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Biomedical subjects

R M Philen

Publications and source records attributed to R M Philen.

34 records · Page 2Linked to original sources
PubMed1994

Factors associated with pathogenicity of oils related to the toxic oil syndrome epidemic in Spain.

The toxic oil syndrome (TOS), which affected over 20,000 persons in Spain in 1981, has been linked to the consumption of aniline-denatured rapeseed oil, but the precise etiologic agent is still unknown. We attempted to validate the use of high concentrations of oleyl anilide as a marker for oils that contain (or contained) the causal agent. We compared the chemical compositions of oils obtained from ill (N = 59) and unaffected (N = 70) families in 1981. Case oils had higher concentrations of fatty acids and sterols in which rapeseed oil is particularly rich. In addition, case oils had more frequent and extensive contamination with oleyl anilide and other fatty acid anilides. We observed a dose-response effect; risk increased sharply with increasing concentrations of oleyl anilide, and no control oil had more than about 825 micrograms per liter of that compound. We conclude that high concentrations of oleyl anilide specifically mark oils that contain (or used to contain) the TOS etiologic agent.

Aniline Compounds↗
PubMed1993

Tryptophan contaminants associated with eosinophilia-myalgia syndrome. The Eosinophilia-Myalgia Studies of Oregon, New York and New Mexico.

Eosinophilia-myalgia syndrome (EMS) has been linked to ingestion of tryptophan contaminated with 1,1'-ethylidene-bis[L-tryptophan] (EBT), but other contaminants have received little study. The authors identified 101 lots of L-tryptophan that had been consumed either by persons with EMS or by asymptomatic tryptophan users and quantified the amounts of EBT and five other contaminants in each lot. After stratification of case and noncase lots by time of manufacture to adjust for the strong sequential pattern over time among case and noncase lots, higher EBT levels were still associated with a lot's case status, but the association lacked statistical significance (p = 0.120, odds ratio = 1.56, 95% confidence interval 0.758-3.23). While these findings do not rule out the possibility that EBT is the etiologic agent in EMS, they raise the possibility that other chemical contaminants in manufactured tryptophan modify the effects of EBT or that the causal agent of EMS is an entirely distinct compound.

Drug Contamination↗
PubMed1993

Contaminants in L-tryptophan associated with eosinophilia myalgia syndrome.

In late 1989, an epidemic of eosinophilia-myalgia syndrome (EMS) that resulted in several thousand cases of the syndrome and 36 deaths was recognized in the United States. Physicians in New Mexico linked the epidemic to the ingestion of L-tryptophan (LT). Results of studies indicated that one or more trace contaminants in LT were likely causes of the EMS epidemic. Investigators traced the LT that was taken by most patients with EMS to a single manufacturer, Showa Denko K.K. of Japan. We now report results of high performance liquid chromatographic analysis of LT samples from this manufacturer. Three sets of blind-coded samples were analyzed: the priority case lot set, which included 54 case-associated LT lots and 50 noncase-associated LT lots that were taken by case and control subjects who used only one brand of LT; the single lot case set, which included 73 case-associated LT lots and 25 noncase associated LT lots taken by case and control subjects who used only a single lot of LT; and the South Carolina tablet set, which included LT tablets taken by case subjects (n = 26) and by control subjects (n = 52). We statistically compared the concentration of each contaminant in case-associated, noncase-associated, and control samples of each sample set. The analyses showed that there were more than 60 minor contaminants in the LT from Showa Denko K.K., and that six of these contaminants were associated with EMS. The structures of three contaminants are known, but the identities of the other three contaminants are currently unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacillus↗
PubMed1993

Toxic oil syndrome and eosinophilia-myalgia syndrome: May 8-10, 1991, World Health Organization meeting report.

In May 1991, researchers and clinicians from throughout the world met at a workshop sponsored by the Regional Office for Europe of the World Health Organization in collaboration with the Fondo de Investigación Sanitaria, Spain, and the U.S. Food and Drug Administration, National Institutes of Health, National Institutes of Mental Health, and Centers for Disease Control and Prevention to share information about two very similar diseases--toxic oil syndrome and eosinophilia-myalgia syndrome. In this paper the interpretation of conference proceedings is presented, current knowledge of the two disorders is summarized, and some possible areas for future research are mentioned. Toxic oil syndrome and eosinophilia-myalgia syndrome have many similarities. Both are related to consumer products that were presumed to be safe but have been found to have numerous trace contaminants, many of which remain to be identified, including the etiologic agents of both disorders. Both illnesses affect patients clinically by causing intense, incapacitating myalgias and a marked peripheral eosinophilia. Other rheumatologic manifestations are common in both, including arthralgias, sicca syndrome, scleroderma-like skin changes, carpal tunnel syndrome, and joint contractures. No clinical or laboratory feature has been found to be pathognomonic of either disease, and accurate diagnosis rests on the clinical judgment of the attending physician. Deaths have occurred in both diseases, and the cumulative mortality for each is approximately 2.5% for the first 2 years. Long-term complications include pulmonary hypertension, peripheral neuropathies, and joint contractures. Although treatment with corticosteroids has resulted in significant symptomatic relief in persons with either disorder, it does not alter the clinical course or long-term outcome. Research into the etiologic agents, preferred treatments, and ways to avoid similar problems in the future is needed.

Animals↗
PubMed1992

Survey of advertising for nutritional supplements in health and bodybuilding magazines.

The use of food supplements by the general public is poorly quantified, and little information on this subject is available in the medical literature. We surveyed 12 recent issues of popular health and bodybuilding magazines (1) to quantify the number of advertisements for food supplements, the number of products advertised, and the number and type of ingredients in these products; (2) to identify the purported health benefits of these products; and (3) as a preliminary effort to identify areas for future research. We counted 89 brands, 311 products, and 235 unique ingredients, the most frequent of which were unspecified amino acids; the most frequently promoted health benefit was muscle growth. We also found many unusual or unidentifiable ingredients, and 22.2% of the products had no ingredients listed in their advertisements. Health professionals may not be aware of how popular food supplements are or of a particular supplement's potential effects or side effects. In addition, patients may be reluctant to discuss their use of these products with traditional medical practitioners. We recommend that routine history taking include specific questions about patients' use of food supplements and that any possible adverse effects or side effects be reported to public health authorities.

Advertising↗
PubMed1991

Eosinophilia-myalgia syndrome. A clinical case series of 21 patients. New Mexico Eosinophilia-Myalgia Syndrome Study Group.

We reviewed 21 cases of eosinophilia-myalgia syndrome to describe the range of clinical findings in these patients. Most patients were women (20 [95%]) and middle-aged (mean, 46 years) and had taken the food supplement L-tryptophan (95%). All cases involved eosinophilia (eosinophil count, greater than or equal to 2.0 x 10(9)/L) and incapacitating myalgias. Fourteen (88%) of the 16 patients tested had mild liver function abnormalities. Aldolase levels were abnormal in all patients tested. Muscle biopsies were done in five patients; four showed eosinophilic perimyositis, and one had interstitial inflammation. No physical finding was pathognomonic or universal, but muscle tenderness, tachycardia, and rash were the most common signs found during physical examinations. Seven patients were treated with prednisone, and six showed improvement in muscle pain and a decrease in eosinophilia. The cause of this disorder is still unknown.

Biopsy↗
PubMed1991

Manufacturing processes at two French rapeseed oil companies: possible relationships to toxic oil syndrome in Spain.

The toxic oil syndrome (TOS) epidemic that occurred in Spain in spring 1981 has been associated with the consumption of rapeseed oil that was denatured with aniline for industrial use but diverted for human consumption. The precise aetiologic agent in the oil responsible for the outbreak has not been identified. To learn more about possible contaminants and how the contamination might have occurred, we visited two French companies that process rapeseed oil and that were identified in Spanish administrative and judicial records as the ones exporting aniline-denatured rapeseed oil to Spain in 1981. With the apparently full and voluntary co-operation of personnel at both companies, we reviewed the processes involved in manufacturing, treating and transporting rapeseed oil, and we have summarized the information provided to us. Of particular importance is the finding that oil exported to Spain was taken from stock, the rest of which was sold for human consumption in the French domestic market, apparently without any adverse health effects. The differences between the oil exported to Spain and the oil sold as food in France were that aniline equivalent to 2% of the weight of the oil was added to most of the Spanish oil but not to that sold in France, and that contamination of the Spanish oil may have occurred in the tank trucks used for transportation to Spain, which had previously carried industrial chemicals. There is no assurance that the trucks were cleaned appropriately for transporting a food product before the oil was loaded for the journey to Spain. Since the clinical manifestations of TOS are not those of aniline toxicity, we conclude that the aetiological agent of TOS is likely to be one of the following: (1) a contaminant in the aniline, (2) a contaminant introduced during transportation, (3) a reaction product of normal oil components or materials used in refining with either aniline or the potential contaminants mentioned under (1) or (2) above.

Aniline Compounds↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1977

Synthsis and antitumor properties of bis(quinaldine) derivatives.

A series of 7-nitro- and amino-N,'-bis(4-quinaldinyl)-alpha, omega-diaminoalkanes related to the 6-amino derivative 1 was synthesized and tested in the mouse P-388 lymphocytic leukemia screen. There of the 7-nitro derivatives (12, 14, and 15) were found to have moderate activity (T/C 140-150%), while other nitro derivatives (11 and 13) were devoid of any antitumor properties. All five 7-amino compounds (2-6) were moderately to strongly active (T/C 134-196%). In addition, binding of amino derivatives 2-6 to DNA was examined by their ability to (1) stabilize DNA to thermal denaturation and (2) inhibit the DNA-dependent RNA polymerase reaction in vitro. Tm data suggest that these compounds bind to DNA and are strong inhibitors of the polymerase reaction (I50 = 6-9 X 10(-6) M).

Animals↗