Association of clinical findings in Yusho patients with serum concentrations of polychlorinated biphenyls, polychlorinated quarterphenyls and 2,3,4,7,8-pentachlorodibenzofuran more than 30 years after the poisoning event

<p>Abstract</p> <p>Background</p> <p>The Yusho poisoning incident, which was caused by rice bran oil contaminated with polychlorinated biphenyls (PCBs), polychlorinated quarterphenyls (PCQs) and polychlorinated dibenzofurans (PCDFs) generated by heat denaturation of PCB, occurred in 1968 in western Japan. Annual physical, dermatological, dental, ophthalmological and laboratory examinations were conducted for Yusho patients after the incident. From 2001, blood levels of individual PCDF congeners were also measured. The blood levels of 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PeCDF), PCBs and PCQs in Yusho patients were found to be significantly higher than those of the general population. We investigated the relationships between blood concentrations of 2,3,4,7,8-PeCDF, PCBs and PCQs in Yusho patients and the items measured in the annual medical examination.</p> <p>Methods</p> <p>Medical and laboratory examination data from 501 Yusho patients enrolled in the study from 2001 to 2004 were analyzed. The relationships between blood 2,3,4,7,8-PeCDF, PCB and PCQ concentrations and medical/laboratory examination data were investigated using principal components and logistic regression analyses.</p> <p>Results</p> <p>Serum Concentrations of 2,3,4,7,8-PeCDF, PCBs and PCQs in blood tended to correlate with either acneform eruptions, black comedones, cutaneous and mucosal pigmentation, and hypersecretion of meibomian glands as well as general fatigue, headaches, cough/sputum, abdominal pain, arthralgia, increased blood sugar, increased serum γ-GTP and decreased total bilirubin. The majority of these signs and symptoms are included in the diagnostic criteria for Yusho.</p> <p>Conclusion</p> <p>After Yusho patients had suffered chronic exposure to these chlorinated compounds for more than 35 years, the serum concentration of 2,3,4,7,8-PeCDF in blood was significantly related to arthralgia and decreased albumin/globulin (A/G) ratio; the serum concentration of PCBs was significantly related to ophthalmologic symptoms; and the serum concentration of PCQ to increased total cholesterol. These findings suggest that the co-contaminants may affect other functions than those originally associated with Yusho.</p

Cutaneous symptoms such as acneform eruption and pigmentation are closely associated with blood levels of 2,3,4,7,8-penta-chlorodibenzofurans in Yusho patients, using data mining analysis

<p>Abstract</p> <p>Background</p> <p>Yusho an intoxication caused by oral dioxins and polychlorinated biphenyls occurred in 1968. Patients suffered from various systemic symptoms, including general fatigue, nausea, muscular and articular pain, acneform eruptions, black comedones, cutaneous and oral pigmentation, and increased eye discharge. The major causative factor was the contamination of rice oil with 2,3,4,7,8-penta-chlorodibenzofuran (PeCDF). Recent technical advances have allowed us to measure blood levels of PeCDF. However, there is little information on which symptoms and laboratory data are directly associated with PeCDF levels.</p> <p>Methods</p> <p>Yusho patients underwent annual medical check-ups from 2001 to 2003. Blood PeCDF levels were correlated with the presence or absence of symptoms in medical, hematological, dermatological, dental and ophthalmological examinations. This study analyzed all combinations by using the association analysis. This is the most suitable method to evaluate all combinations of the data comprehensively. This method was used to determine the rate of patients with high PeCDF level in the population with each symptom, and to extract combinations of three symptoms which were strongly associated with high PeCDF level.</p> <p>Results and Conclusion</p> <p>The rate of the patients with high PeCDF level was high in populations with high uric acid, black comedones (face), second highest quartile of age, or high urea nitrogen. The combination of three symptoms associated with the highest rate of patients with high PeCDF level was "high uric acid, female sexuality, and history of acneform eruptions", followed by "history of Yusho in and after 1968, high cholesterol level, and subjective symptoms." This analysis newly suggested that PeCDF concentration may be associated with history of dermatological symptoms, high uric acid, and elevated erythrocyte sedimentation rate.</p

Relationship between Blood Dioxin Levels and Present /Past Clinical Symptoms in Kanemi Yusho Patients

特集号 油症とPCB及びダイオキシン関連化合物 研究報告第21集 責任編集者 古江増隆The Twenty-first Reports of the Study on Yusho―PCBs and Dioxin-Related Compounds―Guest Editor Masutaka Furue［Background］Kanemi Yusho was a food poisoning incident caused by rice bran oil that occurred in western Japan, particularly in northern Kyushu, in 1968. It is difficult to determine the symptoms in patients after many years since the occurrence. Techniques for measuring blood dioxins have advanced recently. More accurate data measurement has now become possible, and techniques for mass data analysis, such as data mining, have also advanced. It has also become possible to find unknown characteristics,even in an object group with elusive characteristics, by checking all the combinations in all the patients. ［Aim］There are already several reports on the incidence of symptoms in Yusho patients. These reports are limited to symptoms in a single period,and there has been no analysis taking into account the time that has elapsed. Here,we evaluated the relationship between recent and past symptoms and 2,3,4,7,8-penta-chlorodibenzofuran (PeCDF) levels in the same subject patient, in order to demonstrate the correlation between PeCDF levels and symptoms at a time point close to the incident. ［Methods］Subjects were examined for symptoms of Yusho and had blood PeCDF levels measured, both recently and in the past. Combinations were extracted using association analysis of data mining technique for comparison, which had strong correlations between the presence or absence of symptoms in the medical examination, tests including blood test, dermatological examination, dental examination and ophthalmologic examination in recent years (2001-2004)and the blood PeCDF levels and those between the presence or absence of past (1986- 1989) symptoms and recent blood PeCDF levels. ［Results］Subjects with higher PeCDF levels were more likely to present with pigmentation, a symptom included in the diagnostic criteria for Yusho. Pigmentation was a commonly found symptom in the past. Past pigmentation was a common symptom in the present. ［Discussion］PeCDF levels were measured recently and therefore should not be compared directly with past symptoms. However,among the symptoms included in the diagnostic criteria, past symptoms tended to have a stronger relationship with PeCDF levels than did recent symptoms. We suggest that the present PeCDF level is strongly related to the past symptoms since the present PeCDF level is correlated with the past PeCDF level due to constant emission rate. More specifically,if the past PeCDF level is strongly related to the past symptoms,it can indirectly be concluded that the present PeCDF level is also strongly related to the past symptoms. Thus, the present PeCDF level cannot be related to the past symptoms directly but can indirectly. ［Conclusions］Combining recent and past symptoms further demonstrated that clinical symptoms are strongly related to PeCDF toxicity. This may have resulted from the increase in symptoms with aging, however, it was demonstrated that the symptoms of each patient were relieved and become obscure

Average of the PCDFs Value in Blood in Patients with Yusho in the 2001 to 2003 Fiscal Year and Comparison between the Clinical Features and PCDFs

特集号 油症とPCB及びダイオキシン関連化合物 研究報告第21集 責任編集者 古江増隆The Twenty-first Reports of the Study on Yusho―PCBs and Dioxin-Related Compounds―Guest Editor Masutaka Furue［Background］Kanemi Yusho is the name given to a 1968 food poisoning incident resulting from the ingestion of PCB contaminated rice bran oil that had been used as a heating medium. At the time, victims presented with mainly cutaneous manifestations and various other symptoms such as of the eyes and teeth,general fatigue,headaches,and paresthesia of the extremities. The characteristic symptoms then resolved with time. Yusho patients have been followed from immediately after the incident. Blood levels of dioxins such as PeCDF have been measured for those who wishing to since 2001.［Subjects and methods］The presence or absence of relationships between blood PeCDF level and various examination items/symptoms was investigated in 359 subjects whose blood levels of PCB-related chemical compounds such as PeCDF were measured in the Yusho related examinations between 2001 and 2003. Characteristic symptoms were also compared with the results of examinations done 15years previously. ［Results and discussion］The average blood 2,3,4,7,8-PeCDF level in designated Yusho patients was 177.50 pg/g lipids ; showing a markedly higher value than that of the normal control group (15.2 pg/g lipids). As well,the blood PeCDF level was related to PCB level,hexachlorobiphenyl level,urinary sugar,erythrocyte sedimetation rate (ESR)(2-hour),thymol and Na. There were also relationships with cutaneous findings (acneiform eruption and comedones),mucosal findings (oral pigmentation), constipation, numbness in the extremities, body weight loss, and abnormal abdominal ultrasonography. Symptoms seen in the skin and eyes in 2001 and 2003 had decreased compared with those in seen 1988.However,PCB and blood PeCDF levels remained high. Patients are continuing to present with mucosal and subjective symptoms as chronic conditions

2001～2003年度に血中PCDFs濃度を測定した油症患者の平均値と現在残留する症状等の比較

［Background］Kanemi Yusho is the name given to a 1968 food poisoning incident resulting from the ingestion of PCB contaminated rice bran oil that had been used as a heating medium. At the time, victims presented with mainly cutaneous manifestations and various other symptoms such as of the eyes and teeth,general fatigue,headaches,and paresthesia of the extremities. The characteristic symptoms then resolved with time. Yusho patients have been followed from immediately after the incident. Blood levels of dioxins such as PeCDF have been measured for those who wishing to since 2001.［Subjects and methods］The presence or absence of relationships between blood PeCDF level and various examination items/symptoms was investigated in 359 subjects whose blood levels of PCB-related chemical compounds such as PeCDF were measured in the Yusho related examinations between 2001 and 2003. Characteristic symptoms were also compared with the results of examinations done 15years previously. ［Results and discussion］The average blood 2,3,4,7,8-PeCDF level in designated Yusho patients was 177.50 pg/g lipids ; showing a markedly higher value than that of the normal control group (15.2 pg/g lipids). As well,the blood PeCDF level was related to PCB level,hexachlorobiphenyl level,urinary sugar,erythrocyte sedimetation rate (ESR)(2-hour),thymol and Na. There were also relationships with cutaneous findings (acneiform eruption and comedones),mucosal findings (oral pigmentation), constipation, numbness in the extremities, body weight loss, and abnormal abdominal ultrasonography. Symptoms seen in the skin and eyes in 2001 and 2003 had decreased compared with those in seen 1988.However,PCB and blood PeCDF levels remained high. Patients are continuing to present with mucosal and subjective symptoms as chronic conditions.特集号 油症とPCB及びダイオキシン関連化合物 研究報告第21集 責任編集者 古江増隆The Twenty-first Reports of the Study on Yusho―PCBs and Dioxin-Related Compounds―Guest Editor Masutaka Furu

カネミ油症患者における，ダイオキシン濃度と，最近及び過去の臨床症状の関係

［Background］Kanemi Yusho was a food poisoning incident caused by rice bran oil that occurred in western Japan, particularly in northern Kyushu, in 1968. It is difficult to determine the symptoms in patients after many years since the occurrence. Techniques for measuring blood dioxins have advanced recently. More accurate data measurement has now become possible, and techniques for mass data analysis, such as data mining, have also advanced. It has also become possible to find unknown characteristics,even in an object group with elusive characteristics, by checking all the combinations in all the patients. ［Aim］There are already several reports on the incidence of symptoms in Yusho patients. These reports are limited to symptoms in a single period,and there has been no analysis taking into account the time that has elapsed. Here,we evaluated the relationship between recent and past symptoms and 2,3,4,7,8-penta-chlorodibenzofuran (PeCDF) levels in the same subject patient, in order to demonstrate the correlation between PeCDF levels and symptoms at a time point close to the incident. ［Methods］Subjects were examined for symptoms of Yusho and had blood PeCDF levels measured, both recently and in the past. Combinations were extracted using association analysis of data mining technique for comparison, which had strong correlations between the presence or absence of symptoms in the medical examination, tests including blood test, dermatological examination, dental examination and ophthalmologic examination in recent years (2001-2004)and the blood PeCDF levels and those between the presence or absence of past (1986- 1989) symptoms and recent blood PeCDF levels. ［Results］Subjects with higher PeCDF levels were more likely to present with pigmentation, a symptom included in the diagnostic criteria for Yusho. Pigmentation was a commonly found symptom in the past. Past pigmentation was a common symptom in the present. ［Discussion］PeCDF levels were measured recently and therefore should not be compared directly with past symptoms. However,among the symptoms included in the diagnostic criteria, past symptoms tended to have a stronger relationship with PeCDF levels than did recent symptoms. We suggest that the present PeCDF level is strongly related to the past symptoms since the present PeCDF level is correlated with the past PeCDF level due to constant emission rate. More specifically,if the past PeCDF level is strongly related to the past symptoms,it can indirectly be concluded that the present PeCDF level is also strongly related to the past symptoms. Thus, the present PeCDF level cannot be related to the past symptoms directly but can indirectly. ［Conclusions］Combining recent and past symptoms further demonstrated that clinical symptoms are strongly related to PeCDF toxicity. This may have resulted from the increase in symptoms with aging, however, it was demonstrated that the symptoms of each patient were relieved and become obscure.特集号 油症とPCB及びダイオキシン関連化合物 研究報告第21集 責任編集者 古江増隆The Twenty-first Reports of the Study on Yusho―PCBs and Dioxin-Related Compounds―Guest Editor Masutaka Furu