Biomedical subjects
Publications and source records attributed to J T Walker.
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This paper assesses the cause of particulate formation in vials of the experimental antitumor agent bisnafide and investigates pharmaceutical techniques to reduce the number of particulates in the product. Solution preparation and particulate isolation were performed under Class 100 laminar air flow. Reversed-phase HPLC and infrared microscopy were used to characterize drug and isolated particulate matter, whereas a Hiac particle counter was used to quantify the particulate matter. Particulate matter was observed following agitation of the drug solutions and was found to be associated with specific lots of drug substance. HPLC of the isolated particulate matter indicated that the particulates consisted largely of bisnafide and impurities that were identified as the products of photodegradation, confirmed to be the result of the photolytic cleavage of bisnafide to form a poorly soluble aldehyde. The aldehyde may, in turn, interact with bisnafide molecules to form the particulate matter as suggested by the observed pH-dependent reversibility of the particulate phenomenon. The particulate matter could be reduced by protecting solutions of bisnafide from light during chemical synthesis and production of the dosage form and, alternatively, by reducing the solution pH to 3.0 or less, addition of surfactants below their critical micelle concentration, and removal of impurities by froth flotation of the bisnafide solutions.
The objective of this work was the development and validation of procedures designed to clean glass and stainless steel surfaces after exposure to the experimental anticancer drug, bisnafide. The cleaning procedures, using 5% acetic acid water, Alconox, and water, were validated using a wipe test and an HPLC method developed to quantitate low levels of bisnafide. The procedure developed for cleaning stainless steel is more stringent than that for glass because of the apparent greater affinity of bisnafide for stainless steel. The HPLC method is shown to be linear and reproducible (RSD 4.4% or less), with a detection limit of 4 ng/ml. Recoveries of 95.1, 83.5, and 70.0% were obtained from the wipe pads, glass plates, and stainless steel plates, respectively, at levels of approximately 0.7-1.7 ng/cm2. The cleaning procedures are shown to clean glass and stainless steel plates to less than 0.19 and 0.33 ng bisnafide/cm2, respectively. These results further demonstrate the need to fully characterize the recovery of drugs from surfaces and swabs in order to properly validate cleaning procedures. In addition, they demonstrate the potential need to develop surface-specific cleaning procedures.
Aqueous solutions of 5% and 10% trisodium phosphate (TSP), 0.1% and 0.5% cetylpyridinium chloride (CPC), 1% and 2% lactic acid (LA), and 0.1% and 0.5% grapefruit seed extract (DF-100) were evaluated in prechill spraying for reducing Salmonella typhimurium attached on chicken skins. Chicken skins were inoculated with S. typhimurium and then sprayed with the selected chemical solutions for 30 sec at 206 kPa and 20 degrees C. After chemical spraying, the skins were rinsed by spraying tap water for 30 sec. Each skin was stomached in buffered peptone water (BPW) for 1 min. The stomaching water was then diluted serially, inoculated onto both xylose lysine tergitol (XLT4) agar and Aerobic Plate Count (APC) Petrifilm, and incubated for 24 hr at 37 degrees C. The results showed that the numbers of Salmonella on the chicken skins after the chemical spraying were significantly lower than those without spray (P < 0.05). The CPC reduced Salmonella by 1.5 to 1.9 log10. TSP resulted in a 2.1 to 2.2 log10 reduction of Salmonella and DF-100 produced a 1.6 to 1.8 log10 reduction of Salmonella. The LA had a number of Salmonella with a 2.2 log10 reduction. The 0.5% CPC resulted a significantly greater reduction in Salmonella than 0.1% CPC. There were no significant differences in Salmonella reduction between different concentrations of the other three chemicals.
A cancer mortality study of 8,163 deaths occurring among persons formerly employed as laundering and dry cleaning workers in 28 states is described. Age-adjusted sex-race cause-specific proportionate mortality ratios (PMRs) and proportionate cancer mortality ratios (PCMRs) were computed for 1979 through 1990, using the corresponding 28-state mortality as the comparison. For those aged 15-64 years, there were excesses in black men for total cancer mortality (PMR = 130, 95% confidence interval (CI) = 105-159) and cancer of the esophagus 1 (PMR = 215, 95% CI = 111-376), and in white men for cancer of the larynx (PMR = 318, 95% CI = 117-693). For those aged 65 years and over, there were statistically nonsignificant excesses for cancer of the trachea, bronchus, and lung in black women (PMR = 128, CI = 94-170) and for cancer of other and unspecified female genital organs in white women (PMR = 225, CI = 97-443). The results of this and other studies point to the need for the effective implementation of available control measures to protect laundry and dry cleaning workers.
Urinary catheters and legs bags were simultaneously colonized by Escherichia coli and Proteus vulgaris using a model urinary drainage system. the system was continuously supplied with filter-sterilized artificial urine using a diurnal flow pattern. The extent of colonization was determined by assessment of both planktonic and biofilm formation over time. Contamination of the catheters resulted in rapid colonization of the whole system within a 24 h period. Contamination of the leg bags resulted in an ascending biofilm formation over a four-day period. Results indicated that infection risk could be minimized by changing the catheter and leg bags at least once a week. The design of the leg bags was not found to influence the rate or extent of biofilm formation.
Biofilms containing diverse microflora were developed on bitumen-painted steel and glass tiles suspended in a chemostat model of a water distribution system. Escherichia coli, taken from a naturally occurring biofilm, was transformed with a plasmid containing the anaerobically induced nirB promoter fused to the lacZ reporter gene. The resulting transformant, PRB1, was introduced into the chemostat. After 7 and 13 days, an E. coli strain with an anaerobically induced Lac+ phenotype was present in the biofilm. Development of an episcopic differential interference contrast technique combined with UV fluorescence microscopy enabled the simultaneous visualization of E. coli in the biofilm using a fluorescent probe to detect expression of the gusA reporter gene and a lacZ fluorescent probe to monitor anaerobic expression of beta-galactosidase from pnirB.
Immuno-compromised patients are particularly susceptible to Legionnaires' Disease. After three cases of the disease occurred in a hospital, a continuous dosing regime using chlorine dioxide was initiated to replace chlorination of the water system. This study identified a number of factors which may have resulted in conditions that would encourage the growth of the water-borne pathogen Legionella pneumophila. The residual chlorination was inadequate for microbial control at the taps furthest from the four storage tanks, of which two were found to be in excess for demand. The temperature of the water in the storage tanks was also found to be above 20 degrees C; a temperature that would encourage microbial growth. A back-up calorifier was present and was found to contain L. pneumophila, and linseed oil-based sealants that provide nutrients for microbial growth were also prevalent as jointing compounds in the water circuit. Although the shower heads were routinely disinfected, a requirement was identified to also disinfect the shower hoses. No L. pneumophila were recovered from the water system after the chlorine reduced dioxide disinfection trial. Biofilm was also dramatically reduced after disinfection; however, small microcolonies were identified and proved to be metabolically active when tested with a metabolic indicator. Using light and fluorescence microscopy, the pipe samples removed from the water system were rapidly analysed for biofouling, complementing existing microbiological methods.
Women comprise the majority of workers exposed to ethylene oxide during sterilization of medical instruments and supplies. This article evaluates molecular, cytogenetic, and hematologic effects of ethylene oxide on 68 women workers employed in nine hospitals in the United States and one hospital in Mexico. Workers were classified by three exposure categories: none (0), low (> 0-32 ppm-hrs), and high (> 32 ppm-hrs). Hematologic effects were evaluated using complete blood count with differential, which has been questioned as a test for screening ethylene oxide-exposed workers. A statistically significant decrease in hematocrit (n = 0.02) and hemoglobin (P = 0.03) levels, an increase in lymphocyte percentages (P = 0.04), and a relative decrease in neutrophil percentages (P = 0.03) with exposure were observed in US workers. The absolute number of lymphocytes, however, showed no relationship with exposure. No statistically significant results were seen for Mexican workers, although hematocrit decreased with exposure. An exposure-response relationship for the percentage for lymphocytes (positive) and neutrophils (negative) in US subjects and for neutrophils (positive) in Mexican subjects was seen. No overall relation with exposure was observed for total number of white cells. Molecular and cytogenetic results are also reported for the 68 women, who constitute a subgroup from a previous report. US women workers showed a statistically significant exposure-response relationship for ethylene oxide and hemoglobin adducts (P = 0.0002) and sister chromatid exchanges (P = 0.001). For micronuclei, the difference (P = 0.02) between low and high exposure was statistically significant. In Mexican workers, an exposure-response relationship was observed (P = 0.002) for hemoglobin adducts but not for sister chromatid exchanges or micronuclei.
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A gas chromatographic-mass spectrometric method was used to detect Legionella pneumophila in biofilms in potable water containing a complex microbial consortium. The unique 3-hydroxy and 2,3-dihydroxy fatty acids of the L. pneumophila lipopolysaccharides (LPS) were detected in both the planktonic phase of the continuous culture model and in the biofilms forming on both copper and polyethylene substrata. The technique confirmed that lower numbers of Legionella colonised and grew on copper in comparison to polyethylene and offers promise for routine detection of Legionella in biofilms in the environment.
Until the late 1980s, epidemiologists in general did not individually notify subjects of the results of epidemiological studies. Now that they are beginning to do so, the question arises of how best to notify those involved. In general, the methods, the processes and the policies related to effectively communicating risks to workers have not been thoroughly examined in the scientific literature. This is especially true in situations where workers have already experienced the exposures that led to increased risks for disease. The recent increasing numbers of notifications have raised several methodologic issues, which are examined in terms of: (1) the content of notification, (2) the process of notification, and (3) the evaluation of the impact and effectiveness of notification. Too often in the discussion concerning notification, attention is paid to the content but the process and evaluation are rarely considered. The potential impact and effectiveness of notification have been raised as reasons for or against notification, but rarely has there been a concerted effort to evaluate a notification in this regard. This workshop was designed to address all these issues. The ultimate goal is to improve communications for workers.
A retrospective cohort mortality study was conducted among 7814 white shoe manufacturing workers followed from 1940 through 1982. The workers were potentially exposed to solvents (including toluene) and solvent-based adhesives. Benzene may have been present as an impurity of toluene. Mortality due to leukemia and aleukemia was not statistically significantly elevated. Statistically significant excess mortality due to cancer of the trachea, bronchus and lung was observed in the total cohort [standardized mortality ratio (SMR) 147, 95% confidence interval (95% CI) 120-180] and showed a statistically significant trend in standardized relative risk with increasing potential latency, but not with increasing duration of employment. Chronic nonmalignant respiratory disease was significantly elevated among the men (SMR 158, 95% CI 114-217) but was less than expected among the women (SMR 79), a finding suggesting a possible contribution of smoking to the mortality from respiratory cancer. However, adjustment for the potential effects of smoking did not completely eliminate the increased risk for lung cancer.
Operators of hospital sterilizers that use ethylene oxide were studied to determine if there was a relationship between exposure and a battery of biological markers. A total of 73 workers from nine hospitals in the United States (U.S.) and one hospital in Mexico City was evaluated for ethylene oxide exposure during four months prior to collection of peripheral blood. The frequency of hemoglobin adducts (p = 0.0006) and sister-chromatid exchanges (SCEs) (p = 0.002) increased with cumulative exposure to ethylene oxide in U.S. subjects when controlling by regression analysis for various confounding factors, including cigarette smoking. Hemoglobin adducts, but not SCEs, were also increased in Mexican subjects (p = 0.0012). Chromosomal micronuclei showed no consistent relationship with exposure. The U.S. study participants were classified by four-month cumulative exposure levels of 10 ppm-h (n = 8), greater than 0 to 32 ppm-h (n = 32) and greater than 32 ppm-h (n = 11) of ethylene oxide exposure. The group with an exposure of greater than 32 ppm-h had an increased frequency of hemoglobin adducts (p = 0.002) and SCEs (p = 0.0001) compared to the nonexposed group. The estimated mean of the 8-h time-weighted average (8-h TWA) exposure levels for the highest U.S. exposure group (greater than 32 ppm-h) was 0.16 +/- 0.007 ppm (mean +/- SD). A similar exposure-related differential was observed in the Mexican subjects for hemoglobin adducts (p = 0.04) but not for SCEs. The latter finding may have been due to longer shipping times for the specimens in the cytogenetic assays. The estimated mean of the 8-h TWA exposure levels for the highest Mexican exposure group (greater than 32 ppm-h) was 0.48 +/- 0.08 ppm. This study is the third to suggest that exposures less than the U.S. OSHA standard of 1 ppm 8-h TWA result in biochemical and biologic changes. It is not known whether these changes may be indicative of increased risk of disease; however, they do appear to reflect exposure to relatively low levels of ethylene oxide. The exact meaning of these changes is unknown.
Minimally invasive surgery appears to be gaining popularity, and removal of the gallbladder by laparoscopic methods is one such procedure for which there is recent enthusiasm. The concerns about safety, morbidity, and mortality in contrast to standard cholecystectomy are being evaluated. To address these concerns we reviewed the first 230 laparoscopic cholecystectomies done by one surgical group from October 1990 to September 1991. There were 161 women and 69 men with an average age of 50 years. The average length of stay was 2.1 days, most patients being discharged in 24 hours. Complications occurred in 14 patients (6%). The one death was unrelated to the gallbladder surgery. Operative cholangiograms were done as frequently as possible. It appears that laparoscopic cholecystectomy can be done safely and with a shorter hospital stay. Complications are similar to those seen with standard cholecystectomy.
Attempts to improve radiation dose estimates to infants and children are hampered because of the lack of mathematical models that describe the age variation in anatomical and physiological parameters. Specifically, for one anatomical parameter, organ size, there are no growth models available to the health physics community. In this paper, an empirical mathematical model is introduced for estimating age-specific masses of two ICRP target organs: the spleen and liver. That model, the Power Logistic Additive (PLA) growth model, is fitted to ICRP 23 organ growth data to determine five growth parameters. This model assumes that organs grow under the influence of two main processes: a primary (power function) and a sexual maturation (logistic function) process, which are additive from birth to adulthood. The results show that the model describes the ICRP growth data quite well. Growth parameters and tables listing the predicted masses and mass velocities as a function of age for each organ are provided for application in the ICRP modeling system.
This study was designed to assess the effects of organization, luminance contrast, sector angle, and orientation on a new, highly ambiguous Cs-keyhole figure. Organization and contrast were the most important factors, and sector angle also influenced figure-ground relationships. There was no significant effect of orientation, nor was there any significant interaction between any of the factors. Several new measures of figure-ground organization were developed, such as ambiguity ratios based on reaction times and on ratings of the strength of perceived organizations, providing new quantitative measures of figure-ground relationships. Distances measured across figural regions appeared smaller than equal distances across the ground in the new reversible figure, and also in Rubin's classic vase-face figure presented in real and subjective contours. Inducing a perceptual set to see a particular organization in a reversible figure influenced the apparent distance across that organization. Several possible explanations of the observed effects are considered: (1) an instance of Emmert's law, based on the difference in apparent depth of figure and ground; (2) an aspect of the Müller-Lyer illusion; (3) a feature-detector model of contour attraction; (4) a natural set or predisposition to see a figure as smaller; and (5) framing effects. The first two explanations appear the most promising.
Suppose an observer views a distant object through a window in the far wall of a room or corridor--a visual scene constituting a vista. If the observer moves toward the window, then the distant object will shrink in apparent size and appear farther away. These effects are paradoxical, because the distant object appears smaller as its visual angle increases. The vista paradox occurs under many other real-world conditions, such as viewing a distant object while moving out of the mouth of a valley, or driving across a topographic crest. In the present study, framing effects and the equidistance tendency are considered as possible factors. However, an explanation based on the dynamic relationship between the visual angle of the framing portion of a vista and the visual angle of a distant object appears more promising.