Document MJ4G8k91yJ6VnZarLLVB882rj

papers. The concepts of central control of di^fcragm are well supported by the cJ^^^ports of Dr Korczyn. However, we preferred the other more accepted entity, viz, phrenic nerve palsy, to ex plain our findings. Balu h. Athreya, md Srinivas Prasad, MO Children^ Seashore House Atlantic City, NJ 1. Korczyn AO, Leibowitx U, Bruderm&n I; Involve ment of the diaphragm in hemiplegia. Neurology 19:97100, I960. 2. Korczyn AO: Respiratory and cardiac abnormalities in brain-stem ischaemia. J Neurol Neurosurg Psychiatry 38:187-190, 1975, Iron-Deficiency Pruritis To the Editor.--I read the article "Pruritus: A Manifestation of Iron Deficiency" (236:2319, 1976) and would like to draw attention to work on iron deficiency and generalized pruritus dating back to 1967. Then Sneddon and Garretts1 described the relationship between itching and iron deficiency. Also, in 1972 Rook, Wilkinson, and Ebling2 described this condition, and in 1974 I published a paper3 describ ing the relationship of iron deficiency to generalized pruritus in 87 patients. JMpuld entirely agree with your au^^s but would disagree that this condition has not been described. C. F. H. Vickers, MD, FRCP Liverpool Royal Infirmary University of Liverpool Liverpool, England 1. Sneddon IB, Garretts M: The significance of low se rum iron levels in the causation of itching. Proc 12th Int Congress Dermatol, Munich 2:1061-1063, 1967, 2. Rook A, Wilkinson D$, Ebling FJG; Textbook ofDer~ matology. Oxford, England, Blackwell Scientific Publica tions, ed 2, 1972. 3. Vickers CFH; Nutrition and the skin: Iron defi ciency in dermatology. Proceedings of Tenth Symposium on Advanced Medicine. London, Royal College of Physi cians, 1974, 311-315. infection and Total Joint Replacem nt To the Editor.--Total joint replace ment, particularly of the hip, is rapidly becoming one of the more commonly performed orthopaedic sur gical procedures. Deep infection, in volving the prosthetic devices and their anchoring acrylic cement, is the greatest threat to the success of these operations. We have observed, from our own experience and the reports of others, that a small but substantial proportioi^f the late postoperative infectio^^hat is, those becoming apparen^^^eral months to several years after surgery, can be attributed to he matogenous seeding of the prosthetic joint from distant primary sources of acute or chronic infection. Broad ly speaking, two categories seem to be involved: substantial bacteremia from infections of lung, kidney, skin, and other foci of acute infection, and surgical or dental manipulations, such as abdominal surgery, genitourinary procedures, and periodontal and exodontal surgery. We are taking this means to sug gest that all patients who have had total joint replacement, particularly those at high risk of infection (patients with rheumatoid arthritis, on continual corticosteroid dosage or immunosuppressive medication, and with debilitating diseases including malignant neoplasms) be promptly and vigorously treated with appropri ate antibiotics for any acute infec tious process of bacterial origin. We also suggest that they receive prophy lactic antibiotics before, during, and after any surgical or dental manipu lation that can produce a substantial bacteremia. Mark G. Lazansky, MD J. Phillip Nelson, MD Nas S. Eftekhar, MD Col John Feaoin, MC, USA J. Drennan Lowell, md Edward Miller, MD New YorK Late Effects of Botulinum Intoxication To the Editor.--After reading the ar ticle by Barker et al (237:456,1977) re garding the outbreak of bolulism and the subsequent management of the involved patients, we had occasion to examine their case 1 3% years after his intoxication. He was seen because of persistent fatigue, intermittent di plopia, and decreased sexual ability. Prior to the patient's botulism intoxi cation, he was physically and sexually active for his age; subsequent to this, although not incapacitating, these symptoms remain substantially dis tressing and have resulted in multiple consultations with different special ists. Barker et al reported good, immedi ate response to the trivalent botu lism antitoxin and further commented that all cases of intoxication returned to normal after a few weeks. Al though this is usually the case with botulism intoxication, we believe it is quite easy to overlook, at times, the subtle disturbances that may persist but are not incapacitating. Cherington1 notes, for example, that recovery may be prolonged but nearly total in all patients. Other authors2 have noted pathological fatigability in long-term survivors of botulism in toxication. Sexual dysfunction, al though uncommon, is also not a unique presentation.' We would like to emphasize that despite the fact that most patients subsequently do have a normal gen eral physical examination, important symptomatic complaints may persist, as noted in the aforementioned case and others. Joseph c. Maroon, md Presbyterian-Universlty Hospital David Bissonette University of Pittsburgh Pittsburgh 1. Cherington M: Botulism: Ten-year experience. Arch Neurol 30:432-437, 1974, 2. Rayn DW, Cherington M; Human type A botulism. JAMA 216:513-514, 1971, 3. Jenzer G, et al: Autonomic dysfunction in botulism B: A clinical report Neruol 25:156-153, 1975. Laryngeal Coccidioidomycosis To the Editor.-Platt (237:1234, 1977) is indeed correct that Coccidioides immitis is seldom recognized as a cause of pathogenic conditions of the upper respiratory tract. However, his asser tion that there are only two other published reports of coccidioidomyco sis of the upper respiratory tract, one of endolaryngeal and the other of epiglottic involvement, is erroneous. Oliver1 described a case of coccidioi domycosis in a 34-year-old man, in volving nose, left hand, left index fin ger, larynx, and epiglottis. Biopsy of cutaneous as well as laryngeal and epiglottic lesions was positive for C immitis. Jata S. Ghosh, MS Ardmore. Pa 1. Oliver EA: Coccidioidomycosis with cutaneous in volvement. AMA Arch Dermatol Syphilol 70:537-538, 1954. Considerations on Etiologic Factors in Meat Wrappers' Asthma To the Editor.-A recent letter (237:1826, 1977) reports interesting clinical and respiratory-function find ings in meat wrappers and a nonexposed control population. Irritative respiratory symptoms and the meat wrappers' asthma syn drome have generally been thought to be etiologically related to decomposi tion products of polyvinyl chloride (PVC), such as hydrochloric acid and/or minute amounts of phosgene, and not to PVC itself or to the mono mer vinyl chloride. The distinction is important to avoid confusion, especially since dif ferent mechanisms seem to be in volved. Ruth Lilis, MD Mount Sinai School of Medicine of the City University of New York New York JAMA, July 11, 1977 --Vol 238, No. 2 Letters 129 Thermoactivated Price-Label Fume Intolerance A Cause of Meat-Wrapper's Asthma Ruediger H. Andrasch, MO, Emil J. Bardana, Jr, MD REACTIVE airway disease has been reported to occur with increased fre quency among meat wrappers. Pro longed exposure to pyrolysates of polyvinyl chloride (PVC) soft-wrap films was initially implicated in the cause of this occupational disorder.1 Severe asthma developed in a meat cutter after repeated occupational ex posure to fumes of thermoactivated price-label adhesives. Report of a Case A 43-year-old man with a history of heavy cigarette smoking (45 cartons an nually) was employed as a meat cutter for 25 years. He was asymptomatic until 1968 when he noted recurrent episodes of chest tightness and productive cough. Initially, these attacks developed only at work and appeared to be closely related to exposure to fumes of PVC meat-wrap film gener ated when the PVC resin was cut by the hot wire of the meat-wrapping console. His symptoms intensified at the end of the work week, decreased on weekends, and were virtually absent during vacation. In mid-1973, he had a severe asthmatic attack at work and required hospitalization. His chest x-ray film showed moderate hyper inflation, and results of pulmonary func tion tests indicated mild restrictive and moderate obstructive disease with notice able improvement following isoproterenol hydrochloride inhalation. Intradermal skin testing detected no reactivity to a variety of allergens. See also pp 915 and 943. He was readmitted a year later with a similar attack. The patient was afebrile, his respirations were 28/min, and severe bronchospasm as well as sibilant and so norous rhonchi were noted bilaterally. The hemogram disclosed a hemoglobin value of 15.9 gm/100 ml, and white blood cell count of 9,000/cu mm, with a normal differential cell count except for 6% eosinophils. Spu tum and nasal smears were negative for eosinophils. There were bilateral inter- From the Division of Immunology and Allergy. University of Oregon Health Sciences Center. Portland. Reprint requests to University of Oregon Health Sciences Center, 3181 SW-Sam Jackson Park Rd, Portland. OR 97201 (Dr Bardana). stitial pulmonary infiltrates on chest roent genograms. Sputum cultures and bronchial washings obtained at bronchoscopy did not disclose a substantial number of patho gens. Immunologic evaluation included normal levels of immunoglobulins and third component of complement. A survey of the patient's work environ ment showed the presence of PVC fumes as well as thermoactivated price-label ad hesive fumes. The latter were generated when label adhesive was activated on the heating element of the label machine. Two weeks after the acute broncho spasm was controlled, a series of worksimulated inhalation provocation studies were initiated to assess the effects of fumes of PVC soft-wrap film and ther moactivated price-label adhesive on the pa tient's ventilatory capacity. Base-line studies at that time showed moderate re strictive and severe obstructive pulmonary disease. The forced vital capacity (FVC) was 72%; forced expiratory volume in one second (FEV,), 25%; forced expiratory flow (FEF),,*.,,*, 11%; and FEF,,^,,t, 27%, of predicted normal values. The Pao, was 60 fnm Hg, and white blood cell count was 9,000/cu mm, with 5% eosinophils. The to tal eosinophil count was 576/cu mm. Spu tum and nasal smears remained negative for eosinophil cells. The patient was challenged with PVC soft>wrap fumes operating a meat-wrapping console for three hours. Rhinorrhea, cough, and transient bronchospasm devel oped after 20 minutes of exposure, but im proved without treatment while the provo cation study was in progress. Immediately after the three-hour challenge and during the four-hour observation period, his pul monary function, arterial blood gases, and hematologic indexes were essentially un changed from prechallenge values. One month later, the patient was ex posed to thermoactivated price-label fumes for 15 minutes. The fumes were produced with an electric heating element at a tem perature of 106 C. After five minutes of ex posure, progressive dyspnea, increasing bronchospasm, paroxysmal cough, tachy cardia, diaphoresis, and extreme nervous ness developed. Exposure was discontinued after 15 minutes. His FVC and FEV, de creased to 36% and 31% of prechallenge values, respectively. The Pao, decreased from 80 to 43 mm Hg. Subcutaneous epi nephrine did not relieve his bronchospasm, which gradually remitted after four hours of treatment with intravenous aminophylline and isoproterenol (Isuprel) hydrochlo ride by inhalation. Approximately 12 hours following exposure, the patient had a de layed, but less severe, asthmatic reaction. Comment The major components of thermal decomposition of PVC soft-wrap film include phthalate plasticizers, hydro chloric acid, toluene, benzene, several hydrocarbons, CO,, and CO.1'5 Prelim inary inquiry into the composition of price-label adhesives indicated the presence of elastomers, thermoplastic co-polymers, sulfonamide stabilizers, and phthalate plasticizers. The sensi tizing substance, if any, of PVC and price-label fume intolerance has not yet been identified. Pulmonary func tion tests done on 17 meat wrappers before and after a work shift showed no substantial difference from 21 nor mal controls.4 The occupational history of our pa tient suggested a close relationship between his symptoms and exposure to meat-wrapping fumes. Our inhala tion provocation studies indicated that the recurrent episodes of severe asthmatic attacks, paroxysmal cough, and mucous membrane irritation were primarily related to the price-la-` bel fumes. Intolerance to fumes of heat-activated price-label adhesive in meat wrappers had not been iden tified prior to our initial report.5 His peripheral eosinophilia, transient noninfectious interstitial pulmonary in filtrates, and severe deterioration in ventilatory function following worksimulated inhalation provocation sug gests a hypersensitive reaction to one or more components of thermoacti vated price-label fumes. These studies were supported by grant RR-334 from the Clinical Research Centers Branch of Research Resources. References 1. Sokol WN, Aelony Y, Beall GN: Meat-wrap pers' asthma: A new syndrome? JAMA 226:639641, 1973. 2 O'Mara MM: High temperature pyrolysis of poly(vinyl chloride): Gaschromatographic-mass spectrometric analysis of the pyrolysis products from PVC resin and plastisols. J Polymer Sci 8:18g7-1899, 1970. 3. Takahashi T, Serizawa M: Pyrolysis of poly vinyl chloride. Plast Ind News 12:17-21, 1972. 4. Polakolf PL, Lapp NL, Reger R: Polyvinyl chloride pyrolysis products: A potential cause for respiratory impairment. Arch Environ Health 30:269-271, 1975. 5. Andrasch RH, Roster F, Lawson WH, et al: Meatwrappers' asthma: An appraisal of a new occupational syndrome. J Allergy Clin Immunol 55:130, 1975. JAMA, March 1, 1976-Vol 235, No 9 - Meat-Wrapper's Asthma--Andrasch & Bardana 937 o2966Q s^ Bilateral Renal Artery Reconstruction A Ten-Year Arteriographic Follow-up Richard H. Dean, MD; Henry Burko, MD; John H. Foster, MD RECENT reports have indicated that operative treatment of renovascular hypertension in patients over 50 years of age is not warranted because of high morbidity, high mortality, and poor response.*-2 This has not been our experience; of 162 patients with renovascular hypertension who underwent operative treatment, 70 were over 50 years of age and 56 (80%) of these were either cured or improved one year later.3 The overall operative mortality was 8.6%, but five of the six operative deaths occurred in patients who were simultaneously undergoing operative treatment for abdominal aortic aneurysm or for oc clusive disease. Only one death (1.9%) occurred in a patient in whom oper ative treatment was limited to the re nal arteries. We describe a patient with severe renovascular hypertension and bilat eral renal artery stenosis who was treated with bilateral aortorenal by pass grafts and who has had a tenyear serial arteriographic follow-up. Report of a Case A 52-year-old man was first admitted to the Vanderbilt Medical Center in October 1963. The duration of his hypertension was unknown, but it was first recorded two months before admission. He had had fre quent occipital headaches and was easily fatigued, symptoms referrable to hyper tension. He denied having vertigo, blur ring of vision, syncopal episodes, angina, or epistaxis. There was no history sugges tive of heart disease or peripheral vascular disease, but he had had a left-sided stroke two years previously. All antihypertensive medications had failed to control diastolic blood pressures ranging from 110 to 130 mm Hg. There was no known family his tory of hypertension. On admission, blood pressure was 205/ 110' mm Hg, supine, and 180/100 mm Hg, standing. Class 3 hypertensive retinopathy with hemorrhages and exudates was pres ent. Cardiac examination disclosed no ab normalities, and all peripheral arterial pulses were present and normal. There was no abdominal bruit Laboratory analysis disclosed the follow ing levels: serum creatinine, 1.17 mg/100 ml; total serum cholesterol, 346 mg/100 ml; and serum potassium, 5.2 mEq/liter. Uri nary protein excretion was 1.55 gm/24 hr. Urinary catecholamine levels and a rapid sequence intravenous pyelogram were nor mal. The radioisotope renogram made with iodohippuratc sodium I 131 (Hippuran I 131) showed bilateral disease. There was a prolonged functional segment and an ab normal excretory segment but a normal vascular segment. The Howard test of split renal function showed a decreased urine volume and increased creatinine concen tration on the right side. The preoperative transfemoral aortogram revealed bilateral proximal renal artery atherosclerotic ste- From the departments of surgery (Drs Dean and Foster) and radiology (Dr Burko) and the Specialized Center of Research in Hyperten sion, Vanderbilt University School of Medicine, Nashville, Tenn. Reprint requests to Department of Surgery, Vanderbilt University Hospital, .Nashville, TN 37232 (Dr Dean). 938 JAMA, March 1, 1976-Vol 235, No 9 Artery Reconstruction-Dean et al SL 029661 The prognostic paradox of subendocardial infarction needs explaining. Why should a limited area of myocardial damage be potentially more lethal than an area involving the entire thickness of the myocardium? A recent observa tion by Fuster et al2 may provide a clue to the answer. Having performed coronary angiography within one year of a coronary infarction in 73 patients with transmural and 63 with subendocardial infarction, these investigators cor related the presence of collateral vessels supplying the distal segment of the occluded artery with the occurrence of angina. Ninety-three percent of all patients with sub endocardial infarction had abundant collaterals; they also had angina. Collaterals were also frequent in 78% of the 32 patients with transmural infarction who had angina, but contrastingly they were evident in only 35% of the 28 patients who did not. Apparently, collateral circulation prevents necrosis but keeps alive an ischemic perinfarction zone. The latter favors development of angina and poten tially lethal ectopic beats. The greater frequency of col laterals in subendocardial infarction may thus account for its unfavorable prognosis. Samuel Vaisrub, MD Senior Editor 1. Levy WK, Cannon DS, Cohen LS: Prognosis of subendocardiol myocardiol infarction, abstracted. Circulation 52(suppl 2):107, 1975. 2. Fuster V, Frye RL, Danielson MA, et al: Collateral circulation after acute myocardial infarction: Protective or detrimental?, abstracted. Circu lation 52(suppl 2): 185, 1975. Neonatal Mortality As repeatedly noted in American Medical News from re ports provided by the National Center for Health Statistics, infant mortality in the United States has declined dra matically during the past three decades. Although the factors contributing to the improvement are not disclosed by the cold, overall statistics, analysis by states or by census tracts within states has suggested that low socioeconomic status of mothers contributes substantially to infant mortal ity risk.. The latter fact gives special meaning to a report by Lee and co-workers1 of experience at the Bronx Municipal Hos pital Center (BMHC), an affiliated teaching hospital of Albert Einstein College of Medicine. The hospital is rep resentative of the kind of US municipal institution that draws its patients predominantly from a population of low socioeconomic class. For purposes of comparison, the au thors analyzed neonatal mortality (birth through 28 days of life) during the years 1966 through 1973, with special attention to two periods--1966 through 1971 (period 1) and 1972 through 1973 (period 2). Important changes occurred at BMHC in 1970 with conversion of-the hospi tal's center for premature infants to a complete neonatal intensive care unit and initiation of an active abortion program. During the entire period there were no significant trends in number of deliveries and mean annual stillbirth rate. However, the incidence per 1,000 live births of infants weighing 2,500 gm or less (low birth-weight) was con sistently lower during period 2, and the frequency of live births of infants weighing 1,500 gm or less (very low birth-weight) declined sharply in 1973. Also, there was a significant reduction in mean neonatal mortality during 1972 and 1973. Throughout the study period, neonatal mortality correlated closely with the very low birth-weight. rate (P<.001). From these and other data, Lee et al concluded that 75% of reduction in neonatal mortality resulted from a decline in the proportion of very low birth-weight infants, while 25% of the reduction could be attributed to improved neonatal medical care, to improved health status of the infants at birth, or to both. The authors also concluded that comparison of neonatal death rates among different populations (infer also nations) "may lead to falsely reas suring or alarming conclusions, while rarely pinpointing the critical determinant variables." For some years, proponents of drastic changes in the method of financing health and medical care in the United States have often used comparisons of neonatal mortality reports in our nation with those in other countries, for example, Sweden, where nationalized health insurance pre vails. The fallacies of such comparisons have been recorded repeatedly by spokesmen for the American Medical Asso ciation and by other careful observers of available data. As Lee et al have shown for a single hospital and as Geijerstam2 had earlier confirmed, the difference in neonatal mor talities for the two nations could be explained primarily by differences in birth-weight distributions in the two pop ulations. In any event, however one studies the data about neo natal mortality in the United States--whether by analyzing socioeconomic factors, infant birth weights, variations in ages of childbearing women, availability of abortion and satisfactory means of contraception, or some, or all, or more---comparison with facts about Sweden or a similar nation will vary like statistical mixtures of oranges and apples. Perhaps orange juice and applesauce would be more apt as a simile. Hugh II. Hussey, MD 1. Lee K-s, Tseng P-I, Eidelman Al, et al: Determinants of the neonatal mortality. Am J Dis Child, to be published. 2. Geiierstam G: Low birth weight and perinatal mortality. Public Health Rep 84:939-948, 1969. 944 JAMA, March 1, 1976--Vol 235, No 9 SL 2966" Editorials editorials Meat-Wrapper's Respiratory Tract Disease In 1973, Sokol et al1 reported three instances of respiratory symptoms (dyspnea, cough, wheezing) occurring in women exposed to fumes produced when the polymer, polyvinyl chloride, was cut with a hot wire during the course of their work as meat wrappers in supermarkets. Although all three patients were cigarette smokers and had been employed for years in the same line of work, they had no respiratory symptoms prior to introduction of the polymer as the meat wrapping material. All patients had evidence of airway obstruction, reversible or preventable by stopping work or by inhaling bronchodilating drugs. The authors speculated that they were describing a new syndrome, which they named meat-wrapper's asthma; however, historical evidence suggested that the syndrome was not new but simply not reported previously. In this issue of The Journal, Andrasch and Bardana (p 937) report the case of a meat cutter who was exposed to both the fumes of polyvinyl chloride and the fumes from thermoactivated price-label adhesive. Symptoms of respira tory-tract irritation were intensified at the end of the work week, decreased on weekends, and were virtually absent during vacation. On one occasion, his symptoms at work culminated in a severe asthmatic attack that led to hospital ization. Results of pulmonary function tests indicated mild restrictive and moderate obstructive disease, with improve ment following isoproterenol hydrochloride inhalation. There were transient bilateral interstitial pulmonary infil trates on chest roentgenograms. Two weeks after the asthma had been controlled, the patient was exposed to polyvinyl chloride fumes, and one month after that exposure, he was challenged with thermoactivated price-label adhesive fumes. On the first occasion, rhinorrhea, cough, and transient bronchospasm developed after 20 minutes of exposure but improved without treat ment while the provocation study progressed for a total of three hours. In contrast, exposure to thermoactivated price-label adhesive fumes soon evoked progressive dysp nea, increasing bronchospasm, cough, and tachycardia to the extent that the provocation study was terminated after 15 minutes. One must suppose that, although the patient was possibly sensitive to polyvinyl chloride fumes, the ma jor cause of his respiratory tract symptoms lay with fumes from thermoactivated price-label adhesive. In a companion article (p 915), Falk and Portnoy were stimulated by reports of two cases of meat-wrapper's asthma to conduct a more thorough assay of the prevalence of the syndrome among meat wrappers in the Houston area. A questionnaire was delivered to a large number of meat wrappers and to control persons, namely, super market grocery checkers and meat cutters. About 10% of the meat wrappers exposed to polyvinyl chloride fumes had multiple, rather severe respiratory tract symptoms (wheezing, dyspnea, chest pain or tightness), and a con siderably larger number had lesser respiratory tract symp toms. Falk and Portnoy concluded that the spectrum of symptoms is too broad to merit the exclusive designation, "meat wrapper's asthma." Rather, a substitute term such as "meat wrapper's respiratory tract disease" seems more appropriate. Prevention of an illness that has proved to be surprising ly prevalent might include the installation of proper ven tilating equipment and use of lower-temperature cutting wires. However, Falk and Portnoy emphasize that the best solution to the problem would be to use mechanical-blade cutting machines that do not create fumes. Hugh H. Hussey, MD 1. Sokol WN, Aelony Y, Beall GN-. Meat-wrapper's asthma: A new syndrome? JAMA 226:639-641, 1973. Subendocardial Infarction: A Prognostic Paradox The absence of Q waves coupled with the presence of de pressed rather than elevated ST segments, characteristic of the "current of injury," used to convey a modicum of re assurance. True, the patient suffered an acute myocardial infarction, but it was after all only subendocardial, not transmural. The extent of the damage was limited, and the associated clinical manifestations and complications were less severe than in infarcts involving the entire thickness of the myocardial wall. Although still reassuring with regard to short-range com plications of shock and congestive heart failure, the longrange prognosis of subacute myocardial infarction--Levy et al1 inform us--is anything but heartening. Comparing data on 119 patients at a mean follow-up period of 36 months with corresponding data on 36 patients whose in farcts were subendocardial, these investigators found that the latter group had a higher (33% vs 15%) incidence of sudden death from other cardiac causes. Survivors of sub endocardial infarction also had a higher (61% vs 35%) rate of angina and of recurrent infarction (26% vs 12%). In view of this unexpected malignant course of what previously appeared to be the lesser evil, Levy et al recom mend coronary arteriography and serious consideration of coronary bypass surgery for patients with subendocardial infarction. . Address editorial communications to the Editor, 535 N Oearborn St, Chicago 60610 JAMA, March 1, 1976--Vol 235, No SL 029663 Editorials 943 Polyvinyl Chloride Toxicity in Fires Hydrogen Chloride Toxicity in Fire Fighters Robert F. Dyer, MD, Victor H. Esch, MD Polyvinyl.chloride, of all the plastic polymers, has been implicated pri marily in causing the most serious problem in fire fighting today because it releases hydrogen chloride gas when burning. One hundred seventy fire fighters who experienced symptoms from its toxicity have been studied from 1970 to 1975. One died. (JAMA 235:393-397, 1976) A RECENTLY identified hazard that is of paramount importance to prac ticing physicians is that of chemical injury incurred by persons exposed to fumes from fires. Specifically, such in juries are caused by the inhalation of vapors created by the thermal degra dation of polyvinyl chloride, a plastic polymer. Such substances have now become widely used in the construc- See also p 390. tion of homes, furnishings, office equipment, electric wire, telephone and cable covering, and vehicles. A particular hazard exists in the case of the fire fighter, although it could be equally serious in any circumstance in which an individual might be exposed to such plastic combustion products, THE FIRE . At 10:30 am on Jan 6,1970, an alarm sounded for a fire reported to be on the sixth floor of Building 213 at the Washington, DC, Navy Yard. Units of the District of Columbia Fire De partment arriving on the scene found the floor filled with a heavy concen tration of toxic fumes. Although all of the fire fighters carried masks, none were used, since neither the fire nor From the Police and Firemens Clinic, Wash ington. DC. Reprint requests to Chairman ot the Board of Surgeons. Suite 1445. dhevy Chase Bldg, 5S30 Wisconsin Ave, NW. Washington. DC 20015 (Dr Dyer). the smoke was so excessive as to pre vent entry without masks. The fire, which was confined to an office copy ing machine constructed of plastic and Teflon parts, was quickly extin guished. The fire companies entered the building via the elevator, placed sev eral portable fans for ventilation, and left the building about 20 minutes later. On returning to their quarters, many of the fire fighters experienced unusual and unexplainable symp toms, including a constricting tight ness localized to the anterior part of the chest. This chest discomfort was described as a searing, burning sensa tion accompanied by dyspnea as well as a "burning sensation appearing to close off the throat." These symptoms were in addition to the usual head ache, dizziness or vertigo, and nausea, which, in our experience, is fre quently seen in cases of nonchemical smoke inhalation. Some symptoms persisted over a course of several days following exposure to the fumes. The dyspnea was noted on mild exer tion and was associated with moder ate apprehension by all of the af fected fire fighters. A number of the fire fighters exposed at this fire expe rienced severe conjunctivitis, lacrimation, and dyspnea persisting for 24 hours after the fire. An intense head ache, localized anteriorly and persist ing about 24 hours, was also common. REPORT OF.A CASE. Approximately 24 hours after the fire, a 33-year-old fire fighter fainted in the sit ting room of the truck company. If was also reported that he had a muscle spasm similar to an epileptic seizure, but recov ered, was fully conscious, and got up im mediately. His superior officer asked how he felt, and he replied that he was "fine" and walked into the kitchen. Following lunch, the acting sergeant on duty looked for the man to check his condition for driv ing and found him lying on the floor next to his bed. He was cyanotic and, despite all resuscitative efforts by an-ambulance crew and the rescue squad, was pronounced dead on arrival by a fire surgeon at the George Washington University Hospital at 1:10 pm. Postmortem examination by the District of Columbia Department of Public Health Medical Examiner showed severe pulmonary hemorrhage and edema due to chemical pneumonitis secondary to expo sure to chemical smoke and fire. The pathologist also reported coronary atherosclerosis. EFFECT OF FUMES It has been suspected for several years that the smoke and fumes from electrical fires produced greater in jury now than similar fires in the past.12 It was strongly suspected that hydrogen chloride released by ther mal degradation of PVC, a common electrical wiring insulation material, was the lethal product causing death in this instance. The medical exam iner's report and the microscopic findings subsequently confirmed our original clinical impression of the cause of death. Hydrogen chloride, inhaled either _ in the gaseous state or combined with water vapor, acts as an irritant to the mucous membranes of the eyes and JAMA, Jan 26, 1976-Vol 235, No 4 - Polyvinyl Chloride--Dyer & Esch 393 ST 0296&4 Fig 1 .--Hydrogen chloride concentration and optical density of polyvinyl chloride electri cal insulation decomposition products. the respiratory tract. An HC1 concen tration of 15 ppm causes localized irritation to the throat after short ex posure. Hydrogen chloride concentra tions of 50 to 100 ppm are tolerable for one hour by humans. More severe exposures result in pulmonary edema and often in laryngeal spasm. Con centrations of 1,000 to 2,000 ppm of HC1 are dangerous even with brief exposure3 (Fig 1). Quantitative release of HC1 on thermal degradation of PVC has been well documented in the scientific and medical literature. Polyvinyl chloride, of all the synthetic plastic polymers, has been implicated as causing one of the most insidious, serious problems in fire fighting today, due to its re lease of HC1 gas while burning. Mists of hydrochloric acid are considered less harmful than anhydrous HC1 be cause the droplets have no hydrating action. Animal Experiments The toxicity of PVC has been sub stantiated by Kishitani^ in his com prehensive animal experiments per formed at the University of Tokyo. With respect to the toxicity of carbon monoxide, Kishitani states that the injurious nature of PVC is unique. All mice exposed to harmful gas products died, but the carboxyhemoglobin con centration in the dead animals was low (average, 21.2%). This clearly in dicated that the fatalities were not due directly to CO poisoning. At au topsy, the eyes of the mice were closed, their mucous membranes were injured by chemicals, and the sclerae were discolored. The latter had be come white due to the action of chlo rine gas. All of the mice died in a pe riod of 15 minutes after exposure to PVC fumes. Electrocardiographic ab normalities appeared prior to gener ation of large quantities of smoke. This indicated that a 'harmful gas produced at an early stage was caus ing the effect. Similar results were found on exposure, to polyurethane gas. Kishitani concluded that the in jurious properties of burning mate rials such as wood, fire retardant ply wood, melamine finishing board, and acrylic resin are due to CO. In the fatalities due to CO, the average concentration of CO was 45%. The burning of cellulose mate rial resulted in nothing but the re lease of CO. In the mouse study with exposure to burning building mate rials, the ECG abnormalities were recorded before the smoke from the burning materials was evident. In regard to the harmful properties of PVC to mice, as well as those from polyurethane, polysterene, and phe nol, the pathologic effects of the gases, rather than those of the smoke, appeared first, as shown by atypical ECG changes. It requires less CO in combination with HC1 to cause death. In conclusion, HC1 and CO have a re ciprocal, potentiating adverse effect. EFFECT OF SMOKE Smoke is a suspension of small par ticles in hot air and gases. It has a particulate fraction and a gaseous fraction. The particles consist of car bon and are coated with combustible products such as organic acids and al dehydes. The gaseous fraction has an extremely variable composition. Car bon monoxide and carbon dioxide are always present and constitute the bulk of this fraction. However, a wide variety of other toxic gases are present at the scene of a fire. These may be formed by the combustion process or leak from com mercial processing or storage equip ment. The particulate and gaseous fractions combine to exert a large space-occupying effect and can fill an enclosed space at the expense of air. The gaseous fraction of smoke is much more dangerous to life than the particulate fraction. The nose, mouth, and throat, which filter out and trap the particulate fraction, cannot filter out the toxic gases. These gases enter the upper respiratory tract and lungs freely when inhaled. Damage to the lungs may result from exposure to a group of gases and vapors called pul monary irritants (chlorine, phosgene, nitrogen dioxide, sulfur dioxide, and ammonia). On entering the lungs, these- agents react chemically with water to produce strong acids or al kalis. A violent inflammatory re sponse occurs, causing destruction of lung tissue. Fire fighters and victims of fires iti homes, offices, and industrial com plexes are exposed to smoldering and 394 JAMA, Jan 26, 1976-Vol 235, No 4 Polyvinyl Chloride--Dyer & Esch sL 029665 burning plastics and synthetics from furniture, floor and wallcoverings, textiles, and building materials. Many plastics produce large volumes of pulmonary-irritant gases when burned. Polyvinyl chloride is used ex tensively in furniture, both in the foamed plastic stuffing as well as the covering. Burning 450 gm of this ma terial produces 320 gm of chlorine, phosgene, and HC1, all of which are strong pulmonary irritants. In all, there are 75 known products of PVC degradation. Practically every struc ture today contains plastics capable of producing lung-damaging gases when burned. Therefore, the fire fighter faces a great, new risk in al most any fire. It became obvious that a particular pattern was emerging in which cer tain fire situations were productive of insidious and unpredictable fire casu alties. The lethal chemical smoke was determined to be HC1 resulting from the decomposition of PVC plastic used in telephone cable and electrical equipment installations. We have found electrical and tele phone cable fires to be especially haz ardous to the fire fighters, due to the toxic gases produced. We have found that when a short circuit developed in a main switch, usually located in a sub-basement or penthouse of an of fice building or apartment house, the area was always poorly ventilated, and the plastic-covered switches quickly heat to temperatures in ex cess of 93.3 C. The heated conductors cause the plastic insulation to decom pose and emit white, mist-like HC1 fumes that resemble steam. When the temperature range of 232 to 321 C is attained, the gas may be invisible. The fire fighter may be fatally de ceived if he does not know plastic-cov ered cable is involved in the fire he is fighting. OVERHAUL PHASE The period of time just after the fire is extinguished is termed the "overhaul phase." This is when the fire fighters clean up the foreground. Toxic smoke and fumes are still being emitted. This is a serious time for toxic gas inhalation to occur since many fire fighters remove their selfcontained breathing apparatus dur ing this phase. Another special hazard during this phase is the "heat sink," ie, concrete that retains a great amount of heat and releases fumes throughout the overhaul phase. Our testing has shown highly toxic con centrations of HC1 in this concrete for as long as one hour after the fire has been extinguished. FUEL LOADING In the late 1960s, the type of "fuel loading" in office and high-rise build ings (ie, contents of the buildings) changed significantly and initiated a new awareness. The noncombustible buildings were not burning, but fur niture within them, building insula tion, ceiling tile, wall paneling, and decorations made partly or wholly of plastic were fueling disasters. While a building may be con structed of fire-resistant elements, there is no control over the combus tible material that an individual may elect to bring into the structure. This is the "fuel load" and may be ex pressed as kilograms of combustible material per square meter of floor area. Large differences exist in com bustibility, smoke, and toxic gas re lease among different combustible materials. More than 50 sq m of red oak, all burning at its maximum rate, would be required to produce the same rate of smoke as 2.5 meters of acrylonitrile-butadiene-styrene plas tic pipe. A fire of plastic materials de velops extremely high temperatures because plastics possess a heat of combustion 2xk times that of other combustibles. Therefore, the fire would magnify the normal problems of radiant heat, structural damage, and exposure. The fire would exhibit a very high burning rate because the flammability of plastics is much higher than that of other combus tibles. The four most common plastics pro duced in the United States in the past few years are polystyrene, polyethyl ene, polypropylene, and PVC. A chlorethylene polymer is a plastic solid marketed under a variety of trade names, and currently being manufac tured at a rate over 8.3 billion kilo grams annually. Polyvinyl chloride (Pig 2) is a plas tic solid widely used as a rubber sub stitute and as electric and telephone wire and cable covering. It is also uti lized frequently in electrical fixtures, plastic drains, as well as waste pipe Fig 2.--Polyvinyl chloride. for interior plumbing, pliable thin sheeting, film finishes for textiles, "noninflammable" upholstery, rain coats, tubing, belting, gaskets, shoe soles, disposable unbreakable plastic bottles, packaging materials, auto mobile and aircraft seatcovers, cor rugated fence toppings, tarpaulins, shower curtains, phonograph records, plastic trays, baby pants, toys, cur tains, and office copying-machines. It is used as an exterior finish in many vehicles, including buses and subway cars, because of its high resistance to wear and soiling. When PVC is heated to 225 C, noth ing happens. When heated above that, up to 475 C, PVC does not burn. The combustion range or flame point is 475 C. Between 225 C and 475 C, PVC loses over 60% of its weight. During this process, it thermally de grades and HC1 is released. Four hun dred fifty-three grams of PVC at deg radation releases 320 gm of chlorine, phosgene, and HC1. The individual toxicity factors of phosgene and the other major decom position products of PVC, ie, benzene, toluene, total xylenes, naphthalene, and vinyl chloride, are very small, compared with the toxicity factor of HC1. Further, the total or additive toxicity factors of these minor compo nents are also very small in compari son with HC1 toxicity. Unfortunately, very little is known about the syner gistic effects of toxic gases (ie, the ability of one chemical to increase or decrease the toxicity of another). The main toxic risks from the decomposi tion products of PVC are HC1 and CO.5 Stone et als elucidated the nature of smoke aerosol and its role in the transport of toxic gases in fire situ ations. They confirmed the fact that the toxic gas, HC1, is adsorbed on soot aerosol. Possible inhalation hazards of such soot are positively related to the size of the soot particles and particle agglomerates. It has been shown that JAMA Jan 26, 1976-Vol 235, No 4 Polyvinyl Chloride--Oyer & Esch 395 SL 029666 the amount and location of particle deposition in the respiratory tract de pends on the particle size.6 On inhala tion, soot aerosols would enter the lower lung region and, to an extent, be retained there. Soot particle clus ters, with sizes ranging from O.lji to 2.5ji in diameter, would be retained in the alveolar sacs to an extent of from 20% to 40% of those particles inhaled.6 At a breathing rate of 18 liters/min for an exposure of one hour, a max imum of 0.7 gm of soot bearing 13 mg of loosely bound HC1 would be re tained in the lower lungs. The effect of HC1 in the gas phase is largely limited to irritability, mainly affecting the upper respira tory tract, whereas loosely bound HC1 condensed on soot aerosol gains ac cess to the lower lungs. Experiments have shown that water droplets of respirable size rapidly adsorb HC1 from the gas phase and approach equilibrium concentrations in frac tions of a second.7 SMOKE INHALATION Respiratory distress may develop in fire fighters or fire victims immedi ately or within one to two days of ex posure to combustion products. The best protection against these agents is the mandatory use of the self-con tained breathing apparatus by every fire fighter. When anyone without a breathing apparatus is exposed to more than a few breaths of "choking smoke'' characteristic of burning or smoldering plastics, he should receive prompt medical attention. Prior to our investigation, we con sidered most foreground pulmonary casualties to be due to "smoke inhala tion" or CO poisoning. Carbon mon oxide had long been considered the leading cause of death and pulmonary morbidity in fires. Though CO is not noxious and does not actually cause serious pulmonary injury, the amount of CO in a patient is a good indicator of whether more harmful gases are present. Before the introduction of massive fire loads of combustible and ther mally decomposable plastic products, fire surgeons usually considered the CO victim to be "home safe" in four hours after exposure due to the fast half-life of CO in the blood. After ex posure to plastic degradation prod ucts, a period of one to six hours elapses between exposure and onset of severe respiratory and chest symp toms. Treatment is most effective if given during this quiescent phase. Once the symptoms of difficult breathing, cyanosis, or other symp toms, as noted in the reported case, have appeared, it may be too late to prevent severe morbidity or even mortality. The "overhaul phase" after the fire is extinguished is dangerous with respect to fumes also. A Harvard research team headed by Donald P. Dressier, MD, reported in 1973 that when burned, plastics and modern fibers produced colorless, odorless fumes that quickly displace oxygen and cause a dramatic rise in the C02 level of the atmosphere/ Therefore, a person either dies or is rendered unconscious in the early stages of a fire involving these mate rials. If he is unconscious, he soon dies of other lethal fume inhalations/ Tests performed in Cambridge, Mass, showed that fire fighters were proba bly affected adversely by the high level of COj rather than by the initial release of toxic gases/ In establishing the importance of detecting the presence of certain toxic gases, the difficulty in detecting CO has been emphasized.8 Some hu man response mechanisms are more sensitive than others to CO inhala tion/ Fairly high levels of CO affect a human's vision, but even higher levels do not affect his sense of timing. A re search team headed by R. A. McFar land, MD, of Harvard University, found that when CO replaces 11% to 17% of the blood's normal oxygen, the peripheral vision is affected and the subject has difficulty viewing stimuli at a 20 angle from the line of sight/ The Harvard team also found that at a 17% concentration of COHb, some subjects had a momentary lapse of at tention and failed to respond to all the stimuli presented. This is impor tant in disproving the once-held con cept that once an individual has de tected the sharp odor of. HC1 he can walk away. It has been our observa tion that the fire fighter cannot es cape the HC1 fumes. Cornish and Abar reported that CO and hydrochloric acid were the major toxic products from the combustion of PVC.` They pyrolized PVC polymers in a stream of air by gradually in creasing the temperature from am bient to 600 C. Exposure to this air stream supplemented with oxygen produced pulmonary and interstitial edema in rats. Some of these animals also showed focal bronchial and intraalveolar hemorrhage. In a sealed environment (such as a centrally air-conditioned house, of fice, high-rise unit, or hospital), fumes from plastic degradation could kill, even if the fire is brought under con trol. It has been observed that a sleeping person needs an estimated 12 to 15 minutes to awaken, react to danger, and take appropriate action to save himself. With inhalation of fumes from burning plastic, he will not have that much time. ' COHb LEVEL AND CIRCULATION As noted by E.P. Radford (writ ten communication), 43 deaths due to fire demonstrated that a blood COHb level of over 65% is nearly always lethal due to the depression of res piration and circulation. Ventricular fibrillation from acute myocardial hy poxia induced by a rapid rise of the COHb level in individuals with a restricted coronary circulation was found to be the likely explanation of a lower terminal blood COHb level. These individuals were found to have severe, preexisting coronary vascular disease. We believe that any compromise of the coronary circulation, eg, ath erosclerosis such as found in the fatal case, would be potentiated by highly irritating chemical fumes. We also believe that other pyrolysis products, especially HC1, have contributed to ventricular fibrillation since its con centration is comparable to that of CO in real fire situations involving plastics. Kishitani has demonstrated that chlorine affects the myocardium more rapidly and more severely than CO. Carbon monoxide may cause changes in enzyme activities suggestive of myocardial damage. Hydrogen chlo ride has been found to be a more po tent myocardial irritant whose ef fects may be difficult to determine by clinical observation. This is in con junction with the development of pul monary edema over a 24-hour period following exposure to HC1. This fur ther complicates and compromises coronary artery oxygen saturation. This could lead to sudden death syn- 396 JAMA. Jan 2g, 1976-Vol 235, No 4 Polyvinyl Chloride--Dyer & Esch SL 029667 drome, similar to that in the reported case. Although in the cases of CO poi soning noted by G- Gordon, (written communication) the ECG changes did appear late if at all and the COHb varied in individuals at the same fire as well as in different fire situations, it has been our experience that all fire fighters exposed to PVC do mani fest ECG signs of its toxicity. There are variable levels of its toxic effect on the lungs, mucous membranes (tra cheal peeling effect), eyes, and other parts of the body. CLINICAL STUDY In Washington, DC, a clinical study of fire fighters suspected and later known to have been exposed to toxic products from thermal degradation of PVC was conducted by the DC Board of Police and Fire Surgeons between January 1970 and September 1975. One hundred seventy individuals were exposed from one to four differ ent times to these products and re ported two or all of the symptoms of acute toxicity, ie, pain in the anterior aspect of the chest, neck and throat pain, dyspnea, severe headache, dizzi ness, and irregular pulse within a few hours after exposure. Initial physical examinations were performed by the fire surgeon on the fireground, in the hospital emergency room, or at the Police and Firemens Clinic. Laboratory studies including complete blood cell count, determina tions of serum glutamic oxaloacetic transaminase, blood urea nitrogen, or creatinine, and a complete urinalysis were done. Electrocardiograms were performed initially when there was chest pain, extrasystoles, or cardiac arrhythmia. However, ECG studies were not incorporated as part of the physical evaluation until the latter part of the study when their impor tance was appreciated. About one fifth of the fire fighters had extrasystoles during the first few hours after exposure. Fourteen of the 1. Lowery R: Injury Control at Heavy Service Electrical Fires, safety bulletin. City of New York Fire Dept, September 1969. 2. Lee 1: Smoke Analysis of Specimens Sub mitted by Fire Marshal Clark of Prince Georges County, Maryland, US Dept of Commerce, Sept 25, 1969. 3. Sax NI: Dangerous-Properties of Industrial Materials, ed 3. New York, D Van Nostrand Co Inc, 1968, p 883. '~ 4. Kishitani K: Study on injurious properties last 26 firemen exposed had prema ture ventricular contractions. Some have had recurrence of extrasystoles within the subsequent year. Chest xray films were done at. the initial examination and have remained nor mal. Serum electrolyte and arterial blood gas determinations were per formed on 12 of the fire fighters who were more acutely ill, or required hos pitalization. Because of the excellent clinic facilities provided by the Dis trict of Columbia government, all fire fighters were observed in a holding area after exposure and examined at the clinic or the hospital emergency room after transportation from the fireground. Twelve men were ad mitted to the hospital for treatment. If symptoms did not worsen over the first 24 hours in the hospital, they were released and followed up on an outpatient basis at the clinic. Specific treatment, including oxy gen given intranasally at 5 liters/ min, bronchodilators, antihistamines, and decongestants in oral suspension, has been utilized in controlling most of the acute respiratory symptoms. Steroids were given intravenously to three of the fire fighters during hospi talization due to the severity of their signs and symptoms of respiratory distress. Initial and follow-up liver function tests have remained normal in all of these patients. There has been no di rect correlation between severity of symptoms and history of cigarette smoking. None of the fire fighters has had to retire for permanent airway dis orders. Serial studies and follow-up examinations will continue. Since the onset of this study among profes sional fire fighters, the use of the selfcontained breathing apparatus has been required at all fires where toxic fumes could be present. This is neces sary during the "overhaul phase" also. We urge all physicians to advo cate restriction of unsupervised use References of combustive products of building materials at the initial stage of fire. J Faculty ofEngineering University Tokyo (B) 31:1-35 (No. 1) 1971, 5. Woolley Wl): Decomposition products of PVC for studies of fires. Br Polymer J 3:186-193, 1971. 6. Stone JP, Hazlett RN, Johnson JE, et al: The transport of hydrogen chloride by soot from burning polyvinyl chloride. J Fire Flammability 4:42-51, 1973. 7. Stone JP: Transport of hydrogen chloride of PVC products. Fire research activ ity should be maintained at a na tional level to continue study as well as preventive measures for HC1 tox icity in PVC fires. CONCLUSIONS Hazards of Plastic Fires.--Respira tory distress may develop in fire fighters and fire victims after expo sure to combustion products. The complexity of the problem is empha sized when it is recognized that the thermal degradation of PVC results in the formation of at least 75 identi fiable potentially toxic compounds. Three characteristics of plastic fires are the extremely high temperatures, very high burning rates, and thick toxic smoke. The main danger to ex posed fire fighting personnel at the fireground results from the massive formation of HC1 gas, and in many instances, its adsorption on spherical soot particles that are carried into the victims' respiratory tracts. Prevention.--The mandatory use of the self-contained breathing appa ratus by all who will be vulnerable to toxic smoke will aid in the prevention of plastic fires. Control of hazardous building designs, including equip ment and ventilation is also neces sary. Protection by masks during the "overhaul phase" should be required. Sophisticated air-sampling tech niques are required for definitive study, including gas chromatography. Electrocardiographic studies utilizing base line tracings directly after HC1 exposure are stressed. Areas of Future Study.--All atmo spheres should be suspected by the fire fighter. There should be a search for an effective gas analyzer that can immediately assess gas concentra tions released by burning or smolder ing plastics. Further definitive car diologic studies are indicated. The term "smoke inhalation" should be abandoned and replaced by "inhala tion of toxic combustion products." by water aerosol in simulated fire. J Fire Flammability 2:127-138, 1975, 8. Fibers, plastic fumes cause smoke deaths, editorial. Int Fire Fighter 55:8, 1973. 9. Medical tribune report: Human response mechanism may vary in carbon monoxide sensi tivity. Med Tribune Nov 8, 1972, pp 15-16. 10. Cornish H, Abar E: Toxicity of pyrolysis products of vinyl plastics. Arch Environ Health 19:15-21, 1969. JAMA, Jan 26, 1976-Vol 235, No 4 sL 0296&8 Polyvinyl Chloride--Dyer & Esch 397 Paint-Remover Hazard Richard D. Stewart, MD, MPH, Carl L. Hake, PhD The in-home use ot paint removers containing methylene chloride re sults in the absorption of this solvent, which is metabolized to carbon mon oxide. Exposure for two to three hours can result in the elevation of carboxyhemoglobin (COHb) to levels that stress the cardiovascular system. The metabolic formation of COHb continues following the paint-remover expo sure, doubling the duration of the cardiovascular stress produced by a com parable COHb level after exposure to CO. Patients with diseased cardio vascular systems may not be able to tolerate this unexpected stress. (JAMA 235:398-401, 1976) THE REMOVAL of old paint from wood by applying a liquid paint strip ping formulation, long regarded as a laborious, messy task, has not been considered particularly hazardous to health. However, recent research has shown that the main ingredient in most paint removers, methylene chlo ride (dichloromethane, CH,C1>), is rap idly metabolized to carbon monox ide.14 The amount of CO formed in the body is directly related to the amount of CHZC1, absorbed during the paint stripping operation and can be sufficient to produce a substantial stress on the cardiovascular system. From the Department of Environmental Medi cine, The Medical College of Wisconsin, Mil waukee. Reprint requests to The Medical College of Wisconsin, Allen-Bradley Medical Science Lab oratory, 8700 W Wisconsin Ave,"Milwaukee, Wl 53226 (Dr Stewart). The first case illustrates the trag edy that can occur when a patient with coronary heart disease is ex posed to a paint and varnish remover containing CHjCl* and the solvent is metabolized to a toxic amount of CO. The second case is the one in which the in vivo metabolism of CHzClj to CO was first observed. REPORT OF CASES Case 1.--A 66-year-old man with no prior history of heart disease, was admitted to the coronary care unit with severe, crush ing retrosternal pain of two hours' dura tion that radiated to his shoulder and left arm. The patient was a recently retired ex ecutive who had chosen furniture refinish ing as a hobby. Six hours prior to admis sion he had applied a commercial liquid gel paint and varnish remover to part of a large wooden chest of drawers. He had worked at this task for three hours in his basement workshop, which was a room measuring 10.7x6.1x2.7 meters and was heated with hot air from a gas furnace. One hour after leaving the basement, he experienced the onset of his chest pain. The patient related the history of the paint stripping to the attending physician who examined the paint and varnish remov er container. The label cautioned that the product contained 80% methylene chloride by weight and was to be used only with ad equate ventilation. No causal relationship between the inhalation of the paint remov er vapor and the acute anterior myocardial infarction was made. The patient had an uncomplicated hospi tal course, and two weeks following dis charge he elected to strip the remaining paint from the chest of drawers. He again applied the paint remover, working for three hours in his basement workshop. The severe retrosternal pain developed again, and he was readmitted to the coronary care unit. His hospital course during this second acute myocardial infarction was complicated by cardiogenic shock, dysrhyth mia, and heart failure. The patient sur vived, and six months after discharge returned once again to his basement work shop to complete the paint stripping oper ation. Assisted by his wife, he worked slowly for two hours. Two hours later he experienced chest pain, collapsed, and died before the arrival of the ambulance. Case 2.--A 35-year-old male cardiologist, who was enjoying excellent health, volun teered to participate in a research project, the purpose of which was to correlate the subject's carboxyhemoglobin (COHb) level 398 JAMA, Jan 26, 1976-Vol 235, No 4 Paint-Remover Hazard--Stewart & Hake SL 02Q6cn -------- Exposure ----------- `I*--------- __ Postexposure -- ----- ---------------------------- ---------------------- -------- Hours Short exposures to methylene chloride result in formation of carboxyhemoglobin (COHb) that continues to increase after exposure before slowly returning to normal levels. The presence of methanol further prolongs period of COHb elevation and cardiovascular stress. with the air pollution in his section of Mil waukee. This nonsmoker was discovered to have a COHb saturation of 6%, and of 8% on each of the two mornings following a two-hour exposure the previous evening to paint-and-varnish-remover vapors. After a fruitless search to discover the exogenous source of CO, the cardiologist was exposed for one hour to a low concentration of methylene chloride vapor in a controlledenvironment chamber,1 The subject's COHb level rose from a preexposure level of 0.4% to 2.4%, Because there was no evi dence of a hemolytic process, it was pre sumed that the CO was a metabolite of CHZC1,. To confirm this isolated observa tion, a series of experiments were con ducted in which 21 male and nine female volunteers were exposed to CH2C1, vapor concentrations of 50, 100, 250, 500, and 1,000 ppm for varying periods of time. A prompt elevation of COHb was observed in each subject exposed to CH,C1S.5-' EXPERIMENTAL PROCEDURE Paint Remover Exposure.--To inves tigate the potential of paint and var nish removers that contain CH^Cl, to elevate COHb to.-toxic levels, four three-hour paint stripping, operations were carried out in a controlled-envi- ronment chamber where the ventila tion rate could be regulated, the CHjClj vapor concentration accurately monitored, and careful medical sur veillance of the four volunteer partic ipants was possible. Two individuals participated in each experiment. One actively applied the paint remover and did the stripping while the sec ond subject remained sedentary, making it possible to assess the effect of alveolar ventilation on absorption. Three room-ventilation rates were studied. The first simulated the air turnover commonly encountered in home basements, while the other two simulated the higher rates of air turnover that could be encountered in industrial settings. In each threehour experiment, one quart of a liquid gel paint remover was applied to a baby crib with a paint brush and later, scraped off. The volatile compo nents of the paint remover were 80% CH,C12 and 20% methanol by weight. Subjects.--Four healthy men rang ing in age from 19 to 47 years volunteered for the study after the purpose, procedure, and risks of the investigation had been fully ex plained. None of the subjects used drugs or consumed alcohol during the 24-hour periods preceding and follow ing each experiment. One subject, who was a smoker, abstained for 12 hours prior to the experiment and was not permitted to smoke until a final COHb determination had been made. Exposure Chamber.--The four exper iments were conducted in an 817-cu m (2,680-cu ft) controlled-environment chamber,2-7 Air flow was adjusted so that the half-life of the CH2C12 vapor would range from 33 to 11 minutes. Air temperature was 22.3 to 23.3 C and the relative humidity was 55%. Analysis of Exposure Chamber Atmo sphere.--The CH2C12 vapor concentra tion in the breathing zone of the sub jects was continuously recorded by an infrared spectrometer equipped with a 10-meter path-length gas cell. This gas cell was continuously- supplied with air drawn from the subject's breathing zone through a polyethyl ene tubing that measured 0.635 cm in diameter.2-7 The absorbance of 13.3g JAMA, Jan 26, 1976-Vol 235, No 4 - Paint-Remover Hazard--Stewart & Hake 399 0296'' Table 1.--Concentration of Solvents in Breathing Zone During Paint Stripping Expertment 1 2 3 4 Ventilation .Rate, cu m/hr* 70.28 70.28 210.84 147.11 Breathing Zone CH3CI2 Concentration, ppm ,______ ______ *------ .--------------- ( Mean Range SO 788 0-1277 354 654 0-1278 358 368 0-576 122 216 0-379 101 'Chamber Volume=75 cu m (2,680 cu ft). Breathing Zone Methanol Concen- tration, ppm 1B(L_ 115 77 Table 2.--Carboxyhemoglobin Levels During and Following Paint-Remover Exposure Exposure Hours ]ect ' 0 1 2 3 Experiment 1 * 1 0.8 2.6 3.6 4.6 2 1.0 2.0 2.8 4.4 Experiment 2* 3 1.0 2.3 3,3 4.0 f--- %1 Hours Postexposure 2 3 4 5 20 5.3 5.7 7.2 8.2 9.1 9.0 4.4 4.6 5.2 5.5 5.8 6.0 5.6 2.0 ... 5.2 6.1 6.7 6.9 6.5 3.0 4 2.2 2.8 3.8 4.1 5.0 5.5 5.9 5.9 5.5 3.0 Experiment 3 (lorced ventilation [11.1 min to turn over 50% of air]) 1 0.9 2.8 4.0 4.8 6.0 6.8 7.3 6.5 3.1 2.9 2 1.3 2.3 3.4 4.3 5.5 5.8 5.5 4.8 1.9 1.5 Experiment 4 (forced ventilation [15.3 min to turn over 50% of air]) 3 0.9 1.2 1.9 2.9 3.4 3.4 3.3 3.2 1.8 1.6 4 1.5 2.0 2.7 3.7 4.3 4.3 3.7 3.5 1.5 1.6 22 3.8 1.8 3-5 (21 hr post) 2.6 (21 hr post) * Normal home-basement ventilation (33 min to turn over 50% of air). through a path length of 2.25 meters was measured. The infrared signal to the recorder was monitored each sec ond by an on-line computer that dis played the mean vapor concentration, as compared to standards for each 30-second interval of exposure, and calculated the time-weighted average exposures. During the final five min utes of each hour of exposure, addi tional breathing zone samples were collected in large saran bags for methanol analysis. Medical Surveillance.--Each subject was given a. medical examination prior to exposure., This examination included a history, physical examina tion, and the following laboratory studies: complete blood cell count, 18factor automated chemical analysis survey panel, and a 12-lead electro cardiogram. Prior to each day's expo sure, the subjects were given a repeat medical examination. During expo sure, the subjects were under contin ual surveillance by a physician, and lead II of each subject's ECG was con tinuously monitored-by means of te lemetry. Serial venous blood samples were obtained for COHb determina tion during and after the use of the paint remover (Figure).8 The 18-fac tor automated chemical analysis and 12-lead electrocardiogram were re peated the morning following each exposure. RESULTS The use of the paint-remover for mulation under the three ventilation rates produced the breathing zone CHjClj and methanol concentrations listed in Table 1. The higher ventila tion rates significantly reduced the breathing zone concentrations of the two solvents. Each subject's COHb level began to increase shortly after exposure had begun (Figure). These COHb levels steadily increased during the expo sure, continued to rise for several hours following cessation of exposure, and then very slowly returned to nor mal (Table 2). The more active volun teer in each experiment absorbed larger quantities of CH2C12, which re sulted in higher COHb levels. In contrast to the usual pattern of COHb formation following CH2C12 exposure, with peak COHb level ele vations occurring one hour after ex- '* posure, the COHb level in those exposed to paint-remover vapors con tinued to increase for several hours following exposure. This suggested that the methanol was altering the usual metabolic degradation of CHjCIj. No untoward responses occurred during the 24-hour period following each exposure. None of the four sub jects found the paint-remover vapors to be irritating to their eyes, nose, or throat. All described the odor as mild and not objectionable. No abnormal ities in the ECGs or blood chemical values were recorded. COMMENT The use of a paint remover contain ing CHjClj in a large interior room results in the absorption of a signifi cant amount of solvent, its prompt metabolism to CO, and an elevation of blood COHb level. The greater the minute-respiratory volume or the poorer the room ventilation, the greater the absorption of CH2C12 and the higher the COHb level elevation. Use of the paint remover for a period of three hours, following the direc tions on the label, can easily produce a COHb saturation of 5% to 10%. Ex posure for periods longer than those investigated or under conditions of poorer ventilation would result in even higher COHb elevations. It has been well documented that elevation of COHb level to satura tions greater than 5% can adversely affect patients with angina pectoris or cardiovascular disease.,1J Exercise tolerance is decreased and anginal pain is of longer duration. Yet paint stripping for furniture refinishing purposes has become extremely popu lar with older persons.13 Until re cently, a prominent Milwaukee hospi tal introduced paint stripping and furniture refinishing to coronary vein bypass patients in the early convales cent period. The COHb resulting from the me tabolism of CH2C12 is additive to the COHb level resulting from exposure to other exogenous sources of CO.7 For example, a paint-remover expo sure that results in a 10% COHb satu ration level when added to a heavy smoker's preexisting COHb level of 10% will produce headache and nau sea in the healthy, and sufficient car- 400 JAMA, Jan 26, 1976-Vol 235, No 4 Paint-Remover Hazard--Stewart & Hake SL 029671 diovascular stress in the patient with coronary heart disease to be dan gerous.'12 The elevated COHb level resulting from CH,C1S exposure has a biological half-life twice that of COHb produced from exposure to CO. This occurs be cause the absorbed CH2C12 is released slowly from storage in body tissues and then is metabolized to CO over a protracted period of time.. Thus, be cause it is so sustained following exposure, the cardiovascular stress produced by elevated COHb levels, derived from CH2C12 metabolism, is greater than that resulting from equally high COHb levels derived from CO. The addition of methanol to paint-remover formulations extends the biologic half-life of COHb derived from CH2C12 (Figure), further prolong ing the period of cardiovascular stress. The ethical responsibility for in forming the public -about the poten tial hazard of CH2C12 in paint remov ers lies with the manufacturer who is obliged to'market a product that can be used safely. This is the purpose of the label. It should warn the suscep tible segment of the population of the CO hazard. The manufacturers of paint removers have been cognizant of the problem since 1972, yet product labels make no mention of CO. Only one manufacturer of paint removers has acted positively. This Racine, Wis, firm has withdrawn its product from the market. The legal responsibility for protect ing the public currently rests with the Consumer Product Safety Commis sion. It has remained mute, as did the governmental agency originally re sponsible, the Environmental Protec tion Agency, when in 1971 the CH2C12 hazard was formally called to its at tention. The medical responsibility for pro tecting patients unable to tolerate the cardiovascular stress of elevated COHb levels must rest with the physi cian until the general public is made aware of the CH2C12 hazard and all paint-remover formulations are ap propriately labeled. This is a critical duty because one sixth of the 180 mil lion kg of CH2C12 produced in the United States is being consumed in the rapidly expanding paint-remover market.13 This investigation was supported in part by contract HSM-99-72-84 from the National Insti tute of Occupational Safety and Health. Anthony Wu, PhD, and Sally A. Graff provided technical assistance. References L Stewart RD, Fisher TN, Hosko MJ, et al: Carhoxyhemoglobin elevation after exposure to dichloromethane. Science 176:295-296, 1972, 2. Stewart RD, Fisher TN, Hosko MJ, et al: Experimental human exposure to methylene chloride. Arch Environ Health 25:324-348, 1972. 3. Kubic VL, Anders MW, Engel RR, et al: Metabolism of dihalomethanes to carbon monox ide. Drug Metabolism and Disposition. 2:53-57, 1974. 4. Ratney RS, Wegman DH, Elkins HB: In vivo conversion of methylene chloride to carbon monoxide. Arch Environ Health 28:223-226, 1974. 5. Fodor GG, Prajsnar D, Schlipkoter H: En dogenous CO formation by incorporated halogenated hydrocarbons of the methane series. Staub Rcinhaltung der Lu.fi 33260-261,1973. 6. DiVincenzo GD, Hamilton ML: Fate and disposition of methylene chloride in the rat. Tox icol Appl Pharmacol 32285-393, 1975. 7. Stewart RD, Hake CL, Forster HV, et al: Methylene chloride: development of a biologic standard for the industrial worker by breath analysis, report No. NIOSH-MCOW-ENVM-MC74-9. Cincinnati, National Institute of Occupa tional Safety and Health, 1974. 8. Stewart RD, Baretta ED, Platte LR, et al: Carboxyhemoglobin levels in american blood do nors. JAMA 229:1187-1195, 1974. 9. Aronow WS, Harris CN, Isbell MW, et al: Effect of freeway travel on angina pectoris. Ann Intern Med 77:669-676, 1972. 10. Arenow WS, Isbell MW: Carbon monoxide effect on exercise-induced angina pectoris. Ann Intern Med 79:892-395, 1973. 11. Anderson EW, Andelman RJ, Strauch JM, et al: Effect of low-level carbon monoxide expo sure on onset and duration of angina pectoris: A study in ten patients with ischemic heart dis ease. Ana Intern Med 79:46-50, 1973. 12. Scharf SM, - Thames MD, Sargent RK: Transmural myocardial infarction after expo sure to carbon monoxide in coronary artery dis ease: Report of a case. N Engl J Med 29125-86, 1974. 13. Paint-remover sales take off. Chemical Week 65-66, Oct 20, 1971. JAMA U 75 YEARS AGO Jan 26, 1901 Gastric Disorders [Current Medical Literature, p 289] After describing the anatomy of the stomach and its blood-supply, Mayo notices the methods of examination. He believes that too much attention is paid to labora tory and too little to clinical examination at the present time; the two should go hand in hand and neither be neglected. For in stance, the salol test for loss of motor power is unreliable, but the finding of food in the fasting stomach regularly seven hours after taking is most practical and reliable; fourteen hours after indicates stagnation or retention. For getting the outlines of the stomach neither the gastrodiaphanoscope nor gastroscope are of real use, nor can the giving of bismuth or the using of metal sounds for X-ray ex amination be compared in the efficiency with simple dilatation with bicarbonate of soda and tartaric acid, or better still, a stomach-tube and a Davidson syringe with which it is easy to distend the stomach with air. If on distension the lesser curva ture and pylorus remain in the normal po sition while the greater curvature lies be low the umbilicus, dilatation is evident If they are detected below the costal margin the stomach has descended. The history of the patient, his present condition and the chemical and biological examination of the gastric contents, taken into account with position and size of the stomach, give a basis for diagnosis and as a rule indicate whether an abdominal incision would be expedient. In the beginning nearly all op erations on the stomach are exploratory; for the most important primary investiga tion seldom relieves the exact condition. The technique of the operation is described and ulcer and its operative needs are no ticed at length. Some forms of gastrectasia of uncertain origin are also dwelt upon, such as what has been called spasm of the pylorus, of which he thinks he has met with four cases; the special forms of pyloric ob struction are described by him, in which a high lying and fixed pylorus became more and more compressed as the stomach filled, and the distension finally relieved itself by copious vomiting. He thinks this is often the cause of dilatation, and has oper ated on four such cases. The so-called "fish-hook" pylorus in which the opening is directed upward, increases the muscular efforts and acts in a similar manner by in creasing the stomach's work. As regards operation, he says gastroenterostomy is the most generally advisable and has few contraindications. Pyloroplasty may be of benefit in certain cases. As a result of his own experience he believes that much de pends on the condition of the pylorus. JAMA Jan 26, 1976-Vol 235, No 4 029&72 SA Paint-Remover Hazard--Stewart & Hake "401 Immunogenetic Factors in Preeclampsia and Eclampsia Erythrocyte, Histocompatibility, and Y-Dependent Antigens James R. Scott, MD; Alan E. Beer, MD; Peter Stastny. MD Determination of ABO and HL-A antigens and sex ratio of infants born to 46 women with preeclampsia or eclampsia, in comparison with normal con trols, disclosed no predominant blood group, HL-A haplotype, or qualitative difference in maternal-fetal incompatibility. These results suggest that a link between immunologic mechanisms and the pathogenesis of toxemia syn dromes, if present at all, must be associated with feto-placental tissue-spe cific antigens. (JAMA 235:402-404,-1976) THE CAUSE of toxemia of preg nancy remains unknown, but sugges tions that it might be an immune dis order date back to the beginning of the century. Underlying immuno genetic possibilities that have been proposed include (1) an inherited tendency for the disorder, (2) patho genesis related to maternal-fetal in compatibility, or (3) an abnormal ma ternal immune response to placental antigens. A genetic predisposition has been suspected since it was shown that there is an increased incidence of pre eclampsia in daughters of women who themselves were eclamptic.1 If women in whom preeclampsia or ec lampsia was destined to develop dem onstrated an unusual distribution of ABO or HL-A antigens or both com pared to the normal population, typ ing for these antigens would be a po tentially useful clinical test for predicting which primigravidas are at risk for the disease. Moreover, a com- From the Department of Obstetrics and Gyne cology. University ot Iowa College of Medicine, (owa City (Dr Scott), and the departments of ob stetrics and gynecology, cell biology, and inter nal medicine. University of Texas Health Sci ence Center at Dallas (Drs Beer and Stastny). Reprint requests to Department of Obstetrics and Gynecology, University of-lowa Hospitals and Clinics, Iowa City, IA 52242 (Dr Scott). parison of maternal and infant blood groups and tissue types, as well as the sex ratio of infants born to women with toxemia, would help to establish whether or not immunogenetic dis parity between the mother and her fetus plays a role in the pathogenesis of this disorder. MATERIALS AND METHODS Twenty-three preeclamptic and twentythree eclamptic primigravidas from the obstetric services at Parkland Memorial Hospital and University of Iowa Hospitals were studied. The 46 patients included 28 blacks, 11 whites, and seven Latin Ameri cans, Preeclampsia was defined as acute hypertension developing in a primigravida whose blood pressure was normal before the third trimester of pregnancy, and per sistent elevation of blood pressure to at least 140/90 mm Hg, with an increase in the diastolic blood pressure of at least 20 mm Hg above previous levels during preg nancy, Edema or proteinuria or both were present in most cases; no patients who had equivocal findings were included. Eclamp sia was defined as the syndrome of preg nancy-induced hypertension further com plicated by grand mal seizures that were the consequences of pregnancy and not the result of some other cause. Standard blood group determinations were done by testing the red blood cells (RBC) against anti-A and anti-B serum and by testing the scrum against group A and group B red blood cells. The blood groups of preeclamptic and eclamptic pa tients were compared with those of 4,494 normal pregnant women who gave birth at Parkland Hospital. HL-A typing was done by the microdroplet lymphocytotoxicity test for 23 specificities in all of the mothers with preeclampsia and eclampsia and in ten of the infants, as well as in comparison with the tissue types of 343 black and white control patients seen during the same period of time. RESULTS All maternal , and fetal blood groups, HL-A antigens, and sex of the infants born to mothers who were preeclamptic or eclamptic are listed in Table 1. The male-female sex ratio of infants born to toxemic women was 1.13, which is not significantly different from the 1.06 sex ratio of normal pregnancies.3 As shown in Table 2, the blood group distribution in these women did not differ from that of the normal population. Eleven of the 46 infants were ABO incom patible with their mothers, a fre quency that is not greater than in nonaffected pregnancies.' There was also no unusual distribution of HL-A antigens (Table 2) in the preeclamptic or eclamptic women or their infants, and the HL-A antigen frequencies compared well with those published.* Although the number of infants with HL-A antigen, determinations is too small to make any statement about a recurring haplotype, the high inci dence of HL-A incompatibility be tween mother and fetus is not differ ent from that in normal pregnancies. COMMENT Striking associations have been demonstrated between both ABO blood groups and HL-A antigens of 402 JAMA, Jan 26, 1976-Vol 235, No 4 Preeclampsia and Eclampsia--Scott efal SL 029673 Original Contributions Respiratory Tract Illness in Meat Wrappers Henry Falk, MD, Benjamin Portnoy, MD A questionnaire survey was done in 152 Houston supermarkets to as sess the prevalence of respiratory tract symptoms in meat wrappers exposed to the thermal decomposition fumes of polyvinyl chloride (PVC) film wrap and in two supermarket control groups (checkers and meat cutters). Meat wrappers had increased respiratory tract symptoms; 12% of meat wrappers who smoked (vs 6% and 2% of controls) and 5% of meat wrappers who did not smoke (vs 0% and 0% of controls) had multiple respiratory tract symp toms. It is probable that a large number of meat wrappers have mild symp toms with some progressing to more severe respiratory impairment or clini cal asthma. (JAMA 235:915-917, 1976) A RECENT report1 described a new syndrome called "meat-wrapper's asthma." Three women experienced dyspnea, wheezing, and coughing while at work as supermarket meat wrappers. Their jobs involved cutting strips of polyvinyl chloride (PVC) meat-wrap film by pulling the film across an electrically-heated wire. The fumes generated by this process were implicated in the asthma syn drome. In addition, the National In stitute for Occupational Safety and Health has investigated a larger number of reported1 cases of this syn- See also pp 937 and 943. drome in recent years,2 suggesting that the disease is more widespread than was first apparent. Since there are currently about 70,000 meat wrap pers in the United States (according to a recent estimate of the Joint La bor Management Committee of the Retail Food Industry, Washington, DC), the potential for a widespread hazard exists. In January 1974, the Houston City From the Cancer and Birth Detects Division, Bureau of Epidemiology, Center tor Disease Control. Atlanta (Dr Falk), and the Communi cable Disease Division, City of Houston Health Department (Dr Portnoy). Dr Portnoy is now an Infectious Disease Fellow, University of Texas Health Science Center, Houston. Reprint requests to Cancer and Birth Defects Division, Bureau of Epidemiology, Center for Disease Control, 1600 CliUon Rd,JtE. Atlanta, GA 30333 (Dr Falk). Health Department was notified of two cases of meat-wrapper's asthma, and interviews with the affected women suggested that there might be other workers in local supermar kets with similar symptoms. As a re sult, a questionnaire study was de signed to define the prevalence of meat-wrapper's asthma and respira tory tract symptoms among Houston meat wrappers. METHODS The five largest supermarket chains in Harris County, Texas (Houston and envi rons), were chosen for the study, and a to tal of 152 of these chain stores were in cluded (98% of total). In each store, the meat wrapper on duty and. two control em ployees. were interviewed with a standard questionnaire. The. controls included one grocery checker and one meat cutter. The meat cutters were used as controls because they work in the same refrigerated envi ronment (most are at 10 to 12 C) as the wrappers do but do not usually wrap meat. (In this study only a small minority of meat cutters spent any portion of their time wrapping meat.) The three subjects at each supermarket. were interviewed simultaneously by a team of three investi gators who rotated between subjects and controls. The survey was conducted during May and June 1974. The questionnaire was adapted for this study from a standard respiratory tract disease questionnaire used in a study of coal worker's pneumoconiosis (form HSM591, US Department of Health, Education, and Welfare, National Institute of Occupa tional Safety and Health). The questions were designed to elicit a full history of oc cupation, respiratory tract symptoms, and smoking. In each store, the investigators recorded the temperature of the meat room, the type of wrapping device, and the manufac turers of the PVC film and film cutters that were in use. Written consent was obtained from each subject. Each supermarket chain and labor union involved in the study granted writ ten permission to the investigators to con duct the survey. RESULTS Interviews were conducted with 145 meat wrappers and 150 persons in each control group. All but one of the meat wrappers and most of the check ers were women, while all the meat cutters were men (Table 1). The meat wrappers as a group were somewhat older than both groups of controls. The duration of work in their job categories was similar for meat wrap pers and meat cutters, with approxi mately 50% having worked longer than ten years at their jobs. Checkers, however, worked fewer years. Table 2 shows the results for the portion of the questionnaire relat ing to the presence of the major res piratory tract -symptoms (wheezing, shortness of breath, and chest pain); the meat wrappers have a significant increase of these symptoms. This table shows that the increase is pri marily in meat wrappers who smoke, although a smaller increase, while not significant in our study, is also seen in meat wrappers who do not smoke. A comparison of smoking patterns in the three groups shows the meat wrappers and checkers to be almost identical, with both groups smoking considerably less than the male meat cutters (Table 3). Smoking by itself (or in combination with the cold envi ronment) is therefore not- an ade quate explanation for the increased symptoms seen in meat wrappers. In addition, although the wrappers as a group are somewhat older than the JAMA, March 1, 1976--Vol 235, No 9 Respiratory Tract Illness--Falk & Portnoy 915 SL 029674 controls, the increased respiratory lated to your work?" (an unstandard (Table 5). Nasal symptoms, however, tract symptoms are independent of ized addition to the questionnaire in are equally prominent in meat cutters age (Table 4). use that should be evaluated cau and wrappers and appear to be re The response to the question, tiously) suggests that irritation of the lated to working in the cold environ "Have you ever had any of the follow eyes and throat may be a prominent ment. ing problems that you believe is re part of the meat-wrapper's syndrome The data also suggest that meat wrappers have had an increased inci Table 1.--Meat Wrappers and Controls by Age, Sex, and Race (Houston, 1974) dence of nonspecific respiratoiy tract Mean age, yr Race White Nonwhite Sex M F Total Meat Wrappers 39.0 131 14 1 144 145 Checkers 35.4 Controls A Meat Cutters' 33.4 131 138 19 12 16 ISO 134 0 ISO 150 illnesses (Table 6). For some of these categories (pneumonia, pleurisy, bronchitis), however, the timing of the ill nesses (before vs after employment) was not dealt with in the question naire, and it is therefore possible, al though somewhat unlikely, that these differences antedate and are unre lated to employment. The incidence of respiratory tract Table 2.--Respiratory Tract Symptoms* in Meat Wrappers and Controls By Smoking Category (Houston, 1974) symptoms in meat wrappers was un related to the supermarket chain where employed, duration of work, Nonsmokers Shortness of breath Checkers, No.(%) 3(5) Controls Meat Cutters, No.(%) 0(0) Meat Wrappers, No.(%) 3(5) temperature of the meat room, or brand of PVC film wrap or hot-wire machine used. Seventeen of the 145 meat wrappers were working with mechanical blade machines and not Wheezing Chest pain Multiple No. at risk Smokers, past and current Shortness of breath Wheezing Chest pain Multiple 0(0) 4(6) 0(0) 63 3(3) 7(8) 6(7) 5(6) 0(0) 2(7) 0(0) 30 6(5) 11(9) 10(8) 2(2) 3(5) 8(13) 3(5) 61 13(15)f 14(17) 17(20)1 10(12)f with fume-producing hot wires. None of these had any respiratory tract symptoms related to work. There were no significant differ ences between meat wrappers and checkers (the two female groups) in responses to the remainder of the questionnaire, including history of al No. at risk 87 120 84 lergy, history of medication, previous Total hazardous occupation, use of hair Shortness of breath Wheezing Chest pain Multiple Total at risk 6(4) 7(5) 10(7) 5(3) 150 6(4) 11(7) 12(8) 2(1) 150 16(11)t 17(12) 25(17)t 13(9)t 145 sprays, history of cardiac or other res piratory tract illness, or level of edu cation. The male meat cutters dif fered somewhat, with fewer medical complaints and use of medications, * Shortness of breath was considered present it subject responded "yes" to (1) Are you troubled by shortness of breath when hurrying on level ground or walking up a slight hill? and (2) Do you become short of breath walking with other persons your own age on level but with a slightly greater exposure to other hazardous occupations. ground? or (3) Do you have to stop for breath when walking at your own pace on level ground? COMMENT Wheezing was considered present if subject'responded "yes" to (1) Do you ever have a wheezing or whistling sound in your chest? and (2) Do you get this most days or nights? Earlier reports have shown the re Chest pain was considered present if subject responded "yes" to: Do you ever have attacks lationship between meat wrapping of chest pain? fP<.01. tP<.05 (2 df x7 test). Table 4.--Mean Age and Age Distribution* Table 3.--Average No. of Cigarettes Smoked Per Day,* Meat Wrappers and Controls (Houston, 1974) Controls No. <1 1-19 20-39 >40 Total Checkers 63 38 42 7 150 Meat Cutters 30 31 64 25 150 Meat Wrappers 61 35 41 8 145 'Includes current smokers and former smokers when they smoked regularly. Meat Wrappers Age, yr <20 20-29 30-39 40-49 50-59 >60 Total Mean age, yr All, No.(%) 1(i9i 32(22) 45(31) 42(29) 22(15) 3(2) 145 39.0 Any Chest Symptom, No.(%) 1(2) 13(31) 12(29) 9(21) 5(12) 2(5) 42 37.4 Multiple Chest Symptoms, No.(%) 0(0) 4(31) 3(23) 3(23) 3(23). 0(0) 13 38.5 'All meat wrappers and meat wrappers with.chest symptoms, Houston, 1974. 916 JAMA, March 1, 1976-Vol 235, No 9 Respiratory Tract Illness--Falk & Portnoy SL 029675 Table 5.TMResponses of Meat Wrappers and Controls,* Houston, 1974 Symptom Dry or sore throat Burning or itchy eyes Tearing of eyes Stuffy nose Runny nose Coughing Chest tightness, soreness or heaviness Wheezing or whistling in chest Shortness of breath Chest pain Total at risk Checkers, No.(%) 18(12) 13(9) 6(4) 13(9) 9(6) 9(6) 3(2) 4(3) 5(3) 5(3) 150 Meat Cutters, No.(%) 24(16) 15(10) 11(7) 49(33) 51(34) 29(19) 10(7) 7(5), 14(9)12(8) 150 Meat Wrappers, No.(%) 41(28)f 38(26)1 28(19)f 42(29)f 46(32)f 26(18)t 26(18)t 15(10)* 25(17)1 13(9) 14S "Have you ever had any of the following problems that you believe Is related to your work?" fPC.01 (2 df xJ test). |P<.05. Table 6.--Respiratory Tract Illness in Meat Wrappers and Controls (Houston, 1974) Recent illness In the past three years have you had a period of increased cough and,phlegm lasting for three weeks or more? During the past three years have you had any chest illness that has kept you from your usual activities for as much as a week? History of illness Bronchitis Pneumonia Pleurisy Total at risk Checkers 14 18 19 27 16 150 Meat Cutters Meat Wrappers 15 30* 12 32* 13 31* 21 36 9 33* 150 145 PC.01 (2 df x2 test). and asthma13 and have sought to identify the toxic thermal decomposi tion products of PVC film wrap."'7 Our study was designed to estimate the prevalence of respiratory tract problems in a large group of meat wrappers. Our results show that about 10% of the meat wrappers stud ied have multiple respiratory tract symptoms (wheezing, shortness of breath, chest pain, or tightness) and that a considerably larger number have lesser respiratory tract symp toms or eye, throat, or nose irrita tion. In most cases, this spectrum of common respiratory tract problems is not severe enough to cause workers to seek medical attention and treat ment; in some, however, more severe impairment, including clinical asthma, can develop and may be se vere enough to force the wrapper to quit her job (as in the case of two for mer workers whose illnesses prompted this study). We gannot esti mate how often this more severe form of respiratory tract illness oc curs, since our study was confined to current workers at the supermarkets included; a detailed analysis of for mer meat wrappers is needed to an swer this question. The results also suggest that wrap pers may have an increased incidence of acute respiratory tract illnesses (including illnesses characterized as pleurisy, bronchitis, or pneumonia). We suggest, therefore, that the term meat-wrapper's asthma is inappro priate in describing acute and chronic respiratory tract symptoms related to meat wrapping. Meat wrappers who smoke appear to be at greater risk to respiratory tract problems, although a larger number of meat wrappers who do not smoke will have to be studied to eval uate fully the risk in this group. Working in a refrigerated environ ment, however, does not seem to be an important risk factor for the de velopment of lower respiratory tract disease. We cannot assess from this study the long-range effects of in haling PVC thermal decomposition fumes or of the increased respiratory symptoms, and further studies are needed to address these problems. This study was designed to detect respiratory tract illness, and no con clusions can be drawn about disease in other organ systems. Prior to this study there had been some discussion in the local press and among labor leaders of the potential health problems related to wrapping meat. Although all efforts were made to minimize potential bias in this study, we realize that there is a possi bility for subjective bias on the part of those interviewed; it is important that additional studies, such as pul monary function analyses, be per formed on groups of meat wrappers to confirm the associations noted here. Where hot-wire machines are still used, the installation of proper venti lating equipment and lower-tempera ture wires may help reduce the risk to meat wrappers. It would appear, how ever, that the best solution to this problem would be to use mechanical blade machines that do not create fumes. Robert Vandervort, MS, and P. L. Polakoff, MD, Division of Technical Services, National In stitute for Occupational Safety and Health, Cin cinnati, Ohio; R. A. MacLean, MD, Chief, Com municable Disease Division, Houston City Health Department; and Vincent Mandola, Houston City Health Department, assisted us in this study. References 1. Sokol WN, Aelony Y, Beall GN: Meat-wrap per's asthma; A new syndrome? JAMA 226.639641, 1973. 2. Polakoff PL, Vandervort R, Flesch JP; Health Hazard Evaluation Determination Re port 72, Cincinnati, US Department of Health, Education, and Welfare, National Institute for Occupational Safety and Health, 1972, pp 53-58. 3. Polakoff PL, Lapp NL, Reger R: Polyvinyl chloride pyrolysis products. Arcli Environ Health 30:269-271, 1975. 4. Bovee HH, Monteith LE.Orheim RM: Ther mal decomposition of meat wrapping film. Read before the American Industrial Hygiene Confer ence, San Francisco, May 1972. 5. Van Houten RW, Cudworth AL, Irvine CH: Evaluation and reduction of air contaminants produced by thermal cutting and scaling of PVC packaging film. Am hid Hyg Assoc J 35:218-222, 1974. 6. Jaeger RI, Hites RA: Pyrolytic evaporation of a plasticizer from polyvinyl chloride meat wrapping film. Bull Environ Contam Toxicol 11:45-48, 1974. 7. Andrasch RH, Roster F, Lawson WH Jr, et al: Meatwrappers' asthma; An appraisal of a new occupational syndrome, abstracted. J Allergy Clin Immunol 55:130,1975.* JAMA, March 1, 1976-Vol 235, No 9 * Respiratory Tract Illness--Falk & Portnoy 917 SL 029676 Rates of Cutaneous Reactions to Drugs A Report From the Boston Collaborative Drug Surveillance Program Kenneth A. Arndt, MD, Hershel Jick, MD Rates of allergic skin reactions to commonly used drugs were estimated from data obtained on 22,227 consecutively monitored medical inpatients. A total of 57 drugs were implicated in skin reactions. Five or more reactions were attributed to each of 22 drugs (or drug groups). Many commonly used drugs did not appear to cause any allergic reactions. The study provides the practicing physician with drug-specific quantitative data that can be used to valuate the causes of drug-induced rash, itching, or hives. (JAMA 235:918-922, 1976) SKIN REACTIONS are among the most common undesired effects of drugs--occurring in 2% to 3% of medi cal inpatients.1 The attribution of a cutaneous reaction to a particular drug frequently entails a difficult judgment, since patients generally receive many drugs simultaneously. This judgment requires quantitative information about the rate of such re actions to each drug received by the patient. In order to estimate the frequency of skin reactions to commonly used drugs, we examined the records of the Boston Collaborative Drug Surveil lance Program (BCDSP), which now includes data on over 22,000 medical inpatients. MATERIAL AND METHODS The methods of the BCDSP have been described in detail elsewhere.1 All drug treatments of the consecutively monitored medical inpatients were recorded, includ ing dates of starting and stopping, dosage, and route of administration. All drug-at tributed adverse events were also re corded, together with the date of onset, From the Department of Dermatology, Har vard Medical School (Dr Arndt), and the Depart ment of Medicine, Boston University School of Medicine (Or Jick), Boston. Reprint requests to Bostpn Collaborative Drug Surveillance Program, Boston University Medi cal Center. 400 Totten Pond,Rd, Waltham, MA 02154 (Dr Jick). and a full description of the event was se cured by the monitor regardless of wheth er the reaction could be attributed to a par ticular drug. As a preliminary to data analysis, a de tailed review of each drug-attributed skin reaction was carried out to identify those that conformed to the generally accepted concepts of "allergic" reactions. (The com monly used term "allergic" is used in this communication for convenience. It should be noted, however, that mechanisms of drug-induced skin reactions are obscure and that some may be nonimmunologic in nature.) Case histories and descriptions on all pa tients who experienced drug-attributed skin reactions were examined by a derma tologist (K. A. A,). Included for further study were (1) eruptions characterized by the rapid onset and widespread, bilateral involvement with erythematous macules or papules or both, often termed morbilli form, maculopapular, or exanthematous in appearance, (2) hives, and (3) generalized itching. Some 565 drug-attributed skin re actions occurred among 22,227 monitored patients. Of these reactions,.58 were ex cluded because they did not appear to rep resent clinically typical allergic skin re actions: several were acne attributed to steroids, some were preexisting rashes, many were local injection reactions, and the remainder represented vague and illdefined localized cutaneous changes. The remaining 507 reported events, occurring in 491 patients, were considered to be "al lergic" drug-induced skin reactions, and the review of the data was confined to these. Data analysis was first directed to the qualitative identification of allergenic drugs. (Cephalosporins, [cephalothin, cephaloglycin, cephaloridine, and cephalexin], barbiturates [secobarbital, pentobarbital, phenobarbital, barbital, butabarbital, amobarbital, butethal, and mephobarbital], mecurial diuretics [meralluride and mercaptomerin], and semisynthetic penicillins [methacillin, nafcillin, oxacillin, cloxacillin, carbenicillin, and dicloxacillin] were exam ined as groups rather than individual drugs.) A major principle in this analysis was the removal from the data base of pa tients exposed to known allergens. The pro cedure was a sequential one: In the first stage, all patients receiving any penicillin or blood product were removed. This re moval was based on an a priori recognition of these products as major causes of skin allergies on medical wards. It involved 8,401 (38%) of the patients and 357 (70%) of the skin reactions. In the remaining patients, the detection of individual drugs that produced skin re actions was based on two criteria. First, the frequency of reactions in patients re ceiving the drug had to be at least twice as high as the frequency of reactions in the remaining patients at large. Second, there had to be a characteristic cluster of rashes in the days following the first exposure to the drug. The application of these criteria was based on computer-produced scattergrams that showed, for recipients of any given drug, the occurrence of allergic skin reactions in relation to first exposure to that drug. Additional causative drugs were detected by these criteria, and the recipi ents of these drugs were also removed from the data base to provide for the de tection of the next set. The procedure was repeated until all skin reactions were ac counted for. Having identified a set of apparent al lergens, the next step was to assign each reaction to a single drug in order to obtain 918 JAMA, March 1. 1976-Vol 235, No 9 Cutaneous Reactions--Arndt & Jick SL 029677 A Medical Tribune Wednesday, June 19, 1974 Polyvinyl Chloride Implicated in Liver Ills By R. S. Grimshaw, Jr. Medical Tribune Staff New York--Preliminary indications that workers involved in the fabrica tion of plastics from polyvinyl chloride (PVC) may be at risk for impaired liver function were presented here by West German investigators. Drs. C. E. Lange and W. K. Leblbach, of the University of Bonn, told a conference on vinyl chloride toxicity sponsored by the New York Academy of Sciences that of 15 persons em ployed in the manufacture of PVC floor tiles, six had evidence of "vinyl chloride disease," including sensations of pain in the upper abdomen, slight to moderate thrombocytopenia, in creased BSP retention by the liver, reticulocytosis, and liver fibrosis upon peritoneoscopy--lesions that, in one case, were termed possible precursors tof a more advanced, perhaps malignant Resion. Leukocytopenia was noted in one case, as was splenomegaly, al though selective splenograms were done. . Exposur to Monomer Postulated Dr. Lehlbach postulated that the workers had probably been exposed to vinyl chloride, the monomer of PVC, which could have been leached from PVC when the material was heated in the tile-forming process. Exposure to vinyl chloride gas has been found to be strongly associated with angiosarcoma of the liver, and is presumed to be the source of 13 such cases found so far in persons em ployed in vinyl chloride manufacture or polymerization in the United States. While the number of persons work ing directly with the monomer is small --approximately 6,500--the number working with PVC is many times greater. Dr. Irving J. Selikoff, Professor of Medicine at the Mount Sinai School >f Medicine and cochairman of the Conference, termed the reports "our first hint," although still unconfirmed, that vinyl cloride risk extends beyond the monomer workers. Dr. Cesare Maltoni, director of the Institute of Oncology of Bologna, Italy, reported new animal studies demon strating oncogenicity of vinyl chloride at a level of 50 parts per million. At that level, Dr. Maltoni found cases of liver angiosarcoma, peritoneal angio sarcoma, and nephroblastoma in very old rats, while no malignancies were found in control animals. Fifty parts per million is the current emergency temporary standard of ex posure set by the U.S. Department of Labor's Occupational Health and Safety Administration. This agency has proposed a new job safety stand ard that would allow "no detectable level" of occupational vinyl chloride exposure. The Food and Drug Administration and the Environmental Protection Administation have recently acted to limit consumer exposure to vinyl chloride, requesting recall of aerosol products that use vinyl chloride as a propellant, specifically hair sprays and indoor-use pesticides. In addition to potentiating malignan cies, vinyl chloride appears to be as sociated with other clinical manifesta tions, according to reports presented by investigators from Germany. Japan, and Romania. These include skin le sions. acroosteolysis, Banti syndrome and Banti fibrosis, pulmonary lesions, nervous system lesions, impotence, and hormonal imbalances. "We have." said Dr. Selikoff, "a multisystem disease." Evidence of Oncogenicity Was Available in *72 Medical Tribune Repoet New York--Evidence that vinyl chloride causes a variety of cancers in rats and mice was available as early as 1972, one and a half years before action was taken to determine its toxicity in man. Dr. Cesare Maltoni, director of the Institute of Oncology of the University of Bologna, told Medical Tribune in interviews here and in Italy. Dr. Maltoni, who began studies on the oncogenicity of vinyl chloride under the sponsorship of several European chemical companies in 1971, said the results were com municated to the Manufacturing Chemists Association, an American industry trade group, by the end of 1972. A team of M.C.A. scientists visited his laboratory in January, 1973, he said, and the National In stitute of Occupational Safety and Health was notified in July. Yet, he charged, nothing was done about possible vinyl chloride effects in man until the death, from liver angiosarcoma, of a worker at the Louisville plant of the B.F. Good rich Company last December. Dr. Maltoni said that the experience with vinyl chloride underscores the need to accept animal studies of carcinogenicity and the need to perform bioassays "for all new products that are developed." j ! j ' I < , I > . I j j ! i ! i ' 1 Reduced Drinking Age Raises Highway Toll Medical Tribune Report Washington--State laws reducing le gal minimum drinking ages'to 18 years represent "social policy that carries a price in increased fatal motor vehicle collisions," a research report by the Insurance Institute for Highway Safety declared. The study compared fatal-crash im plication of drivers under 21 in Mich igan, Ontario, and Wisconsin--where the legal drinking age was dropped from 21 to IS in either 1971 or 1972 --with corresponding figures for In diana, Illinois, and Minnesota, where the age was 21. The investigators estimated that for each 100,000 of their numbers in the population, 15-to-2G-year-old$ were a party to 2.6 to 3.3 more fatal crashes in the first year after the legal drinking age was lowered than would have been expected from prior experience. SL 029678