Putative Exposure Research Articles

Posttransfusion and Community‐Acquired Hepatitis C in Childhood

Following a longitudinal study of chronic non‐A, non‐B hepatitis in Italy and Spain, we evaluated the epidemiologic and clinical features of chronic hepatitis C in 77 consecutively observed children (35 male; mean age, 4 years) without underlying systemic diseases. All subjects were positive for antibody to hepatitis C virus in serum by second‐generation tests. Forty‐six patients had received blood transfusions in the perinatal period; 12 had a mother with antibodies to HCV in serum (five of these mothers were drug users or partners of a drug user); seven had a history of putative percutaneous exposure; and 12 had not been exposed to any risk factors for viral hepatitis. At presentation, only 22% were symptomatic, mean alanine‐aminotransferase levels were three times the upper normal value, and liver histology showed active disease in only nine of 28 cases (32%). During a mean observation period of 6 years, only 11 of 57 patients (19%) complained of symptoms and 11 of 40 cases (27%) had histologic features of active hepatitis. Two patients had severe hepatitis with associated cirrhosis. However, only six of 57 cases (10%) achieved sustained biochemical remission. The clinical features and the outcome were similar in both the posttransfusion and the community‐acquired cases. These results indicate that transfusions in the perinatal period are the single most important cause of hepatitis C in otherwise healthy children. Community‐acquired cases represent an heterogeneous epidemiologic group in which maternal transmission, whether perinatal or postnatal, could be relevant. Histologically severe hepatitis and cirrhosis seem to be an infrequent feature of chronic hepatitis C virus infection in childhood and adolescence, in spite of persistent liver damage.

Posttransfusion and community-acquired hepatitis C in childhood.

Following a longitudinal study of chronic non-A, non-B hepatitis in Italy and Spain, we evaluated the epidemiologic and clinical features of chronic hepatitis C in 77 consecutively observed children (35 male; mean age, 4 years) without underlying systemic diseases. All subjects were positive for antibody to hepatitis C virus in serum by second-generation tests. Forty-six patients had received blood transfusions in the perinatal period; 12 had a mother with antibodies to HCV in serum (five of these mothers were drug users or partners of a drug user); seven had a history of putative percutaneous exposure; and 12 had not been exposed to any risk factors for viral hepatitis. At presentation, only 22% were symptomatic, mean alanine-aminotransferase levels were three times the upper normal value, and liver histology showed active disease in only nine of 28 cases (32%). During a mean observation period of 6 years, only 11 of 57 patients (19%) complained of symptoms and 11 of 40 cases (27%) had histologic features of active hepatitis. Two patients had severe hepatitis with associated cirrhosis. However, only six of 57 cases (10%) achieved sustained biochemical remission. The clinical features and the outcome were similar in both the posttransfusion and the community-acquired cases. These results indicate that transfusions in the perinatal period are the single most important cause of hepatitis C in otherwise healthy children. Community-acquired cases represent an heterogeneous epidemiologic group in which maternal transmission, whether perinatal or postnatal, could be relevant.(ABSTRACT TRUNCATED AT 250 WORDS)

Asbestos exposure, physical activity and colon cancer: a case-control study.

An association between colon cancer and the occupation of model or pattern maker in the car industry has been repeatedly suggested. The aim of our study was to investigate colon cancer and occupational exposures (in particular in the car industry) in an industrialized area of northern Italy. We conducted a hospital-based case-referent study on colon cancer (n = 131; hospital controls, n = 463). All subjects were interviewed, and jobs in the car industry were investigated. Occupational exposure to asbestos and the level of physical activity were blindly assessed. All the jobs were classified according to energy expenditure (less than 8, 8-12 and more than 12 kJ/min). We found no association between colon cancer and any job in the car industry. No subject had worked as a model or pattern maker. Sedentary work was associated with colon cancer in men but not in women. An excess risk was demonstrated among males for job titles involving putative exposure to asbestos (4 cases and 3 controls; OR = 4.8, 95% c.i. 1.05-21.5), in particular pipe fitters and boilermakers (3 cases and 1 control; OR = 10.7; 1.07-103).

Retrovirus-associated adult T-cell leukemia-lymphoma: an epidemiologic study of five cases among Hawaii-born offspring of migrant Japanese.

Adult T-cell leukemia-lymphoma (ATLL) is a distinct clinicopathologic entity etiologically linked to HTLV-I infection. We have identified five cases of retrovirus-associated ATLL among Hawaii-born first generation offspring (nisei) of migrant Japanese. Four patients were offspring of migrant Japanese (issei) who emigrated to Hawaii from Okinawa, an HTLV-I endemic area. The fifth patient was born of parents who emigrated to Hawaii from Fukushima and Miyagi prefectures, HTLV-I nonendemic areas. Epidemiologic implications and family studies with regard to HTLV-I antibody testing of the index cases are discussed. The high rate of HTLV-I antibody seropositivity among family members and relatives indicates that the risk of acquiring HTLV-I infection and of developing ATLL persists long after migration. Documentation of ATLL among offspring of Japanese immigrants to Hawaii is an important observation because it confirms the potential for long latency between putative exposure to virus and the development of overt disease. Changing marriage patterns among the Hawaii-Japanese may weaken the risk of vertical virus transmission to the descendents of migrants from southern Japan, while increasing the risk to children born of mixed marriages. In addition, blood products derived from high-risk donors will constitute a continuing hazard if they are not subject to screening.

Can the birth certificate yield clues to parental occupational exposures?

An analysis of reported birth record variables by parental occupation suggests that certain birth outcomes may identify toxic or carcinogenic occupational exposures of the parents. Fathers coded to an asbestos and insulation worker rubric sired fewer plural births, and more stillbirths than expected. A number of other fathers' occupations with putative exposure to asbestos and increased lung cancer mortality also showed a deficit of plural births.

Screening for Neurotoxic Disease in Humans

Detection of neurotoxic disease is a formidable task requiring clinical, epidemiologic and detective skills,(1) Rarely does neurotoxic insult occur in isolation, and rarely are precise details of the putative exposure known. False positive and false negative diagnoses of neurotoxicity are common because of the similarity of the major signs and symptoms with those associated with metabolic, traumatic, or age-related diseases. No single test or sign is pathognomonic for neurotoxic disease; routine clinical laboratory results and imaging procedures are generally of little value. Exposure to a specific toxin can result in a vastly different clinical profile depending on the magnitude and route of exposure. For example, acute high level exposure to acrylamide causes a toxic encephalopathy with convulsions and hallucinations; prolonged low level exposure causes distal sensory loss. Since metabolites are often the toxic moiety, it is rarely possible to predict neurotoxicity by examining the chemical formula of agents. Thus, the neurotoxic properties of n-hexane and methyl- n-butylketone are attributable to a common gamma-diketone metabolite (2,5-HD), whereas chemically related compounds (i.e., heptane, pentane) have failed to produce experimental neuropathy. Nontoxins also can enhance toxic situations. Symptoms may intensify for months after exposure is stopped (coasting), and, conversely, dysfunction may not appear until years of low level exposure. Preexisting subclinical nervous system dysfunction (i.e., carpal tunnel syndrome) may first become manifest after toxic exposure (unmasking phenomena). The onset of symptoms, particularly negative symptoms, can be insidious and may continue undetected by patient and physician. It is suggested that neurotoxic damage in early life can enhance late life central nervous system dysfunction, such as Parkinson's disease.

Emerging issues in extremely-low-frequency electric and magnetic field health research

Concern has increased over potential consequences of exposure to electric and magnetic fields of extremely low frequency (0-100 Hz), particularly from power transmission and distribution. Also at issue are electrical environments in homes and workplaces. Until recently, research focused on the electric, rather than the magnetic, field; now, both are under extensive investigation. A review of research to date indicates the following: Electric and magnetic fields can produce effects in vitro, with the locus of field interaction believed to be at the cell membrane. Chronic in vivo electric field exposure fails to produce effects except in behavior, neurophysiology, endocrinology, and, possibly, fetal development. The extrapolation of these animal data to humans requires further research. The epidemiological literature has, in some cases, reported an association between increased cancer rates and putative field exposure. Exposure assessments indicate that, in all likelihood, human exposures to 60-Hz electric fields of the magnitudes found under transmission lines are very infrequent; assessments are continuing to characterize exposure to 60-Hz magnetic fields and to measure the field frequency spectra found in residential and workplace settings. The public health issues emerging from this research focus on fetal development and on the initiation or promotion of cancer. It is critical to reduce existing uncertainties in order to enable valid risk assessment.

Chronic Airflow Limitation: Its Relationship to Work in Dusty Occupations

The classic diseases of dusty occupations may be on the decline, but this is not the case for chronic nonmalignant lung disease characterized by airflow limitation. This group of diseases, almost certainly multifactorial in etiology, occurs in those engaged in dusty occupations as well as in those who are not. Among the environmental factors concerned, cigarette smoking is clearly one of the most important, but occupational exposures are increasingly implicated. It is also clear that not all with similar exposures are affected, pointing to the importance of host or personal factors. Evidence is now accumulating in support of what has been called the Dutch hypothesis. This explanation of the natural history of chronic airflow limitation suggests that an "asthmatic tendency" is a necessary factor whether the putative exposure is to cigarettes or to other airborne pollutants. Further research should therefore be directed towards clarifying the relationships of acute and chronic airway dysfunction in response to airborne pollutants of all types.

Perspectives in mutation epidemiology: 2. Epidemiologic and design aspects of studies of somatic chromosome breakage and sister-chromatid exchange

Some aspects of the design and analysis of studies of the association of chromosome breakage and rearrangement (CBR) in human populations with exposure to possible environmental hazards are reviewed. While many of these are well known to most working in the field, lack of knowledge of them by some regulatory agencies had led to unfortunate episodes. The need for use of a simultaneous and appropriate matched control for each exposed individual studied is emphasized. It is suggested all studies involve matching upon age, sex, race, socioeconomic status and marital status. If there are numerous individuals exposed to a substance to be investigated which is not yet known to induce chromosome breakage, it is suggested a subsample with lowest likely level of possible confounding factors be selected for study, and that exposed individuals who are likely to have a history of confounders such as malignancy, other chronic disease, or even apparent moderate exposure to ionizing radiation be excluded because of great difficulty in finding appropriate controls for such individuals. (Other things being equal, in an episode of community exposure children are likely to have a lower level of possible confounders than adults.) If a control is chosen whose match with an exposed case is questionable then it is suggested that less weight be given in the analysis of results from this exposed-control pair than to pairs for which matching is acceptable. Attempts should be made to quantify exposure even if this can be done only crudely by using variables such as length of exposure or distance from a putative exposure source, and a dose-response curve established if possible. If a substance is not known definitely to produce chromosome breakage it may be efficient initially to study those with highest known levels of exposure—at least 5 individuals if available. Negative results in this group may well indicate the rest of the population need not be studied. In the event of an environmental disaster and there is limited time and opportunity to study those exposed and to ascertain appropriate matched controls, at least some simultaneous control specimens should be obtained. The most plausible, readily available source may be the study team itself. Even if exposed individuals are not appropriately matched with putative controls it may be possible to adjust for different levels and types of confounders in the subsequent statistical analysis. But as this may not always be the case and as restudying an exposed population may be impossible in some circumstances, the greatest possible attention should be given to designing the study and to controlling possible confounding factors before it begins.

Virology and cancer

Viruses remain powerful tools for probing the mechanisms and etiology of cancer. They clearly are a cause of naturally occurring cancers in many animal species. Of the human viruses studied to date, the strongest associations are represented by (a) Epstein-Barr virus and Burkitt lymphoma and nasopharyngeal carcinoma; (b) hepatitis B virus and liver cell carcinoma; and (c) herpes simplex virus type 2 and cervical carcinoma. In all cases, virus nucleic acids and proteins are associated with the tumor cells and putative exposure to the virus prior to onset of the neoplastic disease has been documented. It appears probable that cocarcinogenic events, represented by early exposure, lifestyle, genotype of the host, or environmental factors, also play a role in initiation or promotion of the cancer. In the absence of definitive etiology for many other types of neoplasms (i.e., leukemia), it does not appear to be prudent to rule out a role for human counterpart viruses of animal retroviruses at this time.