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Biomedical subjects

E M Kilbourne

Publications and source records attributed to E M Kilbourne.

At least 37 records · Page 2Linked to original sources

Toxic oil syndrome: a current clinical and epidemiologic summary, including comparisons with the eosinophilia-myalgia syndrome.

In the spring and summer of 1981, an epidemic of a new illness now referred to as the toxic oil syndrome occurred in central and northwestern Spain, resulting in some 20,000 cases, 12,000 hospital admissions and greater than 300 deaths in the 1st year of the epidemic. The initial onset of illness was usually acute, and patients presented primarily with a respiratory syndrome involving cough, fever, dyspnea, hypoxemia, pulmonary infiltrates and pleural effusions. While approximately 50% of patients recovered from this acute phase of the illness without apparent sequelae, the remaining patients developed an intermediate or chronic phase, or both, of illness involving severe myalgia, eosinophilia, peripheral nerve damage, sclerodermiform skin lesions, sicca syndrome, alopecia and joint contractures, among other findings. Epidemiologic and analytic chemical studies have clearly linked the toxic oil syndrome to the ingestion of oil mixtures containing rapeseed oil denatured with aniline. However, the precise identity of the etiologic agent within this oil has never been determined. Aniline itself did not cause the illness, but the causal agent may be a reaction product of aniline with some oil component. Although many aspects of disease activity in the involved patients have lessened with time, the ultimate consequences of their disease are not clear and are the subject of ongoing study. The recently described eosinophilia-myalgia syndrome in the United States clinically resembles the toxic oil syndrome.

Aniline Compounds↗

The eosinophilia-myalgia syndrome: the Los Alamos Conference.

On June 12 and 13, 1990 the Los Alamos National Laboratory in cooperation with the New Mexico Department of Health and Environment, the Centers for Disease Control (CDC), the Food and Drug Administration (FDA), and the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) hosted a conference on the eosinophilia-myalgia syndrome. Fifty presentations covered a variety of important issues which are summarized herein.

Centers for Disease Control and Prevention, U.S.↗

Mercury exposure from interior latex paint.

BACKGROUND: Many paint companies have used phenylmercuric acetate as a preservative to prolong the shelf life of interior latex paint. In August 1989, acrodynia, a form of mercury poisoning, occurred in a child exposed to paint fumes in a home recently painted with a brand containing 4.7 mmol of mercury per liter (at that time the Environmental Protection Agency's recommended limit was 1.5 mmol or less per liter). METHODS: To determine whether the recent use of that brand of paint containing phenylmercuric acetate was associated with elevated indoor-air and urinary mercury concentrations, we studied 74 "exposed" persons living in 19 homes recently painted with the brand and 28 "unexposed" persons living in 10 homes not recently painted with paint containing mercury. RESULTS: The paint samples from the homes of exposed persons contained a median of 3.8 mmol of mercury per liter, and air samples from the homes had a median mercury content of 10.0 nmol per cubic meter (range, less than 0.5 to 49.9). No mercury was detected in paint or air samples from the homes of unexposed persons. The median urinary mercury concentration was higher in the exposed persons (4.7 nmol of mercury per millimole of creatinine; range, 1.4 to 66.5) than in the unexposed persons (1.1 nmol per millimole; range, 0.02 to 3.9; P less than 0.001). Urinary mercury concentrations within the range that we found in exposed persons have been associated with symptomatic mercury poisoning. CONCLUSIONS: We found that potentially hazardous exposure to mercury had occurred among persons whose homes were painted with a brand of paint containing mercury at concentrations approximately 2 1/2 times the Environmental Protection Agency's recommended limit.

Adolescent↗

Eosinophilia-myalgia syndrome. Results of national surveillance.

Eosinophilia-myalgia syndrome, a newly recognized disorder that occurred in epidemic proportions during 1989, is associated with ingestion of manufactured tryptophan. A case is defined by debilitating myalgias and absolute eosinophilia greater than or equal to 1.0 x 10(9) cells/L. As of July 10, 1990, a total of 1531 cases had been reported nationwide, including 27 deaths. The highest rates of reported illness are concentrated in the western states, 68% are non-Hispanic white women aged 35 years and older, and data on associated clinical findings suggest a multisystemic disorder. The most frequent features include arthralgia (73%), rash (60%), cough or dyspnea (59%), peripheral edema (59%), elevated aldolase level (46%), and elevations in the results of liver function tests (43%). Neuropathy or neuritis, resulting in paralysis and death in some patients, was seen in 27%, and chest roentgenogram abnormalities were noted in 21% of those tested. Ninety-one percent reported onset of symptoms during or after May 1989, and 97% reported having taken tryptophan before the onset of symptoms. Since the recall of over-the-counter preparations of tryptophan in November 1989, the number of new cases of this potentially fatal disorder has fallen dramatically.

Adolescent↗

L-tryptophan and eosinophilia-myalgia syndrome in New Mexico.

On Oct 30, 1989, the New Mexico Health and Environment Department learned of 3 patients with eosinophilia and severe myalgia who had been taking L-tryptophan. Further review of these and similar cases led to the initial recognition of the eosinophilia-myalgia syndrome (EMS) epidemic. To elucidate the apparent association between L-tryptophan-containing products (LTCPs) and EMS a case-control study was done. The case definition was unexplained peripheral eosinophilia (2000/microliters or more) and incapacitating myalgia. Cases were found through review of white blood cell counts from May 1 to Oct 31, 1989, in nine medical laboratories in New Mexico. 11 cases and 22 matched controls were interviewed for information on symptoms and other clinical findings, on the use of LTCPs, and on potential confounding factors. All 11 cases (100%) used LTCPs compared with only 2 controls. These findings led to a ban on the sale of LTCPs in New Mexico, followed by a nationwide recall of such preparations in the United States.

Adult↗

Participation of eosinophils in the toxic oil syndrome.

The participation of eosinophils in the Spanish toxic oil syndrome (TOS) was investigated. Eosinophil infiltration and degranulation in tissues from 52 patients with the TOS were examined by immunofluorescence staining for the eosinophil granule major basic protein (MBP). Serum MBP levels were determined in sera from 323 patients. Eosinophil infiltration and degranulation were found in several tissues, especially during the acute phase of the TOS, and serum MBP was significantly elevated during all phases of the disease, suggesting that eosinophils play a role in the pathogenesis of the TOS.

Blood Proteins↗

Lethal paralytic shellfish poisoning in Guatemala.

An outbreak of paralytic shellfish poisoning occurred in Champerico, on the Pacific coast of Guatemala, July-August 1987. Of 187 people affected with characteristic neurologic symptoms, 26 died. A case study implicated a species of clam, Amphichaena kindermani, harvested from local beaches as the vehicle of the neurotoxins (saxitoxins). Children less than 6 years old had a higher fatality rate (50%) than people greater than 18 years of age (7%). The minimum lethal dose for 1 child was estimated to have been 140 mouse units of toxin/kg body weight; thus children may be more sensitive to the saxitoxins than are adults. This is the first large outbreak of paralytic shellfish poisoning recognized in Guatemala.

Adolescent↗

Mass sociogenic illness by proxy: parentally reported epidemic in an elementary school.

In a cluster of illness reported among students at an elementary school parents mentioned many signs and symptoms including headache, pallor, dark circles under the eyes, nausea, and vomiting--which they attributed to exposure to recurrent leaks of natural gas at the school. It is likely that the parents spread among themselves the notion of toxic exposure at the school. A questionnaire revealed no spatial clustering, but increased reports of symptoms were related to intense media coverage. A thorough environmental and epidemiological investigation was negative, there being no evidence of a continuing gas leak or other potential causes. At a strictly biological level, the complaints in this reported "cluster" apparently represented the sporadic occurrence of common childhood illnesses. The possibility of an epidemic from toxic exposure at the school caused intense parental concern and led to a major public health problem. The established term "mass sociogenic illness" seems inapplicable here because complaints did not come principally from the students and the apparent epidemic illness was not transmitted among them. The term "mass sociogenic illness by proxy" is proposed to describe this incident, in which transmission in one group (the parents) resulted in reports of an epidemic in another group (students).

Absenteeism↗

Geographic distribution of heat-related deaths among elderly persons. Use of county-level dot maps for injury surveillance and epidemiologic research.

Mapping is a useful tool for initiating data analysis of relatively infrequent injury events and can lead to interesting hypotheses that can then be tested in further epidemiologic studies. From national death certificate data for the years 1979 through 1985, we made dot maps of fatalities due to excessive heat (International Classification of Diseases code E900) among persons 65 years or older. The maps show clusterings of deaths, particularly in the central, south central, and southeastern sections of the United States, to an extent not fully explained by the population density or temperature extremes. The counties principally affected were highly urbanized and, for races other than white, were relatively poor. Our maps identify counties in which heat-related health problems in the elderly are particularly severe. Public health officials in high-risk areas should undertake heat-wave contingency planning and physicians practicing in such areas should familiarize themselves with the treatment of the spectrum of heat-related illnesses.

Aged↗

Late cases of toxic oil syndrome: evidence that the aetiological agent persisted in oil stored for up to one year.

The symptoms of toxic oil syndrome (TOS), an epidemic that occurred in central and north-western Spain, developed in the great majority of patients during May or June 1981. We now describe the clinical and epidemiological data of five patients with TOS whose onset of symptoms was considerably later than the great majority of cases. In June 1982, one person became symptomatic as a result of consuming a suspect oil two months earlier. Four members of a family that started consuming a suspect oil in November 1981 became ill in December 1981. These data indicate that the aetiological agent of TOS persisted in stored oil for periods as long as one year. The apparent stability of the TOS aetiological agent increases the likelihood of its continued presence in significant concentrations in oils that have been stored since 1981. Thus, the use of such oils in further in vivo and in vitro toxicological studies may yet lead to the isolation and identification of the causal agent of TOS.

Adolescent↗

Synthesis of N-(5-vinyl-1,3-thiazolidin-2-ylidene)phenylamine and analysis of oils implicated in the Spanish toxic oil syndrome for its presence.

Previous reports have implicated 1-phenyl-5-vinyl imidazolidine-2-thione (PVIZT), a cyclic reaction product of aniline and naturally occurring rapeseed oil isothiocyanates, as the potential causative agent of the Spanish toxic oil syndrome (TOS). This report describes the synthesis, preliminary characterization and analysis of that reaction product, which has been identified as N-(5-vinyl-1,3-thiazolidin-2-ylidene)phenylamine (5-VTPA) rather than PVIZT. Oil samples (n = 21) that contained fatty acid anilides and were epidemiologically linked to TOS were analysed for the presence of 5-VTPA by extraction of the oil with methanol and clean-up on an ion-exchange column, followed by capillary gas chromatography-mass spectrometry using selected ion detection. A limit of detection of less than 500 ppb was established for these analyses. No 5-VTPA could be detected, however, in any of the TOS oils. As 5-VTPA was shown to be unstable in both heated and unheated food oils, it is possible that the compound had been lost from the oils since the time of the epidemic in 1981. However, no direct evidence for the involvement of 5-VTPA in TOS could be obtained in this study.

Brassica↗

Chemical correlates of pathogenicity of oils related to the toxic oil syndrome epidemic in Spain.

The identity of the etiologic agent that caused the 1981 epidemic of toxic oil syndrome in Spain has not been established, and toxicologic study of oil specimens from the outbreak has been hampered by uncertainty about which oils were actually capable of causing illness. To identify chemical characteristics associated with pathogenicity, the authors compared specimens collected during the Spanish government's oil recall program in June and July 1981 from affected and unaffected households in the two contiguous towns of Alcorcón and Leganés (Madrid Province). Oils were blind-coded for laboratory analysis, and personnel with no knowledge of the laboratory results determined whether illness was present in a family. Contamination with free aniline and oleyl, linoleyl, and palmityl anilides was strikingly more frequent and extensive in oils collected from the case (affected) families. There was a clear-cut dose-response effect, with increasing concentrations of aniline and anilides associated with increasing risk of illness. Differences in fatty acid and sterol compositions among oils indicated more rapeseed oil admixture in the case group, but these indicators of rapeseed oil admixture did not contribute significantly to risk after the degree of aniline/anilide contamination had been taken into account. The authors conclude that the presence of relatively high levels of aniline and fatty acid anilides in oil specimens collected during the epidemic in the two towns studied indicates a high probability of the current or prior presence of the etiologic agent of toxic oil syndrome. Although these data do not necessarily indicate that any of the compounds measured actually caused the illness, further toxicologic work should concentrate on oils with substantial concentrations of the marker compounds.

Anilides↗

Toxic-oil syndrome: case reports associated with the ITH oil refinery in Sevilla.

Toxic-oil syndrome (TOS), a new disease that occurred in epidemic form in Spain in 1981, has been associated with the ingestion of unlabelled oil bought principally from travelling salesmen. Chemical analysis of oils taken from ill families has shown them to consist of varying proportions of different vegetable oils and animal fats, often showing chemical evidence of prior treatment with aniline. We investigated the unusual circumstances surrounding the reported occurrence of three TOS cases in two families in Sevilla, a city located far away (approximately 300 km) from the group of 14 provinces in central and northwestern Spain where 99% of the TOS cases occurred. Each case we investigated fitted the clinical picture of TOS and was not consistent with any other diagnosis. Illness apparently occurred as a result of ingestion of oil taken from the ITH oil refinery in Sevilla, a plant in which rapeseed and grapeseed oils were refined for the distributing firm through which oil bearing the causative agent of TOS is thought to have entered the market. These data provide further strong support for the hypothesis that food oil was the vehicle by which the aetiological agent of TOS was transmitted. Because ingestion of refined denatured rapeseed oil was most closely associated with the illness in time, the TOS agent was probably contained initially in this type of oil. The agent very probably entered later oil mixtures through such contaminated rapeseed oil.

Adult↗

Oil ingestion and the toxic-oil syndrome: results of a survey of residents of the Orcasur neighbourhood in Madrid, Spain.

To elucidate the aetiological role of food oil in toxic-oil syndrome (TOS), 212 families of a working class neighbourhood in Madrid were interviewed regarding the sources of food oil they consumed and whether they had become ill with TOS. Health information was later verified by review of the patients' medical records. All five case families consumed oil sold by travelling salesmen in five-litre plastic containers, but only 34% of the 207 non-case families did so (p = 0.005). Oil bought from travelling salesmen in the local weekly open-air market was associated with a particularly high risk of illness. Consumption of oil from sources other than travelling salesmen was similar in the two groups. Our results support the view that a food oil transmitted the causative agent of TOS.

Brassica↗

The association of oil ingestion with toxic oil syndrome in two convents.

The authors studied the pattern of occurrence of toxic oil syndrome, a previously undescribed disease that occurred in Spain in epidemic form in 1981, in two convents in Madrid. In one convent, the disease affected 66% of 35 novices and nuns who ingested oil from a suspect source, but none of 56 laywomen who ate the same meals but used a different type of oil. In the second convent, in which nuns were also exposed but laywomen were not, 98% of 43 nuns developed toxic oil syndrome compared with none of 70 laywomen. These findings support the hypothesis that a food oil transmitted the etiologic agent of toxic oil syndrome.

Brassica↗