Document ba5je7ZRzaM9MQJgdZyG116Z1

TECHNICAL REPORTS Vnsho, a poisoning caused by rice oil contaminated tvith polj chlorinated biphenvU__1083 isanorr htrraTSttne,-Takesutni Yosiinttura, Junichi Matsuzaka, and A tsuko Yarnaguclii An epidemiologic study of amputees in the East Harlem community_______ __ 1092 Courtney IS. Wood, Roberta S. Volante, and Robert Berenson Welfare and Medicaid coverage of the poor and near-poor in low-income areas Gerald Sparer atid Louise M. Okada _ Alabama diphtheria outbreak, 1967 : 1107 Michael C. Sinclair, Raymond Overton, and William J. Donald Mass Immunization campaign in El Salvador, 1969. Evaluation of receptivity and recommendations for future campaigns 1112 Nan Lin, Ralph Hingson, and Juan Allwood Paredes Risk management and consumer participation in medical decision making llan Vertinsky and Dean H. Uyeno Factors in reducing children's anxiety about clinic visits Michael Hejjernan and Pat A zarnoff 9 1971 index 1099 IU1 1131 1136 U.8. DEPARTMENT OF HEALTH, EDUCATION, ANO WELFARE Public Health Service Health Services and Mental Health Administration DSW 028818 ) STLCOPCB4012780 msqp, a poisoning caused by rice oil contaminated with polychlorinated biphenyls MASANORI KURATSUNE, M.D., TAKESUMl YOSHIMURA, M.D., JUNICHI MATSUZAKA, M.D., and ATSUKO YAMAGUCHI, M.O. SPORADIC outbreaks of a peculiar skin dis ease were reported in Fukuoka-Kcn (Fuku oka Prefecture), Japan, in early October 1968. It was characterized by such symptoms as foilicuiar accentuation, acneform eruption, pigmentation of the skin and nails, and hypersecretion of the_Meibomian 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 rice oil was also suspected in view of the distinct familial ag gregation of the patients and their common use of the nil (/). 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. Kutsuki 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 arid carried 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 Kitakyushu, Fukuoka, and Ohmuta. The epidemic spread not only over FukuokaKen 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 Fukuoka-Ken, and the 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 in the world if sufficient care is not exercised. The authors are with the department of public health, Faculty of Medicine, Kyushu University, Fukuoka, Japan. Dr. Kuratsune is a professor of public health, Dr. Yoshimura and Dr. Matsuzaka are working toward doctoral degrees in pub lic health, and Dr. Yamaguchi is a research stu dent. The study on Yusho was supported by a special research grant from the Japanese Govern ment. Tearshect requests to Masanori Kuratsune, M.D., Faculty of Medicine, Kyushu University, Fukuoka, Japan. Dc*mber 1971, Vol. 86, No. 12 1083 DSW 028819 V STLCOPCB4012781 Most of the results of our study have already been published in Japanese (2-5). We refer also, when necessary, to some important observations made by a clinical study subgroup headed by Pr<f>[. 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. Clinical Symptoms The subjective symptoms of the 89 male and the 100 female patients whose cases of Yusho had been diagnosed by the end of October 1968 are listed in table I. Most of these symptoms related to the skin and eyes. Detailed clinical examina tions of these 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 hyperkcratotic plaque on the soles of the feet and palms of the 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, milia near the joints. Table 1. Percent distribution of symptoms of Yusho reported by 189 patients examined be fore October 31, 1968 Symptoms Mates Females (N-89) (N-100) Dark brown pigmenfaiion of nails........... Distinctive hair follicles............................. Increased "sweating at palms...................... Acnelike skin eruptions.............................. Red plaques on limbs................................ Itching....................................................... Pigmentation of skin.................................. Swelling of limbs........................................ Stiffened soles in feet and palms of hands........................................................ Pigmented mucous membrane................ Increased eye discharge.............................. Hyperemia of conjunctiva......................... Transient visual disturbance...................... Jaundice....................................................... Swelling of upper eyelids........................... Feeling of weakness.................................... Numbness in limbs.................. Fever............................................................ Hearing difficulties...................................... Spasm of limbs......................................... Headache..................................................... Vomiting...................................................... Diarrhea....................................................... 83.1 64.0 50.6 87.6 20.2 42.7 75.3 20.2 24.7 56.2 88.8 70.8 56.2 11.2 71.9 58.4 32.6 16.9 18.0 7.9 30.3 23.6 19.1 75.0 56.0 55.0 82.0 16.0 52.0 72.0 41.0 29.0 47.0 83.0 71.0 55.0 11.0 74.0 52.0 39.0 19.0 19.0 8.0 39.0 28.0 17.0 Ophthalmic observations. Hypersecretion of the meibomian gland and abnormal pigmentation of the conjunctiva. Neurological observations. Numbness, pain, hypoesthesia, and lowered sensory conduction by the radial and sural nerves. Other observations. Elevated serum triglycer ide. 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 qs 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 the 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. 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 antitheses when interpreting any result. Descriptive Epidemiologic Studies 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 their local health departments. From October 1963 until the epidemic practically terminated in Janu ary 1969, a total of 6,611 persons in FukuokaKen had reported that they were affected. Among them, 325 cases of Yusho were diagnosed by the clinical study subgroup. An early analysis of a portion of the 325 persons with confirmed cases, carried out in late October 1968, revealed several peculiar features in the geographic distribution of cases, features which did not basically change dur ing the epidemic. Therefore, only the results of 108* 'HSMHA Health Reports DSW 028820 STLCOPCB4012782 analysis of these 32 ases 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 ^he 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 vfas 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 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 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 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- Table 2. Distribution of 325 patients with Yusho diagnosed by January 20, 1969, by sex and month when symptoms appeared Month Males Number Percent Females Number Percent Total Number Percent Before 1968............................................ ........ J96S January................................................... February................................................. ........ March...................................................... ........ April........................................................ ........ May....................................................... . June......................................................... ........ July................................................................... August.................................................... ........ September............................................... ........ October................................................... ........ November............................................... ........ December............................................... Total................................................ . 2 1.3 .0 4 2.5 8 5.1 15 9.5 It.4 23 14.6 27 17.1 34 21.5 17 10.8 8 5.1 I .6 .6 100.0 2 1.2 0 .0 6 3.6 12 7.2 10 6.0 15 9.0 33 19.8 32 19.2 30 18.0 12 7.2 14 8.4 1 .6 0 .0 167 100.0 4 1.2 0 .0 10 3.1 20 6.2 25 7.7 33 10.2 56 17.2 59 18.1 64 19.7 29 8.9 22 6.8 2 .6 1 .3 325 100.0 Table 3. Distribution of 325 patients with Yusho diagnosed by January 20, 1969, by sex and age group Males Number Percent Females Number Percent Total Number Percent 0-9........................................................... ........ 10-19......................................................... 20-2?......................................................... 30-39......................................................... ____ 40-49................................................................. 50-59......................................................... 60-69......................................................... 70-79......................................................... ___ Total.................................................. ____ 37 23.4 24.1 17.7 30 19.0 11 7.0 5.7 2.5 t .5 158 too.o 27 16.2 28 16.8 36 21.6 39 23.4 23 13.8 11 6.6 3 1.8 0 .0 167 100.0 64 19.7 66 20.3 64 19.7 69 21.2 34 10.5 20 6.2 7 2.2 1 .3 325 100.0 December 1971, Vol. 85, No. 12 1085 DSW 028821 STLCOPCB4012783 partment covers an area that is primarily agricul tural. Most areas where few Yusho patients were seen were agricultural. No other common socioe conomic or environmental factor was observed that might explain the geographic distribution of patients. ' Oil Used by Patients f As stated, K rice oil had been suspected as the possible cause of the epidemic. K rice 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 can), 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 visited 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. All the persons with Yusho had used, for varying periods. K rice oil which came cither 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 5). Wc 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 rice oil that was shipped by the K Company on February 5 and 6, J968<Q according to the lot numbers on the few remaining cans. Even the four patients for whom we could not confirm shipping dates of the oil had also undoubtedly used a canned rice oil 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 they buy new oil. Nevertheless, all the shipping, pur chase, or selling records at K Company, at ihc oil dealers, and at the retail stores were examined to learn whether any bottled K. rice oil had been shipped to. and had reached, the retail stores from 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 Any of them had been made on February 5 or 6, 1968, or immediately before or after these dates. By this method, we discovered that 143 of the 155 patients might have bought the bottled oil shipped from the K Company in the period Feb ruary 6-15, 1968. Whether the remaining 12 pa tients might have also purchased oil shipped in 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 rice 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 (years) 0-9.................................... 10-19.................................. 20-29.................................. 30-39.................................. 40-49.................................. $0-59.................................. 60-69.................................... 70 and over........................ All ages...................... Incidence rates per 100.000 Males Females 11.4 . 8.9 9.1 9.6 5.4 5.4 3.5 1.7 8.3 8.6 6.6 10.3 11.9 9.3 7.2 2.4 .0 8.1 Table 5. Distribution of 325 patients and 112 households that used K rice oil, by type of oil container and shipping dates of oil Container and Patients Households Number Percent Number Percent Users of canned oil... Shipped February 5 and 6.................. Shipping dates unknown.............. Users of bottled oil. .. Probably used oil shipped February 5-15...................... Shipping dates unknown.............. Total..................... 170 52.3 166 51.1 4 1.2 155 47.7 143 44.0 12 3.7 325 100.0 49 43.8 47 42.0 2 1.8 63 . 56.3 56 50.0 7 6.3 112 1 100.1 1 Does not add to 100.0 percent because of roundirtg. 1086 HSMHA Health Reports 0SW 028822 // STLCOPCB4012784 FLOW SHEET OF RICE Oil PRODUCTION Rlct bran l------- Difittid bran N-hexine uttd to ixtraet "1 Crude oil After removal of solvent. It treated With todium metaphosphate i------ NaOH layer Neutralized with H SQ. "Dark" oil Treated with NaOH 1 Oil Washed with hot water Filtered Color removed with white porcelain clay Deodorized by heating at over 200* C. at 3 to 4 mm. Hg Final products 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 rice 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 (2). K Oil From Other Shipments An additional survey seemed necessary to de termine whether those persons who regularly used K rice oil but had not used any from shipments mude in the period in question were free of the disease. For this purpose, a group of persons was needed who 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 the 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 fairly regularly from December 1967 to September 1968 except for the period from January to April 1968, when this bulk purchasing was not carried 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 December 1971, Vol 86. No. 12 1017 DSW 028823 STLCOPCB4012785 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 did not suffer from Yusho (2). Retrospective Case-Control Studies Ail 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 and those without had different personal back grounds, home interviews were conducted with 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 controls having various allergies and dietary and per gonal habits, based on case-control study Items investigated Patients Con trols Allergic to fish............................................ Allergic to aspirin....................................... Allergic to drugs other than aspirin......... Bathing facilities at home.......................... Bath e\ery day............................................ Pels at home............................................... Floor space of house smaller than 66 square meters.......................................... Handling agricultural chemicals......... . Taking codiiver oil..................................... Taking vitamin pills................................... Taking other restorative drugs.................. Water supply available at home............... Dining out occasionally............................. Taking all meals with the family.............. Green vegetables daily............................... Milk nearly every day................................ Butter nearly every day.............................. Eggs nearly every day................................ Fried foods or tempura nearly every day. Foods prepared with oil nearly every day. Fish nearly every day................................. Mayonnaise nearly every day.................... Instant "rahmen" or Chinese noodles nearly every day...................................... 5.0 .0 7.5 84.7 73.0 1 18.3 66.9 2.5 10.8 23.2 9.1 81.3 28.1 88.8 63.1 49.0 22.4 64.7 1 22.4 45.7 21.6 10.8 10.8 * P <0.05. 7.5 4.2 6.6 85.5 70.6 '36.5 66.1 6.6 8.3 18.3 7.5 74.7 30.6 89.6 58.9 39.0 24.9 59.8 *11.6 3J.7 29.1 10.8 10.0 Table 7. Distribution of 69 households with pa tients and 207 control households, by use of various fats or oils, based on case-control study Fat or o3 Households with patients Control households Number Percent Number Percent Butter............................ Margarine.................... Sesame oil.................... Rape-seed oil............... Rice-bran oil................ Lard.............................. Other oils................. 35 50.7 44 63.8 21 30.5 10 14.5 66 95.7 12 17.4 13 18.8 105 30.7 127 61.4 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 characteristics of their 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 foods or tempura nearly every day were more numerous among the patients than among the controls, while ipore of the controls than the patients had pets. To compare the use of oil and fats, 69 house holds with Yusho patients were maiched 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 parients affirmed its 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). Dose-Response Relationship To prove that a causal relationship existed, a distinct dose-response relationship needed to be demonstrated. Estimating the quantity of coniaminated rice oil consumed by each patient and mem bers of his family was not fcasibte. Nevertheless, if wc disregarded age and sex, wc could estimate roughly the average amount of oil each person had consumed by dividing the amount used in a loss nsmn/t mrtrtn mrporte OSW 028824 r, STLCOPCB4012786 household by the number of persons in it, taking into account the frequency with which these per sons ate at home, but not the possible loss of oil during and after cooking, nor the .varying tastes and food intake of the family members. Dr. Masayasu Goto, a dermatologist, with no knowledge of the amount of oil used by the 146 consumers of the contaminated oil. examined these persons and then graded the cases of Yusho he diagnosed according to their clinical severity. Only later did we link the severity 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 standard ization 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 changed 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 (3). Toxic Agent 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. Kancchior is a commer cial brand of polychlorinated biphenyls containing 48 percent chlorine. Skin fat collected from the patients also contained Kanechlor (10). In this discdvcry\ Prbf. K. Inagartii of the de partment of food technology. Faculty of Agricul ture,.Kyushu University, and his associates played a leading role. A technological inspection of the K Company plant revealed that Kancchior 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 1968 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 only 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 (10). No analysis could be made of bottled 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 patient with Yusho had a stillbirth in* which the fetus was unusual; the skin, nails, 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 Decambw 1971, Vol. 86, No. 12 1089 DSW 028825 7 STLCOPCB4012787 subgroup questioned all female patients with Yusho and all unafTcctcd women in the house holds of patients with Yusho about any preg nancies and deliveries in the period from Febru ary 15, 1968, to the end of the year. Thirteen women--10 with Yusho. two without, and one with status unspecified--had given birth to 11 live born 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, 10 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 in the women's medical histo ries, health conditions, or use of drugs during pregnancy also supported such au 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 Kancchlor,/ 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 plainly lower than the national standard curves. A clear 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 the 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 children's growth, the af fected school children, 23 boys and 19 girls, were compared in 1967, 1968. and 1969 with 719 healthy children matched in height and bodv weight. The gain in height or in body wcicht which each sick child showed before the poison ing, namely from 1967 to 1968. and the gain after 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 in both height and weight decreased significantly after the poi soning, while the affected girls showed no definite change in this respect. Because of the limited number of cases available for analysis, no signifi cant relationship could be found between the clin ical severity 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 substances like Kanechlor. 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 to avoid the hidden risks in the use of such sub stances. A greatly increased effort is needed to im prove this 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 adverse ef fects, since they have an extremely slow rate of metabolization or excretion. Many patients with Yusho are still Jortured by the disease even after more than 2 years of treatment. A 1971 report has indicated that the subcutaneous fat of the patients still contains a large amount of polychlorinated biphenyls although their dermal conditions are slowly improving (12). Recently, also, it has been demonstrated that wide environmental pollution with polychlorinated biphenyls is quietly growing in many countries (11). To prevent another epidemic of Yusho, 1090 KSMHA Health Report* DSW 028826 STLCOPCB4012788 which wiH break out on a global scale if the pollu tion worsens, radical efforts arc urgently needed. Out success'irridcmifying'ttie' cause of'the epi demic seems to have 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 the 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 (A) 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 (/) Goto, M., and Higuchi, K.: The symptomatology of Yusho (chlorobiphenyl poisoning) in dermatol ogy. Fukuoka Acta Medica 60: 409-431 (1969). (2) Kuratsune, M., el al.: An epidemiologic study on "Yusho" or chlorobiphenyl poisoning. Fukuoka Acta Medica 60: 513-532 (1969). (3) Yoshimura. T.: Epidemiological analysis of "Yusho" pauents with special reference to sex. age. clinical grades and oil consumption. Fukuoka Acta Medica 62: 104-108 (1971). (4) Yamaguchi, A., Yoshimura, T,, and Kuratsune, M.: A survey of pregnant women havins con sumed rice oil contaminated with chlorobipbenyls, and of their babies. Fukuoka Acta Medica 62: 117-122 (1971). (5) Yoshimura, T.: A case control study on growth o( school children with "Yusho." Fukuoka Acta Medica 62: 109-116 (1971). (6) IVui, H., Sugi, K., and Uga, 3.: Ocular signs of chronic chlorobiphenyl poisoning ("Yusho"). Fu kuoka Acta Medica 60: 432-439 (1969). (7X Okumura. M., and Katsuki. S.: Clinical observa tion on Yusho (chlorobiphenyl poisoning). Fuku oka Acta Medica 60: 440-448 (1969). (8) Uzawa, H,, lto, Y., Notomi, A., and Katsuki. S.: Hyperglyceridemia resulting from intake of rice oil contaminated with chlorinated biphenyls. Fukuoka Acta Medica 60: 449-454 (1969). (9) Kuroiwa. Y., Murai, Y., and Santa. T.: Neurologi" cal and nerve conduction velocity studies on 23 patients with chlorobiphenyl poisoning. Fukuoka Acta Medica 60: 462-463 (1969). (10) Tsukamoto, H., et al.: The chemical studies on detection of toxic compounds in the rice bran oils used by patients with Yusho. Fukuoka Acta Medica 60 : 496-512 (1969). (//) Risebrough, R. W., et al.: Polychlorinated biphen yls in the global ecosystem. Nature (London) 220: 1098-1102 (1968). (12) Kojima, T.: Chiorobiphenyls in the sputa and tis sues. Fukuoka Acta Medica 62: 25-29 (1971). (13) Taki, I., Hisanaga, S., and Amagase, Y.: Report on Yusho (chlorobiphenyl poisoning) in pregnant women and their fetuses. Fukuoka Acta Medica 60: 471-474 (1969). ROR.ATSUNE, MASA.NOHI (Kyushu University), YOSHIMURA, TAKESUMI, MATSUZAKA, JU.MCIH, anti YAMAGUCHI, ATSUKO: Yusho, a poisoning caused by rice oil contaminated tcilh polyvhlorinateil biphenyls. HSMilA Health Reports, Vol. 86, December 19 71, PP. 1083-1091. A peculiar skin disease, Yusho, was observed in residents of Fukuoka-Ken. Japan, in Octo ber 1968, which later spread over the western part of the country. By use of basic 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 die 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. OSbembar 1971, Vol. 86, No. IS 1091 DSW 028827 r1 I STLCOPCB4012789 / An Epidemiologic Study of Amputees in the East Harlem Community '\ / COURTNEY B. WOOD, M.D., ROBERTA S. VOLANTE, R.Nn MA, and ROBERT BERENSON, M.M.S. MASS screening for one or the extent that mass screening or a number of diseases is 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 arc weak, espe accessibility of followup care. To cially in reaching the desired population and in the area of Dr. Wood is associate professor followup care. The question of community medicine. Mrs. arises as to whether there is any Volatile is Community 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 son is a fourth year medical stu community with an approach that dent, Mount Sinai School of would be more responsive to its Medicine of the City University health needs and more effective of New 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 pilot 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 Universitj of New York, cine, Mount Sinai School of Medi 19 E. 9Sth jit.. 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 and 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 aj! amputees in the East Harlem community and to review their medical and socio economic characteristics 2. To assess the current need 1092 HSMHA Health Report* DSW 028828 /t STLCOPCB4012790 analysis of these 32 ases 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 (he most important characteristics of Yusho. ilime 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. 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 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 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 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- Table 2. Distribution of 325 patients with Yusho diagnosed by January 20, 1969, by sex and month when symptoms appeared Month Before 1968.................. 1968 January.,....................... February......................... March............................. April................................ May................................. June................................. July.................................. August............................. September....................... October........................... November....................... December....................... Total........................ Males Number Percent Females Number Percent Total Number Percent 2 1.3 0 .0 4 2.5 8 5.1 15 9.5 18 11.4 23 14.6 27 17.1 34 21.5 17 10.8 8 5.1 l .6 1 .6 158 100.0 2 1.2 0 .0 6 3.6 12 7.2 10 6.0 15 9.0 33 19.8 32 19.2 30 18.0 12 7.2 14 8.4 1 .6 0 .0 167 100.0 4 1.2 0 .0 10 3.1 20 6.2 25 7.7 33 10.2 56 17.2 59 18.1 64 19.7 29 8.9 22 6.8 2 .6 1 .3 325 100.0 Age group (years) 0-9........ 10-19.... 20-29.... 30-39..... 40-49.... 50-59.... 60-69.... 70-79.... Total with Yusho diagnosed by January 20, 1969, by sex and age group Males Number Percent Females Number Percent Total Number Percent 37 23.4 38 24.1 28 17.7 30 19.0 11 7.0 9 5.7 4 2.5 1 .5 158 100.0 27 16.2 28 16.8 36 21.6 39 23.4 23 13.8 11 6.6 3 1.8 0 .0 167 100.0 64 19.7 66 20.3 64 19.7 69 21.2 34 10. J 20 6.2 7 2.2 1 .3 325 100.0 December 1971, Vol. 86, No. 12 1085 DSW 028829 STLCOPCB4012791