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Manuel Posada De La Paz - One of the best experts on this subject based on the ideXlab platform.
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Printed in Great Britain Mortality among People Affected by Toxic Oil Syndrome
2016Co-Authors: Ignacio Abaitua, Manuel Posada De La Paz, Mercedes Díez Ruiz-navarro, Borda Edwin, M Kilbourne, Rafael Gabriel Sanchez, Henry FalkAbstract:The authors conducted a mailed questionnaire survey of a 5 % sample of the cohort of 20643 people officially recog-nized by the Spanish government as having had Toxic Oil Syndrome, a previously undescribed illness that was epidemic in Spain in 1981. After three mailings of a letter and questionnaire, responses for only 66 % of the sample had been received. Nevertheless, responses were obtained from virtually all remaining patients (or surrogates for them in the cases of patients that had died) when they were sought by telephone. In 1981, there was clear-cut excess mortality in the cohort (standardized mortality ratio [SMR] 6.51; 95 % confidence interval [Cl] : 3.92-10.17). During the period January 1982 through 7 March 1988, there was no statistically significant overall mortality excess except during the period 1982-1983 among people aged <65 years (SMR 2.26; 95 % Cl: 1.03-4.29). Toxic Oil Syndrome substantially altered the patterns of mortality among affected people. Analysis of deaths by cause among the TOS cohort will be useful for further evaluation of the long-term impact of the TOS epidemic. In 1981, an epidemic of a previously unrecognized illness occurred in central and northwestern Spain. Some 20000 people were affected, and the disease was severe enough to require hospitalization for more than 11000. ' The illness, now called Toxic Oil syndrom
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Printed in U.S.A. Toxic Oil Syndrome: The Perspective after 20 Years
2015Co-Authors: Manuel Posada De La Paz, Rossanne M. Philen, Ignacio Abaitua BordaAbstract:In 1981, a progressive multisystem disease, later called Toxic Oil Syndrome, abruptly broke out in epidemic propor-tions in central and northwestern Spain (1). This previously unknown Syndrome affected thousands of people, and sev
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Articles Pharmacogenetic Profile of Xenobiotic Enzyme Metabolism in Survivors of the Spanish Toxic Oil Syndrome
2013Co-Authors: Margarita G Ladona, Maravillas Izquierdo-martinez, Coral Ampurdanés, Jordi Segura, Rafael De La Torre, Manuel Posada De La Paz, Emilio J SanzAbstract:In 1981, the Spanish Toxic Oil Syndrome (TOS) affected more than 20,000 people, and over 300 deaths were registered. Assessment of genetic polymorphisms on xenobiotic metabolism would indicate the potential metabolic capacity of the victims at the time of the disaster. Thus, impaired metabolic pathways may have contributed to the clearance of the Toxicant(s) leading to a low detoxification or accumulation of Toxic metabolites contributing to the disease. We conducted a matched case–control study using 72 cases (54 females, 18 males) registered in the Official Census of Affected Patients maintained by the Spanish government. Controls were nonaffected siblings (n =72) living in the same household in 1981 and nonaffected nonrelatives (n = 70) living in the neighborhood at that time, with no ties to TOS. Genotype analyses were performed to assess the metabolic capacity of phase I [cytochrome P450 1A1 (CYP1A1), CYP2D6] and phase II [arylamine N-acetyltransferase-2 (NAT2), GSTM1 (glutathione S-transferase M1) and GSTT1] enzyme polymorphisms. The degree of association of the five metabolic pathways was estimated by calculating their odds ratios (ORs) using conditional logistic regression analysis. In the final model, cases compared with siblings (72 pairs) showed no differences either in CYP2D6 or CYP1A1 polymorphisms, or in conjugation enzyme polymorphisms, whereas cases compare
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Tarkowski 9 (WHO/CISAT Scientific Committee for the Toxic Oil Syndrome)
2013Co-Authors: Emilio Gelpí, Manuel Posada De La Paz, Rossanne M. Philen, Edwin M. Kilbourne, Carlos Lahoz, Ignacio Abaitua, Agustin Gomez De La Camara, Benedetto Terracini, Bénoit Nemery, Luis SoldevillaAbstract:In 1981, in Spain, the ingestion of an Oil fraudulently sold as olive Oil caused an outbreak of a previously unrecorded condition, later known as Toxic Oil Syndrome (TOS), clinically characterized by intense incapacitating myalgias, marked peripheral eosinophilia, and pulmonary infiltrates. Of the 20,000 persons affected, approximately 300 died shortly after the onset of the disease and a larger number developed chronic disease. For more than 15 years, a scientific committee supported by the World Health Organization’s Regional Office for Europe and by the Institute of Health Carlos III in Madrid has guided investigation intended to identify the causal agent(s), to assess Toxicity and mode of action, to establish the pathogenesis of the disease, and to detect late consequences. This report summarizes advances in research on this front. No late mortality excess has been detected. Among survivors, the prevalence of some chronic conditions (e.g., sclerodermia, neurologic changes) is high. Attempts to reproduce the condition in laboratory animals have been unsuccessful, and no condition similar to TOS has been reported in the scientifi
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Environmental Medicine Article Neurologic Outcomes of Toxic Oil Syndrome Patients 18 Years after the Epidemic
2013Co-Authors: Manuel Posada De La Paz, Rossanne M. Philen, Ignacio Abaitua Borda, Fredric Gerr, Richard Letz, María José Ferrari Arroyo, L. Vela, Maravillas Izquierdo, Concepción Martín Arribas, Ro RamosAbstract:Toxic Oil Syndrome (TOS) resulted from consumption of rapeseed Oil denatured with 2 % aniline and affected more than 20,000 persons. Eighteen years after the epidemic, many patients continue to report neurologic symptoms that are difficult to evaluate using conventional techniques. We conducted an epidemiologic study to determine whether an exposure to Toxic Oil 18 years ago was associated with current adverse neurobehavioral effects. We studied a case group of 80 adults exposed to Toxic Oil 18 years ago and a referent group of 79 adult age- and sex-frequency–matched unexposed subjects. We interviewed subjects for demographics, health status, exposures to neuroToxicants, and responses to the Kaufman Brief Intelligence Test (K-BIT), Programa Integrado de Exploracion Neuropsicologica (PIEN), and Goldberg depression questionnaires and administered quantitative neurobehavioral and neurophysiologic tests by computer or trained nurses. The groups did not differ with respect to educational background or other critical variables. We examined associations between case and referent groups and the neurobehavioral and neurophysiologic outcomes of interest. Decreased distal strength of the dominant and nondominant hands and increased vibrotactile thresholds of the fingers and toes were significantly associated with exposure to Toxic Oil. Finger tapping, simple reaction time latency, sequence B latency, symbol digit latency
Ignacio Abaitua Borda - One of the best experts on this subject based on the ideXlab platform.
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Printed in U.S.A. Toxic Oil Syndrome: The Perspective after 20 Years
2015Co-Authors: Manuel Posada De La Paz, Rossanne M. Philen, Ignacio Abaitua BordaAbstract:In 1981, a progressive multisystem disease, later called Toxic Oil Syndrome, abruptly broke out in epidemic propor-tions in central and northwestern Spain (1). This previously unknown Syndrome affected thousands of people, and sev
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Environmental Medicine Article Neurologic Outcomes of Toxic Oil Syndrome Patients 18 Years after the Epidemic
2013Co-Authors: Manuel Posada De La Paz, Rossanne M. Philen, Ignacio Abaitua Borda, Fredric Gerr, Richard Letz, María José Ferrari Arroyo, L. Vela, Maravillas Izquierdo, Concepción Martín Arribas, Ro RamosAbstract:Toxic Oil Syndrome (TOS) resulted from consumption of rapeseed Oil denatured with 2 % aniline and affected more than 20,000 persons. Eighteen years after the epidemic, many patients continue to report neurologic symptoms that are difficult to evaluate using conventional techniques. We conducted an epidemiologic study to determine whether an exposure to Toxic Oil 18 years ago was associated with current adverse neurobehavioral effects. We studied a case group of 80 adults exposed to Toxic Oil 18 years ago and a referent group of 79 adult age- and sex-frequency–matched unexposed subjects. We interviewed subjects for demographics, health status, exposures to neuroToxicants, and responses to the Kaufman Brief Intelligence Test (K-BIT), Programa Integrado de Exploracion Neuropsicologica (PIEN), and Goldberg depression questionnaires and administered quantitative neurobehavioral and neurophysiologic tests by computer or trained nurses. The groups did not differ with respect to educational background or other critical variables. We examined associations between case and referent groups and the neurobehavioral and neurophysiologic outcomes of interest. Decreased distal strength of the dominant and nondominant hands and increased vibrotactile thresholds of the fingers and toes were significantly associated with exposure to Toxic Oil. Finger tapping, simple reaction time latency, sequence B latency, symbol digit latency
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Neurologic outcomes of Toxic Oil Syndrome patients 18 years after the epidemic.
Environmental health perspectives, 2003Co-Authors: Manuel Posada De La Paz, Ignacio Abaitua Borda, R. M. Philen, Fredric Gerr, Richard Letz, María José Ferrari Arroyo, L. Vela, Maravillas Izquierdo, Concepción Martín Arribas, Alejandro RamosAbstract:Toxic Oil Syndrome (TOS) resulted from consumption of rapeseed Oil denatured with 2% aniline and affected more than 20,000 persons. Eighteen years after the epidemic, many patients continue to report neurologic symptoms that are difficult to evaluate using conventional techniques. We conducted an epidemiologic study to determine whether an exposure to Toxic Oil 18 years ago was associated with current adverse neurobehavioral effects. We studied a case group of 80 adults exposed to Toxic Oil 18 years ago and a referent group of 79 adult age- and sex-frequency-matched unexposed subjects. We interviewed subjects for demographics, health status, exposures to neuroToxicants, and responses to the Kaufman Brief Intelligence Test (K-BIT), Programa Integrado de Exploracion Neuropsicologica (PIEN), and Goldberg depression questionnaires and administered quantitative neurobehavioral and neurophysiologic tests by computer or trained nurses. The groups did not differ with respect to educational background or other critical variables. We examined associations between case and referent groups and the neurobehavioral and neurophysiologic outcomes of interest. Decreased distal strength of the dominant and nondominant hands and increased vibrotactile thresholds of the fingers and toes were significantly associated with exposure to Toxic Oil. Finger tapping, simple reaction time latency, sequence B latency, symbol digit latency, and auditory digit span were also significantly associated with exposure. Case subjects also had statistically significantly more neuropsychologic symptoms compared with referents. Using quantitative neurologic tests, we found significant adverse central and peripheral neurologic effects in a group of TOS patients 18 years after exposure to Toxic Oil when compared with a nonexposed referent group. These effects were not documented by standard clinical examination and were found more frequently in women.
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Toxic Oil Syndrome: The Perspective after 20 Years
Epidemiologic reviews, 2001Co-Authors: Manuel Posada De La Paz, Rossanne M. Philen, Ignacio Abaitua BordaAbstract:Toxic Oil Syndrome burst upon the scene in Spain in May of 1981, draining the resources of a newly evolving political and social medicine system. The vehicle of the causative Toxic agent was identified as an illicit Oil that had been diverted from industrial use and refined in order to remove the aniline denaturant, and that was sold in unlabeled 5-liter containers by itinerant salesmen. Over 20,000 people were ultimately affected, and over 1,200 deaths from all causes have been recorded in the affected cohort. The epidemiologic investigation of Toxic Oil Syndrome involved all facets of investigative and analytical work; from visits to factories and interviewing workers, to sophisticated chemical and statistical analytical techniques. This investigation serves as a further illustration that data and information of all types, and from a wide range of fields, need to be systematically collected and evaluated in order to best resolve an epidemiologic mystery. Astute clinical observation of the patients, however, led to the hypothesis that Toxic Oil Syndrome was a result of a Toxic exposure. In this and other epidemics of unknown etiology, clinical observation and the intense scrutiny of patients' histories, signs, and symptoms by treating clinicians have often led to hypotheses that could be tested epidemiologically. When there are medical unknowns, the role of the astute clinician continues to be crucial. The Toxic Oil Syndrome epidemic is an example of how even a developed country can be affected by a massive epidemic of environmental origin if failures occur in the systems that control and regulate the food supply or other consumer products. However, such failures could occur anywhere that large commercial networks operate on the regulatory edge, and if these business lack an in depth knowledge of the consequences of alterations in manufacturing conditions. Such was the case with eosinophilia-myalgia Syndrome as well, when apparently minor alterations in manufacturing conditions of L-tryptophan led to an increase in impurities in the product that were later associated with the illness. These risks are even greater in countries with few or inconsistent control systems, making the food and drug supply potential portals of entry for serious health hazards, as is further exemplified by the tragic episode of pediatric renal failure in Haiti associated with a legitimate consumer product, paracetamol elixir, that had been manufactured using a fraudulently supplied Toxic ingredient, diethylene glycol (81). The potential Toxicants in the adulterated rapeseed Oil were present in extremely small amounts. If fatty acid anilides or related compounds are indeed the etiologic agents in Toxic Oil Syndrome, then these compounds must be extremely Toxic at the parts per million concentrations at which they were found. Further, the roles of causative agents in the development of disorders such as scleroderma, eosinophilic fasciitis, eosinophilic perimyositis, and other similar diseases are unknown, but scientists can speculate that some sort of low level environmental agent may play a role if such extremely small quantities of contaminants are indeed capable of causing disease. Although the exact identity of the etiologic agent in Toxic Oil Syndrome remains unknown, work on Toxic Oil Syndrome continues. Follow-up clinical studies and long-term mortality studies are under way. Investigation of the mechanisms involved in Toxic Oil Syndrome continues. The identification of suspect chemical compounds, their characterization, and effects will hopefully one day contribute to the prevention of other similar diseases.
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Toxic Oil Syndrome mortality the first 13 years
International Journal of Epidemiology, 1998Co-Authors: Ignacio Abaitua Borda, Manuel Posada De La Paz, Rossanne M. Philen, Agustin Gomez De La Camara, Mercedes Diez Ruiznavarro, Olga Gimenez Ribota, Jorge Alvargonzalez Soldevilla, Benedetto Terracini, Serapio Severiano Pena, Carmen Fuentes LealAbstract:Background The Toxic Oil Syndrome (TOS) epidemic that occurred in Spain in the spring of 1981 caused approximately 20 000 cases of a new illness. Overall mortality and mortality by cause in this cohort through 1994 are described for the first time in this report. Methods We contacted, via mail or telephone, almost every living member of the cohort and family members of those who were known to have died in order to identify all deaths from 1 May 1981 through 31 December 1994. Cause of death data were collected from death certificates and underlying causes of death were coded using the International Classification of Diseases, 9th Revision. Results We identified 1663 deaths between 1 May 1981 and 31 December 1994 among 19 754 TOS cohort members, for a crude mortality rate of 8.4%. Mortality was highest during 1981, with a standardized mortality ratio (SMR) of 4.92 (95% confidence interval [CI] : 4.39-5.50) compared with the Spanish population as a whole. The highest SMR, (20.41, 95% Cl : 15.97-25.71) was seen among women aged 20-39 years during the period from 1 May 1981 through 31 December 1982. Women <40 years old, who were affected by TOS, were at greater risk for death in most time periods than their unaffected peers, while older women and men were not. Over the follow-up period, mortality of the cohort was less than expected when compared with mortality of the general Spanish population, or with mortality of the population of the 14 provinces where the epidemic occurred. We also found that, except for deaths attributed to external causes including TOS and deaths due to pulmonary hypertension, all causes of death were decreased in TOS patients compared to the Spanish population. The most frequent underlying causes of death were TOS, 350 (21.1%); circulatory disorders, 536 (32.3%); and malignancies, 310 (18.7%). Conclusions We conclude that while on average people affected by Toxic Oil Syndrome are not at greater risk for death over the 13-year study period than any of the comparison groups, women <40 years old were at greater risk of death.
Angel Messeguer - One of the best experts on this subject based on the ideXlab platform.
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Potential implication of aniline derivatives in the Toxic Oil Syndrome (TOS).
Chemico-biological interactions, 2010Co-Authors: Angel MesseguerAbstract:The Toxic Oil Syndrome (TOS) was an epidemic disease appeared in central Spain in 1981, causing over 400 deaths and affecting more than 20,000 people, mainly women and children. The disease was linked to the consumption of rapeseed Oil denatured with aniline, illegally refined at the ITH Oil refinery in Seville, mixed with other Oils and sold as edible olive Oil. Among the aniline derivatives detected in the Oil batches generated by an uncontrolled deodorisation procedure during the refining process, fatty acid anilides were first postulated as the causal agents. Nevertheless, compounds identified as 3-(N-phenylamino)propane-1,2-diol (PAP) and its mono-, di-, and triacyl derivatives (mPAP, dPAP and tPAP, respectively), were subsequently considered better biomarkers of Toxic Oils and the best candidates for causing the inToxication. In this account, we will discuss the results obtained in recent years by our group concerning: (a) The effect of different variables intervening in the deodorisation process that could influence the formation of PAP derivatives. To this end we decided to take the aniline derivatives linked to oleic acid as compound models since this is the fatty acid present in highest amounts in rapeseed Oil. The study was focused on the influence of different parameters on the formation of the diester PAP derivative (OOPAP) the monoester derivative (OPAP) and the corresponding amide (oleanilide, OA), and the interactions between any two of these variables. Of particular interest was the interaction observed between OOPAP and OA, due to its potential relevance to the final composition of the Toxic Oil model. (b) Xenobiochemical aspects of PAP derivatives, specifically: the stereospecific hydrolysis of OPAP and OOPAP by human pancreatic lipase, the in vitro activation of PAP by human and rat liver microsomes as well as by recombinant 450 enzymes, and the formation and stability of GSH and N-acetylcysteine adducts of a highly reactive iminoquinone intermediate generated in the biotransformation of PAP.
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Studies on the Toxic Oil Syndrome: proposal of a mechanism for the thermal conversion of 3-N-phenylamino-1,2-propanediol esters into anilides under deodorisation conditions
Tetrahedron, 2009Co-Authors: Jordi Escabrós, Ramon Crehuet, Angel MesseguerAbstract:A study on the reaction mechanism for the conversion of title esters, the species recognised as Toxic biomarkers of the Oil batches responsible for the Toxic Oil Syndrome, into the corresponding anilides under the thermal conditions of an Oil deodorisation process was performed using experimental and computational techniques. The results obtained suggest a reaction course that includes two basic steps: an intramolecular process involving the reaction of the amine group of the diester derivative with the secondary ester of the same compound, followed by the attack of an aniline molecule to form the (E)-isomer of an imidic acid, which would finally tautomerise to give the final anilide.
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In vitro bioactivation of 3-(N-phenylamino)propane-1,2-diol by human and rat liver microsomes and recombinant P450 enzymes. Implications for Toxic Oil Syndrome.
Chemical research in toxicology, 2007Co-Authors: Anna Martínez-cabot, Anna Morató, Jan N. M. Commandeur, Nico P. E. Vermeulen, Angel MesseguerAbstract:Toxic Oil Syndrome (TOS) was a massive food-borne inToxication that occurred in Spain in 1981. Epidemiological studies imputed 3-( N-phenylamino)propane-1,2-diol (PAP) derivatives as the Toxic agents. The in vitro bioactivation of PAP by rat and human liver microsomes was studied. In both cases, 3-[ N-(4'-hydroxyphenyl)amino]propane-1,2-diol ( 1) was detected as the main metabolite. Inhibition studies with pooled human liver microsomes in the presence and absence of P450-specific inhibitors suggest that 2C8 and 2E1 are the main enzymes involved in PAP bioactivation, followed by 3A4/5, 1A1/2, and 2C9. Incubations of PAP with 10 different recombinant P450 enzymes showed that 2C8, 2C9, 2C18, 2D6, and 2E1 catalyzed PAP 4'-hydroxylation. Incubations of phenol 1 with rat and human liver microsomes in the presence of GSH resulted in the formation of a glutathione conjugate of a quinoneimine metabolite derived from 1. In rat liver microsomes, P450 enzymes play a key role in the bioactivation of 1, whereas in human liver microsomes, autoxidation appears to be the major mechanism. The implications of these results for Toxic Oil Syndrome are discussed.
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Synthesis and stability studies of the glutathione and N-acetylcysteine adducts of an iminoquinone reactive intermediate generated in the biotransformation of 3-(N-phenylamino)propane-1,2-diol: implications for Toxic Oil Syndrome.
Chemical research in toxicology, 2005Co-Authors: Anna Martínez-cabot, And Anna Morató, Angel MesseguerAbstract:Epidemiological studies have pointed to fatty acid mono- and diesters of 3-(N-phenylamino)propane-1,2-diol (PAP) as the biomarkers of the Toxic Oil batches that caused Toxic Oil Syndrome (TOS), an ...
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Metabolism of R,S enantiomers of 3-phenylamino-1,2-propanediol, a compound associated with the Toxic Oil Syndrome, in C57BL/6- and A/J-strain mice.
Advances in experimental medicine and biology, 2001Co-Authors: Margarita G Ladona, Coral Ampurdanés, Angel Messeguer, Jordi Bujons, Anna MoratóAbstract:The Toxic Oil Syndrome (TOS) appeared in Spain in spring 1981 as a massive food-borne inToxication in the central and northwestern areas of the country. A huge population of over 20,000 people was afflicted and over 400 deaths occurred1. The clinical features of TOS resembled an allergic-Toxic Syndrome in the acute phase and an autoimmune condition in the chronic phase1,2. Although some patients recovered after a long period of time (several months), many continue to suffer severe sequel or mild symptoms.
Rossanne M. Philen - One of the best experts on this subject based on the ideXlab platform.
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Printed in U.S.A. Toxic Oil Syndrome: The Perspective after 20 Years
2015Co-Authors: Manuel Posada De La Paz, Rossanne M. Philen, Ignacio Abaitua BordaAbstract:In 1981, a progressive multisystem disease, later called Toxic Oil Syndrome, abruptly broke out in epidemic propor-tions in central and northwestern Spain (1). This previously unknown Syndrome affected thousands of people, and sev
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Tarkowski 9 (WHO/CISAT Scientific Committee for the Toxic Oil Syndrome)
2013Co-Authors: Emilio Gelpí, Manuel Posada De La Paz, Rossanne M. Philen, Edwin M. Kilbourne, Carlos Lahoz, Ignacio Abaitua, Agustin Gomez De La Camara, Benedetto Terracini, Bénoit Nemery, Luis SoldevillaAbstract:In 1981, in Spain, the ingestion of an Oil fraudulently sold as olive Oil caused an outbreak of a previously unrecorded condition, later known as Toxic Oil Syndrome (TOS), clinically characterized by intense incapacitating myalgias, marked peripheral eosinophilia, and pulmonary infiltrates. Of the 20,000 persons affected, approximately 300 died shortly after the onset of the disease and a larger number developed chronic disease. For more than 15 years, a scientific committee supported by the World Health Organization’s Regional Office for Europe and by the Institute of Health Carlos III in Madrid has guided investigation intended to identify the causal agent(s), to assess Toxicity and mode of action, to establish the pathogenesis of the disease, and to detect late consequences. This report summarizes advances in research on this front. No late mortality excess has been detected. Among survivors, the prevalence of some chronic conditions (e.g., sclerodermia, neurologic changes) is high. Attempts to reproduce the condition in laboratory animals have been unsuccessful, and no condition similar to TOS has been reported in the scientifi
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Environmental Medicine Article Neurologic Outcomes of Toxic Oil Syndrome Patients 18 Years after the Epidemic
2013Co-Authors: Manuel Posada De La Paz, Rossanne M. Philen, Ignacio Abaitua Borda, Fredric Gerr, Richard Letz, María José Ferrari Arroyo, L. Vela, Maravillas Izquierdo, Concepción Martín Arribas, Ro RamosAbstract:Toxic Oil Syndrome (TOS) resulted from consumption of rapeseed Oil denatured with 2 % aniline and affected more than 20,000 persons. Eighteen years after the epidemic, many patients continue to report neurologic symptoms that are difficult to evaluate using conventional techniques. We conducted an epidemiologic study to determine whether an exposure to Toxic Oil 18 years ago was associated with current adverse neurobehavioral effects. We studied a case group of 80 adults exposed to Toxic Oil 18 years ago and a referent group of 79 adult age- and sex-frequency–matched unexposed subjects. We interviewed subjects for demographics, health status, exposures to neuroToxicants, and responses to the Kaufman Brief Intelligence Test (K-BIT), Programa Integrado de Exploracion Neuropsicologica (PIEN), and Goldberg depression questionnaires and administered quantitative neurobehavioral and neurophysiologic tests by computer or trained nurses. The groups did not differ with respect to educational background or other critical variables. We examined associations between case and referent groups and the neurobehavioral and neurophysiologic outcomes of interest. Decreased distal strength of the dominant and nondominant hands and increased vibrotactile thresholds of the fingers and toes were significantly associated with exposure to Toxic Oil. Finger tapping, simple reaction time latency, sequence B latency, symbol digit latency
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Toxic Oil Syndrome: The Perspective after 20 Years
Epidemiologic reviews, 2001Co-Authors: Manuel Posada De La Paz, Rossanne M. Philen, Ignacio Abaitua BordaAbstract:Toxic Oil Syndrome burst upon the scene in Spain in May of 1981, draining the resources of a newly evolving political and social medicine system. The vehicle of the causative Toxic agent was identified as an illicit Oil that had been diverted from industrial use and refined in order to remove the aniline denaturant, and that was sold in unlabeled 5-liter containers by itinerant salesmen. Over 20,000 people were ultimately affected, and over 1,200 deaths from all causes have been recorded in the affected cohort. The epidemiologic investigation of Toxic Oil Syndrome involved all facets of investigative and analytical work; from visits to factories and interviewing workers, to sophisticated chemical and statistical analytical techniques. This investigation serves as a further illustration that data and information of all types, and from a wide range of fields, need to be systematically collected and evaluated in order to best resolve an epidemiologic mystery. Astute clinical observation of the patients, however, led to the hypothesis that Toxic Oil Syndrome was a result of a Toxic exposure. In this and other epidemics of unknown etiology, clinical observation and the intense scrutiny of patients' histories, signs, and symptoms by treating clinicians have often led to hypotheses that could be tested epidemiologically. When there are medical unknowns, the role of the astute clinician continues to be crucial. The Toxic Oil Syndrome epidemic is an example of how even a developed country can be affected by a massive epidemic of environmental origin if failures occur in the systems that control and regulate the food supply or other consumer products. However, such failures could occur anywhere that large commercial networks operate on the regulatory edge, and if these business lack an in depth knowledge of the consequences of alterations in manufacturing conditions. Such was the case with eosinophilia-myalgia Syndrome as well, when apparently minor alterations in manufacturing conditions of L-tryptophan led to an increase in impurities in the product that were later associated with the illness. These risks are even greater in countries with few or inconsistent control systems, making the food and drug supply potential portals of entry for serious health hazards, as is further exemplified by the tragic episode of pediatric renal failure in Haiti associated with a legitimate consumer product, paracetamol elixir, that had been manufactured using a fraudulently supplied Toxic ingredient, diethylene glycol (81). The potential Toxicants in the adulterated rapeseed Oil were present in extremely small amounts. If fatty acid anilides or related compounds are indeed the etiologic agents in Toxic Oil Syndrome, then these compounds must be extremely Toxic at the parts per million concentrations at which they were found. Further, the roles of causative agents in the development of disorders such as scleroderma, eosinophilic fasciitis, eosinophilic perimyositis, and other similar diseases are unknown, but scientists can speculate that some sort of low level environmental agent may play a role if such extremely small quantities of contaminants are indeed capable of causing disease. Although the exact identity of the etiologic agent in Toxic Oil Syndrome remains unknown, work on Toxic Oil Syndrome continues. Follow-up clinical studies and long-term mortality studies are under way. Investigation of the mechanisms involved in Toxic Oil Syndrome continues. The identification of suspect chemical compounds, their characterization, and effects will hopefully one day contribute to the prevention of other similar diseases.
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Toxic Oil Syndrome mortality the first 13 years
International Journal of Epidemiology, 1998Co-Authors: Ignacio Abaitua Borda, Manuel Posada De La Paz, Rossanne M. Philen, Agustin Gomez De La Camara, Mercedes Diez Ruiznavarro, Olga Gimenez Ribota, Jorge Alvargonzalez Soldevilla, Benedetto Terracini, Serapio Severiano Pena, Carmen Fuentes LealAbstract:Background The Toxic Oil Syndrome (TOS) epidemic that occurred in Spain in the spring of 1981 caused approximately 20 000 cases of a new illness. Overall mortality and mortality by cause in this cohort through 1994 are described for the first time in this report. Methods We contacted, via mail or telephone, almost every living member of the cohort and family members of those who were known to have died in order to identify all deaths from 1 May 1981 through 31 December 1994. Cause of death data were collected from death certificates and underlying causes of death were coded using the International Classification of Diseases, 9th Revision. Results We identified 1663 deaths between 1 May 1981 and 31 December 1994 among 19 754 TOS cohort members, for a crude mortality rate of 8.4%. Mortality was highest during 1981, with a standardized mortality ratio (SMR) of 4.92 (95% confidence interval [CI] : 4.39-5.50) compared with the Spanish population as a whole. The highest SMR, (20.41, 95% Cl : 15.97-25.71) was seen among women aged 20-39 years during the period from 1 May 1981 through 31 December 1982. Women <40 years old, who were affected by TOS, were at greater risk for death in most time periods than their unaffected peers, while older women and men were not. Over the follow-up period, mortality of the cohort was less than expected when compared with mortality of the general Spanish population, or with mortality of the population of the 14 provinces where the epidemic occurred. We also found that, except for deaths attributed to external causes including TOS and deaths due to pulmonary hypertension, all causes of death were decreased in TOS patients compared to the Spanish population. The most frequent underlying causes of death were TOS, 350 (21.1%); circulatory disorders, 536 (32.3%); and malignancies, 310 (18.7%). Conclusions We conclude that while on average people affected by Toxic Oil Syndrome are not at greater risk for death over the 13-year study period than any of the comparison groups, women <40 years old were at greater risk of death.
Margarita G Ladona - One of the best experts on this subject based on the ideXlab platform.
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Articles Pharmacogenetic Profile of Xenobiotic Enzyme Metabolism in Survivors of the Spanish Toxic Oil Syndrome
2013Co-Authors: Margarita G Ladona, Maravillas Izquierdo-martinez, Coral Ampurdanés, Jordi Segura, Rafael De La Torre, Manuel Posada De La Paz, Emilio J SanzAbstract:In 1981, the Spanish Toxic Oil Syndrome (TOS) affected more than 20,000 people, and over 300 deaths were registered. Assessment of genetic polymorphisms on xenobiotic metabolism would indicate the potential metabolic capacity of the victims at the time of the disaster. Thus, impaired metabolic pathways may have contributed to the clearance of the Toxicant(s) leading to a low detoxification or accumulation of Toxic metabolites contributing to the disease. We conducted a matched case–control study using 72 cases (54 females, 18 males) registered in the Official Census of Affected Patients maintained by the Spanish government. Controls were nonaffected siblings (n =72) living in the same household in 1981 and nonaffected nonrelatives (n = 70) living in the neighborhood at that time, with no ties to TOS. Genotype analyses were performed to assess the metabolic capacity of phase I [cytochrome P450 1A1 (CYP1A1), CYP2D6] and phase II [arylamine N-acetyltransferase-2 (NAT2), GSTM1 (glutathione S-transferase M1) and GSTT1] enzyme polymorphisms. The degree of association of the five metabolic pathways was estimated by calculating their odds ratios (ORs) using conditional logistic regression analysis. In the final model, cases compared with siblings (72 pairs) showed no differences either in CYP2D6 or CYP1A1 polymorphisms, or in conjugation enzyme polymorphisms, whereas cases compare
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Pharmacogenetic profile of xenobiotic enzyme metabolism in survivors of the Spanish Toxic Oil Syndrome.
Environmental Health Perspectives, 2001Co-Authors: Margarita G Ladona, Maravillas Izquierdo-martinez, Coral Ampurdanés, Jordi Segura, Rafael De La Torre, Emilio J SanzAbstract:In 1981, the Spanish Toxic Oil Syndrome (TOS) affected more than 20,000 people, and over 300 deaths were registered. Assessment of genetic polymorphisms on xenobiotic metabolism would indicate the potential metabolic capacity of the victims at the time of the disaster. Thus, impaired metabolic pathways may have contributed to the clearance of the Toxicant(s) leading to a low detoxification or accumulation of Toxic metabolites contributing to the disease. We conducted a matched case-control study using 72 cases (54 females, 18 males) registered in the Official Census of Affected Patients maintained by the Spanish government. Controls were nonaffected siblings (n =72) living in the same household in 1981 and nonaffected nonrelatives (n = 70) living in the neighborhood at that time, with no ties to TOS. Genotype analyses were performed to assess the metabolic capacity of phase I [cytochrome P450 1A1 (CYP1A1), CYP2D6] and phase II [arylamine N-acetyltransferase-2 (NAT2), GSTM1 (glutathione S-transferase M1) and GSTT1] enzyme polymorphisms. The degree of association of the five metabolic pathways was estimated by calculating their odds ratios (ORs) using conditional logistic regression analysis. In the final model, cases compared with siblings (72 pairs) showed no differences either in CYP2D6 or CYP1A1 polymorphisms, or in conjugation enzyme polymorphisms, whereas cases compared with the unrelated controls (70 pairs) showed an increase in NAT2 defective alleles [OR = 6.96, 95% confidence interval (CI), 1.46-33.20] adjusted by age and sex. Glutathione transferase genetic polymorphisms (GSTM1, GSTT1) showed no association with cases compared with their siblings or unrelated controls. These findings suggest a possible role of impaired acetylation mediating susceptibility in TOS.
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Metabolism of R,S enantiomers of 3-phenylamino-1,2-propanediol, a compound associated with the Toxic Oil Syndrome, in C57BL/6- and A/J-strain mice.
Advances in experimental medicine and biology, 2001Co-Authors: Margarita G Ladona, Coral Ampurdanés, Angel Messeguer, Jordi Bujons, Anna MoratóAbstract:The Toxic Oil Syndrome (TOS) appeared in Spain in spring 1981 as a massive food-borne inToxication in the central and northwestern areas of the country. A huge population of over 20,000 people was afflicted and over 400 deaths occurred1. The clinical features of TOS resembled an allergic-Toxic Syndrome in the acute phase and an autoimmune condition in the chronic phase1,2. Although some patients recovered after a long period of time (several months), many continue to suffer severe sequel or mild symptoms.
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metabolism of r s enantiomers of 3 phenylamino 1 2 propanediol a compound associated with the Toxic Oil Syndrome in c57bl 6 and a j strain mice
Advances in Experimental Medicine and Biology, 2001Co-Authors: Margarita G Ladona, Coral Ampurdanés, Angel Messeguer, Jordi Bujons, Anna MoratóAbstract:The Toxic Oil Syndrome (TOS) appeared in Spain in spring 1981 as a massive food-borne inToxication in the central and northwestern areas of the country. A huge population of over 20,000 people was afflicted and over 400 deaths occurred1. The clinical features of TOS resembled an allergic-Toxic Syndrome in the acute phase and an autoimmune condition in the chronic phase1,2. Although some patients recovered after a long period of time (several months), many continue to suffer severe sequel or mild symptoms.