Clinical surveillance and management of occupational asthma. Tertiary prevention by the primary practitioner.
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Asthma↗
Biomedical subjects
M R Cullen
Publications and source records attributed to M R Cullen.
The role of clinical investigations in biological markers research.
As the agenda of the occupational and environmental health community proceeds from the study of the effects of high doses of toxins causing grossly altered disease patterns to examination of the impact of lower doses on prevalent disorders, new scientific approaches have become necessary. The emerging concept of molecular epidemiology, substituting biologically determined markers of dose and early effect for traditional measures of exposure and morbidity, offers a heuristically appealing direction for the field. However, the transition to this evolving approach has been slow and its potential has yet to be validated. In this essay, some of the limitations of this approach are discussed and theoretical modifications developed. The central proposition is that existing modalities of clinical research, widely employed in subspecialty medicine research but heretofore unexploited in the study of environmental diseases, offer great promise. By incorporating clinical investigations centrally, some historically rate-limiting problems such as variability of host responses, multiplicity of environmental risks, and differences between human and animal responses could be transformed from major impediments at present to realistic objects for future study.
Animals↗
The effect of lead on thyroid function in children.
Exposure to inorganic lead has been associated with impaired uptake of iodine by the thyroid as well as depressed estimated free thyroxine levels in occupationally exposed adults. Consideration of the serious consequences of impaired thyroid function in young children prompted investigation of the effects of lead on thyroid function in children. Blood lead determinations and thyroid function tests were performed on 68 children examined at a hospital outpatient pediatric clinic. Serum thyroxine (T4) and free thyroxine (FT4) levels were within the normal range for all patients. No statistically significant relationship was found between lead levels and T4 or FT4 levels. We conclude that lead is unlikely to have a clinically significant effect on thyroid function in children exposed in inner cities at prevailing levels.
Child↗
Spectrum of occupational disease in an academic hospital-based referral center in Connecticut from 1979 to 1987.
The inability to characterize the extent of occupational disease in the United States limits clinical diagnosis and public health interventions. We present an 8-year (1979 to 1987) experience with clinic-based reporting in Connecticut. Altogether, 3566 cases were sequentially coded for demographics, diagnoses, workplace identification, and exposures at two academic occupational medicine clinics. The lungs were the principal organs of diagnosed effect, with asbestos-related disorders predominating, whereas the urinary tract, endocrine organs, and cardiovascular systems were rarely involved. Of all diseases, 64.8% were diagnosed as chronic and irreversible. Three common disorders, lead intoxication (acute and chronic), asbestosis, and occupational asthma were selected for illustration. Patients with lead poisoning and asbestosis, although collectively numerous (40 and 504, respectively), came from a small number of worksites and industries. Occupational asthma was more variable: 141 diagnosed cases came from 56 different trades and industries and were caused by 28 recognized agents. While we recognize that clinic-based reporting suffers from obvious problems with referral bias and misclassification, our experience shows that it provides an important index of disease burden. Our data document the effects of legislation and litigation on lead poisoning and asbestosis, and correspondingly helps characterize diseases that will respond to broad intervention. On the other hand, occupational asthma is more pervasive and would require a more specialized, partially clinical approach.
Adult↗
Effects of exposure to ethylene glycol ethers on shipyard painters: I. Evaluation of exposure.
An industrial hygiene survey was performed to characterize exposure of shipyard painters to 2-ethoxyethanol (2-EE) and 2-methoxyethanol (2-ME). One hundred and two samples were taken over six workshifts. Overall results showed that the time-weighted average (TWA) of airborne exposure to 2-EE ranged from 0-80.5 mg/m3 with a mean of 9.9 mg/m3 and a median of 4.4 mg/m3. Samples for 2-ME TWA ranged from 0-17.7 mg/m3 with a mean of 2.6 mg/m3 and a median of 1.6 mg/m3. Limitations of the sampling and a few prior measurements suggest that these data may underestimate usual or previous exposure. These data are discussed in the context of available data on airborne exposure to ethylene glycol ethers from other workplaces.
Adult↗
Effects of exposure to ethylene glycol ethers on shipyard painters: II. Male reproduction.
To determine whether 2-ethoxyethanol (2-EE) and 2-methoxyethanol (2-ME) affected the reproductive potential of exposed men, we examined the semen of 73 painters and 40 controls who work in a large shipyard. An industrial hygiene survey was performed to characterize the work environment. The men supplied information on demographic characteristics, medical conditions, personal habits, and reproductive history; underwent a physical examination; and provided a semen sample. Semen samples were analyzed for pH, volume, turbidity, liquidity, viability by stain exclusion and hypo-osmotic stress, sperm density and count per ejaculate, motility using a videotape technique, morphology, and morphometry. Serum was analyzed for testosterone, FSH, and LH. The industrial hygiene survey revealed that the painters were exposed to 2-EE at a time-weighted average (TWA) of 0-80.5 mg/m3 with a mean of 9.9 mg/m3, and to 2-ME at a TWA of 0-17.7 mg/m3 with a mean of 2.6 mg/m3. Painters had an increased prevalence of oligospermia and azoospermia and an increased odds ratio for a lower sperm count per ejaculate, while smoking was controlled. This finding is consistent with prior animal studies and with one human study. Potential biases and confounding of the data are discussed.
Adult↗
Effect of exposure to ethylene glycol ethers on shipyard painters: III. Hematologic effects.
Hemoglobin, hematocrit, red cell indices, total and differential white blood cell counts, and platelet count were measured in shipyard painters and control subjects as part of a cross-sectional, observational study of the effects of ethylene glycol ethers. Although the means of all variables were comparable between the groups, a significant proportion of painters were anemic (10%) and granulocytopenic (5%); none of the controls were affected. Review of company records documented that most of these abnormalities were acquired during employment; preexisting disease and other exposure could not explain the findings. These findings are consistent with prior animal studies and human case reports. Potential biases and confounding of the data are discussed.
Adult↗
Liver disease associated with occupational exposure to the solvent dimethylformamide.
STUDY OBJECTIVE: to characterize an outbreak of liver disease among workers in a fabric coating factory; and to determine the outbreak's cause and natural history and strategies for clinical recognition, treatment, and prevention. DESIGN: clinical-epidemiological investigation. SETTING: academic medical center, Occupational Medicine Clinic, and worksite. PATIENTS: fifty-eight of sixty-six workers participated in the study. All had standard liver function tests at least once. Forty-six workers completed a questionnaire; 27 had more extensive clinical evaluation for recognized liver abnormalities. RESULTS: a plant-wide outbreak of liver disease was recognized after a new employee presented with signs and symptoms of hepatitis. Evaluation of the worksite showed that dimethylformamide, a widely used industrial solvent and known hepatotoxin, was being used to coat fabric in poorly ventilated areas without appropriate skin protection. No other major hepatotoxic exposure was identified. Overall, 36 of 58 (62%) workers tested had elevations of either aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels. Enzyme abnormalities occurred almost exclusively in production workers (35 of 46 were abnormal), whereas only 1 of 12 nonproduction workers showed any elevations in enzyme levels (P less than 0.0001). Serologic tests excluded known infectious causes of hepatitis in all but 2 workers and changes characteristic of toxic liver injury were confirmed by histologic examinations of biopsy specimens from 4 workers. The ratio of AST to ALT levels was one or less in all but 1 worker. After modification of work practices and removal of workers most severely affected from exposure, improvement in liver enzyme abnormalities and symptoms in most patients were seen, although some patients showed persistent elevations of enzyme levels. CONCLUSIONS: an outbreak of toxic liver disease has been associated with exposure to dimethylformamide in the workplace. The diagnosis of toxic liver disease was established by the clinical histories, negative viral serologies, an enzyme pattern of ALT levels being greater than AST levels, epidemiologic data on coworkers, and liver biopsy specimens. The high prevalence of unsuspected liver enzyme abnormalities in these workers suggests that occupational liver disease may occur more frequently than is generally recognized.
Adolescent↗
Proliferative response of bronchoalveolar lymphocytes to beryllium. A test for chronic beryllium disease.
STUDY OBJECTIVE: to ascertain whether measuring the proliferative response of bronchoalveolar lymphocytes to beryllium salts is useful for diagnosing chronic beryllium disease. DESIGN: prospective case series compared to normal volunteers and patients with sarcoidosis. SETTING: university referral center. PATIENTS: twenty-three consecutive beryllium workers were evaluated. Fourteen had chronic beryllium disease diagnosed on the basis of histologic evidence of a progressive pulmonary granulomatosis. Four had biopsy evidence of non-beryllium disease. Three had probable chronic beryllium disease but did not have lung biopsies. Two did not have biopsies and had basilar fibrosis on chest roentgenogram suggestive of non-beryllium lung disease. These patients were compared with 6 normal volunteers and 16 patients with sarcoidosis. MEASUREMENTS AND MAIN RESULTS: bronchoalveolar lavage was done and the proliferative response of the lung cells to two beryllium salts was tested. A positive proliferative test was defined as a stimulation index of more than five on two determinations. The sensitivity of this test was 100% in the 14 patients with definite chronic beryllium disease. The specificity of the test was also 100% among the normal volunteers and the 16 patients with sarcoidosis. The test was positive in none of the four patients with biopsy evidence of non-beryllium disease, none out of two patients with lower lobe fibrosis suggestive of non-beryllium disease, and all of three patients with probable chronic beryllium lung disease. CONCLUSIONS: the proliferative response of bronchoalveolar lymphocytes to beryllium appears to be a useful test for chronic beryllium disease.
Berylliosis↗
The challenge of teaching occupational and environmental medicine in internal medicine residencies.
Using a mailed survey questionnaire directed toward division chiefs of general internal medicine, we have confirmed that despite increased interest among faculty, few medical residents currently receive required or elective training in occupational medicine. However, recent changes in societal perceptions about environmental risks, corporate health care practices, and medical reimbursement patterns favoring provision by hospitals of contractual outpatient services to healthy workers all portend expanded involvement of residents in certain occupational medicine activities in the future, in response to economic pressures on both consumers and providers. These same forces may, unfortunately, undermine the scientific and ethical quality of such training experiences, compared with emerging, more academically motivated approaches. The implications of these prospects are analyzed in the hope that a proper balance can ultimately be struck between economic and academic imperatives.
Environmental Health↗
Development of innervation within syngeneic thymus tissue transplanted under the kidney capsule of the nude mouse: a light and ultrastructural microscope study.
The developing thymus, prior to the onset of its functional and structural organization, is innervated by the autonomic nervous system (ANS). The present study extends these earlier findings by analyzing at the light and ultrastructural microscope level the distribution of ANS nerves within normal 18-day-old embryo thymus, adult thymus, and thymic tissue transplanted under the kidney capsule of syngeneic nude mice. The results of this study showed that prior to birth the murine thymus is innervated by AChE-positive fibers that are distributed at the corticomedullary boundaries and throughout the adjacent cortex, as well as to cells beneath the thymic capsule. This pattern of distribution remains constant during adult life. The examination of the various thymic tissues by ultrastructural analysis demonstrated that myelinated and nonmyelinated fiber bundles penetrate the thymic capsule and the interface between the kidney and the thymus transplant. The myelinated fibers measured 2 micron or less in diameter; the nonmyelinated fibers were 1 micron in diameter. Myelination did not accompany the nerves into the parenchyma of the normal gland but was observed in the intralobular trabeculae of the transplanted thymus. Subcapsular nerves form a network that terminates among the thymocytes, whereas intrathymic nerves enter the parenchyma in bundles along the vasculature and interlobular septa before penetrating into the deeper layers of the thymic cortex. Some larger nerve fibers terminate in the corticomedullary boundaries and in the interlobular septa. Smaller fibers form en passant boutons near parenchymal cells. The innervation of both the normal thymus and the transplanted thymus prior to the onset of thymic immune function supports a role for ANS innervation in the development of thymic competency.
Animals↗
Chronic beryllium disease in a precious metal refinery. Clinical epidemiologic and immunologic evidence for continuing risk from exposure to low level beryllium fume.
Five workers at a precious metal refinery developed granulomatous lung disease between 1972 and 1985. The original diagnosis was sarcoidosis, but 4 of the workers were subsequently proved to have hypersensitivity to beryllium by in vitro proliferative responses of lymphocytes obtained by bronchoalveolar lavage. Review of medical records of coworkers and extensive industrial hygiene surveillance of the plant demonstrated that 4 cases occurred in the furnace area where air concentrations of beryllium fume were consistently below the permissible exposure limit of 2 micrograms/M3. A single case has been recognized from parts of the refinery where exposures to cold beryllium dust often exceeded the standard by as much as 20-fold. These data demonstrate that chronic beryllium disease still occurs and confirm the importance of specific immunologic testing in patients suspected of having sarcoidosis but with potential exposure to beryllium. The data raise concern about the adequacy of modern industrial controls, especially in the setting of exposure to highly respirable beryllium fume.
Adult↗
Drug screening: ethical guidelines.
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Drug Evaluation, Preclinical↗
Recognition of occupation-induced posttraumatic stress disorders.
Because many occupationally exposed workers are disabled by medically unexplained symptoms, the authors set out to develop etiologically, prognostically, and therapeutically distinct diagnostic categories for these patients. Rigorous diagnostic criteria were applied to a sample of 21 patients with disproportionate disability: three patients had typical posttraumatic stress disorders (PTSD), seven had atypical PTSD, and the remainder suffered somatoform disorders. Recognition of PTSD is important because, unlike somatoform disorders, PTSD often responds to appropriate treatment. Some of the factors that may lead to PTSD are discussed, based on the case series. Using case examples, the authors discuss the diagnostic criteria for typical and atypical PTSD; differentiate these from somatoform disorders; and discuss the implications of the study for prevention of PTSD and for case management.
Accidents, Occupational↗
Occupational medicine. A new focus for general internal medicine.
In the past two decades, occupational medicine has advanced from a formerly clinical discipline to one focused on epidemiology and toxicology. However, because efforts to prevent occupational disease by concerted application of industrial hygiene have not eliminated the problem, there remains a strong need for clinical interventions. Appropriate interventions could result in a further substantial reduction in the morbidity and mortality of work-connected illness. Unfortunately, neither adequate training nor the necessary scientific foundation for clinical decision making presently exist. Studies are needed to characterize the modern spectra and natural histories of virtually all recognized occupational diseases and to evaluate the efficacy of available therapeutic strategies. Sections of general internal medicine potentially offer an ideal academic setting to address these educational and scientific deficiencies.
Female↗
Thyroid function and lead.
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Dose-Response Relationship, Drug↗
Occupation-induced posttraumatic stress disorders.
The authors describe a variant of posttraumatic stress disorder that presents as a somatoform disorder. Applying clearly specified diagnostic criteria, they found that seven of 21 patients who were severely disabled by medically unexplained symptoms following occupational exposure to toxic substances had atypical posttraumatic stress disorder, while three patients had typical posttraumatic stress disorder and the remainder suffered from somatoform disorders. Analysis of these cases revealed specific exposure factors and personality characteristics that favor the development of atypical posttraumatic stress disorder. The authors discuss the theoretical, clinical, and therapeutic advantages of this diagnosis.
Accidents, Occupational↗
Organic affective illness associated with lead intoxication.
Psychiatrists treating patients with depression or nonspecific somatic complaints seldom think of lead intoxication as a possible cause. Because occupational exposure to lead is so common, these disturbances may often be associated with lead intoxication. To facilitate earlier clinical recognition and proper treatment among the many individuals at risk, the authors describe four cases of organic affective disturbance associated with lead intoxication, review the neuropsychiatric disturbances that have been reported with chronic exposure to lead, and report the results of their experience evaluating the psychiatric aspects of lead intoxication among individuals exposed in their work.
Adult↗