Biomedical subjects

G Ramachandran

Publications and source records attributed to G Ramachandran.

At least 19 recordsLinked to original sources

PubMed2001

Particle size and chemical species 'fingerprinting' of aerosols in primary nickel production industry workplaces.

A field study was conducted at a range of worksites at a number of plants, for two companies, in the primary nickel production industry. The aim of the field study was to provide direct measurements of the distributions of both particle size and relevant nickel species groups (soluble, sulfidic, metallic and oxidic). and to use the data to characterize health-relevant aerosol exposures of workers at the worksites in question. Since there was no commercially-available sampler that could provide samples of sufficient quantity to enable chemical speciation for the species fractions of interest, as well as particle size distribution information, new instrumentation was developed, based on a modified version of the Andersen cascade impactor, incorporating a porous foam media top stage that produced particle classification over the upper end of the inhalable range (Kerr, Vincent and Ramachandran, Annals of Occupational Hygiene, 2001, in the press). This modified-Andersen sampler was used in extensive field studies, along with other sampling instruments, including, in particular, the IOM personal inhalable aerosol sampler. The results of the field study provided results that could be represented succinctly in terms of the distributions of the four nickel species groups and the three health-related particle-size fractions: inhalable, thoracic and respirable. They showed that, for practical purposes, the distributions of the four nickel species groups were consistently uniform across the full range of particle-size distribution. For the purpose of characterizing the distribution of nickel species for each worksite, this finding enabled incorporation of additional data taken at those same sites using the IOM personal inhalable aerosol sampler. This yielded a data set sufficient to permit the development of exposure 'fingerprints' for each worksite. Such 'fingerprints' make it possible for the occupational hygienists at the plants in question to estimate workers' exposure to individual nickel species fractions based on measurement only of overall inhalable nickel. In addition, by reference to the differing threshold limit values (TLV) for the various nickel species, the 'fingerprints' also allow the individual worksites to be characterized by hazard indices (in the form of 'equivalent sulfidic fractions', or ESFs) that reflect the weightings of the risks experienced by workers at each worksite.

Aerosols↗

PubMed2001

Mixtures of nickel and cobalt chlorides induce synergistic cytotoxic effects: implications for inhalation exposure modeling.

Workers are often simultaneously exposed to two or more chemicals, yet little is known about the toxicity of most chemical mixtures. The traditional assumption, in the absence of further information, has been that the chemical components of a mixture have mutually independent effects, and the toxic response to multiple chemicals is additive. The data presented here show that mixtures of NiCl(2) and CoCl(2) induce a synergistic (that is, greater than additive) toxic response in cell culture. Immortalized alveolar epithelial type II cells were incubated for 4 h with various concentrations of either NiCl(2), CoCl(2), or NiCl(2) and CoCl(2) together, and cell viability assessed 24 h later. The LD(50) for NiCl(2) was 5.7 mM. CoCl(2), with an LD(50) of 1.1 mM, was about five times more potent than NiCl(2). Mixtures of NiCl(2) and CoCl(2) decreased cell viability synergistically. For example, a mixture of 750 microM NiCl(2) and 750 microM CoCl(2) reduced cell viability by more than three times the value predicted by the additive approach. We used concentration-response data from these studies in a mathematical model; this model describes the equivalent inhalation exposure to an aerosol composed of a mixture of chemicals with different toxicities and also accounts for synergistic responses to these chemicals. Our results along with previous studies using an animal model suggest that these synergisms should be taken into account when conducting future exposure assessments.

Air Pollutants↗

PubMed2001

A new approach to sampling for particle size and chemical species "fingerprinting" of workplace aerosols.

A commercially-available, high-volume (28.3 Lpm) Andersen-type cascade impactor was modified in order to extend its operational range further into the range of large inhalable particles for purposes of use in an exposure assessment study in the primary nickel production industry. The modification involved incorporating a 10-ppi (pores per inch) porous plastic foam top stage that has a wide penetration curve with a (50)d(ae)-value of approximately 27 microm. This enabled the upper end of the range of the instrument to be extended from about 10 to greater than 70 microm. The inlet of the original instrument was also modified to incorporate the new top stage and provide "representative" aspiration of total airborne particulate with an efficiency of close to 100% over the range of aerodynamic particle sizes of interest. A mathematical inversion algorithm developed in earlier research was modified so that it could be applied to this new instrument. This enabled raw data on particulate material recovered from all stages of the instrument (including the new porous foam top stage) to be used for the determination of continuous particle size distributions, as well as chemical speciation, over the inhalable range. The new instrument was deployed in a pilot field study in the nickel primary production industry by which to demonstrate the potential of the new instrument for generating useful information pertaining to health-relevant aerosol size tractions (e.g., inhalable, thoracic, and respirable), and for soluble, sulphidic, metallic, oxidic and total nickel chemical species groups.

Aerosols↗

PubMed2001

Retrospective exposure assessment using Bayesian methods.

This paper presents the application of a Bayesian framework for retrospective exposure assessment of workers in a nickel smelter. Using only sparsely available historical measurements will result in exposure estimates with large uncertainties. However, additional information, in the form of expert judgments informed by knowledge of historical plant conditions, can be brought to bear on this process. The experts are provided with an information packet that contains historical process information, process throughput levels for each year, the dimensions of the workplace, ventilation records, and task descriptions for each job category. Based on this information, the experts provide subjective prior probability distributions for input parameters to a general ventilation model that predicts building concentrations. These priors can be synthesized with the historical measurements using Bayes theorem. The prior distributions of exposures are updated using the average measured exposures (historical measurements) and their associated variances to obtain the posterior probability distributions for building concentrations as well as concentrations at specific locations in the building. Expert input was also obtained from a plant industrial hygienist, in the form of probability distributions, regarding the amounts of time spent by each job category in different locations in the building. Monte Carlo sampling, from the posterior probability distributions of concentrations in different micro-environments and the probability distributions of time spent by each job category in those micro-environments, was used to obtain worker exposures using a time-weighted averaging model.

Air Pollution↗

PubMed2000

Comparison of short-term variations (15-minute averages) in outdoor and indoor PM2.5 concentrations.

Measurements of 15-min average PM2.5 concentrations were made with a real-time light-scattering instrument at both outdoor (central monitoring sites in three communities) and indoor (residential) locations over two seasons in the Minneapolis-St. Paul metropolitan area. These data are used to examine within-day variability of PM2.5 concentrations indoors and outdoors, as well as matched indoor-to-outdoor (I/O) ratios. Concurrent gravimetric measurements of 24-hr average PM2.5 concentrations were also obtained as a way to compare real-time measures with this more traditional metric. Results indicate that (1) within-day variability for both indoor and outdoor 15-min average PM2.5 concentrations was substantial and comparable in magnitude to day-to-day variability for 24-hr average concentrations; (2) some residences exhibited substantial variability in indoor aerosol characteristics from one day to the next; (3) peak values for indoor short-term (15-min) average PM2.5 concentrations routinely exceeded 24-hr average outdoor values by factors of 3-4; and (4) relatively strong correlations existed between indoor and outdoor PM2.5 concentrations for both 24-hr and 15-min averages.

Activities of Daily Living↗

PubMed1999

Application of recent advances in aerosol sampling science towards the development of improved sampling devices: the way ahead.

This paper reviews the framework that underpins the development of a new generation of personal samplers capable of operating at much lower flowrates that those of the current generation and so capable of being used for exposure assessment not only for 'traditional' occupational populations (i.e., industrial workers) but also for people exposed to aerosols in the ambient atmosphere (including children). The opportunity for this new generation of samplers stems from the availability of very light and compact low-flowrate pumps. The development and deployment of such instruments presents: (a) physical challenges in terms of how to collect particle size fractions in a manner which is consistent with the new particle size-selective sampling criteria, and (b) analytical challenges in terms of how to quantitate the much smaller amounts of collected material that need to be analysed. The paper lays out the physical and analytical scenarios, and points the way forward to how such challenges can be overcome. Work is already in progress in several countries to develop prototype instruments for applications like those described.

Adult↗

PubMed1999

New experimental studies of the basic performance characteristics of aerosol samplers.

The study of the basic physical performance characteristics of aerosol samplers, like those used in the occupational hygiene setting, will provide insights to enable the improved development of new instruments and cost-effective testing procedures. These will be required as the new particle size-selective sampling criteria become the basis of new occupational exposure standards. A new body of work is being conducted, in which the factors influencing sampler performance are being investigated using idealized samplers of spherical shape in small wind tunnels. By the experimental methods described, a large amount of performance data can be acquired in a very short time. The results for wide ranges of particle size, wind speed, sampling flow rate, and sampler orientation conditions show that there are strong trends as functions of these variables. Those trends are very complicated. But it is encouraging that they are broadly consistent with recent semi-empirical models, suggesting that extensions of that type of modelling approach--supported by the large amount of new experimental data now being generated by such experiments--might provide new models of aerosol sampler performance accessible to researchers and occupational hygienists.

Aerosols↗

PubMed1999

A Bayesian approach to retrospective exposure assessment.

A variety of health effects are caused by chronic, cumulative exposure over time to pollutants. In these cases, to establish dose-response relationships for epidemiological and risk assessment purposes, it is vital to determine the exposures of individuals or cohorts as functions of time. Most existing occupational exposure databases, however, do not contain continuous records of historical exposures to airborne contaminants. These gaps in the historical record may be filled by using the knowledge base that experts and professionals in the field possess. In this article we present a new framework, based on Bayesian probabilistic reasoning, for obtaining estimates of exposure histories for airborne particulates from limited historical measurements, using subjective expert judgment. The framework has great potential applications in instances where there is sparse information or missing data on past exposures. Expert judgment, in the form of inputs to physical models, provides additional knowledge to retrospectively estimate exposure as a function of time from discrete and incomplete measurements. The expert judgments are informed by knowledge of historical plant conditions and work practices, and models describing process-dependent aerosol generation, ventilation, and worker activity patterns. The result will be probability distributions of the exposure of task-groups of workers as a function of time, in the form of a matrix.

Air Pollution↗

PubMed1999

Bioavailability of rifampicin, isoniazid and pyrazinamide in a triple drug formulation: comparison of plasma and urine kinetics.

SETTING: The present study assesses bioavailability indices for rifampicin, isoniazid and pyrazinamide when administered to healthy volunteers separately or in a fixed triple-drug formulation, Rifater 125 SCT. OBJECTIVE: To compare the pharmacokinetics of rifampicin, isoniazid and pyrazinamide based on their blood concentrations up to 12 hours with the proportions of the doses of the drugs and their metabolites excreted in urine up to 12 hours, and to assess the bioavailability indices for the free and fixed triple drug formulations. DESIGN: An open cross-over study was conducted in 18 healthy volunteers with normal hepatic and renal functions to whom the drug combinations were administered in free and fixed dose formulations a week apart, to the same subject. RESULTS: Concentrations of the three drugs/metabolites were assessed in blood and urine. The results indicated the absence of negative pharmacokinetic interactions between the drugs when administered in both the free and the new fixed triple drug formulation. CONCLUSION: Human bioavailability studies provide direct straightforward information, particularly when studying compounds such as rifampicin and other major anti-tuberculosis drugs. The results of the present study indicate that the pharmacokinetic properties of rifampicin, isoniazid and pyrazinamide as assessed after individual and combined administration do not change when combined in a single pharmaceutical preparation. The bioavailability indices calculated based on plasma concentrations and urinary levels for all three drugs compared well.

Adult↗

PubMed1998

Superficial hyperthermia and irradiation for recurrent breast carcinoma of the chest wall: prognostic factors in 196 tumors.

PURPOSE: To correlate patient-, tumor-, and treatment-related factors with subsequent local tumor control. METHODS AND MATERIALS: From 1977 to 1990, 196 subcutaneous/superficial lesions (179 measurable, 17 microscopic) in 151 patients with recurrent breast carcinoma of the chest wall were treated with superficial 915-MHz microwave hyperthermia and irradiation. The definition of min t43 > or = 10 min is that all monitored tumor catheters had a minimum of 1 hyperthermia session with temperatures > 43 degrees C for at least 10 min. RESULTS: Factors correlating with local control on univariate analysis included length of survival (> or = 1 year vs. < 1 year) (p < 0.0001), specific absorption rate (SAR) (> or = 25% vs. < 25%) (p = 0.0001), minimum t43 > 10 min (p < 0.0001), tumor volume (p < 0.0001), tumor surface area (p < 0.0001), tumor depth (p = 0.0002), number of hyperthermia sessions (p = 0.0003), and current radiation dose (p = 0.0012). On multivariate analysis, the factors best correlated with ultimate local control were SAR (p < 0.001) and number of hyperthermia sessions (p = 0.003). CONCLUSIONS: Multivariate analysis supports the importance of adequate specific absorption rate (SAR) coverage as a better predictor of local control than tumor volume, surface area, or depth. The explanation is that SAR can be correlated with the tumor surface area and depth, depending on the hyperthermia applicator characteristics. It is recommended that future clinical trials stratify study lesions into either SAR > or = 25% or < 25% because this can be readily estimated prior to initiating treatment. It is also recommended that future clinical trials attempt to have adequate lengths of follow-up after therapy to assess the results in long-term survivors.

Adult↗

PubMed1998

Assessment of particle size distributions of health-relevant aerosol exposures of primary lead smelter workers.

Experiments were conducted at a primary lead smelter to investigate the particle size distributions of lead-containing aerosol to which workers were exposed, using personal inhalable dust spectrometers (PIDS) in specific smelter process areas. A total of 46 PIDS samples were evaluated, taken from the ore storage/mill, sinter plant, blast furnace and dross furnace process areas. Continuous particle size distributions were derived from the raw PIDS data employing a recently-developed optimisation routine, enabling determination of the percentages of inhalable, thoracic and respirable aerosol (in terms of lead content) as fractions of total lead aerosol. In addition, the mass ratios thoracic/inhalable and respirable/inhalable were also determined. Although the parameters of the measured particle size distributions ranged widely, some clear trends emerged. Firstly, the aerosols were coarser than had been expected based on measurements of previously reported workplace particle size distributions. This is thought to be due to the fact that the PIDS collects larger particles more efficiently than other instruments which have been used for such measurements. Secondly, there were significant differences in particle size distribution between process areas, in particular that the aerosol in the blast furnace area was generally finer than in the sinter plant. Such results may be used to support the results of workplace studies (reported elsewhere) into the differences between exposures to inhalable and 'total' aerosol as measured using different sampling instruments, especially when they are used together with knowledge of the physical processes governing the performances of such instruments.

Analysis of Variance↗

PubMed1997

Buckling transitions in superhelical DNA: dependence on the elastic constants and DNA size.

Buckling transitions in superhelical DNA are sudden changes in shape that accompany a smooth variation in a key parameter, such as superhelical density. Here we explore the dependence of these transitions on the elastic constants for bending and twisting. A and C, important characteristics of DNA's bending and twisting persistence lengths. The large range we explore extends to other elastic materials with self-contact interactions, modeled here by a Debye-Hückel electrostatic potential. Our collective description of DNA shapes and energies over a wide range of p = A/C reveals a dramatic dependence of DNA shape and associated configurational transitions on p: transitions are sharp for large p but masked for small p. In particular, at small p, a nonplanar circular family emerges, in agreement with Jülicher's recent analytical predictions: a continuum of forms (and associated writhing numbers) is also observed. The relevance of these buckling transitions to DNA in solution is examined through studies of size dependence and thermal effects. Buckling transitions smooth considerably as size increases, and this can be explained in part by the lower curvature in larger plasmids. This trend suggests that buckling transitions should not be detectable for isolated (i.e., unbound) DNA plasmids of biological interest, except possibly for very large p. Buckling phenomena would nonetheless be relevant for small DNA loops, particularly for higher values of p, and might have a role in regulatory mechanisms: a small change in superhelical stress could lead to a large configurational change. Writhe distributions as a function of p, generated by Langevin dynamics simulations, reveal the importance of thermal fluctuations. Each distribution range (and multipeaked shape) can be interpreted by our buckling profiles. Significantly, the distributions for moderate to high superhelical densities are most sensitive to p, isolating different distribution patterns. If this effect could be captured experimentally for small plasmids by currently available imaging techniques, such results suggest a slightly different experimental procedure for estimating the torsional stiffness of supercoiled DNA than considered to date.

Chemical Phenomena↗

PubMed1997

Evaluation of two inversion techniques for retrieving health-related aerosol fractions from personal cascade impactor measurements.

Personal cascade impactors are widely used in occupational aerosol exposure assessment. Appropriate algorithms must be used to determine the total particle size distribution from masses collected on the stages of the cascade impactor. Such algorithms should be regarded as integral components of the measurement system. When evaluating algorithms for reconstruction of size distributions from cascade impactor data, the eventual use of the size distribution must be considered. So, from an industrial hygiene perspective, an appropriate basis for comparison of given measurement systems is the accurate retrieval of the inhalable, thoracic, and respirable aerosol fractions as described by the new, internationally accepted, particle size-selective sampling conventions (which are expected to form the basis of future aerosol standards). This article compares two inversion routines in terms of their abilities to retrieve these aerosol mass fractions relative to the masses that would have been obtained using an ideal sampler that perfectly followed the sampling convention. The routines were used to invert measurements made with the Institute of Occupational Medicine personal inhalable dust spectrometer, a miniature cascade impactor that aspirates the inhalable aerosol fraction, and the results are presented graphically as contours of equal mass bias. The simplest algorithm, based on the a priori assumption of lognormality, appears to provide the best results.

Aerosols↗

PubMed1997

Incidence of extrapyramidal syndromes in AIDS patients and a comparison group of medically ill inpatients.

The authors retrospectively reviewed the charts of 29 inpatients with AIDS and 24 medically ill inpatients, all of whom were exposed to neuroleptics. Results adjusted for age, gender, type and dosage of neuroleptic, and extrapyramidal prophylaxis indicated that inpatients with AIDS were 7 times more likely to develop extrapyramidal syndromes (EPS) from neuroleptics than the comparison group of medically ill inpatients. Possible neuroanatomic, neuropathologic, and neurochemical reasons for the vulnerability of patients with AIDS to EPS are reviewed.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Assessment of particle size distributions in workers' aerosol exposures.

A full description of the regional dosimetry of inhaled workplace aerosols requires information about the particle aerodynamic size distributions of inhaled aerosols for appropriate health-related species. Therefore, since the late 1970s, interest has risen in how to assess workers' aerosol exposures in terms of particle fractions which may be inhaled and penetrate down to different parts of the human respiratory tract. The personal inhalable dust spectrometer (PIDS) was proposed as a versatile sampling instrument for assessing workers' exposures along these lines. Raw data from this cascade impactor-based instrument are obtained initially in terms of discrete particulate masses collected on the individual impactor stages. Recovery of the desired particle size distribution is difficult because the mathematical inversion problem is 'ill-posed' (i.e., there are many possible solutions that would be consistent with the observed masses). However, a routine has been developed that involves considerations of the detailed deposition characteristics of the impactor stages, measurement errors and a priori assumptions about the shape of the expected particle size distribution (e.g., log-normal). These differ from other such routines in that account is taken not only of aerosol deposited at the impactor stages but also that collected inside the entry system. Hence the final result covers the whole inhalable range, for particles up to and exceeding 100 microns in aerodynamic diameter. The PIDS has recently been used in studies in several industries to examine inhalable particle size distributions for individual exposed workers. This paper considers the results of such studies, and discusses how they may be used to provide information not only about the inhalable, thoracic and respirable fractions identified in the latest particle size-selective sampling criteria (upon which it is expected that future aerosol standards will be based), but also other health-related fractions that may be defined numerically (including, for example, alveolar deposition fractions for workers with different breathing patterns relevant to the type of work undertaken).

Aerosols↗

PubMed1996

A simple auditory oddball task in young adult males at high risk for alcoholism.

The reduction in the amplitude of the auditory P300 in young adult males at high risk for alcoholism has not been as consistently replicated as has been the reduction in the visual P300 amplitude in the same group. The easier nature of the auditory task was thought to be responsible for the inconsistency. We examined the auditory P300 amplitude in a group that has not yet been studied, young adult sons of alcoholics (mean age = 24.9 years, n = 48), and compared them with age and sex-matched controls (mean age = 27.8 years, n = 23). We found the auditory P300 amplitude to be reduced in the high-risk group and this reduction to be the greatest over the posterior centroparietal and occipital areas when individual leads were examined. We further analyzed the data using current source density, a mathematical transformation that circumvents some of the errors inherent in measuring scalp-evoked potentials, and found reduced current source density in the high-risk group in the posterior central and parietal areas. Thus, we found that a simple auditory oddball task was effective in eliciting P300 differences in groups at high and low risk for alcoholism. The clinical significance of the P300 is discussed, as well as the relevance of task difficulty in eliciting auditory P300 differences in young males at high risk for alcoholism.

Adult↗

PubMed1996

A preliminary study of apolipoprotein E genotype and psychiatric manifestations of Alzheimer's disease.

We evaluated the frequency of depression and psychosis in 46 patients with AD and 135 control subjects with the apolipoprotein (APO) E3/3 or E3/4 genotype. Patients with AD and the APOE3/4 genotype had a more than threefold increase in the signs of depression and psychosis when compared with either patients with the APOE3/3 genotype or to control subjects. Our preliminary study suggests that the phenotype of AD associated with the epsilon 4 allele is more likely to include psychiatric manifestations.

Aged↗

PubMed1995

Evaluation of an infrared open-path spectrometer using an exposure chamber and a calibration cell.

This study evaluated the use of a controlled exposure chamber and calibration cell to investigate the performance of open-path remote sensing instruments for workplace monitoring of pollutants. An open-path infrared spectrometer was deployed in a chamber, and a range of homogeneous air concentrations were generated using the tracer gas sulfur hexafluoride (SF6). Open-path measurements were compared with point-sample measurements taken along the beam and analyzed using an infrared (IR) and electron capture detector (ECD). A five-compartment calibration cell placed in the optical path was used to simulate heterogeneous concentrations of pollutants. Fifteen concentration patterns were created by injecting different volumes of SF6 into each compartment. Open-path spectrometer measurements were compared with compartment concentrations measured using an ECD. Results indicated that stable homogeneous and heterogeneous concentrations of SF6 were generated in the controlled exposure chamber and five-compartment calibration cell, respectively. Overall, individual open-path measurements were within 20% of point samples measured with the IR and ECDs. The open-path spectrometer measurements had a consistent positive bias of about 12%. Exposure chamber experiments uncovered remote sensing instrument design aspects that could adversely impact its use for indoor monitoring. The weight and size of the instrument make it useable only in a fixed position, thus limiting spatial coverage of the beam in a room. The instrument components were not air-tight, resulting in overestimation of some open-path concentrations. A controlled test chamber and a long calibration cell placed in the optical path are useful tools for evaluating a variety of open-path spectrometer instrument performance issues relevant to industrial hygiene monitoring.

Air Pollutants, Occupational↗