Document QgDpb1d8njvnm7M9g5vvyg5e6

TECHNICAL REPORTS //46'f< . . / 1' / Pag* I <^fnsfto, a poi'oning earned l>j rke oil cont.imi naled hith pi>l;chlorinated biphenvU. ^^-'-WfarUmyrr Ktrrmsimr; Taknumt Yoosnntnnuira. Jnntchi Watsuzuka, and Atsuko Yaruagucht 1083 An epidemiologic study of amputees In the East Harlem community 1092 Courtney it. Wood, Robirta S. Volante, and Robert Bcrenson Welfare and Medicaid coverage of the poor and near-poor in low-income areas Gerald Sparer and Louise M. Okada 1099 Alabama diphtheria outbreak, 1967 _____________________________ _________________ 1107 Michael C. Sinclair, Raynond Qserton, and William ]. Donald Mass Immunization campaign in El Salvador, 1969. Evaluation of receptivity and recommendations for future campaigns ---------------------------------------------- ------------ -------------------- 1112 Nan Ltn, Ralph Hingioti, and Juan Allwood Paredes Risk management and consumer participation in medical decision making Uan Vertinsky and Dean H. Uyeno 1121 Factors in reducing children's anxlbty about clinic visits Michael Hejjernan and Pat A zarnoff 1131 1971 Index. 1136 '17)44* sir' r U.*. DEPARTMENT OF HEALTH, EDUCATION, ANO WELFARE Public Health Service Health Servians and Mental Health Administration MONS 204950 } cYuslio, a poisoning caused by rice oil contaminated with polychlorinated biphenyls MASANORI KURATSUNE, M.D., TAKESUMI YOSHIMURA, M.D., JUNICHI MATSUZAKA, M.D., and ATSUKO YAMAGUCHI, M.D. SPORADIC outbreaks of a peculiar skin dis ease were reported in Fukuoka-Kcn (Fuku oka Prefecture), Japan, m early October 1968. It was characterized by such symptoms as follicular accentuation, acneform eruption, pigmentation of the skin and nails, and hypersecretion of th_e_Meibomia'n gland Staff members of the department of dermatology of the Faculty of Medicine, Kyushu University, Fukuoka, who examined some of the early patients suspected 'they had chloracne. A possible causal relationship between the disease and ingestion of a certain brand of nee oil was also suspected in view of the distinct familial ag gregation of the patients and their common use of thr rl (I) This relationship was subsequently proved, and the disease was called Yusho, or rice oil disease. To clarify the cause of the epidemic, a study group headed by Prof. S. Katsuki of the Kyushu University Faculty of Medicine was organized by the staff of that university, the School of Medicine of Kurumc University, and local health depart ments. An epidemiologic study subgroup was set up within the study group on October 19, 1968, which was directed by Kuratsunc and also in cluded the other three authors. This subgroup im mediately designed and earned out a series of extensive surveys in close cooperation with the department of hygiene of our faculty of medicine and the departments of public health of the Pre fecture of Fukuoka and of the cities of Kitakyu- shu, Fukuoka, and Ohmuta. - The epidemic spread not only over Fukuoka- Ken but also over 20 other prefectures in the western part of Japan. It produced 1,001 patients --502 males and 499 females--according to the latest tabulation by the section of food hygiene. Ministry of Welfare Although our study of the epidemic was confined to Fukuokn-Ken. and ihe epidemic proved to be caused by accidentally con taminated oil, we believe that publication of our results will help prevent similar food poisonings These incidents can occur anywhere m the world if sufficient care is not exercised. The authors are with the department of public health. Faculty of Medicine, Kytshn University, Fukuoka, Japan, Dr, Kuratsune is a professor of public health, Dr. Yoshtmttra and Dr, Matsitzaka are working toward doctoral degrees in pub lic health, and Dr. Yamagucht is a research stu dent. The study on Yusho war supported by a special research grant from the Japanese Govern ment, Tearsheet requests to Masanon Kuratsune, M D., Faculty of Medicine, Kyushu University, Fukuoka, Japan. Ooewnfcor 1*71, VoL IS. No. It 1013 HONS 204951 y Moit of the results of our study have already been published In Japanese (2-5). Wc refer also, when necessary, to some important observations made by a ciimea! study subgroup headed by Prf. K. Higuchi of the department of dermatol ogy at our university and also to studies by a chemical study subgroup headed by Prof H, Tsukamoto of the Faculty of Pharmaceutical Sciences. Ophthalmic observations. Hypersecretion of the meibomian gland and abnormal pigmenuuoo of the conjunctiva. Neurological ofejrrvoniuij. Numbness, p.nn hypoesthciia, and lowered sensory conduction by the radial and sural nerves. Other obiervanLW. Elevated serum triglycer ide. Clinical Symptoms The subjective symptoms of the 89 male and (he 100 female patients whose cases of Yusho had been diagnosed by the end of October 1968 are lilted in table 1, Most of these symptoms related to the skin and eyes. Detailed clinical examina tion! of theie 189 persons by the clinical study subgroup revealed many of the clinical character istics of Yusho (1,6-9). Dermatological observations. Acneform erup tion--marked enlargement and elevation of the follicular opening; pigmentation of the skin, lips, gingiva, the mucous membrane of the oral cavity, and nails; formation of hyperkcratoiic plaque on the soles of the feet and palms of (he hands,* hyperhidrosis; hypertrichosis; swelling of Mont gomery's gland in the breast: cyst formation of the sebaceous gland in the genital region; dry skin; and, in children, mtlia near the joints. Epidemiologic Data Available When the epidemiologic study subgroup began to act, it had several pieces of information that appeared to be important but whose implications were uncertain, such as the following 1. The familial aggregation of patients was not able, and the disease showed no distinct age and sex preference. 2. All the patients seemed to have used one brand of rice oil (abbreviated as K rice oil be cause it was produced by K Company). An emer gency survey undertaken by the health department of the city of Fukuoka had disclosed that some of the patients in a certain area had. as a group, pur chased a can of K rice oil and divided it among the group members. Those who did not buy ihe oil seemed to be unaffected even though they lived next door to the patients, - 3. The patients seemed to be broadly distrib uted throughout Fukuoka-Ken. Table 1. Percent distribution of symptoms ol Yusho reported by 189 patients examined be fore October 31, 1968 These data of course were valuable, but we knew that if we relied on them alone, they might mislead us. We exercised particular caution, there fore, to avoid such a risk, always seeking possible Symplons Males Females (N-I9KN-100) antitheses when interpreting any result, Dtscriptiva Epidemiologic Studies Dark brown pigmentation of nails........... Distinctive hair follicles............................. Increased'sweating at palms.................... Acnelike skin eruptions.............................. Red plaques on limbs...................... ....... Itch inf ...................................................... Piimcniauon of skin.................................. Swelling of limbs........................................ 13.1 *4.0 30.6 17.6 W.2 42.7 73.3 20.2 75.0 36.0 35 0 12.0 16,0 52.0 72.0 41.0 The epidemiologic study subgroup first tried to learn how the 325 patients were distributed by place of residence and time of onset of the disease (2). Those persons who thought they were suf fering from Yusho were asked to report to iheir Stiffened soles in feet and palms of local health departments. From October 1963 hands........................................... . 24.7 Pigmented mucous membrane......... 36.2 29 0 47.0 unlil the epidemic practically terminated in Janu Increased eye discharge .......................... Hyperemia of conjunctjva.......................... Transient visual disturbance...................... U 70 1 36.2 13 0 71 0 JJ.O ary 1969, a total of 6,611 persons in FukuokaKen had reported that they were affected Among 1 Jaundice........................................................ Swelling of upper eyelids........................... Feeling of weakness.................................... 11.2 71.9 Jt.4 11.0 74.0 52.0 them, 325 cases of Yusho were diagnosed by the clinical study subgroup An early analysis of a Numbness m lunbs...................................... 32.6 39.0 portion of the 323 persons with confirmed cases, Fever............................................................ 16.9 Hearing difficulties...................................... II. 0 19.0 19 0 carried out in iate October 1968. revealed several Spasm of limbs.................................. ......... 7.9 1 0 peculiar features in the geographic distribution of Headache..................................................... 30 3 Vomiting...................................................... 23.6 39 O 21 0 cases, features which did not basically change dur Diarrhea....................................................... 19.1 17.0 ing the epidemic. Therefore, oniy the results ol 10M *KWH* Health Saoorta MOWS 204952 >8 analysis of these 32 ascs will be presented to illustrate these peculiarities. Familial aggregation. The 325 patients be longed to 112 families, a result indicating a dis tinct familial aggregation, which is considered one of the most important characteristics of Yusho. Time of occurrence. Nmety-mne percent of the patients were affected during 1968, and 55 percent of the cases were concentrated in the 3 months from June to August (table 2), The monthly distribution of the cases was alike for both sexes. These results indicated that exposure to the causal agent or agents v/hs probably tem poral and indifferent to sex. Sex and age. Distribution of the 325 patients by sex and age revealed no significant sex differ ence (table 3). Age-specific incidence rates per 100,000, calculated by using the census popula tion of 1965, indicated lower risks for both males and females in the age group over 60 years, but again no marked sex difference (table 4). Geograp distribution. We calculated crude incidence rates of Yusho for ihrce large eniet (Ki- takyushu, Fukuoka, and Ohmuta) and for the ju risdictional areas of the 22 local health depart ments of Fukuoka-Kcn A very marked differ ence was noted in their rates. Ten health depart ments reported no cases of Yusho while extremely high incidence rates per 100,000 were noted for the area covered by the health department of Soeda (58 9) and that covered by the health de partment of Tagawa (44 5), intermediately high rates, from 7 to 14, were observed for the three large cities and ihe area of the Kasuya health department There are many coal mines, most of which have recently been abandoned, in the jurisdictional areas of the Soeda and Tagawa health depart ments. The city of Kilakyushu has big steel and chemical industries, Fukuoka is a seat of com merce, and Ohmuta has big coal mines and chem ical industries. In contrast, the Kasuya health de- Table 2. Distribution of 325 patients with Yusho diagnosed by January 20, 1969, by sex and month when symptoms appeared Month Male* Number Percent Female* Number Percent Tour Number Percent Before 196*,.. January.,..... February.......... March...,.... April ........ May............. .. June................. July .............. Auauit............. September.... October......... .. November..,. December........ Tout........ i9ti .............. ............. ............ ____ ......... ............. ............. ...................... .. ............. ............. ............. ....___ ..... ............. ............. 2 1.3 0 ,0 4 2.5 t 5.1 ts 9.5 i* It.4 23 14.6 17.1 34 21 5 n 10.* * 5.t t .6 i .4 ts* too.o 2 1.2 00 6 3.6 12 7.2 to 6.0 15 9 0 33 19 t 32 19.2 30 tl 0 12 1.1 t4 (.4 t .6 0 ' .0 167 ioo.o 4 t .2 09 10 3.1 20 6.2 25 7 7 33 !0 2 56 17 2 59 It 1 64 t9 7 29 S 9 22 6.S 26 1 .3 325 too 0 Table 3. Distribut*on of 325 patients with Yusho diagnosed by January 20, 1969, by sex and age group Age group (yean) _ Males Number Percent Female* Number Percent Total Number Percent 0-9......................... ........... .. .................... 10-l9.ee. *.................... .. ........... 20-29....................... .................... 30-39............................. .. ........... 40-49..................... .. JO-59................ ........... ................ . 60-69..................... .......... .. ........... 70-79................. .. ................ .. Total.......... ........... .. ..................... 37 23.4 3* 24.1 2* 17.7 30 19 0 11 7 0 9 3.1 4 2.3 t .5 15* too 0 27 16.2 2* 16 36 21.6 39 23.4 23 13 tt 6.6 3 1,1 0 .0 167 too 0 64 19 7 66 20 i 64 19 7 69 21 2 34 10 ) 20 6 2 7 2.2 I ,3 325 100 0 * December 1971. VaC tt. Nfc 11 tOIS HONS 204953 partment covers an area that is primarily agricul tural. Most areas where few Yusho patients were seen were agricultural. No other common soctoe* conoroic or environmental factor was observed that might explain the geographic distribution of patients. (ji! U&ed by Patients i As slated, K rice oil had been suspected as the possible cause of the epidemic. K nee oil is a high-quality salad oil. made from rice bran by the procedure shown in the chart. It was popular in Fukuoka-Ken, even though it was slightly more expensive than other oils on the market. A thor ough investigation was undertaken to determine whether the patients with Yusho had actually used this brand of oil before they were affected and if so, whether there were any common characteris tics in regard to the container of the oil (bottle or ean), date of production, date of purchase, or route of marketing. To seek information on these points, an investigation was conducted in coopera tion with the local health departments. All pa tients and their wives were viMied and interviewed in their homes. In addition, all the available ship ping records of K Company and all available rec ords of purchases and sales of K rice oil at whole sale oil dealers' offices and at retail stores were carefully examined. These followup surveys soon disclosed an as tonishing fact. Ail the persons with Yusho had used, for varying periods. K rice oil which came either from 16 5 kg. cans or 1.65 kg. bottles. One hundred seventy of the 325 patients--49 house holds--had used only canned oil. while the re maining 155 patients--63 households--had used only bottled oil (table 51. We were able to con firm the shipping dates for the oil used by all but four of these 170 patients No matter where the persons lived or what their age was. 166 of the 170 had apparently used ncc oil that was shipped by the K Company on February 5 and 6, i968tQ according to the lot numbers on (he few remaining cans. Even ihc four patients for whom we could not confirm shipping dates of the oil had also undoubtedly used a canned nee od produced by the K company. The shipping or production dates could not be confirmed, however, for the bottled K oil that 155 patients had used exclusively, because they had no old bottles at home. Purchasers of oil in bottles return the empty ones to retail stores when ihey buy new oil. Nevertheless, all the shipping, pur chase, ar selling records at K Company, at ihe or! dealers, and at the retail stores wore examined to learn whether any bottled K rice oil had been shipped to. and hid reach.-d. the rci.nl itcircs frnm which the 155 patients bought their oil All ship ments of oil to the stores used by the patients were further investigated to determine whether lny of them had been made on February 5 or 6. 1968, or immediately before or after these dales. By this method, we discovered that 143 of the 155 patients might have bought the bottled oil shipped from the K Company m the period Feb ruary 6-15, 1968 Whether the remaining 12 pa tients might have also purchased oil shipped m this period remains jn doubt because of lack of records. Thus, nearly all of the patients had a distinguishing characteristic--they all had a com mon experience of use. or possible use. of nee oil shipped by one company in a specific period Such a coincidence could hardly be expected to happen by chance. Table 4, Age-specific Incidence rates for Yusho, by sex of patient Age group (yean) 0-9 ............... .............. !0-!9.................................... 20-29..................................... 30-39.................................... 40--49.................................... 50-J9 .................................. 60-69........................ 70 and over.................. All ag........................ Incidence rales per 100 000 Maks Fcmafct !1.4 *9 91 9& 54 J4 3J 1.7 I3 s6 66 10 3 II 9 93 72 24 0 I1 Table 5. Distribution of 325 patients and 112 households that used K rice ml. by type of od container and shipping dates of oil Container and PalienU Household! Number Percent Number Percent Users of canned oil .. Shipped 5 and 6Fe.,b..r.u.a..r.y... Shipping dales unknown.............. Users of bellied oil, . Probably used oil shipped February 5-15.............. Shipping dales unknown Total..................... 170 52.3 166 51.1 * 12 155 47 7 143 44 0 12 3.7 325 100 0 49 43 1 47 42 0 2 I1 63 56 i 56 50 0 7 63 112 l 100 1 > Does not add to 100.0 percent became of roundirtg 10M HSMHA Haaitn MONS 204954 FLOW SHEET OF RICE OIL PRODUCTION Met ben I------OtfattH lifin IHituna uiid to extract "1 Crude oD After removal ef uhrent, h treated vMi tedium mstaphaiphati I-----NaOH layar Treated with NtOH 1 Oil Niutrellzid with H SO. I Dark" lit Washed with hat watir Flltared Cater removed with whita perettain clay fittderized by treat! rg at over 200* C. at 3 to 4 mm. Hg Final product* Our survey also demonstrated a high attack rate for all' persons who consumed the oil. Alto gether, 266 persons in 64 households had con sumed canned K nee oil shipped in the period in question, and 170 had confirmed cases of Yusho. Thus, the attack rate was as high as 63.9 percent <i). K OH Prom Other Shipments An additional survey seemed necessary to de termine whether those persons who regularly used K rice oil but h;:d not used any from shipments made in the period in question were free of the disease. Por this purpose, a group of persons was neededwho had. reliable records of their health status and of their purchases of K rice oil. A group of 113 persons of 29 households living in one apartment house seemed to be appropriate subjects for this study. According to ihc records of this group and the oil dealer who supplied them, these 113 persons had purchased canned K rice oil as a unit from one dealer and divided it among themselves faidv regularly from December 1967 to September 1968 except for (he period from January to April 1968, when this bulk purchasing was not earned out. Their disease experience, particularly any skin disease that occurred during 1968, was care fully explored through interviews and. if necessary, through investigation of their medical records at hospitals. No cases of Yusho were found among Memtw l*7l, Vet M. Ho II loaf HONS 204955 members of this group. Thus, we demonstrated that persons who had used K rice oil regularly for more than a half year but did not use the oil from the specific shipments iii not suffer from Yusho (i). Retrospective Case-Control Studies All these results suggested that Yusho was cau sally connected with use of the K rice oil that was shipped from K Company on February 5 and 6, 1968, or soon thereafter. Nevertheless, some other factors or agents might have been the primary or secondary cause of the epidemic. Therefore two case-control studies were done. In one, the per sonal backgrounds of the patients and matched controls were compared In the other, the use of oil and fats in the households of the patients and the controls were compared. To discover whether persons with Yusho cases end those without had different personal back grounds, home interviews were conducted wh all persons whose cases had been reported by Octo ber 31, 1968, and with healthy controls matched by age, sex, and place of residence. One hundred twenty-one patients and 121 controls (53 males and 68 females) were selected in this manner and asked 60 questions concerning their occupations. Table 6. Percent of 121 patients and 121 control* having various allergies and dietary and per sonal habits, based on case-control study Items investigated Ptuents Con trols Allergic to fish............................................ Allergic to aspirin....................................... Allergic lo drugs other ihtn aspirin......... Bathing facilities at home.......................... Beth es cry day............................................ Pels at home................................................ Floor space of house smeller thin 66 square meters.......................................... Handling agricultural chemicals................ Taking codlivcr oil...................................... Taking vitamin pills................................... Tlkmg other restorative drugs.................. Wgter supply available at home................ Dintnf out occasionally............................. Taking all meals with the family.......... .. Green vegetables daily............................... Milk nearly every day................................ Butler nearly every day.............................. Eggs nearly every day................................ Fried foods or tempura nearly every day. Foods prepared with od nearly eiery day. Fish nearly every day................................. Mayonnaise nearly every day................... Instant "rahmen ' or Chinese noodles nearly every day...................................... 5.0 .0 75 W.7 73.0 11.J 66.9 2.3 to,* 23 I 9.1 (1.3 21, t tt.t 63.1 49 0 22.4 64 7 >22.4 4S.7 21 6 10.1 10.1 11 <0.05. 7.3 4.2 6.6 13.3 70.6 1 36.3 66.1 6.6 (.3 11-3 7.3 74.7 30 6 19 6 31 9 39 0 24.9 59 t * It 6 35.7 29-1 10.t 10.0 Table 7. Distribution of 69 households with padents and 207 control households, by use of various fats or oils, based on Case-control study Fat or ou Households with patients Control households Number Percent Number Percent Butter.................. Margarine.......... Sesame oii. . ,. Rape-seed oil___ .... Rtce'bran oil,,,. .. .. Lard.................. Other oils.......... ........ 50.7 63 1 21 30 5 10 14-5 66 93 7 17 4 13 11 1 105 50 7 127 6] 4 85 41 1 77 37 2 64 30 9 38 18 4 117 56 5 medical background, general health status, habits, customs, diet, pets, and other characteristic:, of thoir lives. The patients and the controls differed signifi cantly in respect to only two of the personal fac tors tested (table 6). Persons who ate fried (oods or tempura nearly every day were more numerous among the patients than among the controls, whjle tpore of the controls than the patients had pets To compare the use of oil and fats, 69 house holds with Yusho patients were matched by place of residence with 207 households without such patients--three control households for each household with cases. As to regular use of fats and oils, a distinct difference was noted between the two groups only for rice-bran oil. About 96 percent of the patients' households and 31 percent of the controls' house holds reportedly used rice-bran oil regularly (table 7). When asked about the use of rice oil from the K Company, all of the households with patients affirmed Us use in comparison with only 32.4 per cent of the control households; 61 3 percent of the control households denied using it; the remaining 6.3 percent were uncertain. Thus, the case-control studies clearly indicated that none of the factors tested except use of K rice oil could account for the disease (2). Doss-Response Relationship To prove that a causal relationship existed, a distinct dose-response relationship needed to he demonstrated. Estimating the quantity of contami nated rice od consumed by each pattern and mem bers of his family was not feasible. Nevertheless, if we disregarded age and sex, we could estimate roughly the average amount of oil each person had consumed by dividing the amount used in a RM hsmmx iwmi wun MQNS 04956 l A household by the number of persons in it, taking into account the frequency with which these per son* ate *i home, but not the possible loss of oil durinc and after cooking, nor the .varying tastes and food intake of the family members, Dij. Masayasu Goto, a dermatologist, with no knowledge of the amount of oil used by the 146 consumers of the contaminated otl. examined these persons and then graded the cases of Yusho he diagnosed according to their clinical severity. Only later did we link the seventy of the cases, as determined by the dermatologist, to the amount of contaminated oil used by the patient. Eighty of the 146 users of the contaminated oil were believed to have consumed, individually, less than 720 ml (table 8). Of these 80 light users, 12 percent were not affected. 49 percent had light cases, and 39 percent had severe cases, the attack rate was 88 percent. The 45 persons who had used 720-1,440 ml. were all affected; 69 percent of this group had severe cases. A still larger pro portion of the severe cases was found among the persons who had used more than 1,440 ml. of the contaminated oil, this group had an attack rate of 100 percent. Since the clinical severity of the disease was not found to differ significantly between the sexes but differed considerably according to age. a standardizmtion for age seemed necessary to achieve a more accurate interpretation of the observed rela tionship between use of the oil and the clinical severity of the disease. With the age composition of the 146 users of the oil as the standard, the factor of age was standardized for each of the three levels of oil intake. The figures, however, hardly chanced from those shown in table 8, Thus a very clear dose-response relationship could be demonstrated, even though the estimates of the dose were inaccurate (J). Toxic Afont In view of all these epidemiologic observations, we concluded that K rice oil from specific ship ments had caused the Yusho. Now the question arose as to why the oil was toxic. To answer this question, we of course had to rely on other ap proaches than epidemiology. In mid-November 1968, the chemical study subgroup discovered, mainly by gas chromatographic analysis, that the canned K rice oil shipped on February 5, 1968, portions of which had been collected from some of the patients, was contaminated with about 2,000 ppm of Kanechlor. Kanechlor is a commer cial brand of polychlorinated biphenyls containing 48 percent chlorine. Skin (at collected from the palients also contained Kanechlor ( JO) Tn this discovery. Prof. K. tnagami of the de partment of food technology. Faculty of Agricul ture, Kyushu University, and his associates played a leading role. A technological inspection of ihc K Company plant revealed that Kanechlor was used as an agent to transfer heat to the processed oil at a reduced pressure so that odorous substances could be removed (see chart). The Kanechlor must have leaked from the heating pipe in which it was being conveyed and contaminated the oil, since small openings were discovered in the old pipe. To discover whether only the K rice oil shipped in February 1963 was contaminated with Kane chlor, the chemical study subgroup analyzed 109 samples of the bottled K rice oil which, according to the lot numbers, had been shipped between October 1967 and October 1968. This analysis revealed that ouly the samples shipped on Febru ary 7, 10, 12, 15, 17, 18, and 19 and on March 11, 18, and 21, 1968. were contaminated with Kanechlor. This contamination was most marked for the oil shipped on February 7, the contamina tion was rapidly reduced to nil after February 10 (JO). No analysis could be made of bouled K rice oil shipped February 5 and 6 because of the lack of samples. Similarly, 479 random samples of bottled rice oil were analyzed for chlorine content by using the X-ray fluorescence method with a count meter from a U.S. instrument manufacturer (the Ap plied Research Laboratory). Again, only those samples shipped from February 7 to 10 contained a large amount of chlorine (maximum 462 ppm). ' None of the oils shipped in other months were contaminated with more than a trace amount of chlorine. Thus, the results of chemical analysis coincided with those achieved by epidemiologic approaches. Other Epidemiologic Results Babies born to patients In late October 1968 a pregnant palien' with Yusho had a stillbirth in' which the fetus was unusual; the skm--oails, and gingiva were a peculiar dark brown and stained Similar fetuses were delivered by other patients with Yusho. Since no such birth or stillbirth was known to have been reported previously in Japan, the study group investigated these occurrences with particular care. The epidemiologic study MeuMr 1*71, Val. M, Na Ut IMS MONS 204957 subgroup questioned alt female patients with Yusho and all unaffected women in the house hold! of patients with Yusho about any preg nancies and deliveries in the period from Febru ary 15, 1968, to the end of the sear. Thirteen women--10 with Yusho two without, and one with status unspecified--had given birth to 11 live bom and two stillborn infants during*} the specified period. (Eight of the live born in fants were males and three were females: one of the stillborn infants was a female and the sex of the other was unspecified.) Among these infants and fetuses, |0 had the characteristic grayish dark-brown stained skin at birth, five the darkcolored nails and gingiva, and nine an increased eye discharge. Women with Yusho accounted for all these deliveries, except for the delivery of one of the nine babies with eye symptoms. The high incidence of these unusual phenomena among pregnant women with Yusho strongly sug gested that the phenomena were caused by inges tion of the contaminated oil The fact that nothing unusual was seen m the women's medical histo ries, health conditions, or use of drugs during pregnancy also supported such an interpretation. All these facts, together with the results of chemical assays which showed that the placenta and the subcutaneous adipose tissue of the still born fetuses contained components of Kancchlpr,/ prove that babies and fetuses were affected be cause of the women's ingestion of this particular complex compound (4). The majority of the babies were small for their periods of gestation. As they grew older, their stained skin gradually faded. Postnatal growth curves for the affected babies were found to be Similar in shape to the national standards when both sexes combined were compared. When only males were compared, the curves for the affected male infants were plainlyjower than the national standard curves- ATlear comparison between the curves for girls could not be made because of the limited number of female infants who were af fected by Yusho. The amount of contaminated rice oil that nine of tlw 13 mothers consumed during pregnancy was estimated to be 0.3 to 2.6 liters. No distinct dose-effect relationship could be demonstrated be tween oil consumption and the babies' symptoms because of the limited number of cases available for analysis. Nor could evidence be obtained in regard to any possible physical and mental retar dation of the babies (4). Growth of affected children To discover whether Yusho disturbs chrldien's growth the af fected school children, 23 boss and 19 girls, were compared in 1967. 1968. and 1969 with 719 healthy children matched in height and budv weight. The gam in hcrght or in body Audit which each sick child showed before the poison ing. namely from 1967 to 1968. and the gjm jficr the poisoning, from 1968 to 1969. were compared with the distribution of the corresponding gains seen in the corresponding control group The gains of the affected boys m both heigh i and weight decreased significantly afier the poi soning, while the affected girls showed no definite change in this respect. Because of the limned number of cases available for analysis, no signifi cant relationship could be found between ihe clin ical seventy of the cases and the decrease in gains in height and weight. Discussion This unfortunate episode of rice oil poisoning taught us some important lessons. In the food industries of many countries, no effective adminis trative control and supervision is apparently exer cised over the use of toxic_subs_iances like Ka- nsshlor. These products do not contaminate the" final products in normal operations, but they do when the operation is accidentally disturbed or carelessly conducted. In contrast to the case with food additives, too little care has been exercised io avoid the hidden risks in the use of such sub stances. A greatly increased effort is needed to im prove ihis situation " The polychlorinated biphenyls seem to be par ticularly hazardous in this respect because their use is still increasing in many industries, including food industries. If these substances are absorbed by the body, they will easily accumulate, gradually reaching a level high enough to exert adv crce ef fects, since they have an extremely slow rate of metabolization or excretion. Many patients with Yusho arc still tortured by the disease even atter more than 2 years of treatment. A 1971 report has indicated that the subcuianeous fat of the patients still contains a large amount of polychlorinated biphenyls although their dermal conditions are e slowly improving (12). Recently, also, it has been demonstrated (hat wide environmental pollution with polychlorinated biphenyls is quietly growing in many countries (II), To prevent another epidemic of Yusho, SOM HSMHA Health ftiparl1 HONS 204958 which will break out on a global scale if the pollu tion worsens, radical efforts arc urgently needed. Oar saccess'imdcntifytng'thc' cause of the epi demic scents to hate been due to many factors: (a) common epidemiologic principles were hon estly followed, (b) local health departments and the patients themselves cooperated fully, (c) the causal agent was not multiple, but single, (d) contamination of the oil with Kanechlor was tem porary and marked, (e) the latent period of the epidemic was several months, and ihe epidemic was relatively short, (/) Yusho had characteristic symptoms, allowing easy differentiation from other diseases, (g) some of the oil used by the patients, along with the original containers, were still available, and {h) some persons who bought the oil as a group had contracted the disease. All these factors facilitated our study. Epidemiologic study of an illness or of adverse effects which were more chronic, less peculiar, which progressed less noticeably than Yusho, and were caused by multiple agents would present greater difficulties. We need to develop more sensitive and more efficient epidemiologic methods. We must, more over, exert constant efforts to make our epide miologic information more accurate, quantitatively and qualitatively, by using the methodology of other disciplines when it seems necessary for our purposes. REFERENCES ii) Goto, M., and Higuchi, K.i Th symptomilofciy of Yusho (chlorobiphenyt poisoning) in dermalotofy. Fukuoka Acta Medici 60 : 409-411 (1969). (2) Kuratmne, M, et at. An epidemiologic nudy oo Yusho or ehlorobiphenyl poisoning Fukuoka Acta Medic* 60 Jl)-}}' ( 1969 1 (J) Yoshimura. T.: Epidemiological inalysis of "Yusho" pant rut with special reference to scs. age. dimcil grades and oil consumption. Fukuoka Act a Medtca 62: 104-101 (1971). (4) Yamaguehi, A., Yoshimura, T, and Kuratsune. M.: A survey of pregnant women having con sumed rice oil contaminated with chlorobiphenyls- and of their babies. Fukuoka Acta Med us $2 ltT-122 (1971). (J) Yoshimura, T : A case control study on growth o( school children with "Yusho." Fukuoka Acta Medici 62: 109-116 (1971) (6) lUut, H, 5ugj, K., and Uga. 3 : Ocular signs of chronic chlorobiphenyt poisoning ('Yuiho' ) Fu kuoka Acta Medics 60 4J2-4J9 (1969). (7k Okumuta, M, and Kalsukt, S: Clinical observa tion on Yusho (chlorobiphenyt poisoning) Fuku oka Acta Medica 60 440-44S (1969). it) Urawa, H,, Iio, Y, Notomt, A, and Kalsukj. S. Hypergtycendemta resulting from intake of rice oil conlaminated *ilh chlorinated biphenyls. Fukuoka Acta Medica 60 449-154 (1969) (9) Kuroiwa, Y, Murat, Y., and Santa, T-: Neurolojt- ' cat and nerve conduction velocity studies on 2} patients with ehforobiphenvt poisoning FuLuoka Acta Medica 60 462-161( 1969). * 110) Taukamoto, H-, es at : The chemical studies on detection of loxic compounds in the rice bran oils used by patients with Yusho Fukuoka Acta Medica 60: 496-512 (1969). 111) Risebrough, R. W., et !.: Polychlorinated biphtn- yli in the global ecosystem. Nature (London) 220 1098-1102 (1961). ill) Kojima. T.: Chlorobiphenyls in the sputa and ut- sues. Fukuoka Acta Medica 62: 25-29 (1971) ill) Takt. I., Hisanaga, S.. and Amagase, Y . Report on Yusho (eblorobtpheny! poisoning) in pregnant women and their fetuses. FuLuoka Acta Medica 60: 471-474 (t969), RCIUTSUSE, MASANORl (Kyushu University), YOSHIMURA, TAKESU.Mf, MATSU2AKA, JUrVICHI, and YA.MAGUCHI, ATSUKOt Yusho, a poisoning caused by rice oil contaminated with polychlorinated biphenyls. HSMIIA Health Reports, Vol- 86, December f971, pp, 108$~1091, A peculiar skin disease, Yusho, was observed in residents of Fukuoka-Ken, Japan, in Octo ber 1964, which later spread over the western part of the country. By use of bask epide miologic methods, the cause of the disease was shown to be a specific brand of rice oil that had become contaminated with a heat transfer agent during processing. This agent, Kanechlor, is a com plex mixture of polychlorinated biphenyls. Women who consumed the contaminated oil delivered babies or fetuses with peculiar darkbrown stained skin, nails, and gingiva. The poisoning signifi cantly decreased the growth of the boys who were affected, while the girls who were affected showed no such change. Many of the persons who contracted the disease are still tortured by it even 2 or more years later, de spite all possible treatment meth ods. . In view of the slow recovery from the poisoning and the in creasing pollution of the environ ment with these compounds on a global scale, radical efforts must be made to avoid the hidden risks of contamination. Ofcuiritwr |97|, Vat ft, Ao. li !09t HONS 204959 9 An Epidemiologic Study of Amputees in the East Harlem Community COURTNEY B. WOOD, M.D-, ROBERTA S. VOLANTE, R-N, MJL, and ROBERT BERENSON, M.M.S. \t i MASS screening for one or a number of diseases is the extent that mass screening or any like programs fulfill these classic public health methodologcyri.teria, they perform a valuable The effectiveness of screening pro health service within a commu grams'depends on several fac nity; that is, they have the poten tors; notably, their success in tial of leading to reductions in reaching high-risk groups, the ex morbidity, mortality, or disability. tent to which the diseases identi The problem often Is, however, fied are subject to therapeutic that existing programs for one attack, and the availability and reason or another are weak, espe accessibility of followup care. To cially in reaching the desired population and in the area of Dr. Wood js associate professor followup care. The question of community jnedieine. Mrs. arises as to whether there is any Volantt Is (immunity nursing way of using the valuable ex consultant and instructor in com perience of traditional public munity medicine, and Mr. Beren health methodology to reach the ice! it a fourth year medical stu community with an approach that dent, Mount Sinai School of would be more responsive to its Madkina of the City University health needs and more effective of Net* York, The New York in meeting these needs. Community Trust provided funds To that end we proposed and for the study. Tearsheet requests executed a pitot study that was to Courtney B., Wood. M.D.. based on the resolve of the de Mount Sinai School of Medicine. partment of community medi City Universiti of New York, cine, Mount Sinai School of Medi 19 E. 98`h St., New York City cine, "to identify and solve health 10029. / problems in the community." We decided to select a disease that was easily identifiable by the gen eral population aad for . which there was a relatively simple and highly visible solution. The ap proach was to be one of search and service, with a view to devel oping a network of indigenous epidemiologic intelligence within a given community; namely. East Harlem. Amputation of an extremity was selected as the most recog nizable disease entity for which followup services are accessible, available, and effective. In this study an amputee is defined as a person lacking part or all of one or more extremities. Objective and Method The project had the following objectives: \ 1. To identify a)l amputees in the East Harlem community and to review their medical and socio economic characteristics 2, To assess the current need lOtt HSMHA MtsHh RWWta HONS 204960 Id analysis of these 31 asea win be presented to illustrate these peculiarities. Familial aggregation. The 325 patients be longed to 112 families, a result indicating a dis tinct familial aggregation, which is considered one of ihe most important characteristics of Yusho. 'Time of occurrence. Ninety-nine percent of the patients were affected during 1968, and 55 percent of the cases were concentrated in the 3 months from June to August (table 2). The monthly distribution of the cases was alike for both sexes. These results indicated that exposure to the causal agent or agents was probably tem poral and indifferent to sex. Sea and age. Distribution of the 325 patients by sex and age revealed no significant sex differ ence (table 3). Age-specific incidence rates per 100,000, calculated by using the census papula tion of 1965, indicated lower risks for both males and females in the age group over 60 years, but again no marked sex difference (table 4). Geograp distribution. We calculated crude incidence rates of Yusho for three large cities (Ki- takyushu, Fukuoka, and Ohmuta) and For the ju risdictional areas of the 22 local health depart ments of Fukuoka-Kcn. A very marked (Infer ence was noted tn their rates. Ten health depart ments reported no cases of Yusho while extremely high incidence rates per 100.000 were noted for the area covered by the health department of Soeda (58.9) and that covered by the health de partment of Tagawa (44.5); intermediately high rates, from 1 to 14, were observed for the three large cities and the area of the Kasuya health department. ' There are many coal mines, most of which have recently been abandoned, in the jurisdictional areas of the Soeda and Tagawa health depart ments. The city of Kitakyushu has big steel and chemical industries, Fukuoka Is a seat of com merce, and Ohmuta has big coal mines and chem ical industries. In contrast, the Kasuya health de- TabEe 2, Distribution of 325 patients with Yusho diagnosed by January 20, 1969, by sex and month when symptoms appeared Month Maks Number Percent Females Number Percent Total ' Number Percent Before 1961............................ 196$ January......................................... ................. February..................................... . March........................................... April............................................ . May,............................................. June.............................................. .................... July.......................................................... August.......................................... September............................... October.................................. November................................................ December............................... Tout............................... . 1.3 0 .0 2.3 3.1 9.3 11.4 23 14.6 IT 17.1 21.3 10.1 3.1 t *6 .4 100.0 2 1.2 0 .0 6 3.6 12 7.2 10 6.0 13 9.0 33 19 1 32 19.2 30 It.O 12 7.2 14 1.4 1 .6 0 - .0 167 100.0 4 1.2 0 .0 10 3. t 20 6 2 23 7.7 33 10 2 36 17.2 39 18.1 64 19.7 29 8.9 22 6.8 26 1 .3 323 100 0 Table 3. Distribution ol 325 patients with Yusho diagnosed by January 20. 1969, by sex and YTMup Age group (yean) Mala Number Percent Female* Number Percent Tout Number Percent 04........................................................ 10-1*................................................. ____ 20-29........................................................ ........ 30-39........................................................ 40-49........................................................ 30-39....................................................... ......... 60-69......................................................... 70-79................................................. Total.............................................. 37 23.4 31 24.1 28 17.7 19 0 7.0 9 3.7 2.3 .3 100 0 n 16.2 2g 16.1 36 21.6 39 23.4 23 13.1 It 6.6 3 l.t 0 .0 167 100.0 64 19 7 66 20 3 64 19 7 69 21 2 34 10 3 20 6 2 7 2.2 1 .3 323 100 0 December It71. VoL as. No. I* IMS HONS 204961