physician services provided. Other service utilization and cost data were obtained for the sample from the outpatient, home health, skilled nursing, hospice and inpatient files. STUDY DESIGN: The dependent variables were: (i) patients with ICD-9 diagnosis for a mood disorder (major depression and other depression), (ii) service utilization (number of outpatient visits, skilled nursing visits, home health visits, physician visits, emergency visits, and inpatient days), and (iii) health care costs (dollar amount of physician cost, outpatient cost, inpatient cost, total mental health cost, total health cost, and other cost). The independent variable was gender. PRINCIPLE FINDINGS: Chi-square tests showed that among the patients with a mood disorder, females had a significantly higher incidence than males of major depression (1.3% vs. .4%, respectively, p < .001) and other depression (1.6% vs. .6%, respectively, p < .001). Further, t-test results indicated that females diagnosed with major depression utilized significantly more outpatient services than males (3.2 vs. 2.6, respectively, p < .04). Total health care costs for those with other depression were significantly higher for males than females ($15,060 vs. $10,240, respectively, p < .002). CONCLUSIONS: The results indicate that mood disorders, outpatient services, and total mental health costs are higher for females than males; however, total health care costs are higher for males than females.

Aged↗
PubMed2000

A comparison of physostigmine and benzodiazepines for the treatment of anticholinergic poisoning.

STUDY OBJECTIVE: To compare the efficacy and safety of physostigmine with benzodiazepines for the treatment of agitation and delirium associated with anticholinergic poisoning. METHODS: We conducted a retrospective study of 52 consecutive patients referred to a university hospital toxicology consultation service who were treated with physostigmine, benzo-diazepines, or both for anticholinergic agitation and delirium. Patients treated with physostigmine were compared with those treated with benzodiazepines with respect to demographics, severity of poisoning, response to treatment, side effects of treatment, and complications. RESULTS: Physostigmine controlled agitation and reversed delirium in 96% and 87% of patients, respectively. Benzodiazepines controlled agitation in 24% of patients but were ineffective in reversing delirium. Initial treatment with physostigmine (n=30) resulted in a significant decrease in the incidence of agitation (P <.001) and level of central nervous system stimulation (P <.001), whereas initial treatment with benzodiazepines (n=22) did not (P =.03 and P =.05, respectively). Patients treated initially with physostigmine had a significantly lower incidence of complications (7% versus 46%; P <. 002) and a shorter time to recovery (median, 12 versus 24 hours; P =. 004) than those treated initially with benzodiazepines. There were no significant differences between these groups in the incidence of side effects (7% versus 14%; P =0.6) and length of stay (median, 32 versus 39 hours; P =.15). CONCLUSION: Results suggest that physostigmine is more effective and safer than benzodiazepines for the treatment of anticholinergic agitation and delirium. A prospective controlled study is necessary to confirm such findings.

Administration, Oral↗
PubMed2000

Myocardial infarction associated with phenylpropanolamine.

Phenylpropanolamine is a sympathomimetic agent widely used in over-the-counter and prescription decongestant medications. We describe a young woman without cardiac risk factors who sustained myocardial infarction after unintentional overuse of a nasal decongestant containing phenylpropanolamine. The pathophysiology of myocardial injury and current management strategies as related to this agent are discussed. Although serious adverse reactions to phenylpropanolamine are uncommon, potentially serious harm may be caused by this widely available drug in healthy individuals.

Adult↗
PubMed2000

The relapsing fever spirochaete, Borrelia crocidurae, activates human endothelial cells and promotes the transendothelial migration of neutrophils.

The blood-borne, erythrocyte-aggregating Borrelia crocidurae, the causative agent of African relapsing fever, have been shown to induce severe cellular lesions in mice. In this paper, we present the first report of how the endothelium is stimulated during an African relapsing fever B. crocidurae infection. B. crocidurae co-incubated with cultured human umbilical vein endothelial cells (HUVECs) activated endothelium in such way that E-selectin and intercellular adhesion molecule 1 (ICAM-1) became upregulated in a dose- and time-dependent fashion, as determined by a whole-cell enzyme-linked immunosorbent assay (ELISA). The upregulation was reduced by treatment that killed the bacteria, suggesting that viability is important for the stimulation of HUVECs by B. crocidurae. Furthermore, conditioned medium from HUVECs stimulated with B. crocidurae contained interleukin (IL)-8, which is a chemotactic agent for neutrophils. Activation of HUVECs by B. crocidurae resulted in migration of subsequently added neutrophils across the endothelial monolayers, and this migration was inhibited by antibodies to IL-8. The activation of endothelium by B. crocidurae may constitute a key pathophysiological mechanism in B. crocidurae-induced vascular damage.

Animals↗
PubMed2000

Toxicokinetics of ethylene glycol during fomepizole therapy: implications for management. For the Methylpyrazole for Toxic Alcohols Study Group.

STUDY OBJECTIVE: The elimination kinetics of ethylene glycol (EG) in human subjects treated with fomepizole (4-methylpyrazole) were analyzed to establish the efficacy of alcohol dehydrogenase (ADH) inhibition and to characterize elimination pathways. METHODS: Drug concentration data from patients enrolled in the EG arm of the Methylpyrazole for Toxic Alcohols trial, a prospective, multicenter, open-label trial of fomepizole, were analyzed and compared with published estimates. RESULTS: In 19 patients analyzed (EG concentrations of 3.5 to 211 mg/dL), elimination was first order during fomepizole monotherapy (half-life of 19.7+/-1.3 hours) and was not affected by the presence of ethanol. The elimination rate was significantly faster (half-life of <8.6+/-1.1 hours, P <.001) in the absence of fomepizole and ethanol. EG elimination by the kidneys was directly proportional to remaining renal function as estimated by creatinine clearance, with a fractional excretion of 25.5%+/-9.4%. Renal elimination and hemodialysis were the only significant routes of EG elimination as long as fomepizole concentrations were maintained well above 10 micromol/L (EG/fomepizole molar ratio, <100:1). All patients with normal serum creatinine concentrations at the initiation of fomepizole treatment had rapid rates of renal elimination (half-life of 16.8+/-0.8 hours). CONCLUSION: At doses used, fomepizole effectively inhibits ADH-mediated metabolism of EG. Serum creatinine concentration at presentation and creatinine clearance can be used to predict EG elimination during fomepizole therapy and can help determine which patients will require hemodialysis to expedite EG elimination. An absolute EG concentration above 50 mg/dL should no longer be used as an independent criterion for hemodialysis in patients treated with fomepizole.

Adolescent↗
PubMed1999

Enhanced mortality from perfluorocarbon administration in a rat model of kerosene aspiration.

BACKGROUND: Aspiration of low-viscosity hydrocarbons may lead to fulminant pneumonitis and acute respiratory distress syndrome. Animal and human studies suggest that partial liquid ventilation with perfluorocarbon improves gas exchange and pulmonary function in acute respiratory failure. The objective of this investigation was to determine the effect of intratracheal perfluorocarbon administration and a brief period of partial liquid ventilation on survival in a rat model of severe hydrocarbon aspiration. METHODS: Two randomized, non-blinded, controlled experiments were performed. First, male Wistar rats (n = 12) were given 0.3 mL/kg kerosene via direct intratracheal instillation and after 5 minutes were randomized to partial liquid ventilation or standard gas ventilation (control) groups. Partial liquid ventilation rats (n = 6) received 20 mL/kg of pre-oxygenated FC-77 intratracheally and positive-pressure gas ventilation (FiO2 = 1.0), and control rats (n = 6) received positive-pressure gas ventilation alone. Animals were observed for survival and 7-day mortality was compared using the Fisher Exact test. The study was then repeated in 12 additional animals using a 15-minute interval between kerosene instillation and treatment (PLV vs control). RESULTS: Mortality was significantly greater in the partial liquid ventilation group (5 of 6; 83%) as compared to the control group (1 of 6; 17% [p = 0.039]). Results were identical in the repeat study. All animals that died succumbed from acute respiratory failure within 24 hours of kerosene instillation. CONCLUSION: In this rat model of severe kerosene aspiration, intratracheal perfluorocarbon administration and a brief period of partial liquid ventilation proved detrimental and significantly increased mortality.

Administration, Inhalation↗
PubMed1998

Borrelia burgdorferi and interleukin-1 promote the transendothelial migration of monocytes in vitro by different mechanisms.

A prominent feature of Lyme disease is the perivascular accumulation of mononuclear leukocytes. Incubation of human umbilical vein endothelial cells (HUVEC) cultured on amniotic tissue with either interleukin-1 (IL-1) or Borrelia burgdorferi, the spirochetal agent of Lyme disease, increased the rate at which human monocytes migrated across the endothelial monolayers. Very late antigen 4 (VLA-4) and CD11/CD18 integrins mediated migration of monocytes across HUVEC exposed to either B. burgdorferi or IL-1 in similar manners. Neutralizing antibodies to the chemokine monocyte chemoattractant protein 1 (MCP-1) inhibited the migration of monocytes across unstimulated, IL-1-treated, or B. burgdorferi-stimulated HUVEC by 91% +/- 3%, 65% +/- 2%, or 25% +/- 22%, respectively. Stimulation of HUVEC with B. burgdorferi also promoted a 6-fold +/- 2-fold increase in the migration of human CD4(+) T lymphocytes. Although MCP-1 played only a limited role in the migration of monocytes across B. burgdorferi-treated HUVEC, migration of CD4(+) T lymphocytes across HUVEC exposed to spirochetes was highly dependent on this chemokine. The anti-inflammatory cytokine IL-10 reduced both migration of monocytes and endothelial production of MCP-1 in response to B. burgdorferi by approximately 50%, yet IL-10 inhibited neither migration nor secretion of MCP-1 when HUVEC were stimulated with IL-1. Our results suggest that activation of endothelium by B. burgdorferi may contribute to formation of the chronic inflammatory infiltrates associated with Lyme disease. The transendothelial migration of monocytes that is induced by B. burgdorferi is significantly less dependent on MCP-1 than is migration induced by IL-1. Selective inhibition by IL-10 further indicates that B. burgdorferi and IL-1 employ distinct mechanisms to activate endothelial cells.

Amnion↗
PubMed1997

Treatment of methanol poisoning with intravenous 4-methylpyrazole.

Treatment of human methanol poisoning with the alcohol dehydrogenase inhibitor, 4-methylpyrazole (fomepizole), has not been previously described. We report the clinical and toxicokinetic data of a patient with methanol poisoning who was treated with fomepizole. Formic acid levels remained undetectable during fomepizole treatment, the toxic effects of methanol were prevented, and the patient made a full recovery.

Adult↗
PubMed1997

Regional intravenous infusion of calcium gluconate for hydrofluoric acid burns of the upper extremity.

STUDY OBJECTIVE: To describe regional intravenous infusion of calcium gluconate as a therapy for hydrofluoric acid (HF) burns of the forearm, hand, or digits. METHODS: This study describes seven patients with HF burns. Calcium gluconate, 10 mL of 10% solution with 30 to 40 mL normal saline solution, was injected intravenously into the affected limb using a Bier block technique. Ischemia was maintained for 20 to 25 minutes. Therapy was considered successful if significant reduction of pain and tenderness was noted after tourniquet release. RESULTS: Seven patients were treated. HF concentration varied from 5% to 49%. Exposure sites included the forearm (two cases), thenar eminence and digits (two cases), or digits only (three cases). Complete pain resolution occurred on tourniquet release in four patients (two with burns to the forearm, two with burns to digits only). One patient had partial relief (thenar but not digital exposure site), and two had no relief of symptoms. Intraarterial calcium gluconate perfusion was subsequently administered to the three patients with persistent subungual and pulp, or thenar pain. Recovery was complete in all cases. No adverse effects were noted. CONCLUSION: Regional intravenous infusion of calcium gluconate should be considered a therapeutic option in HF burns of the forearm, hand, or digits when topical therapy fails.

Adult↗
PubMed1997

Production of interleukin-8 (IL-8) by cultured endothelial cells in response to Borrelia burgdorferi occurs independently of secreted [corrected] IL-1 and tumor necrosis factor alpha and is required for subsequent transendothelial migration of neutrophils.

Previous studies have shown that Borrelia burgdorferi, the spirochetal agent of Lyme disease, promotes inflammation by stimulating endothelial cells to upregulate adhesion molecules for leukocytes and to produce a soluble agent that is chemotactic for neutrophils. We determined that interleukin-8 (IL-8) was the chemotactic agent for neutrophils present in conditioned media from cultured human umbilical vein endothelial cells stimulated with B. burgdorferi. As few as one spirochete per endothelial cell stimulated production of IL-8 within 8 h of coincubation. When 10 spirochetes per endothelial cell were added, IL-8 was detected after 4 h of coculture. Production of IL-8 continued in a linear fashion for at least 24 h. Neutralizing antibodies against IL-8 reduced migration of neutrophils across spirochete-stimulated endothelial monolayers by 93%. In contrast, pretreatment of neutrophils with antagonists of platelet-activating factor did not inhibit migration. Increases in production of IL-8 and expression of the adhesion molecule E-selectin by endothelial cells in response to B. burgdorferi were not inhibited by IL-1 receptor antagonist or a neutralizing monoclonal antibody directed against tumor necrosis factor alpha, used either alone or in combination. These results suggest that activation of endothelium by B. burgdorferi is not mediated through the autocrine action of secreted IL-1 or tumor necrosis factor alpha. Rather, it appears that B. burgdorferi must stimulate endothelium either by a direct signaling mechanism or by induction of a novel host-derived proinflammatory cytokine.

Borrelia burgdorferi Group↗