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Biomedical subjects

M M Burns

Publications and source records attributed to M M Burns.

At least 19 recordsLinked to original sources

Nalmefene for elective reversal of procedural sedation in children.

Nalmefene is a newer, long-acting opioid antagonist. Its use in children for the elective reversal of emergency department procedures has not been investigated. The objective was to evaluate the safety of nalmefene in children. An open-label pediatric clinical trial was performed. The study was conducted at the emergency department of an urban, university-affiliated children's hospital and consisted of children aged 6 months to 12 years who required procedural sedation where an opioid agent was administered. Patients were excluded if there was altered mental status, history of head trauma, history of opioid allergy, or the anticipated need for opioid agents for pain relief after the procedure. At the completion of the procedure, nalmefene was administered in a dose of 0.25 microg/kg increments (max 10 microg) until sedation was resolved, or to a maximum of 1.0 microg/kg (max 40 microg). Serial ECGs, vital signs, and oxygen saturation were recorded. Sedation was assessed using the Clinical Global Impression Scale (CGIS) at baseline, 2, 4, 6, 8, and 10 minutes after the initial nalmefene dose. The observer's assessment of alertness and sedation (OAA/S) was measured at baseline, 10, 30, 60, 90, and 120 minutes after the first dose of nalmefene. Episodes of resedation were recorded. All patients received follow-up by telephone at 4 and 24 hours after the initial dose of nalmefene to identify any potential late adverse effects. Over the study interval 15 patients were enrolled. Mean age was 59.1 +/- 41.5 months. Procedures involved fracture reduction (n=8), laceration repair (n = 4), abscess drainage (n = 2), and arthrocentesis (n = 1). All patients received IV fentanyl and midazolam. The mean dosage of fentanyl and midazolam was 3.21 +/- 1.03 microg/kg and 0.07 +/- 0.03 mg/kg, respectively. The mean dose of nalmefene at the time of complete response (CGIS = 1 or 2) was 0.55 +/- 0.29 microg/kg. The median number of nalmefene doses was 2. All but one patient (93%) had a complete response based on CGIS at 10 minutes after the initial dose of nalmefene was given. Nalmefene resulted in a significant improvement in CGIS (1.60 +/- 0.82 v 3.26 +/- 0.88, P =.001) and OAA/S (median score 5 v 4) when compared at baseline with 10 minutes after the initial dose of nalmefene. Nalmefene also resulted in increased diastolic blood pressure (62.6 +/- 10.5 v 55.8 +/- 10.7, P =.04) as well as improved oxygen saturation when compared at 120 minutes to baseline (99.5 +/- 0.74% v 98.5 +/- 0.4%, P =.03). There were no significant changes in pulse, systolic blood pressure, respiratory rate, and ECG. None of the patients became resedated after nalmefene was given. One patient developed nausea and vomiting within the first 2 hours after nalmefene; this resolved without intervention before discharge. No adverse events occurred in any of the patients at 4 and 24 hours postadministration. The results of this study showed that nalmefene is effective and safe for reversal of procedural sedation by opioids in children.

Analgesics, Opioid↗

Emerging concepts in the diagnosis and management of venous thromboembolism during pregnancy.

Multiple changes in the coagulation system occur during pregnancy and account for the hypercoagulable state of pregnancy. Consequently, pregnant women are five times more likely to experience venous thromboembolism than non-pregnant women. Although the estimated rates of such events are low, venous thromboembolic disease is a leading cause of maternal death. The administration of intravenous or subcutaneous unfractionated heparin is the treatment and prophylaxis of choice. Warfarin is safe and efficacious following delivery, but should be avoided during pregnancy. LMWH is a promising alternative for treatment and prophylaxis, but further clinical experience is required.

Anticoagulants↗

Activated charcoal as the sole intervention for treatment after childhood poisoning.

Childhood poisonings account for approximately two thirds of all human toxic exposures reported annually to the American Association of Poison Control Centers. Activated charcoal (AC) is the mainstay of decontamination in the emergency department setting. This review focuses on six concepts: 1) description of AC and its method of action, 2) evolution of AC in the gastrointestinal decontamination process, 3) prehospital use of AC, 4) superactivated charcoal, 5) multiple-dose AC, and 6) complications of AC administration. The most recent evolving trends in decontamination of the pediatric patient include trends toward earlier decontamination, either in the home or by paramedics in the field. The newer, "super" activated charcoals, with their greater surface area, may improve compliance of oral administration of AC. Finally, guidelines have been set to limit use of multiple-dose activated charcoal regimens to certain pharmaceuticals only, as well as discouraging cathartic use with charcoal dosing.

Charcoal↗

False-positive tricyclic antidepressant drug screen results leading to the diagnosis of carbamazepine intoxication.

Ingestion of toxic substances is a common problem in pediatrics. When presented with the limited history of an unknown ingestion in a patient with altered mental status, a clinician depends on the physical examination and a toxic screen to determine the ingested substance(s). Some toxic screens yield false-positive or false-negative results that confound identification of ingested toxins. Three cases are presented in which carbamazepine ingestions were identified because of the false-positive tricyclic antidepressant serum toxic screen result in each case. Carbamazepine ingestion is one of the most common pediatric overdoses. Side effects include altered mental status, tachycardia, mydriasis, seizures, coma, and death. Several other substances also cause false-positive tricyclic antidepressant toxic screen results, including certain antipsychotic medications, antihistamines, and the muscle relaxant cyclobenzaprine. Specific tests and drugs causing false-positive results are presented in table form. More modern methods, specifically gas chromatographic-mass spectrometric, are more reliable in distinguishing these drugs. Knowledge of which substances commonly cause false-positive results on a given toxic screen can still lead the clinician to the correct diagnosis. tricyclic, carbamazepine, ingestion, intoxication, drug screen.

Adolescent↗

Complexity analysis of oligodendroglial processes expressing myelin-associated glycoprotein.

Oligodendroglia synthesize myelin in the mammalian central nervous system. Mature oligodendroglia have been identified in culture by two criteria; the expression of molecules characteristic of myelin, such as galactocerebroside (galC) and myelin-associated glycoprotein (MAG), and the elaboration of complex processes. Myelin gene expression can be documented by the binding of specific antibodies and antisera to the myelin-specific molecules; process complexity can be described by the fractal dimension, D. In this study, anti-MAG antisera was used to document MAG expression in the processes of oligodendroglia. Eighty percent of the galC+ oligodendroglia bound anti-MAG antiserum. With time in culture, MAG immunoreactivity seemed to extend from the cell soma into the oligodendroglial processes. To quantify this observation, fractal dimensions were calculated using either galC or MAG immunoreactivity to visualize oligodendroglial processes. A fractal dimension of 1.5 was calculated for O1+ processes by day 4 of culture; this value for D remained constant over the course of 1 month in culture. The fractal dimension calculated for MAG+ processes increased from 1.2 to 1.5 over the course of 28 days in culture. This change in fractal dimension confirms our visual impression that galC-containing processes acquire MAG slowly over the course of several weeks in culture.

Animals↗

Alzheimer and vascular dementias and driving. A prospective road and laboratory study.

OBJECTIVE: To characterize on-the-road, behind-the-wheel driving abilities and related laboratory performances of subjects with mild Alzheimer's disease (AD) and vascular dementia. DESIGN: Prospective, experimental study involving two mild dementia and three age and health control groups. Road test reliability and validity were assessed. SETTING: Greater western Los Angeles. Subjects were enrolled from the community by referral and from the Veterans Affairs dementia and diabetes clinics. PARTICIPANTS: Eighty-seven driving subjects were enrolled; 83 completed the study. A sample of eligible dementia clinic subjects consisting of 15 mild AD patients met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association probable AD criteria, while 12 met Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition and Hachinski diagnostic criteria for multi-infarct dementia (vascular dementia). Clinic control subjects consisted of 15 age-matched patients with diabetes and without a history of stroke or dementia. Community controls consisted of 26 healthy, age-matched, older subjects (> 60 years) and 16 young subjects (20 to 35 years). MAIN OUTCOME MEASURES: Drive score from the Sepulveda (Calif) road test and laboratory measures of attention, perception, and memory. RESULTS: The drive scores in the mild AD group (mean, 22.1; SD, 3.8) and in the vascular dementia group (mean, 24.0; SD, 7.8) differed significantly (P < .001 studentized range test) from the drive scores in the diabetic control group (mean, 31.5; SD, 3.9), the older control group (mean, 32.6; SD, 2.8), and the young control group (mean, 33.6; SD, 3.2). Drive score among the three control groups did not vary significantly. Short-term memory (Sternberg), visual tracking, and Folstein Mini-Mental State Examination scores correlated best with drive score, with a cumulative R2 of 0.68. Drive score and number of collisions and moving violations per 1000 miles driven were negatively correlated (r = -0.38; P < .02). CONCLUSIONS: Based on this study, type and degree of cognitive impairment are better predictors of driving skills than age or medical diagnosis per se. Specific testing protocols for drivers with potential cognitive impairment may detect unsafe drivers more effectively than using age or medical diagnosis alone as criteria for license restriction or revocation.

Adult↗

Myelin gene expression in glia treated with oligodendroglial trophic factor.

Oligodendroglia synthesize myelin in the CNS. In vitro, oligodendroglia may be identified by the binding of monoclonal antibodies against galactocerebroside, a myelin-specific galactolipid. Oligodendroglial trophic factor is a protein mitogen for cells of the oligodendroglial lineage. When oligodendroglia in cerebral white matter cultures are treated with oligodendroglial trophic factor, galactocerebroside-positive cells undergo mitosis but fail to express the myelin structural proteins, myelin basic protein and proteolipid protein. Oligodendroglia treated with oligodendroglial trophic factor, however, do express 2',3'-cyclic nucleotide 3'-phosphodiesterase and myelin-associated glycoprotein in a manner similar to oligodendroglia treated with platelet-derived growth factor. Oligodendroglial trophic factor, therefore, generates a population of somewhat 'immature' oligodendroglia, which are galactocerebroside, myelin-associated glycoprotein and 2', 3'-cyclic nucleotide 3' phosphodiesterase positive but myelin basic protein and proteolipid protein negative.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Clinical results and immunologic effects of a mixed bacterial vaccine in cancer patients.

A biological response modifier, mixed bacterial vaccine (MBV), derived from Streptococcus pyogenes and Serratia marcescens was used as a single agent in the treatment of 11 patients with refractory malignancies. MBV's effect on interleukin-2 (IL-2) production, plasma interferon (IFN) and tumor necrosis factor (TNF) levels was monitored. Most patients' peripheral blood mononuclear cells continued to produce baseline to elevated levels of IL-2, in spite of age and disease status. Several patients maintained moderate to high IFN levels. In general there was little correlation between IL-2 and IFN levels or with the response to therapy. One of 11 patients had minor response, 1 of 11 had partial response, 4 of 11 had temporary stabilization of disease, and 5 of 11 had progressive disease. A patient with AIDS and Kaposi's sarcoma experienced a dramatic improvement in performance status and disease stabilization. In all patients side effects occurred only following i.v. and not i.m. administration and included fever and chills. No adverse hepatic, renal or hematologic effects were observed. MBV is a well-tolerated biological response modifier with modest activity in advanced human tumors.

Adult↗

Urinary excretion of the C5b-9 membrane attack complex of complement is a marker of immune disease activity in autologous immune complex nephritis.

The urinary excretion of the C5b-9 membrane attack complex of complement correlates with glomerular deposition of antibody in the passive Heymann nephritis (PHN) model of membranous nephropathy (MN). To determine if this parameter can be correlated with antibody deposition in a model of MN induced by an autologous mechanism and thus more analogous to human MN, the relationship of urinary C5b-9 to ongoing glomerular immune complex formation late in autologous immune complex nephritis (AICN) was studied. Based on urinary C5b-9, the animals were divided into two groups at 12 weeks after induction of AICN, those with persistently high urinary C5b-9 excretion and those in whom urinary excretion of C5b-9 returned to undetectable levels. While all rats developed glomerular deposition of rat IgG and significant proteinuria, high C5b-9 excretors had greater proteinuria and prolonged positive staining for glomerular C3. When normal syngeneic kidneys were transplanted into rats (n = 3) from each group, only those with persistent C5b-9 excretion developed subepithelial immune deposits of rat IgG in the transplanted kidney. As in the PHN model of MN, proteinuria was dissociated widely from urinary C5b-9 excretion, glomerular C3 staining, and evidence of circulating antibody. Thus these findings demonstrate that urinary excretion of C5b-9 serves as an index of on-going immunologic disease activity in the AICN model of MN, while proteinuria does not.

Animals↗

The effect of a bacterial vaccine on tumors and the immune response of ICR/Ha mice.

This study examined the effect of mixed bacterial vaccine (MBV), a biological response modifier prepared from Streptococcus pyogenes and Serratia marcescens, on the immune system of mice and on the regression of a transplantable mouse tumor sarcoma 37. The study examined MBV's biological properties and analyzed its chemical composition. The chemical composition varied with the growth media. A typical centrifuged, dialyzed supernate of the serum-containing preparation was found to consist mainly of protein and minimal amounts of carbohydrate and endotoxin, while MBV made with synthetic medium contained similar amounts of all three. MBV was nontoxic for mice, which gained weight following the injection of 0.5-1.0 ml of MBV. MBV caused regression of 20-100% of well-established mouse tumors without appreciable toxicity. MBV also had a striking effect on the immune response of mice to sheep red blood cells. When administered simultaneously with antigen injection, MBV increased the number of antibody-secreting splenocytes measured by the plaque-forming assay threefold. Serum antibody levels also increased two- to threefold. MBV did not enhance the immune response to pneumococcal polysaccharide type III, a B-cell-dependent response. However, the in vivo administration of MBV increased the in vitro response to MBV and the B-cell mitogen lipopolysaccharide. MBV compares favorably with other biological response modifiers because of its enhancing effect on the immune response and its oncolytic properties at nontoxic levels.

Animals↗

Cognitive performance in geriatric subjects after acute treatment with antidepressants.

The effects of amitriptyline, trazodone and placebo on cognitive skills performance were examined in a group of 15 normal volunteers with a minimum age of 60. Each subject was behaviorally tested after single, acute treatments at weekly sessions using a battery of tasks measuring visual search, division of attention, tracking, critical tracking, rate of information processing, and vigilance. Amitriptyline, 50 mg, produced impairment on the vigilance task, the divided attention task and the critical tracking task. In addition, episodes of extended insensitivity to external stimuli similar to short-term sleep occurred. In contrast, trazodone exhibited impairment only on the critical tracking task. This study indicates that trazodone is less likely than amitriptyline to produce impairment of skills performance aspects of cognition.

Aged↗

Skills performance at low blood alcohol levels.

The effect of low blood alcohol levels (BALs) on driving skills performance was examined experimentally. Ten moderate drinkers were tested on divided-attention and information processing tasks at BALs of zero, 15, 30, 45 and 60 mg/dl. All response measures showed evidence of impairment beginning at 15 mg/dl and increasing impairment with increasing BALs. Thus there is no evidence that low or very low BALs improve performance on driving-related skills, as has sometimes been suggested.

Adolescent↗

Parkinsonism: effects of levodopa treatment on concept formation.

Concept formation was compared in 71 parkinsonian patients and 35 controls matched for age and WAIS vebal IQ. It was found that the patients formed significantly fewer concepts, as measured by the Wisconsin Card Sorting Test (WCST). The patients had difficulties in shifting sets and were unable to attend to the completion of a concept. Levodopa-treated patients were able to produce more correct responses, but were still unable to maintain the correct responses to produce more correct concepts than non-levodopa-treated patients. The behavior of the parkinsonian patients on the WCST is similar to that of patients who have undergone frontal lobectomy. In addition, the results indicate that levodopa therapy may improve "vigilance", without increasing the patient's overall cognitive ability.

Choice Behavior↗