David Vearrier

Methamphetamine: History, Pathophysiology, Adverse Health Effects, Current Trends, and Hazards Associated with the Clandestine Manufacture of Methamphetamine

eveloped as an amphetamine derivative, methamphetamine quickly ecame a popular medication during the 1940s and 1950s, prescribed for variety of indications. Extensive diversion of methamphetamine during he 1960s and an increasing awareness of the adverse health effects ssociated with methamphetamine led to the withdrawal of most of the ndications for licit methamphetamine use and declines in legal producion of the drug. However, the illicit manufacture of methamphetamine ncreased to meet the demand for methamphetamine, and methamphetmine abuse has increased with variable geographic penetrance over the ast 30 years. Methamphetamine is an indirect sympathomimetic agent that is distinuished from amphetamine by a more rapid distribution into the central ervous system (CNS), resulting in the rapid onset of euphoria that is the esired effect for those abusing the drug. Increases in monoamine eurotransmission are responsible for the desired effects—wakefulness, nergy, sense of well-being, and euphoria—as well as the excess ympathetic tone that mediates many its adverse health effects. Methamphetamine is associated with adverse effects to every organ ystem. Although the most significant morbidity and mortality occur ecause of cardiovascular effects, such as myocardial infarction and ypertensive crisis, no organ system remains unscathed by methamphet-

A teenager with agitation: higher than she should have climbed.

A 17-year-old adolescent girl arrives at the emergency department with concerns that she appears agitated and intoxicated. She is previously healthy but is reported to occasionally abuse ethanol and marijuana. She appeared well to friends until she took a single Bbong hit[ from a water pipe approximately 15 minutes before her arrival in the emergency department. Her friends called an ambulance when she became Bviolent[ and Bcrazy[ after inhaling the drug. They believe that she was having visual hallucinations and that, Bshe has never been high like this before.[ The girl appears restless and anxious but is oriented to person, place, and time. She says that her legs feel Bnumb and twitchy.[ Her heart rate is 120 beats per minute, and her blood pressure is 135/85 mm Hg. She is afebrile, and her blood hemoglobin oxygenation is 98% as measured by transcutaneous pulse oximetry. Her pupils are slightly dilated but reactive, and she has normal extraocular muscle function. Her mucous membranes are moist and she has no goiter. Her breath sounds are clear, and her heartbeat is heard without murmur or gallop. She has normally active bowel sounds. Her skin is mildly sweaty but is not flushed, and no rashes are apparent. Result from examination of the cranial nerves is normal, fine touch sensation is intact in the upper and lower extremities, strength appears vigorous, and occasional muscle fasciculations are noted in the quadriceps. She does not display clonus at the Achilles tendon. A bedside blood dextrose measurement is normal. Serum chemistry results were as follows: sodium, 138 mEq/L; potassium,2.9 mEq/L; chloride, 106 mEq/L; bicarbonate, 22 mEq/L; and creatinine, 0.7 mg/dL. A urine radioimmunoassay for amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates, and phencyclidine (PCP) is positive only for tetrahydrocannabinol, which confirms the history of marijuana use. Ethanol is not detected in the blood. She is given lorazepam 2 mg intravenously, and she becomes calmer and her heart rate declines to 95 beats per minute. At this point, it is learned that 2 of her friends have also been taken to the hospital and that they were all trying a Bnew marijuana[ for the first time.

Change in perceived risk associated with marijuana use in the United States from 2002 to 2012

Abstract Context. The role of a dynamic legal, medical, and social setting in affecting the perceived risk associated with smoking marijuana has not been well studied. We sought to determine whether there has been a change in the perceived risk associated with marijuana use over time. Methods. A cross-sectional study was conducted using the 2002–2012 National Survey on Drug Use and Health. Respondents were asked to classify the risk of smoking marijuana. Regression analysis and the Mann–Whitney U test were used to analyze the data. Results. A total of 614579 respondents were identified. Between 2002 and 2012, the percent of respondents who characterized regular marijuana use as being associated with “great risk” decreased from 51.3% to 40.3%, while the percent of respondents who characterized it as being associated with “no risk” increased from 5.7% to 11.7%. The percent of respondents who characterized occasional use as “great risk” decreased from 38.2% to 30.7%, while the percent of respondents who characterized it as “no risk” increased from 10% to 16.3%. There was a significant negative temporal trend in the perceived risk for both occasional and regular use of marijuana from 2002 to 2012 after controlling for age and gender (p < 0.001 for both). Increasing age was significantly associated with increased perceived risk for both occasional and regular marijuana use (p < 0.001). Males have a significantly lower perceived risk for regular marijuana use as compared with females (p < 0.001). Individuals who used marijuana during the preceding month reported a lower risk perception in both regular and occasional use. Conclusion. Between 2002 and 2012, there was a significant decrease in the perceived risk associated with occasional and regular marijuana use. Younger age, male gender, and past month use were also associated with decreased perceived risk.

Occupational health of miners at altitude: Adverse health effects, toxic exposures, pre-placement screening, acclimatization, and worker surveillance

Context. Mining operations conducted at high altitudes provide health challenges for workers as well as for medical personnel. Objective. To review the literature regarding adverse health effects and toxic exposures that may be associated with mining operations conducted at altitude and to discuss pre-placement screening, acclimatization issues, and on-site surveillance strategies. Methods. We used the Ovid (http://ovidsp.tx.ovid.com) search engine to conduct a MEDLINE search for “coal mining” or “mining” and “altitude sickness” or “altitude” and a second MEDLINE search for “occupational diseases” and “altitude sickness” or “altitude.” The search identified 97 articles of which 76 were relevant. In addition, the references of these 76 articles were manually reviewed for relevant articles. Cardiovascular effects. High altitude is associated with increased sympathetic tone that may result in elevated blood pressure, particularly in workers with pre-existing hypertension. Workers with a history of coronary artery disease experience ischemia at lower work rates at high altitude, while those with a history of congestive heart failure have decreased exercise tolerance at high altitude as compared to healthy controls and are at higher risk of suffering an exacerbation of their heart failure. Pulmonary effects. High altitude is associated with various adverse pulmonary effects, including high-altitude pulmonary edema, pulmonary hypertension, subacute mountain sickness, and chronic mountain sickness. Mining at altitude has been reported to accelerate silicosis and other pneumoconioses. Miners with pre-existing pneumoconioses may experience an exacerbation of their condition at altitude. Persons traveling to high altitude have a higher incidence of Cheyne-Stokes respiration while sleeping than do persons native to high altitude. Obesity increases the risk of pulmonary hypertension, acute mountain sickness, and sleep-disordered breathing. Neurological effects. The most common adverse neurological effect of high altitude is acute mountain sickness, while the most severe adverse neurological effect is high-altitude cerebral edema. Poor sleep quality and sleep-disordered breathing may contribute to daytime sleepiness and impaired cognitive performance that could potentially result in workplace injuries, particularly in miners who are already at increased risk of suffering unintentional workplace injuries. Ophthalmological effects. Adverse ophthalmological effects include increased exposure to ultraviolet light and xerophthalmia, which may be further exacerbated by occupational dust exposure. Renal effects. High altitude is associated with a protective effect in patients with renal disease, although it is unknown how this would affect miners with a history of chronic renal disease from exposure to silica and other renal toxicants. Hematological effects. Advanced age increases the risk of erythrocytosis and chronic mountain sickness in miners. Thrombotic and thromboembolic events are also more common at high altitude. Musculoskeletal effects. Miners are at increased risk for low back pain due to occupational factors, and the easy fatigue at altitude has been reported to further predispose workers to this disorder. Toxic exposures. Diesel emissions at altitude contain more carbon monoxide due to increased incomplete combustion of fuel. In addition, a given partial pressure of carbon monoxide at altitude will result in a larger percentage of carboxyhemoglobin at altitude. Miners with a diagnosis of chronic obstructive pulmonary disease may be at higher risk for morbidity from exposure to diesel exhaust at altitude. Conclusions. Both mining and work at altitude have independently been associated with a number of adverse health effects, although the combined effect of mining activities and high altitude has not been adequately studied. Careful selection of workers, appropriate acclimatization, and limited on-site surveillance can help control most health risks. Further research is necessary to more completely understand the risks of mining at altitude and delineate what characteristics of potential employees put them at risk for altitude-related morbidity or mortality.

What is Standard of Care in the Evaluation of Elastosis Perforans Serpiginosa? A Survey of Pediatric Dermatologists

Abstract:  Elastosis perforans serpiginosa is a rare chronic dermatosis characterized by extrusion of altered elastic fibers through the epidermis. It often occurs in association with a variety of connective tissue disorders, and may develop following penicillamine therapy; however, it may also present without comorbidities. There are currently no well‐established protocols for the investigation of possible associated disorders in patients who present with elastosis perforans serpiginosa. We describe three patients with idiopathic elastosis perforans serpiginosa seen at our clinic and review the standard of care among 31 pediatric dermatologists surveyed who have cared for such a patient within the last 2 years. Based upon the results of our survey, we conclude that most pediatric dermatologists limit their evaluation of such patients to a thorough patient history and physical examination. This limited approach may be a sufficient evaluation in affected patients who are otherwise healthy.

Technologically enhanced naturally occurring radioactive materials.

Introduction. Naturally occurring radioactive materials (NORM) are ubiquitous throughout the earths crust. Human manipulation of NORM for economic ends, such as mining, ore processing, fossil fuel extraction, and commercial aviation, may lead to what is known as “technologically enhanced naturally occurring radioactive materials,” often called TENORM. The existence of TENORM results in an increased risk for human exposure to radioactivity. Workers in TENORM-producing industries may be occupationally exposed to ionizing radiation. TENORM industries may release significant amounts of radioactive material into the environment resulting in the potential for widespread exposure to ionizing radiation. These industries include mining, phosphate processing, metal ore processing, heavy mineral sand processing, titanium pigment production, fossil fuel extraction and combustion, manufacture of building materials, thorium compounds, aviation, and scrap metal processing. Methods. A search of the PubMed database (www.pubmed.com) and Ovid Medline database (ovidsp.tx.ovid.com) was performed using a variety of search terms including NORM, TENORM, and occupational radiation exposure. A total of 133 articles were identified, retrieved, and reviewed. Seventy-three peer-reviewed articles were chosen to be cited in this review. Results. A number of studies have evaluated the extent of ionizing radiation exposure both among workers and the general public due to TENORM. Quantification of radiation exposure is limited because of modeling constraints. In some occupational settings, an increased risk of cancer has been reported and postulated to be secondary to exposure to TENORM, though these reports have not been validated using toxicological principles. Conclusions. NORM and TENORM have the potential to cause important human health effects. It is important that these adverse health effects are evaluated using the basic principles of toxicology, including the magnitude and type of exposure, as well as threshold and dose response.

The perception of odor is not a surrogate marker for chemical exposure: a review of factors influencing human odor perception

Context. Clinical toxicologists perform risk assessments and clinical evaluations for patients with potential exposure to airborne toxicants in which the patients self-reported perception of odor may be the only indicator that an exposure may have taken place. Objective. To review the factors that may affect the human ability to perceive chemical odors and relate those odors to specific chemical exposures. Methods. The medical literature, from 1950 through 2012, was searched using the OVID database and the PUBMED database. The searches returned 238 articles, of which 113 involved human studies and were published in the English language. Of these 113 articles, 40 articles discussed odor issues and thus were chosen as specifically relevant to the topic. Bibliographies of all articles were also searched for other relevant references and this found six additional articles, making a total of 46. Factors that may affect olfaction and the ability to perceive odor. Genetic/population. Ethnic background is associated with widely differing odor detection abilities and thresholds. A significant genetic influence for the ability to smell and perceive odor has been reported. Gender. Women are superior to men in their ability to identify odors. Age. Increasing age is correlated with higher odor detection thresholds. Medical conditions. A variety of medical conditions have been associated with deficits in olfaction, including diseases of the nose and sinuses, multiple sclerosis, and schizophrenia. Alcoholism and smoking. Abuse of alcohol results in impaired olfactory sense, and smoking tobacco products alters odor detection threshold in a dose-related manner. Occupational and environmental factors. Repeated inhalation of any chemical results in olfactory fatigue over relatively short time frames that leads to a decreased ability to accurately detect and identify an odor. Recent exposure to relatively high concentrations of a chemical has been shown to affect sensitivity to that particular odorant, altering subsequent detection thresholds by up to three orders of magnitude. Applicability of proposed odor thresholds. Humans are only able to identify three to four components of complex olfactory mixtures and the odorants present in the mixture affect which individual components are detected. Odorants present in suprathreshold concentrations in a mixture may effectively mask the presence of odorants present in perithreshold concentrations. Self-rating of olfactory function may not correlate with actual olfactory ability. It is even more difficult to accurately determine intensity of an odor in a quantifiable way. For example, under conditions of constant stimulation with hydrogen sulfide, perceptual intensity was reported to decrease exponentially with time of stimulation. Concomitant visual stimulation also affects odor intensity. Some chemicals, such as hydrogen sulfide, may induce reactions in humans related solely to their odor, even when they are present in concentrations substantially lower than those levels usually associated with the development of adverse clinical effects. There is a wealth of literature suggesting that the intensity of perceived odor, the degree of irritation, and the reported health effects of exposure to an odorant chemical are affected by psychological state and bias. Multiple theories have been proposed to explain the cognitive basis for perceived illness in association with the perception of odor. The concept of odor has been reported to be intrinsically and cognitively associated with illness rather than with health. Assigning negative bias to an odor prior to an exposure results in the reporting of significantly more health-related symptoms following exposure. This suggests that those symptoms are not mediated by the odor directly, but rather by an individuals cognitive associations between odor and health. Conclusions. Attempts to verify exposure intensity based on the report of a perceived odor is unreliable and has no useful application in legitimate exposure assessment paradigms. Detection of an odor does not imply a medically significant exposure to a toxicant and, due to subject bias and the difficulty of detecting individual odorants in mixtures, may not constitute an exposure to the purported substance.

Biological testing for drugs of abuse

Testing for drugs of abuse has become commonplace and is used for a variety of indications. Commonly employed testing methods include immunoassay and chromatography. Testing methods vary in their sensitivity, specificity, time, and cost. While urine remains the most common body fluid used for testing of drugs of abuse, over the last several decades the use of alternative matrices such as blood, sweat, oral fluids, and hair has increased dramatically. Each biological matrix offers advantages and disadvantages for drug testing, and the most appropriate matrix frequently depends on the indications for the drug test. Drugs of abuse that are most commonly tested include alcohol, amphetamines, cannabinoids, cocaine, opiates, and phencyclidine. Testing may involve detection of the parent compound or metabolites and sensitivity, specificity, and reliability of drug testing may vary depending on the drug being tested. Toxicologists have a responsibility to understand the strengths and limitations of testing techniques and matrices to be able to critically evaluate the results of a drug test.

Sea-dumped chemical weapons: environmental risk, occupational hazard

Abstract Introduction: Chemical weapons dumped into the ocean for disposal in the twentieth century pose a continuing environmental and human health risk. Objective: In this review we discuss locations, quantity, and types of sea-dumped chemical weapons, related environmental concerns, and human encounters with sea-dumped chemical weapons. Methods: We utilized the Ovid (http://ovidsp.tx.ovid.com) and PubMed (http://www.pubmed.org) search engines to perform MEDLINE searches for the terms ‘sea-dumped chemical weapons’, ‘chemical warfare agents’, and ‘chemical munitions’. The searches returned 5863 articles. Irrelevant and non-English articles were excluded. A review of the references for these articles yielded additional relevant sources, with a total of 64 peer-reviewed articles cited in this paper.History and geography of chemical weapons dumping at sea: Hundreds of thousands of tons of chemical munitions were disposed off at sea following World War II. European, Russian, Japanese, and United States coasts are the areas most affected worldwide. Several areas in the Baltic and North Seas suffered concentrated large levels of dumping, and these appear to be the world’s most studied chemical warfare agent marine dumping areas. Chemical warfare agents: Sulfur mustard, Lewisite, and the nerve agents appear to be the chemical warfare agents most frequently disposed off at sea. Multiple other type of agents including organoarsenicals, blood agents, choking agents, and lacrimators were dumped at sea, although in lesser volumes. Environmental concerns: Numerous geohydrologic variables contribute to the rate of release of chemical agents from their original casings, leading to difficult and inexact modeling of risk of release into seawater. Sulfur mustard and the organoarsenicals are the most environmentally persistent dumped chemical agents. Sulfur mustard in particular has a propensity to form a solid or semi-solid lump with a polymer coating of breakdown products, and can persist in this state on the ocean floor for decades. Rates of solubility and hydrolysis and levels of innate toxicity of a chemical agent are used to predict the risk to the marine environments. The organoarsenicals eventually breakdown into arsenic, and thus present an indefinite timeline for contamination. Generally, studies assaying sediment and water levels of parent chemical agents and breakdown products at dumpsites have found minimal amounts of relevant chemicals, although arsenic levels are typically higher in dumpsites than reference areas. Studies of marine organisms have not shown concerning amounts of chemical agents or breakdown products in tissue, but have shown evidence of chronic toxicity. There is believed to be minimal risk posed by seafood consumption. Microbiota assays of dumpsites are significantly altered in species composition compared to reference sites, which may imply unseen but significant changes to ecosystems of dumpsites. Human health concerns: The major human health risk at this time appears to arise from acute exposure to an agent by either accidental recovery of a chemical weapon on a fishing vessel, or by munitions washed ashore onto beaches. Conclusions: Improving technology continues to make the deep sea more accessible, thus increasing the risk of disturbing munitions lying on or buried in the seabed. Pipe laying, cable burying, drilling, scuba diving, trawling, and undersea scientific research are the activities posing the most risk. The long-term threat to the benthic habitat via increased arsenic concentrations, shifts in microbiota speciation, and chronic toxicity to vertebrates and invertebrates is not currently understood. The risk to the environment of massive release via disturbance remains a distinct possibility. Terrorist recovery and re-weaponization of chemical agents is a remote possibility.

Anticholinergic delirium following Datura stramonium ingestion: implications for the Internet age.

Recreational use of Datura to deliberately induce an anticholinergic delirium is not uncommon. We present a case of Datura intoxication in a young adult who learned about the recreational use of Datura on the Internet and subsequently purchased Datura stramonium seeds from an online vendor. Using the Google search engine, we conducted searches for “Datura,” “jimson weed” and “Datura seeds” and reviewed the first 200 search results for each search term. We found 16 websites recommending the recreational use of Datura, 12 vendors selling seeds of genus Datura and one website that both promoted the recreational use of Datura and also sold Datura stramonium leaves. The promotion of recreational use of Datura on the Internet represents a danger to public health and the ability to purchase Datura seeds from Internet vendors may increase the prevalence of Datura abuse.