PCRRT Protocol: Perioperative Cardiac Risk Reduction Therapy Art Wallace, M.D., Ph.D. 1. All patients who either have coronary artery disease (CAD), peripheral vascular disease (PVD), or two risk factors for coronary artery disease (age > 60, cigarette smoking, diabetes, hypertension, cholesterol > 240 mg/dl) should be on perioperative beta blockade unless they have a specific intole
Myua.alaska.eduMycotoxins and Indoor Molds
Sean P. Abbott, Ph.D.
Originally published in Indoor Envronment CONNECTIONS, Vol. 3, Issue 4, 2002.
included irritation of oral/ nasal passages and syndromes include "Hepatitis X" in dogs and swine.
necrotic lesions of respiratory and digestive tracts, All are characterized by congestion and hemorrhage With a growing awareness of the potential hazards in various organs and histological lesions in liver of chemical and biological agents in our homes, schools and workplaces, a greater emphasis has Alimentary Toxic Aleukia (ATA) caused by T-2
been placed on evaluating the role of mycotoxins toxin, another potent trichothecene, reached Recently, together with medical mycologist Lynne and mycotoxin-producing fungi in our indoor epidemic proportions during World War II in Sigler (Univ. Alberta Microfungus Collection, environments. Now, more then ever, the potential Russia. In some districts 10% of the population and Edmonton, Canada) and mycotoxicologist Jens health effects of airborne molds and other biological livestock contracted the often fatal illness. ATA was Frisvad (Technical Univ. Denmark, Lyngby), I was contaminants are being given serious consideration caused by ingestion of grain infected with Fusarium involved with the first confirmed report of human poae and F. sporotrichioides that had overwintered rubratoxicosis (Sigler et al. 1996). Three teens in the field. Symptoms include subcutaneous drinking toxic moldy homemade rhubarb winebecame critically ill with rapid onset of fever, chills What are mycotoxins?
haemorrhages, leukopenia, lymphocytosis, and and severe vomiting and were diagnosed with acute Simply, a mycotoxin is any toxic fungal metabolite.
acute degeneration of internal organs.
liver failure. One received an immediate liver Fungi produce a variety of secondary metabolites as transplant. Mycotoxins in the wine were suspected a byproduct of their metabolism. Those capable of Aflatoxin, perhaps the most famous of all
since mold had been noted during the wine making eliciting deleterious effects on other organisms are mycotoxins, remains one of the most potent classified as mycotoxins. Mycotoxicosis can be carcinogens of natural origin known to man. In defined as illness resulting from ingestion, 1952, an outbreak of 'moldy corn toxicosis' was Initial inspection of the wine and containers showed inhalation, or other involvement with mycotoxins.
caused by the consumption of mouldy corn by no visible mold growth, but the wine was yellowish, Mold mycotoxins of primary concern here elicit a swine in southern USA. Another outbreak in 1960, unlike the typical rosé color of rhubarb wine.
harmful effect on humans. Other substances such as Turkey 'X' disease, caused the death of 100,000 those produced by poisonous mushrooms are also portions of the wine to agar media. Colonies of a mycotoxins, and mycetismus is the term applied to hepatocarcinogens produced by Aspergillus flavus, blue-green mold were isolated and identified by toxin mushroom poisoning as a distinct category of A. parasiticus, and A. nomius. Symptoms include profile and by macroscopic and microscopic features mycotoxicosis. The discovery of antibiotics anorexia, lethargy, muscle weakness, liver produced by fungi revolutionized the treatment of haemorrhages and necrosis, engorged kidneys and disease because the compounds are sufficiently non- liver cancer. There is at least one human case of Animal studies at the Univ. Alberta Hospitals toxic to the host. In nature, mycotoxins are a acute aflatoxicosis (severe hepatitis) in India. Long provided evidence that a mycotoxin was responsible.
chemical defense for fungi and have evolved as term effects of diets containing aflatoxin are Two adult mice were inoculated with 0.5 and 0.2 ml mechanisms for antiherbivory and to provide a correlated with high incidence of liver disease in of filter sterilized wine. The mouse that received the competitive advantage when colonizing new certain regions. While acceptable levels of aflatoxin in food are about 15 ppm, samples of contaminatedfood in Nigeria measured 100 ppm, maize in India Wine samples and a mold isolate were analyzed for Historical Mycotoxicoses
15,000 ppm, and corn in USA reached 320,000 mycotoxins. The main mycotoxin in the wine was The study of mycotoxins originally centered on the rubratoxin B. Analysis of cultures showed the health effects of ingestion of toxic fungal presence of additional toxins, including rugulovasine byproducts from growth of fungi on food and Yellow Rice Disease, or Shoshin-kakke, was
livestock feed. A review of the historical prevalent in Japan during Sino-Japanese war and hepatotoxin, but these were not present in the wine.
significance of mycotoxins sets the stage for more after World War II. This potentially fatal, agonizing P. crateriforme is capable of breaking down colored recent work with inhalation myctoxicosis studies.
disease resulted from consumption of rice infectedwith Penicillium citreoviride. The toxin, matter from the rhubarb accounting for the winediscoloration . The high level of rubratoxin in the Ergotism or St. Anthony's Fire, is one of the oldest
citreoviridin, causes paralysis, cardiovascular wine may be due in part to the acidic environment known mycotoxins. Early records attributable to the disease inlcude the Spartan war with Athens in 430BC. In 1093 the Order of St. Anthony was Ochratoxin mycotoxicoses is linked to endemic
Although ingestion of mold contaminated food rarely established for victims of St. Anthony's Fire, a Balkan nephropathy, a fatal kidney disease of young has consequences as serious as the liver failure crippling disease of unkown origin. In 1673 in people living near the Danube River. Ochratoxin, a reported here, this case demonstrates potential risks France, the disease was linked to consumption of powerful nephrotoxin and hepatotoxin, is also associated with common indoor molds.
grain infected with ergot (sclerotia of Claviceps implicated in an outbreak of procine nephropathy purpurea), and in 1770 an epidemic resulted in the (swine are extremely sensitive) in Denmark in the first ergotism control measures. Today, the FDA 1920's. Aspergillus ochraceus, Penicillium has set limits on ergotalkaloid levels, and food verrucosum and related species commonly produce grains are strictly monitored. Two forms of the ochratoxin in grain, dried beans, peanuts, green disesase, gangrenous and convulsive ergotism, are coffee beans, and hay. Estimates suggest that most European pork has trace amounts of ochratoxin, primarily from Penicillium verrucosum and P.
nordicum, species particularly prevalent in northern Stachybotryotoxicosis was one of the first mold
mycotoxicoses to draw scientific study and pavedthe way for a broader understanding of the hazards Case Study: Rubratoxicosis
posed by mycotoxins. It was first recorded in the First recognized in the 1950's as ‘Hemorrhagic Ukraine in early 1930's, primarily affecting horses Syndrome in Poultry’, the mycotoxicoses caused by fed hay infected with Stachybotrys chartarum rubratoxins after consumption of moldy feed Penicillium corylophilum
containing trichothecene mycotoxins. Symptoms resulted in 40% mortality. Other agricultural HEALTH EFFECTS OF AIRBORNE
present on surfaces and in air allows for assessment TOXIGENIC FUNGI
investigators to quickly and objectively identify the of active growth within buildings and the potential nature, extent, and distribution of building-related for mycotoxin production based on the species health complaints. Investigations (publications identified can be inferred. In many cases, the Organic Dust Toxic Syndrome (ODTS)
pending) utilizing the EpIAQ software have underlying question is simply “Is active mold Inhalation exposure to mycotoxins was first objectively demonstrated the direct association growth occurring indoors”? A genus level recognized in agricultural workers exposed to between indoor toxigenic fungal exposure and identification is sufficient in most cases, but for extremely high levels of airborne molds. A variety particular cases where correlations are being made of fungal and bacterial toxins were potentially to health effects it may be necessary to have all involved in the acute toxicological disease termed fungi identified to species. This can be especially MYCOTOXINS IN INDOOR
important in groups such as Penicillium orAspergillus where different species produce vastly ‘NIFIES’ and ‘Sick Building Syndrome’ (SBS)
differing types and quantities of toxins.
The health effects of mold exposure have been well Referred to simply as ‘stachy’ in the trade, described but the specific mechanism of disease Stachybotrys chartarum has served as the flagship remains incompletely understood. Extensive attention has been given to airborne molds as environments. The sinister reputation as the ‘toxic potential allergens or infectious agents. However, black mold’ may be well founded in the potency of the few published studies of occupants of mold- the suite of trichothecene toxins produced.
contaminated buildings have not convincingly Trichothecenes, including the potent satratoxin, are demonstrated the clinical syndrome is consistent cytotoxic compounds, capable of killing cells.
with an immediate (e.g., allergic rhinitis, asthma) or Carcinogenic effects are occasionally reported, but delayed (e.g., hypersensitivity pneumonitis) there is no evidence of carcinogenicity of these hypersensitivity reaction, with no immunological toxins. Other immune suppressive compounds have markers correlating with clinical illness. Indeed, the also been isolated from Stachybotrys. Although S. consistent finding that most occupants of mold- chartarum is by far the most frequently encountered contaminated buildings experience rapid onset of species, others such as S. cylindrospora and S. symptoms upon entering the building and rapid echinata are also found occasionally indoors and resolution each time they leave strongly suggests a are both known to produce similar toxins. The first toxicological, rather than allergic mechanism. SBS cases of human stachybotrytoxicoses were a result was applied to unexplained symptoms of occupants of inhalation exposure of the spores by handlers of primarily in office buildings, and the disorder has contaminated hay and straw. Without adequate PPE, been described as a “building-related illness arising remediators of mold-contaminated buildings are at from microbial contamination of building materials similar risk of high mycotoxin doses. (See the caused by condensation and leaks” (AIHA 1996) article devoted to Stachybotrys chartarum in the and more vaguely as “building-related symptoms” Chaetomium globosum
Infectious Fungal Indoor Exposure Syndrome Indoor sampling protocols should involve a variety (NIFIES) has been proposed to describe the illness Other trichothecene producing molds can also be of sample types to get a well-rounded assessment.
typically first called SBS (Craner 1999). Symptoms found colonizing wet, cellulosic substrata in indoor Areas of visible mold may be sampled directly by include eye, nose and throat irritiation/ inflamation, environments. These include Fusarium, sending bulk material or tape-lift samples for respiratory symptoms such as cough and chest Myrothecium, Trichothecium and Cylindrocarpon.
identification. Sampling should include air tightness, fatigue, papular rash, and neurocognitive Additionally, Trichoderma species are known to monitoring in selected problem and non-problem symptoms such as short-term memory loss and produce sesquiterpenes, toxins very similar to areas with an outdoor comparison sample.
concentration problems. Medications such as Culturable and non-culturable methods have antibiotics, antihistamines, and asthma drugs are differing sensitivities or capabilities. Although ineffective because mycotoxicoses are non- Penicillium and Aspergillus species are common and either method will usually detect major problems, a infectious, non-communicable, and do not elicit important molds in the human environment and are combination of the two provides for the most among the main agents of spoilage in human and reliable interpretation. The culturable method individuals have complete clinical improvement animal food. Many species are known to produce a employs samplers such as the Andersen N6, Biotest shortly after removal of the mycotoxin source, diversity of toxins (Table 1), making them among the RCS, SAS, EM Science MAS 100 and others that either through relocation or remediation of the mold most important indoor molds to recover and identify.
draw air across agar media, impacting the fungal Carcinogenic effects of inhaling Aspergillus flavus spores have been confirmed by animal studies. identification of the fungi that grow. The main Route of exposure
advantage is that precise identifications are Mycotoxins affect occupants in buildings primarily A number of common molds on decaying leaves possible, crucial for species ID of Penicillium and through inhalation. Many small mold spores (2-10 (phylloplane fungi) are able to colonize cellulosic Aspergillus, and important for the recovery and microns) are respirable into the alveoli, the terminal building materials. Some species of Alternaria, recognition of a wide variety of potentially portion of the lungs where oxygen exchange Cladosporium, Bipolaris and Arthrinium are known toxigenic molds such as Paecilomyces, Fusarium, between the lungs and blood occurs, and in which to produce toxins. Moderate levels of these fungi Trichoderma, Phoma, Acremonium, and Wallemia.
soluble toxins contained in the spores enter the are common as a result of outdoor air exchange Non-culturable or ‘spore-trap’ samplers such as the blood stream. However, the toxicology and with the interior of the building. Several species are Zefon Air-O-Cell, Burkard, Allergenco, BioSIS, also well known allergens and active indoor growth cyclex-d and others have demonstrated excellent distribute throughout the body and selectively is potentially problematic. Other cellulose ability to allow sensitive detection of Stachybotrys produce symptoms remains poorly understood.
degrading species such as Chaetomium and Phoma spores present in low levels. They allow for rapid Currently, no reliable biological marker (e.g., blood may produce toxins. Chaetomium is an ascomycete analysis when required and adequately determine test) has been developed to demonstrate the that is especially common on water damaged paper the levels and proportions of various spore types presence of such agents in the body.
determined to genus or broad category. Althoughthey lack some specificity in identification, they Epidemiology
Sampling for fungi
recover types of spores that do not grow or compete The validation and circumscription of widespread Currently, the method of choice for assessing well in culture. They have the additional advantage health effects in cases of SBS has been hampered potential exposures to mycotoxins in indoor of collecting all airborne particles for microscopic by inadequate occupant questionnaires, incomplete environments involves the detection of mycotoxin- observation and non-fungal biological elements environmental investigations and small sample such as pollen, insect parts, epithelial cells, fiber sizes. New software, EpIAQ™ (Epidemiological identification of fungal propagules. Determining Indoor Air Quality) developed by at Verdi types and prevalence of various species of fungi Abbott, S.P. 2002. Mycotoxins and Indoor Molds. Indoor Environment CONNECTIONS. 3(4):14-24 glass and carbonaceous debris may be detected to and lack of specificity tend to preclude its use in Frisvad, J. and U. Thrane. 2000. Mycotoxin further broaden the scope of the IAQ investigation.
production by common filamentous fungi. In:Introduction to food- and airborne fungi. CBS, Analysis for mycotoxins
SUMMARY AND CURENT STATUS
Although sampling for fungi is standard in IAQ Kirkland, K. 2001. Health hazards from exposure to studies, direct or indirect analysis for toxins is also IN IAQ INDUSTRY
mycotoxic fungi in indoor environments. The possible. Isolates recovered from indoor samples can be assayed for toxin production, but given the Despite a growing body of evidence linking variable nature of toxin production based on Sigler, L., S.P. Abbott, and J. Frisvad. 1996.
mycotoxins produced by indoor molds to adverse Rubratoxin mycotoxicosis by Penicillium effects on human health, a recent AIHCE/AIHA temperature and competition with other microbes, crateriforme following ingestion of home- panel concluded that there is “at this time not the presence or absence of toxins produced under enough evidence to support an association between experimental conditions does not confirm toxin mycotoxic fungi and a change in the spectrum of production was occurring in situ. Examination of illness, severity of illness or an increase in risk of Sean P. Abbott, Ph.D., is Analytical Director of bulk material for toxins is also possible, but more illness” (Kirkland 2001). Reminiscent of early a.k.a.MOLDLAB in Sparks, NV, and oversees complicated due to interference of background doubts regarding health effects of other exposure analysis of air and surface samples to determine material and mixed species assemblages. Perhaps related illnesses such as smoking, we await more whether growth of fungi and bacteria is occurring the most limiting factor is the enormous diversity of detailed scientific studies to corroborate and explain indoors and the level of microbial contamination toxins produced by fungi (Frisvad and Thrane the expanding pool of increasingly convincing present. With over 15 years experience indoor air 2002), including many that remain uncharacterized observational data that we are confronted with in quality and mycology, Dr. Abbott has over 30 (Table 1). Toxicological tests utilize a comparison publications and has written one book, from his standard, so unknowns must be run for each research projects on airborne molds as biological individually profiled mycotoxin, making analytical hazards, opportunistic human pathogens, and References
fungal systematics. His current interests include ACGIH. 1999. Bioaerosols: assessment and control assessing methods of detecting mold contamination Sampling for volatiles, or mVOC’s, given off by in buildings, optimal sampling protocols and microbes as a byproduct of their metabolism has AIHA. 1996. Field guide for determination of sample analysis methods, potential effects of also been used to determine fungal growth in airborne molds on human health, and the biology of buildings. Many of these compounds are alchohols, fungi in the human environment. You can reach him aldehydes, ketones and other organic chemicals that Craner, J. 1999. Building-related illness in by calling (775) 356-6653 or by email at are not mycotoxins and likely have little health occupants of mold-contaminated houses. In: effects on occupants at the levels present. mVOC Bioaerosols, Fungi and Mycotoxins, Eastern testing offers an additional parameter in cases where traditional means are inconclusive, but cost TABLE 1: Selected mycotoxins produced by some common indoor molds and other economically important fungi.
altenuene, altenusin, alternariol, altertoxin, tenuazonic acid aflatoxin, austin, citrinin, cytochalasin, fumitoxin, nidulotoxin, ochratoxin, patulin, sterigmatocystin, tremorgenicmycotoxins (fumitremorgen, penitrem, territrem, verruculogen), viomellein, vioxanthin, xanthomegnin cytochalasin, sporidesmin, sterigmatocystin chaetoglobosin, chetomin, chaetochromin, chaetosin, cochliodinol, sterigmatocystin ergotalkaloids (egrine, ergometrine, ergonovine, ergotamine, ergotoxine, lysergic acid), secalonic acid fumonisin, fusaric acid, fusarin, fusarochromanone, moniliformin, trichothecenes (deoxynivalinol, T2 toxin), zearlenol,zearalenone citrinin, citreoviridin, citromycetin, erythroskyrin, ochratoxin, griseofulvin, luteoskyrin, oxaline, patulin, penicillic acid,roquefortine, rubratoxin, rugulosin, rugulovasine, tremorgenic mycotoxins (penitrem, territrem, verruculogen),verrucosidin, viomellein, viridicatin, xanthomegnin brefeldin, cytochalasin, secalonic acid, tenuazonic acid griseofulvin, trichothecenes (isosatratoxin, roridin, satratoxin, trichodermol, trichoverrol) roseotoxin, trichothecenes (trichothecin) Abbott, S.P. 2002. Mycotoxins and Indoor Molds. Indoor Environment CONNECTIONS. 3(4):14-24
C:\OLIAMM\stampe\aporm001.xls: Export da AMCsodio lattato + sodio citrato + sodio clor BUPULMOCARE * DIETA LIQ VANIGLIA 250ML+ DE F FLsodio cloruro + potassio cloruro + calcioFLacidum clodronicum (sale disodico tetraFIalteplasi per preparazione iniettabile (F FLC:\OLIAMM\stampe\aporm001.xls: Export da AMCacidum clodronicum (sale disodico tetraFIacidum clodronicum (sale disodico tetraFIMAG