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Biomedical subjects

Michael A Miller

Publications and source records attributed to Michael A Miller.

At least 37 records · Page 2Linked to original sources

Treatment of imported fire ant stings with mitigator sting and bite treatment--a randomized control study.

OBJECTIVE: To evaluate the efficacy of the commercially available product Mitigator Sting and Bite Treatment in reducing the pain after imported fire ant stings. METHODS: Twenty-four volunteer subjects were exposed to imported fire ant stings on both fore-arms. The subjects received Mitigator paste on 1 arm and calamine lotion on the opposite arm, in a blinded manner, from 90 seconds to 10 minutes after exposure. Subjects recorded pain on a 100-mm visual analog scale 60 seconds, 20 minutes, and 3 days after exposure. A 2-tailed paired t test was used to compare the difference in reduction of pain over time between the Mitigator-treated arms and the calamine-treated arms. RESULTS: At 60 seconds, the mean visual analog scale pain score was 23.9 mm for the Mitigator group and 24.5 mm for the calamine group. At 20 minutes, the mean score was 7.6 mm (delta = 16.3) for the Mitigator group and 12.7 mm (delta = 11.8) for the calamine group. At 3 days, the mean score was 2.4 mm (delta = 21.5) for the Mitigator group and 2.9 mm (delta = 21.6) for the calamine group. There was no significant difference between groups for change in visual analog scale pain score at 60 seconds, 20 minutes (P = .256), or 3 days (P = .64). CONCLUSIONS: There was no significant difference in pain relief between calamine and Mitigator for imported fire ant stings.

Adolescent↗

Survey of U.S. Army commanders' experiences with brigade/battalion surgeons at Fort Hood, Texas.

This anonymous survey sent to every battalion and brigade commander at Fort Hood, Texas assessed the new concept of residency-trained operational physicians that had completed military unique curriculum series training. Commanders provided anonymous professional information about themselves and their assigned physicians and evaluated their physicians in 22 areas of medical and military competence using a linear scoring method from 2 (indicating poor) to 6 (indicating outstanding). Main effects and interaction effects were analyzed using multiple analysis of variance. The commanders' overall confidence in their physicians was 5.4, suggesting general satisfaction. Prior-service physicians were rated higher on several factors if the commander had combat experience. Non-prior-service physicians were rated the same on nearly all variables regardless of the commander's experience. Commanders with combat experience rated their assigned physicians significantly higher than did commanders without combat experience. Despite high ratings, several candid remarks suggest there is still room for improvement.

Adult↗

Eph and NMDA receptors control Ca2+/calmodulin-dependent protein kinase II activation during C. elegans oocyte meiotic maturation.

Fertilization in the female reproductive tract depends on intercellular signaling mechanisms that coordinate sperm presence with oocyte meiotic progression. To achieve this coordination in Caenorhabditis elegans, sperm release an extracellular signal, the major sperm protein (MSP), to induce oocyte meiotic maturation and ovulation. MSP binds to multiple receptors, including the VAB-1 Eph receptor protein-tyrosine kinase on oocyte and ovarian sheath cell surfaces. Canonical VAB-1 ligands called ephrins negatively regulate oocyte maturation and MPK-1 mitogen-activated protein kinase (MAPK) activation. Here, we show that MSP and VAB-1 regulate the signaling properties of two Ca2+ channels that are encoded by the NMR-1 N-methyl D-aspartate type glutamate receptor subunit and ITR-1 inositol 1,4,5-triphosphate receptor. Ephrin/VAB-1 signaling acts upstream of ITR-1 to inhibit meiotic resumption, while NMR-1 prevents signaling by the UNC-43 Ca2+/calmodulin-dependent protein kinase II (CaMKII). MSP binding to VAB-1 stimulates NMR-1-dependent UNC-43 activation, and UNC-43 acts redundantly in oocytes to promote oocyte maturation and MAPK activation. Our results support a model in which VAB-1 switches from a negative regulator into a redundant positive regulator of oocyte maturation upon binding to MSP. NMR-1 mediates this switch by controlling UNC-43 CaMKII activation at the oocyte cortex.

Animals↗

Cardiovascular collapse from low dose bupivacaine.

Bupivacaine is a long-acting local anesthetic agent that is very widely used for cutaneous infiltration, peripheral nerve blocks, epidural anesthesia, and spinal anesthesia. Well-described cardiotoxic effects of bupivacaine and other members of its class include dysrhythmias, hypotension, and depression of cardiac output. The minimum IV dose of bupivacaine previously associated with significant toxicity in humans is 1.6 mg/kg. A case is reported of bradyasystolic arrest with post resuscitation shock, without significant central nervous system (CNS) toxicity, following the injection of less than 1.1 mg/kg bupivacaine in an adult.

Aged↗

Imaging bone microdamage in vivo with positron emission tomography.

Microdamage accumulation in bone is now considered a contributing cause for bone fragility in older women. However, there is still no method to detect and quantify microdamage in vivo. We have found that positron emission tomography (PET) may be useful to detect and quantify bone microdamage in vivo using a high-resolution PET scanner with [18F]NaF as the tracer. We have done several experiments using the rat ulnar loading model that demonstrate that (1) high-resolution [18F]NaF PET can detect newly created microdamage in vivo; (2) the microdamage detected in this way is co-localized with damage detected by histological and autoradiographic procedures; and (3) high-resolution [18F]NaF PET can distinguish between the effects of mechanical loading that does not produce damage and fatigue loading that creates microdamage. The high-resolution [18F]NaF PET shows promise as a non-invasive means to image bone microdamage.

Animals↗

Facile synthesis and PET imaging of a novel potential heart acetylcholinesterase tracer N-[11C]methyl-3-[[(dimethylamino)carbonyl]oxy]-2-(2',2'-diphenylpropionoxymethyl)pyridinium.

A new AChE tracer N-[(11)C]methyl-3-[[(dimethylamino)carbonyl]oxy]-2-(2',2'-diphenylpropionoxymethyl)pyridinium ([(11)C]MDDP, [(11)C]1) has been synthesized in 40-65% radiochemical yield. Initial PET dynamic studies of [(11)C]MDDP in rat heart showed rapid heart uptake and blood pool clearance to give high-quality heart images. Blocking studies of [(11)C]MDDP with pretreatment drug neostigmine in rats found only minor reductions in rat heart [(11)C]MDDP retention. The results suggest that [(11)C]MDDP delineates the heart very clearly, and the uptakes of [(11)C]MDDP in rat heart might be related to non-specific binding.

Acetylcholinesterase↗

Procedural sedation and analgesia in the emergency department: what are the risks?

The practitioner of emergency medicine is routinely faced with patients in need of emergent procedures and pain control and sedation. Our challenge is to make our patients' experiences as painless and as safe as possible, while maximizing our ability to perform the procedure at hand; this is not always an easy task given the propensity of each human body to react differently to interventions and stimuli. We can best meet this challenge by understanding how our patients and pharmaceutical agents intermingle in the risk-benefit equation we formulate before starting our "experiment." Coupling this information with fundamentally sound patient care and monitoring will minimize bad experiences with PSA for both the patient and practitioner.

Adverse Drug Reaction Reporting Systems↗

Colchicine-related death presenting as an unknown case of multiple organ failure.

A 45-year-old man presented to the emergency department (ED) with acute renal and hepatic failure as well as hypotension and metabolic acidosis. Despite aggressive intensive care, he had continued hypotension, leukocytosis, fever, renal and hepatic failure, and lactic acidosis. On hospital day 3, pancytopenia was noted. Bone marrow biopsy showed marked aplasia without a specific etiology being elucidated. He received granulocyte colony-stimulating factor and antibiotics, but died on hospital day 12 after a cardiac arrest. The patient repeatedly denied intentional drug ingestion. Due to his clinical course, the poison center recommended obtaining a colchicine level. The plasma colchicine level, 72 h after admission, was 6.1 ng/mL (GC/MS). This level exceeds acute levels reported in some cases of prior fatalities. This case is novel in that the patient's multiple organ dysfunction remained unexplained for several days before occult colchicine toxicity was implicated as the probable cause by the colchicine level. Also, there was a paucity of gastrointestinal symptoms on presentation, the opposite of what is expected in colchicine toxicity.

Bone Marrow Diseases↗

Methylenedioxymethamphetamine (ecstasy)-related hyperthermia.

MDMA (or 3, 4 methylenedioxymethamphetamine) was first manufactured in the 1920s and found to have structural similarities to both mescaline and amphetamines. Used briefly by some therapists in the 1970s and early 1980s as an adjunct to psychotherapy, it is now primarily abused by teenagers and young adults as an illicit recreational drug known as "ecstasy." As its popularity has increased, so have the number of fatalities and adverse events related to its use. We report six patients suffering fatal or life-threatening hyperthermia after MDMA use. These cases illustrate that hyperthermia associated with MDMA use cannot be solely attributed to rave parties (high ambient temperatures, excessive dancing, dehydration, and overcrowded conditions), drug contaminants, or co-ingestants. A better understanding of the etiology of hyperthermia after MDMA use is needed so that appropriate harm-reduction measures can be developed and instituted.

Adolescent↗

Methylenedioxymethamphetamine (ecstasy)-related myocardial hypertrophy: an autopsy study.

BACKGROUND: Myocardial hypertrophy is a well-recognized complication of cocaine and methamphetamine abuse and is a strong, independent risk factor for sudden death, myocardial infarction, and congestive heart failure. We sought to determine if use of MDMA (methylenedioxyamphetamine or "ecstasy") is associated with myocardial hypertrophy at death. METHODS AND RESULTS: A matched, retrospective study using medical examiner (ME) death reports. Consecutive MDMA positive (+) and MDMA negative (-) deaths identified from MEs in 10 states and a local county, respectively. Five MDMA(-) cases were matched to each MDMA(+) case for age, sex, and ethnicity. MDMA(+) cases were confirmed using GC/MS and other drugs of abuse (e.g., cocaine and methamphetamine) were absent. Matched MDMA(-) cases were trauma fatalities with intact hearts and blood negative for all illicit stimulants. Cardiac weights were compared between the two groups. Twenty seven MDMA(+) deaths and 135 matched MDMA(-) deaths were enrolled. Mean age was 20 years (range 16--33 years); 44% were female. 70.4% were Caucasian, 14.8% African-American, 11.1% Asian, and 3.7% Hispanic. Mean heart weight of MDMA(+) fatalities was 315.7 and 277.2g for MDMA(-) fatalities (Diff=38.5 g; 95% CI=18.3--8.7). Multivariate analysis revealed that MDMA(+) fatalities were more likely to have an enlarged heart (OR=18.3; 95% CI=3.6--1.6). CONCLUSION: The findings of this study suggest that MDMA users might also be at risk for myocardial hypertrophy and possible cardiac toxicity, similar to other stimulants.

Adolescent↗

Adolescent substance abuse: a simplified approach to drug testing.

Treatment of adolescent substance abusers is difficult. Treatment programs at multiple levels, from inpatient facilities to outpatient support groups, usually are available. Some of the most encouraging results have come from programs that involve family therapy in addition to individual treatment. 22 Knowing what resources are available, as well as the referral processes based on a particular patient's healthcare plans, facilitates access and makes dealing with these issues in a busy outpatient setting much easier. Frequent follow-up with an adolescent after a treatment program has been initiated to monitor for compliance and relapse can ensure a better drug-free outcome. Knowing the extent of the adolescent drug abuse problem should encourage providers to incorporate some type of screening into their routine care of adolescents. None of these methods is 100% sensitive, and incorporating each component into the process where appropriate likely is the best approach. Knowing risk and protective factors for drug use is helpful for both recognition of candidates for screening and counseling of parents regarding drug use prevention.

Adolescent↗

Clustered organization of reproductive genes in the C. elegans genome.

Defining the forces that sculpt genome organization is fundamental for understanding the origin, persistence, and diversification of species. The genomic sequences of the nematodes Caenorhabditis elegans and Caenorhabditis briggsae provide an excellent opportunity to explore the dynamics of chromosome evolution. Extensive chromosomal rearrangement has accompanied divergence from their common ancestor, an event occurring roughly 100 million years ago (Mya); yet, morphologically, these species are nearly indistinguishable and both reproduce primarily by self-fertilization. Here, we show that genes expressed during spermatogenesis (sperm genes) are nonrandomly distributed across the C. elegans genome into three large clusters located on two autosomes. In addition to sperm genes, these chromosomal regions are enriched for genes involved in the hermaphrodite sperm/oocyte switch and in the reception of sperm signals that control fertilization. Most loci are present in single copy, suggesting that cluster formation is largely due to gene aggregation and not to tandem duplication. Comparative mapping indicates that the C. briggsae genome differs dramatically from the C. elegans genome in clustering. Because clustered genes have a direct role in reproduction and thus fitness, their aggregated pattern might have been shaped by natural selection, perhaps as hermaphroditism evolved.

Animals↗

Facile synthesis and initial PET imaging of novel potential heart acetylcholinesterase imaging agents [11C]pyridostigmine and its analogs.

A series of 11C-labeled analogs of the acetylcholinesterase (AChE) inhibitor pyridostigmine have been synthesized for evaluation as new potential positron emission tomography (PET) imaging agents for heart AChE. The appropriate precursors for radiolabeling were slightly modified from commercial reagents. The new tracers [11C]pyridostigmine (1), [11C]para-pyridostigmine (2) and [11C]ortho-pyridostigmine (3) were prepared by N-[11C]methylation of the precursors using [11C]methyl triflate. Pure target compounds were isolated by a solid-phase extraction (SPE) purification procedure with 60-85% radiochemical yields (decay corrected to end of bombardment), and a synthesis time of 10-15 min. The initial PET dynamic studies of compounds (1-3) in rat heart showed rapid heart uptake and blood pool clearance to give high quality heart images. These results suggest the new tracers delineate the heart very clearly and could be potential heart AChE imaging agents.

Acetylcholinesterase↗

Shedding new light on the "safe" club drug: methylenedioxymethamphetamine (ecstasy)-related fatalities.

OBJECTIVES: To report the pathology, toxicology, cause, and manner of death in 3,4-methylenedioxymethamphetamine (MDMA)-associated fatalities in the United States. Although use trends are increasing, data regarding the hazards of MDMA are limited. METHODS: The authors obtained fatality reports from participating medical examiners in the United States. Cases were identified as "drug-unrelated" when MDMA did not directly cause death (e.g., motor vehicle collision); deaths from drug toxicity were judged "drug-related." RESULTS: Thirty-eight (8%) of the surveyed medical examiners reported 102 deaths associated with MDMA use from 1999 to 2001. Ten percent of fatalities occurred in 1999 and 90% thereafter, representing a 400% relative increase. Victims tended to be young (mean age = 25), white (n = 87 [85%]), male (n = 70 [69%]), and otherwise healthy. Seventy-one (70%) deaths were drug-related (DR) and 31 (30%) were drug-unrelated (DU). Twenty-four (35%) DR deaths had a mean delay of 6.7 hours (95% CI = 5.1 to 8.2) in activating emergency medical services. Fifty-five DR cases (81%) were found in asystole and pronounced dead at the scene. CONCLUSIONS: The MDMA-associated fatal events typically occur in young, otherwise healthy individuals. MDMA's impact on the public health and safety of young adults and teenagers needs further assessment.

Adolescent↗