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Biomedical subjects

A J Ruttenber

Publications and source records attributed to A J Ruttenber.

At least 19 recordsLinked to original sources

hprt mutant frequencies, nonpulmonary malignancies, and domestic radon exposure: "postmortem" analysis of an interesting hypothesis.

The hypothesis that exposure to domestic radon raises the risk for leukemia and other nonpulmonary cancers has been proposed and tested in a number of epidemiologic studies over the past decade. During this period, interest in this hypothesis was heightened by evidence of increased frequencies of mutations at the hypoxanthine guanine phosphoribosyl transferase (hprt) gene in persons exposed to domestic radon (Bridges BA et al. [1991]: Lancet 337:1187-1189). An extension of this study (Cole J et al. [lsqb[1996]: Radiat Res 145:61-69) and two independent studies (Albering HJ et al. [1992[: Lancet 340:739; Albering HJ et al. [1994[: Lancet 344:750-751) found that hprt mutant frequency was not correlated with domestic radon exposure, and two well-designed epidemiologic studies showed no evidence of a relation between radon exposure and leukemia in children or adults. In this report, we present additional data from a study of Colorado high school students showing no correlation between domestic radon exposure and hprt mutant frequency. We use reanalyses of previous studies of radon and hprt mutant frequency to identify problems with this assay as a biomarker for domestic radon exposure and to illustrate difficulties in interpreting the statistical data. We also show with analyses of combined data sets that there is no support for the hypothesis that domestic radon exposure elevates hprt mutant frequency. Taken together, the scientific evidence provides a useful example of the problems associated with analyzing and interpreting data that link environmental exposures, biomarkers, and diseases in epidemiologic studies.

Adolescent↗

Cleanup worker exposures to hazardous chemicals at a former nuclear weapons plant: piloting of an exposure surveillance system.

Cleanup of former U.S. Department of Energy (DOE) nuclear weapons production facilities involves potential exposures to various hazardous chemicals. We have collaboratively developed and piloted an exposure database and surveillance system for cleanup worker hazardous chemical exposure data with a cleanup contractor at the Rocky Flats Environmental Technology Site (RFETS). A unique system feature is the incorporation of a 34-category work task-coding scheme. This report presents an overview of the data captured by this system during development and piloting from March 1995 through August 1998. All air samples collected were entered into the system. Of the 859 breathing zone samples collected, 103 unique employees and 39 unique compounds were represented. Breathing zone exposure levels were usually low (86% of breathing zone samples were below analytical limits of detection). The use of respirators and other exposure controls was high (87 and 88%, respectively). Occasional high-level excursions did occur. Detailed quantitative summaries are provided for the six most monitored compounds: asbestos, beryllium, carbon tetrachloride, chromium, lead, and methylene chloride. Task and job title data were successfully collected for most samples, and showed specific cleanup activities by pipe fitters to be the most commonly represented in the database. Importantly, these results demonstrate the feasibility of the implementation of integrated exposure database and surveillance systems by practicing industrial hygienists employed in industry as well as the preventive potential and research uses of such systems. This exposure database and surveillance system--the central features of which are applicable in any industrial work setting--has enabled one of the first systematic quantitative characterizations of DOE cleanup worker exposures to hazardous chemicals.

Colorado↗

Development of an exposure database and surveillance system for use by practicing OSH professionals.

This report summarizes the development of an occupational exposure database and surveillance system for use by health and safety professionals at Rocky Flats Environmental Technology Site (RFETS), a former nuclear weapons production facility. The site itself is currently in the cleanup stage with work expected to continue into 2006. The system was developed with the intent of helping health and safety personnel not only to manage and analyze exposure monitoring data, but also to identify exposure determinants during the highly variable cleanup work. Utilizing a series of focused meetings with health and safety personnel from two of the major contractors at RFETS, core data elements were established. These data elements were selected based on their utility for analysis and identification of exposure determinants. A task-based coding scheme was employed to better define the highly variable work. The coding scheme consisted of a two-tiered hierarchical list with a total of 34 possible combinations of work type and task. The data elements were incorporated into a Microsoft Access database with built-in data entry features to both promote consistency and limit entry choices to enable stratified analyses. In designing the system, emphasis was placed on the ability of end users to perform complex analyses and multiparameter queries to identify trends in their exposure data. A very flexible and user-friendly report generator was built into the system. This report generator allowed users to perform multiparameter queries using an intuitive system with very little training. In addition, a number of automated graphical analyses were built into the system, including exposure levels by any combination of building, date, employee, job classification, type of contaminant, work type or task, exposure levels over time, exposure levels relative to the permissible exposure limit (PELS), and distributions of exposure levels. Both of these interfaces, allow the user to "drill down" or gradually narrow query criteria to identify specific exposure determinants. A number of other industrial hygiene processes were automated by the use of this database. Exposure calculations were coded into the system to allow automatic calculation of time-weighted averages and sample volumes. In addition, a table containing all the PELs and other relevant occupational exposure limits was built into the system to allow automatic comparisons with the current standards. Finally, the process of generating reports for employee notification was automated. The implementation of this system demonstrates that an integrated database system can save time for a practicing hygienist as well as provide useful and more importantly, timely information to guide primary prevention efforts.

Colorado↗

Integrating workplace exposure databases for occupational medicine services and epidemiologic studies at a former nuclear weapons facility.

We outline methods for integrating epidemiologic and industrial hygiene data systems for the purpose of exposure estimation, exposure surveillance, worker notification, and occupational medicine practice. We present examples of these methods from our work at the Rocky Flats Plant--a former nuclear weapons facility that fabricated plutonium triggers for nuclear weapons and is now being decontaminated and decommissioned. The weapons production processes exposed workers to plutonium, gamma photons, neutrons, beryllium, asbestos, and several hazardous chemical agents, including chlorinated hydrocarbons and heavy metals. We developed a job exposure matrix (JEM) for estimating exposures to 10 chemical agents in 20 buildings for 120 different job categories over a production history spanning 34 years. With the JEM, we estimated lifetime chemical exposures for about 12,000 of the 16,000 former production workers. We show how the JEM database is used to estimate cumulative exposures over different time periods for epidemiological studies and to provide notification and determine eligibility for a medical screening program developed for former workers. We designed an industrial hygiene data system for maintaining exposure data for current cleanup workers. We describe how this system can be used for exposure surveillance and linked with the JEM and databases on radiation doses to develop lifetime exposure histories and to determine appropriate medical monitoring tests for current cleanup workers. We also present time-line-based graphical methods for reviewing and correcting exposure estimates and reporting them to individual workers.

Colorado↗

Beryllium particulate exposure and disease relations in a beryllium machining plant.

We examined the relationship between exposure to beryllium and the presence of beryllium sensitization (BeS) and chronic beryllium disease (CBD) in a cohort of workers in a beryllium precision machining facility. Twenty workers with BeS or CBD (cases) were compared with 206 worker-controls in a case-control study. Exposure for each job title was measured using cascade impactors placed in the workers' breathing zone to measure total beryllium exposure and exposure to particles < 6 microns and < 1 micron in aerodynamic diameter. Cumulative exposure was calculated as sigma (job title exposure estimate x years in job title). Individual lifetime-weighted (LTW) exposure was calculated as sigma [(job title exposure x years in job title) divided by total years employment)]. Workers in the case group were more likely to have worked as machinists (odds ratio, 4.4; 95% confidence interval, 1.1 to 17.5) than those in the control group. The median cumulative exposure was consistently greater in the cases compared with the controls for all exposure estimates and particle size fractions, although this was not statistically significant. The median cumulative exposure was 2.9 micrograms/m3-years in the cases versus 1.2 micrograms/m3-years in the controls for total exposure, and 1.7 micrograms/m3-years in the cases versus 0.5 microgram/m3-years in the controls for exposure to particles < 6 microns in diameter. With cumulative exposure categorized into low-, intermediate-, and high-exposure groups, the odds ratios were 2.4 (95% confidence interval, 0.7 to 8.2) for the intermediate-exposure group and 1.2 (95% confidence interval, 0.4 to 4.2) for the high-exposure group compared with the low-exposure group. The median LTW exposure was 0.25 microgram/m3 in both groups. The median LTW exposure to particles < 6 microns was 0.20 microgram/m3 in the cases compared with 0.14 microgram/m3 in the controls. The differences in cumulative and LTW exposure were not statistically significant. None of the 22 workers with LTW exposure < 0.02 microgram/m3 had BeS or CBD. Twelve workers (60%) in the case group had LTW exposures > 0.20. In conclusion, increased cumulative and LTW exposure to total and respirable beryllium was observed in workers with CBD or BeS compared with the controls. These results support efforts to control beryllium exposure in the workplace.

Adult↗

Serotonin transporters upregulate with chronic cocaine use.

Cocaine potently inhibits serotonin (5-HT) reuptake in cell bodies and at nerve terminals and 5-HT has been implicated as a modulator of dopaminergic neurotransmission. Chronic use of cocaine may lead to a "serotonin-deficit" form of 5-HT dysregulation. We have examined the status of the 5-HT transporter (SERT) using ligand binding and autoradiographic methods in subgroups of cocaine overdose deaths. Quantitative autoradiography of [125I]RTI-55 was used to map and measure the effect of chronic cocaine use on SERT densities in the striatum, substantia nigra, amygdala, and adjacent paralimbic cortical areas of cocaine overdose (CO) victims with and without preterminal evidence of excited delirium (ED). SERT densities were elevated in the nucleus accumbens and throughout the anterior and posterior sectors of striatum in CO victims compared with age-matched and drug-free control subjects. In contrast, SERT densities were increased significantly in the anterior striatum, but not the posterior sectors in ED victims. Significant elevations in SERT were measured in the orbitofrontal gyrus (Brodmann area 11), the anterior portion of the insular cortex and the cingulate gyrus (Brodmann area 24) in CO and ED victims. Saturation binding site analysis demonstrated an increase in the density of RTI-55 binding sites with no change in the affinity of the radioligand for the SERT. Chronic cocaine exposure upregulated SERT densities in the substantia nigra of the CO, but not ED victims. The lack of SERT upregulation in the substania nigra and posterior striatum suggests the possibility of a distinct phenotype for fatal ED victims that exhibited an acute onset of bizarre and violent behavior prior to death. Adaptive changes in the SERT densities may contribute to depressed mood and drug craving associated with acute cocaine abstinence.

Adult↗

Cocaine-associated rhabdomyolysis and excited delirium: different stages of the same syndrome.

Previous case reports indicate that cocaine-associated rhabdomyolysis and excited delirium share many similar features, suggesting that they may be different stages of the same syndrome. We tested this hypothesis by comparing data from 150 cases of cocaine-associated rhabdomyolysis reported in the medical literature with data from an autopsy registry for 58 victims of fatal excited delirium and 125 victims of fatal acute cocaine toxicity. Patients with rhabdomyolysis are similar to victims of fatal excited delirium with regard to age; gender; race; route of cocaine administration; the experiencing of excitement, delirium, and hyperthermia; and the absence of seizures. Compared with victims of fatal acute cocaine toxicity, patients with rhabdomyolysis are different with regard to each of these variables. Compared with victims of fatal acute cocaine toxicity, both victims of rhabdomyolysis and fatal excited delirium are more likely to be black, male, and younger; to have administered cocaine by smoking or injection; and to have experienced excitement, delirium, and hyperthermia; they are also less likely to have had seizures. Because cocaine-associated rhabdomyolysis and excited delirium have similar clinical features and risk factors, occur in similar populations of drug users, and can be explained by the same pathophysiologic processes, we conclude that they are different stages of the same syndrome. It appears that this syndrome is caused by changes in dopamine processing induced by chronic and intense use of cocaine rather than by the acute toxic effects of the drug.

Acute Kidney Injury↗

Computer-generated time lines for visualizing and editing epidemiological and biomedical data.

Most biomedical data have a temporal dimension. Time-line displays spatialize this dimension and help the viewer comprehend large sets of complex data. If we add ways for users to selectively expand the details of data visible on a time line, even more information can be organized and accessed. Design issues for this kind of display include: how to display time scales that are often wider than the physical display space; how to display events with brief duration; how to display data for two or more events that overlap in time; how to manage the display of data details; how to allow database editing from a time line; and how to facilitate time-based analytical techniques. We describe a time-line display system that addresses each of these issues, and show how it can be used to organize data for an epidemiological study of parental radiation exposure and childhood leukemia. We also suggest further refinements of the time line technique for other biomedical applications.

Child↗

Irritant-associated vocal cord dysfunction.

Vocal cord dysfunction (VCD) is a poorly understood entity that is often misdiagnosed as asthma. We report eleven cases of VCD in which there was a temporal association between VCD onset and occupational or environmental exposure. We conducted a case-control study to determine if the characteristics of irritant-exposed VCD (IVCD) cases differed from non-exposed VCD controls. Chart review of VCD patients at the authors' institution produced 11 cases that met IVCD case criteria. Thirty-three control VCD subjects were selected by age matching. There were statistical differences between the groups in ethnicity and chest discomfort. There were no statistical differences between the groups for gender, tobacco, smoking habits, symptoms, or pulmonary function parameters. Varied irritant exposures were associated with IVCD. IVCD should be considered in patients presenting with respiratory symptoms occurring after irritant exposures.

Adult↗

Fatal excited delirium following cocaine use: epidemiologic findings provide new evidence for mechanisms of cocaine toxicity.

We describe an outbreak of deaths from cocaine-induced excited delirium (EDDs) in Dade County, Florida between 1979 and 1990. From a registry of all cocaine-related deaths in Dade County, Florida, from 1969-1990, 58 EDDs were compared with 125 victims of accidental cocaine overdose without excited delirium. Compared with controls, EDDs were more frequently black, male, and younger. They were less likely to have a low body mass index, and more likely to have died in police custody, to have received medical treatment immediately before death, to have survived for a longer period, to have developed hyperthermia, and to have died in summer months. EDDs had concentrations of cocaine and benzoylecgonine in autopsy blood that were similar to those for controls. The epidemiologic findings are most consistent with the hypothesis that chronic cocaine use disrupts dopaminergic function and, when coupled with recent cocaine use, may precipitate agitation, delirium, aberrant thermoregulation, rhabdomyolysis, and sudden death.

Adult↗

Variation in cancer risk estimates for exposure to powerline frequency electromagnetic fields: a meta-analysis comparing EMF measurement methods.

We used meta-analysis to synthesize the findings from eleven case-control studies on cancer risks in humans exposed to 50-60 Hertz powerline electromagnetic fields (EMFs). Pooled estimates of risk are derived for different EMF measurement methods and types of cancer. EMF measurement methods are classified as: wiring configuration codes, distance to power distribution equipment, spot measurements of magnetic fields, and calculated indices based on distance to power distribution equipment and historic load data. Pooled odds ratios depicting the risk of cancer by each measurement type are presented for all cancers combined, leukemia for all age groups and childhood leukemia. The wire code measurement technique was associated with a significantly increased risk for all three cancer types, while spot measures consistently showed non-significant odds ratios. Distance measures and the calculated indices produced risk estimates which were significant only for leukemia.

Adult↗

High affinity cocaine recognition sites on the dopamine transporter are elevated in fatal cocaine overdose victims.

Cocaine mediates its powerful reinforcement by binding to recognition sites on the dopamine (DA) transporter. The pharmacological identity of cocaine recognition sites and their relevance to dopamine transport function has remained unclear. Ligand binding studies with transport inhibitors and cocaine congeners have provided evidence for multiple sites or "states" of the DA transporter. The potent cocaine congener [3H]WIN 35,428 ((CFT), 2B-carbomethoxy-3 beta-(4-fluorophenyl)-tropane) has been shown to recognize high and low affinity binding sites on the DA transporter. We have used [3H]WIN 35,428 to map and quantify the high affinity cocaine recognition site on the DA transporter in victims of fatal cocaine overdose. Region-of-interest densitometric analysis of the autoradiograms demonstrated a 2- to 3-fold elevation in the apparent density of [3H]WIN 35,428 binding in particular sectors of the striatum from victims of cocaine overdose as compared to age-matched and drug-free control subjects. The most marked increase in [3H]WIN 35,428 binding was seen in the nucleus accumbens. The apparent increase in the density of high affinity sites was confirmed by saturation binding analysis of [3H]WIN 35,428 to putamen membranes. Saturation analysis revealed high and low affinity binding components with affinities (KD values) of 4.3 +/- 1.2 and 84.7 +/- 19.7 nM (mean +/- S.E.) and densities of 9.9 +/- 4.0 and 193.0 +/- 28.6 pmol/g of tissue, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Epidemiologic studies of cancer in populations near nuclear facilities.

We reviewed over 40 epidemiologic studies around nuclear power stations, fuel reprocessing plants, and weapons production facilities and testing sites in the United Kingdom, the United States, France, and Canada. We examined these studies for their potential to support a cause and effect relationship between cancer risk and radiation exposure. The extent to which an epidemiologic study supports a causal relation between radiation exposure and increased cancer risk can be evaluated using a set of criteria that have become known as Hill's postulates. In our review, epidemiologic studies yielded results that were biologically plausible and were supported by experimental data, but in almost all of the studies the methodologies were not adequate for evaluating causality. In the majority of cases, the methodologies did not permit examination of dose-response associations, making it impossible to support or refute causal relations. We suggest that investigators consider these issues when designing studies and employ dose reconstruction methodology to estimate radiation doses for specific individuals and population groups.

Adolescent↗

Stalking the elusive designer drugs: techniques for monitoring new problems in drug abuse.

In the 1980s, the clandestine synthesis, distribution, and use of analogs of controlled substances became popular in the United States. These designer drugs comprise analogs of many different classes of psychoactive drugs and present a spectrum of adverse health effects ranging from mood changes to severe neurologic disease. Although there has been no unified program of surveillance for these drugs, a number of articles describing their presence in North American communities have appeared in a variety of publications. This paper summarizes the evidence of designer drug production and use, and recommends effective surveillance efforts that might be adopted by drug abuse prevention and public health agencies.

Designer Drugs↗

Emerging patterns of cocaine use and the epidemic of cocaine overdose deaths in Dade County, Florida.

With the increasing use of cocaine in the United States, cocaine overdose deaths are being reported with increasing frequency. To describe patterns of cocaine use involved in cocaine overdose deaths, we reviewed the postmortem records from the Metropolitan Dade County Medical Examiner Department, Miami, Fla. We identified 239 cocaine overdose deaths from 1971 through 1987. During this period, the incidence of cocaine overdose deaths increased 20-fold, with the largest proportional increases occurring among persons aged older than 24 years, white persons, and men. The percentage of deaths that involved use of cocaine by nonparenteral routes, as well as newer and unknown preparations of cocaine (such as "crack" and "free-base" cocaine), increased. For example, the percentage of deaths that involved use of crack or free-base cocaine increased from 8% in 1981 to 20% in 1987. Persons who died after smoking crack or free-base cocaine had lower blood cocaine levels at autopsy (median level, 0.3 mg/L) than persons who died as a result of using cocaine hydrochloride (median level, 3.7 mg/L). Patterns of cocaine use involved in the epidemic of cocaine overdose deaths are changing. The data suggest that the newer preparations of cocaine, such as crack or free-base cocaine are playing an increasingly important role in this epidemic and that these preparations may be more toxic than cocaine hydrochloride.

Age Factors↗