Document GzXMmkg3Rj0jKbKgq8R1Kegvx

/W// J*An. \p6- Civr/ aYSJ-- 4&js U/A -(/<r see *? * Clar/C (2rvff > dird/C V ' ' 1SI S d J \Cf RECEIVED OCT 2 6 1981 BRIEF REPORTS ,V ' lAsLeJL tl\. Briefreports ofnew clinical or laboratory observationsJ cases of unusual importance, anti new developments in medical lour will be considered for publication in this section. Manuscriptis must be typed double-spaced. Teat length must not ex.deed 750 words; no more than 10 references and one figure or iible can be used. See "Information for Authors " on page 1-6 fo\ form of references. Manuscripts should include an abstract of hot over 100 words. Reports will be reviewed by consultants phen, in the opinion of the editors, such review is needed. 77)|; Editor reserves the right to shorten reports and to make cht.inges in style Tumors in Patients with Angiosarcoma of the j-iver NICHOLAS J. VIANNA, M.D., M.S.P.H. The New York State Department of Health, Bureau if Environmental Epidemiology and Occupational Heajth; Albany, New York. Angiosarcoma of the liver is an exceedingly rare vascu lar tumor that has been associated with exposure to thori um dioxide, arsenic, and vinyl chloride monomer (1, 2). Using methods previously described (1), the Buteau of Occupational Health, New York State Health Depart ment, developed a registry of all histologically cor firmed cases of angiosarcoma of the liver diagnosed in re iidents of New York State from 1970 through 1975. Detailed medical, social, occupational, familial, and then peutic histories on each patient were obtained from their :losest living relatives and physicians. Slides of all patieits in cluded in the registry were reassessed blindly for di ignostic accuracy by a panel of pathologists. All other slides relating to diagnoses of other malignancies in these pa tients were also reassessed. Of the 26 patients included in the registry, six were found to have nine histologically confirmed additional primary neoplastic tumors. Table l indicates the proba ble types and duration of exposure for these six patients. In general, persons with a first cancer are at 1.29 times increased risk overall of developing a new independent nonsimultaneous primary cancer compared with persons who never had cancer (3). These findings may well be fortuitous, and the small number of patients (and person years) involved limits the value of statistical analysis.. However, the rarity of an giosarcoma of the liver (annual incidence rates ranging from 0.14 per million [2] to 0.25 per million population) (1), the high frequency of other primary tumors ob served, and the very short interval between the diagnosis of angiosarcoma of the liver and most of the other tumors observed (Patients 1 to 4, Table 1) support the hypothesis that exposure to these three carcinogens might be of etiologic importance in the pathogenesis of many of the dif ferent types of tumors observed in each patient. Morever, evaluation of the past medical, social, and therapeutic histories of the six patients did not suggest that other factors (such as smoking or radiation) could account for these observations. None of the patients had a family his tory of any of the tumors listed in Table 1. Patient 1 had a sister in whom breast cancer was diagnosed; Patient 2 had a father in whom stomach cancer was diagnosed; and the father and mother of Patient 4 had diagnoses of Hodgkin's disease and myeloid leukemia, respectively. Several mortality studies (4, 5) have found a slight to moderate excess of digestive tract, lymphatic, urinary tract, and brain cancers among cohorts with occupational exposure to vinyl chloride. Other studies (6), however, have failed to document these results. Findings of experi- Table 1. Descriptive Oats on Patients with Angiosarcoma of the Liver and Other Primary Malignancies Patient Sex Angiosarcoma of the Number ________ Liver Patient Year Age at of Diagnosis Diagnosis-* Type Other Primary Malignancies Year of Diagnosis Probable Exposure History and Duration Year of Death yrs F 40 M 52 M 68 1965 1968 1971 Squamous cell carfinoma. left finger Giant follicular lymphoma, breast Adenocarcinoma, prostate Cholangiocarcinoma. liver Lymphosarcoma. small intestine M 63 F 43 1975 1970 Transitional cell ca|:reinoma, bladdcr Transitional cell carcinoma, blad der Meningioma, brain FM 1973 Fibromyxoliposarc >mi. knee ' Angiograpny 30 yean before diagnoaia of anfioaercome of the liver. 1965 1968 1968 1968 1955 1971 1973 1959 1969 Lived less than 1 mile from a vinyl chloride factory (15 years) Thorotrast* Unknown, chemist-teacher (1 year) Unknown, cleaning and mainte nance (40 years) Lived less than one mile from a vi nyl chloride factory (22 years) Arsenical pesticides (45 years) 1965 1968 1968 1971 1973 1974 1975 Brief Repent 185 SPI-01341 mental studies have shown that this chemical induces adenoma, adenocarcinoma of the lur brain tumors, lymphomas, and other tumors in varic us animal species (7). Arsenic is generally accepted as a cause of Bowen's disease and probably certain respiratory tract cancers (8). Other neoplasms that have less frequently been attributed to chronic arsenic exposure include ca ncers of bladder, prostate and liver and leukemias and lymphomas (8). Chronic exposure can produce lymphon as experimental- ly (9). Thorium dioxide has been assoc ated with cancer of the maxillary sinuses, meningioma nd bile duct and acute and chronic myelogenous leukemia (10). Further study of the possible spectrfj:im of malignant disorders associated with exposure to <ach of the three agents clearly is warranted. Because mnst patients with well-documented angiosarcoma of thne~ti vg`tOiavr fin Anr. umented posure to'any of these thri e chemicals (1), some considerallfiii Should also Be given To the possibility that "Similar to vinyl chlonde (such as~eliluiupi citcr-mrhlnroethylengj night play a role' in the cause oftKll and possibly other Tjfllipnam dii. . dersr Requests for reprints should be addressed to Nicholas J. Vienna, M.D.; Bureau of Environmental Epidemiology and Occupational Health, Tower Building. The Governor Nelson A. Rockfeiler Empin State Plaza; Albany, NY 12237. REFERENCES 1. Brady J, Liberators F. Harper P, et al. Angi isarcom* of the liver: an epidemiologic survey. J Natl Cancer Inst. 1977 59:1383-5. 2. Heath CW Jr. Falk H. Creech JL Jr. Char ictenstics of cases of angiosarcoma of the liver among vinyl chloride orkers in the United States. Ann NY Acad Sci. 1975;246:231-6. 3. Schoenberg BS. Multiple-primary neoplasms in f ersons ai high risk of cancer. In FraDMEN) JF, ed. An Approach to Zencer Etiology and Control. New York: Academic Press: 1975:103-19 4. Tabershaw JR, GaFFEY WR. Moniliiy study o' workers in the man ufacture of vinyl chlonde and its monomers. J Oca p Med. "1974:16:50918. ?. Waxwejle* RJ. Stringer W, Wagoner JK, h al. Neoplastic nsk among workers exposed to vmyl chlonde. A|nn W Acad Set. 1976;271:40-8. 6. Fox AJ, Collier PF. Mortality experience of wor itn exposed to vinyl chlonde monomer in the manufacture of polyvinyl chlonde m Great Britain. BrJJndust Med. 1977;34:1-10. 7. Viola PL, Biogotti. Carlto A. Oncogenic respa^i*se of rat skin, Jungs and bone to vinyl chlonde. Cancer Res. 1971:31:5 116-9. 8 Schoolmeester WL. White DR. Arsenic pois< nmg. South Med J. 1980:73:198-208. 9. Sunder man FW Jr. a review of the carcmogeniicities of nickel, ehromium and arsenic compounds in man and apimiJs. * Pre\ Med. 1976;5:279-94 10. Meyler L- Radioactive Isotopes in Side Effects Drugs. New York: Exerpta Medica Foundation 1966:468-9. Cl 981 American CoUege of Physicians Estrogen Receptor Activity in.a Case 01 Hodgkin's Disease JAMES J. STARK. M.D.; JOHN W. LLOYD. Ph.D and PAUL F. SCHELLHAMMER. M.D. Eastern Virginia Medical School; Norfolk, Virginia The discovery by Jensen and colleagues (1) and others (2) of the presence of estrogen receptors in human breast cancers and the subsequent correlation of the presence of hormone receptors and response to ther|ipy have had profound effects on the modem managem iint of patients with advanced cancer of the breast. Estrfa gen receptor Figure 1A. Large submandibular mass present on presentation. B. Neck mass has disappeared entirely atter 1 week of high-dose diethylstilbestrol therapy. activity has also been identified in normal'liver, endome trium, and pancreas; in neoplasms other than those of breast, including adenocarcinoma of endometrium, co lon, and ovary; and in malignant melanoma (3). To date these observations have been of only modest therapeutic significance. Presented here is the case of a patient with Hodgkin's disease in whose tumor estrogen receptor ac tivity was found to be very elevated and whose lymphadenoparhy regressed dramatically after fortuitous estro gen therapy. A 72-vear-old man presented to his otolaryngologist with a 1 month history of a left submandibular mass. He was otherwise totally asymptomatic. Past medical history was essentially unre markable. Findings of physical examination including careful evaluation of the structures of the oral cavity were unremarka ble except for a a- by 4- by 6-cm firm, nontender fixed mass in the left submandibular area obliterating the angle of the mandi ble (Figure 1A). The rest of the findings were essentially normal except for diffuse induration of the prostate extending into the seminal vesicles. He was referred for urologic evaluation: Biop sy of prostate showed poorly differentiated adenocarcinoma. In travenous pyelogram. technetium pyrophosphate bone scan, prostatic and total acid phosphatase fractions (sigma), and alka line phosphatase were all within normal limits. The patient had no symptoms on voiding, and a cystoscopy therefore was not done. Diethylstilbestrol therapy was initiated at 25 mg/d as a ther apeutic trial. At the end of 1 week the cervical mass had disap peared totally (Figure IB). The dose of diethylstilbestrol was then reduced to 1 mg/d with regrowth of the mass to its origi nal size over 10 io 14 days. Administration of diethylstilbestrol. 5 mg daily, was then begun, and although the mass did not disappear as it had done on the higher dose, it did regress signif icantly. However, on maintenance estrogen therapy with die thylstilbestrol, 5 mg/d, severe angina developed with T wave changes on electrocardiogram, fluid retention, and epigastric and substemal burning. Diethylstilbestrol was therefore with drawn. and the mass enlarged to its original size. Because of intolerance to estrogen therapy the patient underwent bilateral orchiectomy. The mass did not regress, however, despite a fall in serum testosterone level to less than 10 ng/dL (normal, 300 U- 900 ng/dL). During this period serial rectal examinations showed that the local prostatic lesion had completely disap peared Because of the inconsistent hormonal response, biopsy of the mass was done. Histologic studies showed Hodgkin's disease, nodular sclerosis (pathologic studies reviewed by Dr. Costan Berard, National Cancer Institute). Estrogen receptor analysis August 1983 of internal M#dic volume 95 Number 2 SPI-01342 3X Eradication 3. 493, Geneva mallpox eradl :nd global cer SME/78.21. Ge Towards the 9 May 1980. /orld Health od JOURNAL Of H ' 5 I E N E, EPIDEMIOLOGY. MICROBIOLOGY AND IMMUNOLOGY 25, 1331. No. 3, 233-2A3 JAN 2 1982 /=>7' NEUROLOGICAL CHANGES IN VINYL CHLORIDEEXPOSED WORKERS V. STt BLOVA1, L A M B L *, O. CHUMCAL'. V. KELLEROVX'. V. PAS [OVA', J. VlTOVCOVA'. L. 2 L A B 1 ] Department of Neurolog; Medical Faculty of Hygiene, Charles University, Prague 2) Outpatient Clinic of C: cupatlonal Health, District Centre of National Health, MSlnik, Czechoslovakia Vinyl chloride (VC) toxicity for the human organism Is not still fully clear. The occupational ex >osure to VC is linked with the development of liver hemangiosarcomas, or wttf other malignant processes of varying locality. Some authors diagnose changes in terns of scleroderma, universally are described roentgenologically detectec lesions of interphalangeal Joints and zonal osteoly sis. They are described in association with Raynaud's syndrome (12, 10, 1, 4, 5 and others). Lange with his colleagues (12) describes angiologlcally detect able constriction of digital arteries, stenosis or partial occlusion of phalangeal blood vessels. Described arp also various types of dysesthesia In fingers, particularly cold and numbness sensations. Also Byczkowska (3) reports frequent occurrence of finger pares :hesla, whitening of fingers, but also of palms and soles, and other symptoms ' if peripheral vasomotor disorders. Neurological manifestations are described only sporadically. Spirtas and colleagues (13) emphasize particularly the narcotic action of VC at higher peak exposure eoneentratlo is. This manifests itself by vertigo, nausea and hea dache pains. Mentioned an also hand paresthesiae (princkling, formication). Langauer-Lewowicka (11) imalyzes also the clinical symptoms In her group of 200 examinees who show id most frequently signs of cerebellar symptomato logy. She 'recorded frequem occurrence of headaches and sleep disorders, but also trigeminal neuralgia. Because of a lack of more detailed neurological studies among the VC-ex posed persons, we conductei field investigations among the occupationally ex posed workers In a plant where there was six years before put Into operation a workshop with a considerable VC hazard. ,, 233 PI;01343 ?. ,'iy& SSic\'~' 'St JV- Jr~` Ixr .--V-itf-5'>-V-:'.*- >'>. -r,y?w-.--T,rNs--r--- ------- --------------------- . ..---------- - -------------- - - -cstT! --.--h-it--^t?1jr;--- V-W- *'*,A: .'j-*V < -~^l* -TT - t 12 II si m, h-tS : 3 : is *S MATE RIAL AND METHODS The group of examinees cons sted ot 293 workers (263 males and 30 (emales), age 18--53 years, mean age 32.8 year.;. Of these 76 H were below 40. The average time of exposure was 2.8 years (range ffrom 2 months to 6 years). Alter consultations with plant physician and plant toxlcolf: gist the group was divided Into two subgroups according to the level ot exposure, The subgroup of high-risk workers, In which the tentatlvely established maximum allywable concentration ol 10 mg. m-3 had been Irequently and sometimes highly e iceeded, involved polymerization worker^.. and some maintenance workers (a total of 109 persons). The subgroup of lower-nsk category ot workers Included those engaged drying and bagging operations, but even here they were sometimes exposed to high peak exposure concentrations during cleaning and sampling operations, and those (r cm the other plant workshops -- combustion, compressots, cracking, chlorination, regen iratlon -- where the exposure risk was relatively low (a total of 184 persons). All the workers were examln ;d neurologlcally, some of them repeatedly. A more detailed analysis o( subjective co:npiaints was performed on the basis of EOD and N5 questionnaire surveys. Electroencelp halographic examination with photostimulation was made In 232 persons (255 recordlt gs). The group of controls consisted of 46 persons without exposure to toxic substanci as. RESULTS An overview of subjective complaints is presented in Table 1. Headaches occur frequently, but they are ess frequent than in the control group. The hi cidence of gastrointestinal disonders and other neurovegetative disorders (palpltations, retrosternal pressure s insatlons) are significantly higher than in controls. Psychic disturbances werbj observed only in those exposed. Table 1. Overview of subjective Cbmplaints in workers occupationally exposed to vl- nyl chloride. in a comparison with controls " ....... .... Complaint! VC -- exposed number 11 0/o/ Controls number | % Headache Sleep disorders GIT disorder! Vertigo Pivchic disturbation Dysesthesia Palpitations TouJ number of iTiminwa 48 16 20 3 13 9 14 293 15.7 5.3 6.9 1.0 4.5 3.1 4.8 100.0 9 2 1 1 0 1 0 46 19.6 4.4 2.2 2.2 0.0 2.2 0.0 100.0 Significant differences wen observed between the two subgroups of exposed workers divided according to the level of exposure (Table 2). The sub group of more exposed workers showed a higher tncldenc<a_of headaches and Table 2. Overvn Complai Headache Sleep disorder* GIT disorder! Vertigo Psychic disturber; Dysesthesia Palpitation* Total number of e gastrointestinal was observed e In persons witl ches was doubl more than 4 vpsychic disturb. Table 3. Overt". Complai: Headache Sleep disorders GIT disorders Vertigo Psychic disturbati Dysesthesia Palpitations Total number of e posed workers showed a sign, cent of more s= Graph 1 p: syndromes deteleslon of periph : 8.7 %). Diagn: or loss of tend:  > iaataaiiaF'r<B es). age time of as w;th >ups acthe tenten fred some gory of ire they ng and nmpresely low A more and N5 on was persons daches .'he In(palpin con- to vi- 6 .4 it exe subs and Table 2. Overview of subjective com] lalnts In workers occupationally exposed to vlnyl chloride, rela lon to the level of exposure Complaints Headache Sleep disorders GIT disorders Vertigo Psychic disturbation Dysesthesia Palpitations Total number of examinees To -al number 46 15.7 16 2.0 20 6.9 3 1.0 13 4.5 9 3.1 14 4.ft 293 100.0 More exposed number | % ' 19 7 n o 6 7 5 109 17.4 6.4 10.1 1.8 5.5 6.4 4.6 100.0 Less exposed number I % 14.7 S 4.9 9 4.9 1 0.5 1 3.8 n L*.- i.i 9 4.9 184 100.0 gastrointestinal disorders, and furth ermore, of dysesthesia of extremities. There was observed also a certain correlp tion with the length of exposure (Table 3). In persons with the exposure time longer than 4 years, the incidence of heada- ches was double the incidence in the group with a shorter time of exposed for more than 4 years. Sleep dlsorde4s gastrointestinal complaints, vertigo and psychic disturbances were also more frequent in those with a longer time of ex- Table 3. Overview of subjective coqiplalnts In workers occupationally exposed to vinyl chloride, relati on to the length of exposure Complaints Headache Sleep disorders GIT disorders Vertigo Psvchie disturbation Dvsesthesia Palpitations Total number of examinees Tot a] number O0' 46 15.7 16 5.5 20 6.9 3 1.0 13 4.5 9 3.1 14 4.8 293 100.0 Exposure longer than 4 years number j % 24 23.8 8 7.9 9 8.9 3 3.0 8 7.9 8 7.9 4 4.0 101 100.0 Exposure shorter than ` years number O10' n.o 8 4.2 11 5.7 0 0.0 5 2.6 i 0.5 10 5.2 192 100.0 posed workers is characterized In able 4. The group of more exposed workers showed a significantly lower per cent of normal findings and a higher per cent of more severe findings than he group of less exposed workers, Graph 1 presents incidence of the most frequent, objectively diagnosed syndromes detected In exposed ant control groups. The most'frequent was the lesion of peripheral neurons, either motor or sensory, or both of them (16.8 % : : 8.7 % J. Diagnosed were lmpalrmeits of muscle tonus or trophicity, reduction or loss of tendon and bone rellexes abnormal sensitivity. Compared to controls, 235 SPI-01345 *-f'* -V'v >"1 i> ? i'f *W.*niw. ..- '--Vs.W>">-h* r/i^~--- "V--^-NT^^*rrfcj ' '**- v. irr^. .,-.. ;--4w85 *ii I V. .- Table 4. Severity of objectively dlq,gnosed changes in workers occupationally exposed to vinyl chloride relation to the level of exposure Severity of changes Normal Light changes Manifest changes Total number of examinees Total nnmhii r | 165 37.0 112 38.0 16 5.0 293 100.0 More exposed number | '0 50 46.0 49 45.0 10 9.0 109 100.0 Less exposed number | % 115 63. <> 184 62.5 34.2 3.3 100.0 the group of exposed workers sfnwed also more frequently the symptomatology of peripheral neurovegetative disorders (12 % : 4.4 %], specifically acrohypothermy, acrohyperhldrosis or whitening of fingers, associated with dysesthesia. ''fc'-fci' -rr.'-r; diagnosed In VC bined with the abnormities. Re 45.5 % of cases' 201 y 0V` / io-| / / / / <L A \ n_ Uh el Gx Graph 1: Objectively diagnosed chi nges-in VC-exposed workers In a comparison to controls. X-axis -- objectively dlaj n osed changes: A -- peripheral neuron lesions, B -- peripheral neurovegetative sym ptomatology, C -- cerebellar symptomatology, D -- vestibular symptomatology, F -- ext apyramldal symptomatology, G -- disperse central symptomatology. Blank column -- gnoup of controls, hatched column -- group of VC- -exposed. Y-ax ts -- % of examinees Graph 2 shows objectively d: agnosed symptoms In relation to the level of exposure. A marked difference is In the Incidence of peripheral neuron lesions: more exposed workers are affect d more than twice as often (25.6 % : 11.8 %). Celebellar and vestibular syndrc me Is also more frequent (10%:7.S0/o and 6.4 /o : 3.3 %, respectively). There are also certain Indications of a correlation with the length of exposure, see Graph 3: those with more than 4 years of exposure have more frequently pe lpheral neuron lesions -(22.8 %: 13.6 %) and cerebellar impairments (13.9%: 5.7 /o). Frequency of the vestibulocerebellar syndrome is also higher (5 % : 0.5 %) In these persons. The results of EEG examlna ions of exposed and 81 non-exposed control workers are compared In Table 5 The per cent of abnormal EEG recordings In the group at exposed workers Is higher than In the control group; the EEG abnormities detected in the con|Ifrols were always least severe. Abnormities 236 < Graph 2: Objectlv; of exposure. X-ax. lower exposure )e a higher degree ferences were c only In 40 /o of wards beta and i The additlo: were used to i: Graph 3: Objective of exposure. X-a column -- expos than 4 SPI-01346 m 21-*SCA'' "'? l?vv:*: '' >*... `i-tfi ... - ^C-*- .^-. r; W -/. T'* ,~'.`7r'T~-' ' V-.i >;. .v ,r; - .^>.:r- .:.r>i!<iia-wahrfa i x-.wri*.'. -- r...-- nn---------11 r :'r r '' anamnestic data. The question laire N5 examines superficial personal traits as well as certain clinical symptfj'tnatology, particularly neurovegetative syndrome. neurasthenic, depressive an,d anxiety-phobic symptoms, and the so-called toxic syndrome. Data provided by this type of questionnaire were suggestive of and to our ow: maud's syndrom in terms of sts: lesions diagnos ed by a direct companying m; Table S. Severity of EEG changes In workers occupationally exposed to v.nvi chloride, in a comparison to controls . The narco: changes In the irreversible chr EEG changes Exposed amber CoutloU number ves in EEG re firmed in a rel Normal Suspect Abnormal Total slight medium total 148 48 30 6 36 232 63.8 20.T 12.9 2.6 13.3 100.0 31 19 3 0 3 81 70.4 23.4 6.2 0.0 6.2 100.0 nees as well s solvents (19, 21 more serious a cortical brain diffuse abnorm. ment with the This leads us t: cer.trations, ca a higher frequency of sleep diso rders (36 % ) than originally revealed by ana- structures. mnestlc data, highly frequent % level of significance) was also somnolence (76%|, which had not been alsp indicated in personal histories. More frequent VC-inducec manifest them.s were also feelings of bad perforrr ance, fear of loosing life or health. Furthermore, of changed hy -3 the frequency of hyperhidrosis i^ras also very high (73 %). The Eyseneck perso- authors on the nality questionnaire examines n urotlcism. It reveals subjective tendencies that with our find:.'. are evaluated by the examinee a(nd confronted with the objective reality. In the We also b- examined group there were no detected any significant deviations from the exposed works norm; increased neuroticism co u d not be demonstrated. damage. Comp: in persons exp. 3ISCUSSION # Clinical examination of VC exposed workers revealed significant changes predominantly in neurologic sy mhtoraatology. Some of the subjective complaints, s such as headaches, vertigo, sleep disorders or increased sleepiness during the 1) Exposu: ? day, as revealed by questionnaij-ie N5, are suggestive of the narcotic action of terature, also : 3 VC, similarly as the occurrence of the cerebellar and/or vestibulocerebellar these neurolog symptomatology. These changes have been, already described by Spinets and of exposure. colleagues (16), Langauer-Lewioi|vicka (11), but also by Schwartzovd (15) and 2) Some : nsll others. This characteristic symp omatology was also described in our previous tion of VC, su; ri ' studies concerned with the occ:ubatlonal exposure to trichloroethylene, benzene locerebellar sy and other organic solvents (17, 18, 20). Here we also observed a high Incidence of dysesthesia after exposures io some solvents, particularly to benzene. We ascribed It either to peripheral v isomotor changes, or -- at least in some cases 3) Among tion is, no dou -- to initial phases of polyneuro jathy. In case of VC the presence of peripheral binatlon with vasomotor changes Is evidently very significant: according_fo literature data motor changes 238 "p*' .'riv'W SPI-01348 alts as syndro m-called jstlve of chloride. 0.* 3.4 6.2 0.0 6.2 >0.0 by ananolence requent ermore, t persoies that - In the ti the :hanges plaints, ing the ition of rebellar :as and .5] and revious jenzene zldence ne. We s cases ipheral e data and to our own experience these changes are frequently associated with Ray naud's syndrome and may presun.ably lead to even more severe consequenctes In terms of stenosis or occlusion, as described by Lange (12). Peripheral nerve lesions diagnosed In our group of VC-exposed examinees could be then explain ed bv a direct neurotoilc action er VC, or as a consequence of hypoxia ac companying more severe vasomotbr changes In the periphery. The narcotic action of VC can be either transitory, inducing only reversible changes In the brain function, or persistent, causing more permanent, sometime Irreversible changes in the CNS. Slight functional changes manifest themselves In EEG recordings by waves typical for various stages of sleep, as con firmed in a relatively high per cant (46.5%) of cases in our group'clf exami nees as well as In some of the examined subjects exposed to other organic solvents (19, 21, 22). Detection of episodic or diffuse EEG abnormalities is rather more serious and may be indlca lve of chronic changes in mediobasal and/or cortical brain structures. In our group of examinees, the joint episodic and diffuse abnormality occurred in l|5.6 % of workers. This frequency is in agree ment with the cited literature dita as well as with our previous experience. This leads us to a conclusion that even VC, particularly at higher exposure con centrations, can produce neuro :lc changes in the above described brain structures. VC-tnduced pathophysiological changes are believed by some authors to manifest themselves by the cent al neurovegetative dysregulation, as a result of changed hypothalamus functions (2). This localization, presumed by these authors on the basis of their experimental studies, seems to be in agreement abnormalities. We also believe that even F> reaction changes, recorded in our group of exposed workers, may be of importance In the early diagnosis of VC-induced damage. Compvarable FS reaction :hanges were also described by Rouskovd (14) in persons exposed to other toxic agents. c c NCLUSIONS 1) Exposure to VC may lead, besides to other changes described in the 11terature, also to lesions of the nle rvous system. The onset and development of these neurologic changes depend on the VC exposure level and on the length of exposure. 2) Some of the neurologic ipanifestatlons are caused by the narcotic action of VC, such as certain subject:lve complaints and cerebellar and/or vestibulocerebellar syndrome. These sy;ihptoms can be transitory or persistent. 3) Among the impxortant mapifestatlons that are characteristic for VC action is, no doubt, the peripheral vasomotor symptomatology, sometimes in combination with the Raynaud's synjlrome described ln the literature. These vasomotor changes Ln the periphery may further develop, leading consequently to 239 ;v/` r ' ---t r n- . -Vi-- - -3:^.... i.r -it-- - . - * ------ - , , m,-w-- - ___ .jA more severe lesions of peri fheral blood vessels. Equally important are the ge neral neurovegetatlve manlf stations (gastrointestinal and cardiovascular disorders, byperhldrosis, etc. hat might result from the central neurovegetatlve dysregulatlon. Important are also symptoms of peripheral neuron lesions caused by a direct neurotoxic ac lon of VC or by hypoxia-related mechanisms, 4) Episodic abnormality n EEG recordings seems to agree with the assumed involvement of hypothalami!: structures (Basalajev and colleagues). It occurs even at exposure to the othe: types of organic solvents (15, 19, 2L 22) and may be indicative of a more diffijs e affliction of mediobasal and cortical structures of the brain. Less severe m.an ifestations of EEG sleep activity can be ascribed to the nacrotlc action of VC more pronounced sleep manifestations accompanied with abnormal EEG cha ges may be suggestive of more persistent changes in the CNS. 5) Neurological changes have not been so far sufficiently accentuated in the professional literature and, therefore, the monitoring of workers at risk is not conducted systematica :i y and by suitable methods. It is necessary to ensure a neurological preventic n in these occupationally exposed workers. Of the supplementary methods of elamination there are recommendable, both for prevention and research purposfe:s, to use EEG examination with photostimulation, questionnaires N5 and EOD. ; nd electromyographic examination. SUMMARY Neurological examinations were conducted in 293 workers occupationally exposed to vinyl chloride. Subjective co ipplalnts were evaluated on the background of N5 and EOD questionnare survey analyi is, EEG examinations, including photostimulation, were performed in 232 persons. The c jntrol group comprised 46 nonexposed subjects. Average time of exposure was 2.8 years the longest time of exposure was 8 years, Among the most frequent subjective complaints were headache, neurovegetatlve disorders and dysesthesiae, air ong objective findings dominated cerebellar and/or vestibulocerebellar syndrome e lions of peripheral neurons and peripheral neurovegetatlve symptomatology. Subjectl >e and objective symptoms were found to depend on the exposure level and the time if exposure. EEG examinations confirmed in 15.5 % of cases abnormities, predominantly eptsodie, sometlnmes combined with :he diffuse abnormality. 46.5 % of the exposed showed presence of sleep activity as a consequence of VC narcotic action. The episodic EEG activity could be ascribed to legions of mediobasal structures, or even to changes in brain cortex. Our data have confirmed that vinyl deride has a considerable Impact on the human nervous system. Most fiequent are lesions of vestibulocerebellar system and viglllty disorders due to VC nani otic action. Frequent occurrence of peripheral symptomatology can be explained by a dlrect neurotoxic action of VC, or as a consequence of hypoxia caused by peripheral vadomotor changes. As a rule, regular check-u jis of VC-exposed workers do not include systematic neurological examinations. The systematic neurologic prevention, based on the assessment of clinical, EEG and/or EMG examinations, should become obligatory. Supplementary use of NS and EOD q ulestlonnaire surveys is highly.advisable. 240 Stable v 4, V., V 11 . ehlornre de v Ua : pos4s au chic a l'aide des a ficatlf produ: l'exposinon s- Les trou: gdtatifs et d-tame vestlbu pfiriphfirique xique direct eyant lieu lor Des done sujets dmcr. (chez 15,5 0,o attelnte des Les suie:-, jour, aux exa dans ce cas, sues de l'EE Stable v4, V., V! rid exponiert Man bee Vlnylchlorid mit Hilfe de: Einwlrkung Expcsltion at Die bcu.' tome und-D;zerebellarsys ren vegetar/wohl als dir-: bel periphery In dem EE test, die die Aktivitat (be durch Affek1 gen erkia.-en Die Vtny glschen Stan SPI-01350 .. -"'2- -ff')'iT-'--l''~`'-'`~<--T-'j'.!.''-T - ^.atf are the geivascular disjrovegetative lesions causanlsms. the assumed s). It occurs 12} and may il structures be ascribed is accompaent changes accentuated kers at risk ssary to enkers. Of the oth for pre stimulation. ally exposed i of N5 and ilatlon. were s. Average rovegetatlve liar and/or neurovegedepend on tntly eptsosed showed ilsodic EEC changes in ct on the ystem and al synptoequence of systematic n the asy. Supple- RESUME S t ? b 1 o v 4, V., Lamb 1, V., Chumchal, C,, Kellerovi, V.. Paikov 4, v., v ! t o v c o v 4, J., 2 1 a b, L.: L'image nearologlqoe che: les sajets exposis au ehlorore de vinyls ii a 6t4 4tudl4 d'une mas il4re coctplexe 1'lmage Deuroiogique chez 293 sujets ex posis au chlcrure de vlnyle. iles troubles cubjectlfs ont 6:6 analyses au plan detains 4 1'alde des anquetes EOD et >15. II a 4te mis en evidence un effet neuroioxique slgnificatif produit par chlorure de vlnyle qui depend de la qualitS et de la quantite de 1'expositton suble. Les troubles subjectlfs retcoDtrds la plus souvant: maux de tete^yrnptOmes v4ggtatlfs et dvsesthesie. Les dt nnees objectives tetnolgnent pour une affection du systeme vestibuloc4r6belleux et sour celle du neurone periph4rique et de ['innervation p4riph6rlque vegetative. La sj mptOmatologie peripherique peut resulter de l'effet toxique direct produit par chlorure de vlnyle aussi bien que du mecanisme d'hypoxie ayant lieu lors des changemen s vasomoteurs periphenques. Oes donnes issues de I'EEG temoignant une activite de sommeil chez -16,5 % de sujets ddmontrent un effet n: rcotique du chlorure de vlnyle. L'activite episoaique [chez 15,5%) assoclde parfois 4 I'anomalie de diffusion pourrait s'expliquer par une atteinte des structures m4diotasales, me.me lies aux changements du cortex. Les sujets exposes 4 l'lnfltence du chlorure de vinyle ne se soumettent, jusqu'4 ce jour, aux examens systematlquiis au pian r.eurologique. II est ndcessaire de poursutvre, dans ce cas, une prophylaxie neurologique etudiant l'image climque, les donnSes is sues de l'EEG ou m6me de I'LMG. II est utile d'employer les anquetes EOD et N5. USA MM ENFASSUNG S t 9 b 1 o v 4, V., L a m b 1, V.. Chumchal. C.. Kellerovi, V., P a 5 k o v 4, V., V 11 o v c o v 4, V.( 1 a b, L.: Neurologisches Bild bei den detn Vinylcblorid exponierten Arbeitenden Man beobachtete kompiexefweise das neurologische Slid bel 293 Arbeitenden, die ubjektive Schwierigkelten analysierte man eingehender mlt Hllfe der EOD- und N 5-Fra|gebogen. Dabel hat man eine slgnifikante neurotoxische Einwlrkung von Vlnylchlorid lachgewiesen, die von der Intensitat und Dauer der Exposition abhBnglg 1st. Die bflufigsten subjektlven fchwierlgkeiten waren Kopfschmerzen vegetative Symptome und DysesthSsle. Der obj kttve Befund zeugt von der Affektion des Vestlbularzerebellarsystems, ferner von d r Affektion des peripheren Neurons und der peripheren vegetatlven Innervation. D periphere Symptomatology kann man erkliren so wohl als dlrekte Einwlrirung vo i Vlnylchlorid, als auch den hypoxlscben Mechanlsmus bel perlpheren vasomotorischen Veranderungen, In dem EEG-Befund stellte m m bei 46,5% Tiele der Gesamtheit die Schlafaktivltat test, die die narkotlscbe Einwl-kung von Vlnylchlorid dokumentlert. Die episodische Aktlvltat (bel 15,5%) manchmal In Verbindung mlt Dlffusionsabnormitat kdnnte man durch Affektion von mediobasalsn Strukturen, gegebenenfals- durch Kortexver&nderungen erkiaren. Die Vlnylchlorid exponlerted Arbeitenden werden bisher systematlscb vom neurologlscben Standpunkt nicht beobachtet. Die Verfasser halten die gezlelte neurologische n- 241 SPI-01351 -Ov Tiy. rpr r:"-` '- vre S j': - ' _.r ^ *' ' ,**,. - -u "-.frv *: ' . ''.,, . . - z'Zfm"Z'Zw; K-.;.' Jk - : -JL-r '. - rv/iiJ*--u. Vorbeugung in Verbindung mlt Beohach ung des kliaiscben Bildes, des EEC- eventuell auch des EMG-Befundes fQr norwendig. lehr geeignet ist die Anwendung der EOD- und N 5-Fragebogen. RESUMEN S t f b 1 o v i, V., L a m b 1, V.. C h u m c h a 1, O., K e 11 e r o v 4. V., P a 5 k o - v 4, V., V 11 o v c o v 4, V., 2 I 4 b, El cuadro nenrolbgico en trabajadores ex- puestos al vinilcloruro Se da examinado globalmente el cu idro neurolbglco en 293 trabajadores expuestos al vinilcioruro. Las dificultades sub) idvos se las aDahzb detalladamente mediante los cuestionarios EOD y N 5. Se mostrb el resultado neurotbxico marcado del vicilcloruro, el que dependla de la altura y dt. racibn de la exposicibn. Las dificultades subjetivas mbs frecuentes eran los dolores le la cabeza, los sintomas vegetativos asl que la dlsestesia. El hallazgo objetlvo muestr,a la afectecibn del ststema vestibulocerebelar, as! que la de la neurona vegetative peri'brica y de a inervacibn vegetativa perifbrica. La sintomatologfa perlfbrlca la pu ide explicar tanto por el efecto tbxico directo Bel vinilcloruro, como por el mecanismc hipbxico con los cambios vasomotbrlcos perifbricos. Se hallb en hallazgos electroencefal^ erblicos una actividad del sueiio en el 46,5 p. c. del conjunto, lo que prueba el res ".ado narcbtico de! vinilcloruro. La .actividad epizbdica (en el 15,5 p. c.), a veces en ; combinacibn con la anormidad difusa podrla se explicar por afectacibn de las estructijras mediobasales, eventualmente por cambios de la epidermis. Los trabajadores expuestos al vinllij! oruro no son aiin examinados neurolbgicamente de manera slstembilca. Hace (alia que se haya realizado neurolbgica prevencibn encaminada incluso el cuadro cllnlco, el l.allazgo electroencefalogrdfico, eventualmente el electromiografico. Se recomienda usar os cuestionarios EID y N 5. R E F E R E ,V C E S 1. Angulescu, F., OtoiQ, m., Dobronescn E.: Med. Int. 4, 1969, pp. 473--480. -- 2 Basalajev, A_ V., Vazin, A. N., Kocetkov A. G.: Gig. truda 2, 1972, pp. 24--27. -- 3, Byczkowska. Z., et al.: Pol. tyg. lekar. 29, 1974, 26, pp. 1461--1464. -- 4. Dlnman, B. ., Warren, A., Wbitehonse, W. M.: Arch. Environ. Hlth. 22, 1971, 1, pp. 61--73. -- 5. Dodson, V. N.t Bertram, D., Dinman, B. D., Whitebouse, W. M.: Arch. Environ. Hlth. 22. 1971, 1, pp. 53--91. -- 0. Engelsmann, F-: Cs. psychol. 3, 1960, pp. 322 -- 337. -- 7. Engelsmann, F., Drdkovd, S.: Cs. psychol. 4, 1964, pp. 340--348. -- 8. Engelxmann, F., Drdkovi. S.: Activ. nerv. sup. 2. 1959, pp. 108 -- 118. -- 9. Eysenck, H. J., Eysenck, S. G. B.: Manual of the Eysenck Personality Inventory. Univ. of London Press, London 24, 1964. -- 10. Harris, D. K., Adams, W. G. M.: Brit. Med. J. 16, 1967, pp. 712--714. -- 11. Langauer-Le- wowicka, H., Kurzbauer, H., Byczkowska, Z., Wocka-Marek, T.: Activ. nerv. sup. 21, 1974, 4, pp. 290. -- 12. Lange, C. E., Juhe, S., Stein, G., Veltman, C.: Int. Arch. Arbeitsmed'. 32, 1974, pp. 1--32. -- 13. Roth, B.: N'arkolepsie a hypersomnie z hlediska fysiologie spdnku. Praha, SZdN. 1957. -- 14. Ronsknvi, V.: Int. Arch. Ameitsmed. 34, 1975, pp. 283--299. -- 15. Schwartzovi, K.: Neurologlckb a EEG nblezv u chronickych prumyslovych otrav nfekterymi organickyml rozpouStSdly. Plzeftsky Ibk. sb. Suppl. 25, 1970, pp. 5--88. -- 16. Spirtas. 242 R., Me Michael, A. L M.: Am. led. Hvg. pp. 779--769. -- :: 16k. VII, 1955, 5. Stfblov*, V.: Acta U: 12, 1950, pp. 269--2' Cs. neurol. 25, 1953, Received Novetc 4gi ~r' -r-:.'-' -- SPI-01352 -arti-i 'r 7* " ^ i- 'V-'- ; C-t;.--'- ventuell IOD- und ?akoares ex- expuesaedtante vinilclodes sub- asl que acerebe/a perl- directo icos pe el 46.5 ctlvidad : podrla rambios oldgicavenclbn almente R_, Me Michael, A. L., Gamble, f., V an Ert, M.: Am. Ind. Hyg. Ass. J. 36, 1175, 10, pp. 779--769. -- 17. Stfblov4, V.: Prac. 16k. VII, 1955, 5, pp. 260-263. -- 18. Styblovi, V.: Acta Univ. Carol. Med. Suppl. 12, 1960, pp. 269--274. -- 19. Stjblt vi, V.: Cs. neurol. 26, 1963, p. 399. -- 20. Stfblo- v4, V.: Dlagnoza a prevence v prumvslov* neurologll. Praha, SZdN, 1968. -- 21. Stjb1ot4, V.: Int. Arch. Occup. Environ. Hlth. 38, 1977, pp. 263 -- 282. -- 22. Styblov4, V., Holanov4, V.: Prac. 16k. 25, 1973, pp. 30-- 98r Received November 10, 1980 V. St?blov4, Dept. Neurology, Medical Faculty of Hygiene, Charles University, Srob4rova^50, 100 42 Praha 10, Czechoslovakia London rria, O. J. 16. ner-Le* owska, up. 21, Juhe, :h. Ar. Roth, lediska 157. -- ed. 34. v4. K.: ironic- orgak. sb. pirtas. A. 243 SPI-01353 V* 1 ' -Jlw.v llsSiC'-r.-i.j~ r i-'Xf -- V *>'**. - erf.. it - V - 3="