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8070774 | [The pressor response induced by electrical stimulation of hypothalamic paraventricular nucleus in the cat]. | The experiments were performed on 24 adult cats anesthetized with chloralose and urethane, paralyzed and artificially ventilated. Electrical stimulation of the hypothalamic paraventricular nucleus (PA) with a 12s train of 0.1-0.5 mA and 0.2ms square wave pulses at a frequency of 80 Hz induced a marked increase in arterial blood pressure (n = 19). The 22 points stimulated with maximum responses were clustered in the posterior dorsomedial part of the PA, among them 11 points were associated with an increase in heart rate and 7 a decrease. The remaining 4 points were associated with no change of heart rate, and situated in the anterior part of the PA. Electrolytic lesion of bilateral caudal half of the nucleus of solitary tract (NTS) had no significant effect on cardiovascular responses elicited from electric stimulation of the PA (n = 5). The results suggest that the PA is one of the important centers regulating cardiovascular activity; the NTS may not be involved in the PA pressor response. |
8070775 | [Effect of nitrendipine on hypoxic myocardial energy preservation]. | To investigate the relationship between post-hypoxic myocardial dysfunction and myocardial energy reserve and the effect of nitrendipine on hypoxic myocardial energy preservation, we submitted the Langendorff isolated perfused rat hearts to 30 minutes of hypoxia and then 20 minutes of reoxygenation. Nitrendipine was infused continuously 10 minutes before hypoxia and throughout the following perfusion. The high energy phosphate contents of isolated perfused rat hearts before and 30 minutes after hypoxia were measured by using reverse high performance liquid chromatography. The results showed that nitrendipine, when administered prophylactically, enhanced myocardial energy reserve and relieved high energy phosphates' depletion during 30 minutes of hypoxia insult. It is suggested that nitrendipine has an effect on hypoxic myocardial energy preservation. |
8070776 | [The effects of superoxide dismutase on acute myocardial ischemia and lipid peroxidation in rabbits]. | There are controversies about the action of superoxide dismutase (SOD) on acute myocardial ischemia, but report about the serial changes of serum malondialdehyde (MDA) levels after myocardial infarction and the relationship between serum levels of MDA and size of myocardial infarct has not yet been found in literature. We made a study, using the acute myocardial infarct model of New Zealand rabbits. The results indicated that SOD significantly reduced the total number of pathologic Q-wave, the myocardial infarct size and serum MDA levels. A significant correlation was found between 48-hour serum MDA levels and 48-hour infarct size. Therefore, it is suggested that free radicals might play an important role in pure acute myocardial ischemic injury; SOD, administered early, could inhibit lipid peroxidation and thus protect the myocardium, and serum MDA levels might be regarded as a specific criterion for the diagnosis of myocardial infarction. |
8070777 | [Relationship between effect of sodium selenite on blocking mesothelioma induced by crocidolite and level of serum lipid peroxidation in rats]. | This paper reports the relationship between the effect of sodium selenite on blocking mesothelioma induced by crocidolite and the level of serum lipid peroxidation in rats. The result showed that sodium selenite solution (5ppm) might not only block and slow down the formation and growth of mesothelioma but also prevent peroxidation produced by crocidolite. The incidence of mesothelioma and the content of LPO in the Se group were lower than those in the positive control group in different periods (0-430 days and 0-530 days respectively). The survival time (341 days) of the first case of mesothelioma and the death peak period (530-630 days) in the Se group were longer than those (237 days and 430-530 days respectively) in the positive group. There was a good correlation between the change of G value in the Se group and the change of G value in the positive control group in different experimental periods (r = 0.9991). These results will provide scientific bases for recognizing the mechanism of mesothelioma and for furthering the practice in the people exposed to asbestos. |
8070778 | [Effects of jute, ramee, flax dusts on rabbit alveolar macrophages in vitro]. | The effects of jute, ramee, flax dusts on alveolar macrophage (AM) were observed by cell culture. The results indicated that AM could be damaged by all of the three kinds of dusts. The viability was decreased. The activity of lactic dehydrogenase (LDH) and acid phosphatase (AcP) in the culture supernatant was increased. The morphology of AM was damaged. But the toxicity effect of the three dusts was less than that of SiO2 and chrysotile asbestos (CH) in the same dosage. Meanwhile, the functions of AM were changed. The levels of IgG, plex (IC) and histamine (HIS) were increased. As to the degree of toxicity and ability of stimulating AM to secrete biomedium by the three dusts, the effect of flax was weakest. |
8070779 | [Histopathologic and bone histomorphometric studies of pigs' phalanges in an endemic fluorosis area]. | This paper presents the histopathologic changes and bone histomorphometry of ten pigs' phalanges in an endemic fluorosis area. Ten pigs from nonendemic area served as control. Results showed that the fluoride contents of blood, urine and bone were markedly increased and the calcium contents of blood were markedly decreased in endemic pigs than those in nonendemic ones. Histopathologic and bone morphometric studies of the phalangeal bones of pigs from endemic area indicate that osteoporosis is the predominant change. |
8070780 | [Computer assisted studies on the structural requirements for the mutagenicity in Salmonella reversion assay for organophosphorus pesticides]. | Computer assisted molecular fragment evaluation (CAMFE) program has been established and applied to the data set analysis of the mutagenicity of 59 organophosphorus pesticides (OPPs) in Salmonella reversion assay. The results favour the hypothesis that the mutagenic properties of OPPs lie in their alkylation to DNA mainly by the molecular fragments containing methyl groups rather than those containing ethyl groups. Oxygen atom in phosphoryl group may prompt the mutagenic ability induced by OPPs; However, the mutagenic ability may be decreased by sulfur atom, the substitute of oxygen atom at the same site in PPs structure. It was suggested that, among the most relevant fragments, the methoxyphosphinyl group appears as mon structural subunit responsible for the activities detected in the Salmonella reversion assay, while the ethyl thionophosphinyl group appears as the descriptor of negative results. |
8070781 | [The causes responsible for recurrence of pituitary adenomas and an evaluation of reoperation effects]. | Four hundred and twenty one cases of transfrontal removal of pituitary adenomas were presented. Of these 23 had recurrence of tumor which was confirmed by reoperation and histopathological examination. The rate of recurrence decreased while the patients' age increased. plete removal of the tumor tissue was one of the most important causes of recurrence. Invasiveness was another important cause. Most of the tumors in this series were large and had pathologically proven invasiveness. At the reoperations, there were evidences of worse invasiveness, especially the infiltration of adenomas into the capsules and adjacent structures. There was a case of Nelson's syndrome, suggesting the endocrine causes of recurrence. Apparent adhesion and topographic disorders were found during reoperation, improvement of visual impairment decreased obviously, and the mortality rate increased; therefore, the reoperations should be decided with great deliberation. |
8070782 | [Risk factors of prostate cancer--a matched case-control study]. | A 1:2 matched case-control study was used to determine the risk factors of prostate cancer. Twenty-seven cases of prostate cancer were matched with an equal number of other malignant tumor cases (non-urological tumor) and other urological cases (non-malignant tumor). Both study and control groups were the same in age, sex, race, and day of admission. All of these patients were treated in the First Affiliated Hospital of West China University of Medical Sciences. The questionnaire was used to survey the both groups of patients. Such data as diet, lifestyle, marital status and past history of other prostate diseases were obtained. Single factor analysis and multiple conditional logistic regression analysis were used to estimate the relative risk (RR), 95% confidence interval (95% CI) and P values. Statistical analysis was performed using the Egret, Epilog soft ware. The results were as follows: 1. Increasing dietary vitamin A was associated with a significant decrease in the risk of prostate cancer (RR = 0.948, 95% CI = 0.9309-0.9947, P = 0.029). This factor also showed dose response gradients. The relative risk was decreasing with exposure dose increasing. 2. The positive previous prostate history, such as prostatitis and benign prostate hyperplasia, increased the risk of prostate cancer (RR = 6.385, 95% CI = 1.046-38.97, P = 0.045). 3. Another finding in the widower, divorce and remarried men (RR = 4.312, 95% CI = 1.367-13.6, P = 0.013). And 4. There was no relationship between the risk of prostate cancer and dietary fat intake, vasectomy, socioeconomic status, familial malignant tumor history, smoking and alcohol consumption.(ABSTRACT TRUNCATED AT 250 WORDS) |
8070783 | [Recurrent astrocytoma versus primary astrocytoma: a comparative study of morphological changes of 32 cases]. | The pathologic morphological changes of 32 cases of recurrent astrocytoma (RA) and primary astrocytoma were reported. During recurrence, 20 cases (62.5%) of astrocytomas transformed into cases at higher grades. Twelve cases remained at the same grades as primary tumors. Among 21 cases of RA at grades III and IV, 15 cases (71.4%) came from primary astrocytomas, grades I and II. The change from astrocytoma grade I to grade III or IV took time longer than that from grade II to grade III or IV. The recurrent time of astrocytomas with different grades showed no statistical differences. Postoperative radiotherapy/chemotherapy did not play a major role in grading changes and recurrent time. |
8070784 | [Malignant lymphomas in childhood in Sichuan province--a clinicopathological analysis of 304 cases]. | A clinicopathological study of 304 cases of malignant lymphomas (ML) in children in Sichuan province is reported. One hundred and sixty of them were Hodgkin's disease (HD). The ratio between males and females was 5.7 to 1. The disease was more prevalent in children aged from 5 to 9. Cervical lymph nodes were more easily involved. Extra-nodal HD wasn't found in these cases. When subtypes of HD were concerned 62.5% of cases belonged to mixed-cellularity HD. The prognosis of HD was better than that of non-Hodgkin's lymphoma (NHL). The remaining 144 cases were NHL. The ratio between males and females was 3.4 to 1. The disease was more prevalent in children aged from 4 to 14. Eighty four percent of NHL primarily originated from superficial lymph nodes and the other 16.0% of NHL was of extranodal involvement. Seventy two point nine percent of cases in this group was of high grade malignancy. Among them the lymphoblastic type of NHL occupied 44.5%. On the other hand, the follicular type of NHL was rare (0.7%). The specialities of malignant lymphomas in childhood in China are also discussed in the present report. |
8070785 | [Biochemical effects of maternal intravenous and intra-amniotic infusion of amino-acids on fetal blood]. | Before elective cesarean section, 58 normal term's pregnant women were randomly divided into three groups: intravenous (25 women), intra-amniotic (8 women) and control (25 women) groups. The first two groups received maternal intravenous and intra-amniotic infusion of amino acids respectively. The results showed that maternal intravenous administration of amino-acids led to increased levels of amino acids in maternal venous blood and fetal umbilical cord blood plasma (P < 0.05). There was no increase in fetal uptake of amino acids (P > 0.05). The levels of amino acids in fetal umbilical cord blood plasma of the intra-amniotic group were higher than those of the control group (P < 0.05) and intravenous group (P < 0.05). In the intra-amniotic group, the fetal uptake of amino acids increased (P < 0.05). There were no significant differences in fetal umbilical arterious pH, PO2 and PCO2 among the three groups (P > 0.2). Intra-amniotic infusion of 250ml amino-acids did not change the pressure of amniotic cavity (P > 0.2). The authors suggested that intra-amniotic infusion of amino acids, as a paraplacental nutritional route, should be more effective in the treatment for cases of intrauterine fetal growth retardation particularly for those panied by severe placental lesions. |
8070786 | A conceptual model of overexertion [correction of oxerexertion], safety, and risk of injury in occupational settings. | A conceptual generic model for fatigue-mediated overexertion, margin of safety, and job-related risk of injury is proposed. The model has been built with the variables of force, effective exposure in time domain, and motion of the exertion in space. With the proposed model, the physical risk factors can be identified and quantified. It also allows one to gauge a relative contribution of various integral factors involved in fatigue-mediated occupational injuries. Although the model is based on established relationships between the job variables (strength [force], frequency-duration of exposure, recovery from exposure, and range of required motion) and the injuries sustained, it has not been validated within any single study. The model provides a framework for numerous validation studies. With availability of more information through such studies, the model can be appropriately refined for accuracy of its prediction. |
8070787 | Effect of mailbag design on musculoskeletal fatigue and metabolic load. | The need for an alternative mailbag to the conventional U.S. postal mailbag, which hangs at the side over one shoulder, was investigated. Based on the results of a pilot study, two types of alternative mailbags, both including waist support and one that splits the load into two parts, are mended. The metabolic energy requirement and lateral trunk muscle fatigue resulting from the use of the alternative mailbags pared with those resulting from the conventional U.S. postal mailbag. The alternative mailbags resulted in no significant change in metabolic load. Both alternative mailbags resulted in significantly less lateral trunk muscle fatigue. It is proposed that this reduction in fatigue would result in reduced musculoskeletal stress and reduced potential for back injury. |
8070788 | Physical fatigue in high and very high frequency manual materials handling: perceived exertion and physiological indicators. | This paper presents the results of a preliminary laboratory study undertaken to determine the perceived exertion and physiological responses of highly trained and experienced workers to high (up to 16 repetitions/min) and very high frequency (above 16 repetitions/min) manual lifting, lowering, and carrying/turning tasks. The results indicate that workers engaged in such highly repetitive and physically demanding tasks may operate at psychophysical workloads that may clearly be considered physically fatiguing and unacceptable according to the current physiological design criteria. In this study subjects performing lifting and lowering tasks, on the average, operated at 57% and 52% of their uphill treadmill aerobic capacity, respectively. For carrying and turning tasks, the average metabolic energy expenditure rate corresponded to 43% of subjects' aerobic capacity. The overall heart rates of the study subjects were 155 beats per minute (bpm) for lifting, 144 bpm for lowering, and 142 bpm for carrying and turning. These physiological responses, pared with mended physiological design criteria, are excessively high. The ratings of perceived exertion (RPE) for the shoulder, back, and whole body were highest for lifting (range, 10.20-15.50) and least for carrying and turning (range, 10.30-13.40; carrying and turning activities also included RPE of arms). Generally workers perceived the associated physical exertions as acceptable. |
8070789 | A large database study of the factors associated with work-induced fatigue. | puter survey was conducted using the records of 3705 temporary employees who reported job fatigue during their assignments; 10,000 additional employees, who did not report fatigue, were also surveyed in order to establish base rates. Low job challenge, poor-quality supervision, low job control, poor job performance, and low pay rates were associated with employees' experiencing job fatigue. Low physical demand and low information-processing demand positions were also associated with the experience of fatigue, possibly because these variables fell below minimal thresholds necessary to maintain arousal and avoid boredom. The upper portion of the arousal-performance curve was not properly evaluated in this survey. Fatigue may result from processing too much or too little information. Motivational factors probably serve to moderate this relationship. |
8070790 | Work practices, fatigue, and nuclear power plant safety performance. | This paper focuses on work practices that may contribute to fatigue-induced performance decrements in mercial nuclear power industry. Specifically, the amount of overtime worked by operations, technical, and maintenance personnel and the 12-h operator shift schedule are studied. Although overtime for all three job categories was fairly high at a number of plants, the analyses detected a clear statistical relationship only between operations overtime and plant safety performance. The results for the 12-h operator shift schedule were ambiguous. Although the 12-h operator shift schedule was correlated with operator error, it was not significantly related to the other five safety indicators. This research suggests that at least one of the existing work practices--the amount of operator overtime worked at some plants--represents a safety concern in this industry; however, further research is required before any definitive conclusions can be drawn. |
8070791 | Extended workdays in an underground mine: a work performance analysis. | panies in different industrial sectors are exploring alternative work schedules to deal with diverse problems associated with shiftwork. The use of extended workday schedules (regular shift lengths exceeding 8 h pressed workweeks) is attracting growing interest in many industries that use continuous operations. To address concerns regarding possible fatigue effects on safety and work performance associated with such schedules, the U.S. Bureau of Mines conducted a two-phase study at an underground metal mine in western Canada. Data were collected before and after a group of workers employed at the mine changed from an 8- to a 12-h schedule. Results indicate nearly unanimous acceptance and improved sleep quality associated with the new schedule. In general, fatigue-sensitive behavioral and physiological performance measures show either no change or improvement with 12-h shifts. We conclude that the extended workday schedule should be retained but periodically reevaluated. |
8070792 | Fatigue and the shiftworker: firefighters working on a rotating shift schedule. | Fatigue has often been viewed as a simple variable that is positively correlated with time on task in the workplace and is produced mainly by physical activity. However, shiftwork researchers have demonstrated time-of-day differences for variables including sleepiness and mood, thereby challenging this notion of fatigue. Using a within-subjects design, the present study advances this research by searching for differences in time-of-day interactions in firefighters' sleep length, sleepiness, and mood ratings as a function of shift. We examined reductions in sleep length associated with shiftwork and used sleepiness and mood scales to assess the effects of these reductions. pleted surveys throughout plete cycle of their shift schedule. The study showed that firefighters working on a rotating 8-h shift schedule will sleep less and will report lower positive mood scores, higher negative mood scores, and greater sleepiness ratings on the night shift. Additionally, it was shown that over the course of a shift (two weeks), firefighters were unable to adapt to changes in their sleep schedule. Finally, the significant interactions that were observed challenge the historical, singular notion of fatigue. |
8070793 | Blink rate: a possible measure of fatigue. | The literature on blink rate as a measure of fatigue is reviewed. The evidence of increases in blink rate as a function of time on task pelling. However, variables other than time on task also affect blink rate. These variables range from perceptual demandingness of the task to cognitive variables. Other aspects of blinking, such as flurries of blinks, timing with respect to information-processing demands, and blink closure duration, are reviewed as additional variables sensitive to task demands and fatigue effects. |
8070794 | Driver fatigue. | Psychological fatigue is defined as a subjectively experienced disinclination to continue performing the task at hand. It generally impairs human efficiency when individuals continue working after they have e aware of their fatigue. It does not depend on energy expenditure and cannot be measured simply in terms of performance impairment. The interacting causal contributions to fatigue are the length of continuous work spells and daily duty periods, time available for rest and continuous sleep, and the arrangement of duty, rest, and sleep periods within each 24-h cycle. Empirical evidence for the separate bined effects of these factors on fatigue, performance decrement, and accident risk are briefly reviewed, and the implications of these findings for driving and road safety are considered, with particular reference to the professional driver. This study shows that fatigue is insufficiently recognized and reported as a cause of road accidents and that its effects stem largely from prolonged and irregular working hours, rather than simply from time spent at the wheel. |
8070795 | Fatal accidents among car and truck drivers: effects of fatigue, age, and alcohol consumption. | Fatigue increases the risk of an accident if the driver, on recognizing symptoms of fatigue, does not stop driving. We studied whether a tendency to continue the current activity plete the task especially affects younger drivers, who are more susceptible to motivational pressures at the wheel in general. The data consisted of Finnish in-depth studies on 586 single-vehicle and 1357 multiple-vehicle accidents in which at least one vehicle occupant died. When excluding alcohol-related cases, the results showed that, first, trailer-truck drivers who either fell asleep or were tired to a degree that contributed to the accident were younger than those involved in the other fatalities. For car drivers, the proportion of fatigue-related cases was approximately constant in each age group, but a variation was seen when studied according to the time of day of the accident, mainly resulting from two distinct peaks. The first was in young drivers 18 to 20 years old between midnight and 6:00 a.m. The other occurred in drivers 56 years and older during the late afternoon hours. These data also indicate that in terms of fatal accidents, fatigue and alcohol seem to be less of a problem for truckers than for car drivers. |
8070796 | Fatigue in operational settings: examples from the aviation environment. | The need for 24-h operations creates nonstandard and altered work schedules that can lead to cumulative sleep loss and circadian disruption. These factors can lead to fatigue and sleepiness and affect performance and productivity on the job. The approach, research, and results of the NASA Ames Fatigue Countermeasures Program are described to illustrate one attempt to address these issues in the aviation environment. The scientific and operational relevance of these factors is discussed, and provocative issues for future research are presented. |
8070797 | Subjective fatigue of C-141 aircrews during Operation Desert Storm. | Airlift crews were exposed to extended work periods, reduced sleep periods, night work, and circadian dysrhythmia caused by shift work and time-zone crossings during Operations Desert Shield and Desert Storm. This research reveals the extent to which severe subjective fatigue was experienced by the crews during Operation Desert Storm. In addition, through the evaluation of long-term and short-term work and sleep histories, this research shows that recent sleep and flight histories are correlated with high fatigue levels. Furthermore, we found a tendency for fatigue to correspond with pilot error. We mend that the training of personnel involved in long-duration operations include fatigue management strategies and, further, that work policies and environments be designed to take into account the importance of regular and restorative sleep when unusual duty hours are required. |
8070798 | Speech intelligibility and protective effectiveness of selected active noise reduction and conventional communications headsets. | An experiment was conducted pare both speech intelligibility and noise attenuation of a conventional passive headset (David Clark H10-76) and an electronic Active Noise Reduction (ANR) headset (Bose Aviation) operated with and without its ANR feature. Modified Rhyme Tests were conducted in pink and tank noise, and with and without bilateral phase reversal between earphones. The Bose ANR unit required a significantly higher speech-to-noise (S/N) ratio in both noise environments than the two passive headset systems to maintain equal intelligibility, in part because of its stronger noise reduction and higher required signal level. Articulation Index calculations corroborated the empirical result that the David Clark parable intelligibility to the Bose ANR device. Bilateral phase reversal proved to be of no benefit, and pink noise proved to be the harsher environment for speech intelligibility. On a speech intelligibility basis alone, the results do not justify the additional cost of the ANR headset; however, when severe noise exposure is at issue, a properly functioning ANR unit may afford more protection than a similar passive headset without electronics, especially in low-frequency noise spectra. |
8070799 | Sample sizes for usability studies: additional considerations. | Recently, Virzi (1992) presented data that support three claims regarding sample sizes for usability studies: (1) observing four or five participants will allow a usability practitioner to discover 80% of a product's usability problems, (2) observing additional participants will reveal fewer and fewer new usability problems, and (3) more severe usability problems are easier to detect with the first few participants. Results from an independent usability study clearly support the second claim, partially support the first, but fail to support the third. Problem discovery shows diminishing returns as a function of sample size. Observing four to five participants will uncover about 80% of a product's usability problems as long as the average likelihood of problem detection ranges between 0.32 and 0.42, as in Virzi. If the average likelihood of problem detection is lower, then a practitioner will need to observe more than five participants to discover 80% of the problems. Using behavioral categories for problem severity (or impact), these data showed no correlation between problem severity (impact) and rate of discovery. The data provided evidence that the binomial probability formula may provide a good model for predicting problem discovery curves, given an estimate of the average likelihood of problem detection. Finally, data from economic simulations that estimated return on investment (ROI) under a variety of settings showed that only the average likelihood of problem detection strongly influenced the range of sample sizes for maximum ROI. |
8070800 | Selective stimulation of sacral nerve roots for bladder control: a study by computer modeling. | The aim of this study was to investigate theoretically the conditions for the activation of the detrusor muscle without activation of the urethral sphincter and afferent fibers, when stimulating the related sacral roots. Therefore, the sensitivity of excitation and blocking thresholds of nerve fibers within a sacral root to geometric and electrical parameters in tripolar stimulation using a cuff electrode, have been stimulated by puter model. A 3-D rotationally symmetrical model, representing the geometry and electrical conductivity of a nerve root surrounded by cerebrospinal fluid and a cuff was used, bination with a model representing the electrical properties of a myelinated nerve fiber. The electric behavior of nerve fibers having different diameters and positions in a sacral root was analyzed and the optimal geometric and electrical parameters to be used for sacral root stimulation were determined. The model predicts that an asymmetrical tripolar cuff can generate unidirectional action potentials in small nerve fibers while blocking the large fibers bidirectionally. This result shows that selective activation of the detrusor may be possible without activation of the urethral sphincter and the afferent fibers. |
8070801 | Design and clinical application of a double helix electrode for functional electrical stimulation. | An electrode, designed to be implanted without a surgical incision, was developed for skeletal muscle stimulation. Stainless steel, Teflon-insulated wire was wound into a helical lead around a polypropylene core and then rewound into a double helix configuration for stress relief during muscle contractions. The electrode tip was augmented with stainless steel barbs to increase anchoring strength. Electrodes were implanted with the help of specially modified hypodermic needles, sheaths, and passing tubes. 775 electrodes were implanted in a five year period in 22 subjects; accumulated implant time was 1,080 electrode years. 453 electrodes (65%) continue to produce strong, stable, muscle contractions. Electrode longevity varied with the location of implant. Electrodes were removed because of (1) inability to locate and properly place the electrode in a suitable site for stimulation during surgery (28.4%), (2) unwanted changes in muscle response to stimulation (91, 12%; one-third occurring during the first six weeks post implant), (3) increase in electrode impedance (74, 10%; assumed breakage, mostly occurring during the first year after implant), (4) intolerable pain during stimulation (8, 1%), and (5) infection (4, 0.5%). 67 (8%) electrodes were removed by accident or when the subjects left the program. This double helix electrode design has proven practical for achieving chronic stimulation of selected muscles in hemiplegic, paraplegic, stroke and brain-injured subjects with minimally invasive surgery. |
8070802 | Effects of the propagation velocity of a surface depolarization wave on the extracellular potential of an excitable cell. | Extracellular electric fields have been proposed as a mechanism for electrical coupling between excitable cells. This study deals with the extracellular potential produced by an isolated excitable spherical cell due to a traveling depolarization wave on the cell's surface. Both uniform and nonuniform propagation velocity profiles are considered. Using boundary element methods, the extracellular potential puted. The polarity of the extracellular potential was found to be space-dependent. The peak extracellular potential increased when a) the propagation velocity decreased, b) the rise time of the depolarization decreased, and c) the extracellular resistivity increased. |
8070803 | Localizing the spatial and temporal electromagnetic fields on the axis of a lossy cylinder. | Given a specified form, both in time and space, for the electromagnetic fields on the axis of a lossy cylinder, we determine, analytically, the required azimuthally symmetric source distribution on the surface of the cylinder that generates such internal fields. We then show that this source is equivalent to an array with finite number of cylindrical slots in a metal encasing that are impulsed by specified voltages at a finite sequence of discrete times. A confirming forward calculation exhibits excellent agreement between the specified field form and that generated by the array of cylindrical slots. Potential applications are to hyperthermic cancer therapy, bioelectromagnetics and nondestructive testing. |
8070804 | Electrical coupling and impulse propagation in anatomically modeled ventricular tissue. | Computer simulations were used to study the role of resistive couplings on flat-wave action potential propagation through a thin sheet of ventricular tissue. Unlike simulations using continuous or periodic structures, this unique electrical model includes random size cells with random spaced longitudinal and lateral connections to simulate the physiologic structure of the tissue. The resolution of the electrical model is ten microns, thus providing a simulated view at the subcellular level. Flat-wave longitudinal propagation was evaluated with an electrical circuit of over 140,000 circuit elements, modeling a 0.25 mm by 5.0 mm sheet of tissue. An electrical circuit of over 84,000 circuit elements, modeling a 0.5 mm by 1.5 mm sheet was used to study flat-wave transverse propagation. Under normal cellular coupling conditions, at the macrostructure level, electrical conduction through the simulated sheets appeared continuous and directional differences in conduction velocity, action potential amplitude and Vmax were observed. However, at the subcellular level (10 microns) unequal action potential delays were measured at the longitudinal and lateral gap junctions and irregular wave-shapes were observed in the propagating signal. Furthermore, when the modeled tissue was homogeneously uncoupled at the gap junctions conduction velocities decreased as the action potential delay between modeled cells increased. The variability in the measured action potential was most significant in areas with fewer lateral gap junctions, i.e., lateral gap junctions between fibers were separated by a distance of 100 microns or more. |
8070805 | A complete linear discretization for calculating the magnetic field using the boundary element method. | An analytic solution is derived for the magnetic field generated by current sources located in a piecewise homogeneous volume conductor. A linear discretization approach is used, whereby the surface potential is assumed to be a piecewise linear function over each tessellated surface defining the regions of differing conductivity. The magnetic field is shown to be a bination of vector functions which are strictly dependent on the geometry of the problem, the surface tesselation, and the observation point. |
8070806 | Nonlinear parameter estimation by linear association: application to a five-parameter passive neuron model. | Linear associative memories (LAM) have been intensely used in the areas of pattern recognition and parallel processing for the past two decades. Application of LAM to nonlinear parameter estimation, however, has only been recently attempted. The process consists in converting the nonlinear function in the parameters into a set of linear algebraic equations. The nature of the linearized system and the factors influencing the accuracy of the parameter estimates have not yet been fully investigated. In this paper, LAM is applied to a nonlinear five-parameter model of the neuron. Ill-conditioning, which is often exhibited in LAM, is treated with the method of regularization as well as by the singular value position (SVD). Simulation results indicate that the parameters estimated by LAM exhibit a remarkable robustness against additive white noise parison with the classical gradient optimization technique. Moreover, it is shown that regularization can be superior to SVD under certain conditions. Our results suggest that LAM can be used both as a noise reduction technique and as a stand-alone nonlinear parameter estimation algorithm. parison between LAM and a gradient technique show that, for this estimation problem, the LAM method can give more reliable estimates. Further improvements in estimation quality may still be achieved by the use of other forms of regularizing functions. |
8070807 | MNLS inverse discriminates between neuronal activity on opposite walls of a simulated sulcus of the brain. | The minimum-norm least-squares inverse for magnetic field measurements is applied to a representation of a sulcus of the human brain, where one or both walls have regions of neuronal activity. Simulations indicate that the magnetic source image (MSI) is largely confined to the appropriate wall of the sulcus, even for a depth of 4 cm where the distance between walls is only 3 mm. Two nearly oppositely oriented dipoles located 3 mm apart are found to be distinguished. Influences on the quality of the MSI by measurement noise and inaccuracy in determining the image surface are discussed in detail. |
8070808 | Multiway sequential hypothesis testing for tachyarrhythmia discrimination. | A multiway sequential hypothesis testing (M-SHT) algorithm is proposed for simultaneous discrimination of cardiac tachyarrhythmias--supraventricular tachycardia (SVT) and ventricular tachycardia (VT)--from normal sinus rhythm (NSR). The M-SHT algorithm calculates a likelihood function from atrio-ventricular delay measurements, pares this function with thresholds derived from specified error probabilities for the arrhythmias to be discriminated. Performance of this algorithm was evaluated on dual channel endocardial electrograms recorded in the cardiac electrophysiology laboratory. Two databases were developed, one for development of the algorithm and another for evaluation. The M-SHT algorithm accurately classified 26 out of 28 NSR (2 misclassified as SVT), 31 out of 31 cases of SVT, and 41 out of 43 VT (2 misclassified as NSR). The average length of time taken for classification of the three rhythms was: 3.6 s for NSR, 5.0 s for SVT, and 1.6 s for VT. Unique features of this algorithm are that acceptable error rates for each arrhythmia are independently specified and accuracy can be traded off for a faster detection time, and vice versa. |
8070809 | Telemedicine using mobile satellite communication. | With a view to providing paramedical care within moving vehicles, a telemedicine technique using mobile munication was proposed. With this technique, the diagnosis from a specialist and the emergency care under his/her instructions would be available on the spot without unnecessary delay. The characteristic problems of this technique were identified as: channel capacity, size of the system, reliability of vital sign transmission, real-time operation and electromagnetic interference. Measures against these problems were devised, and their effectiveness was analyzed. A data format was designed and an experimental system was developed. The system can simultaneously transmit a color image, an audio signal, 3 channels ECG and blood pressures from a mobile station to a ground station. It can transmit an audio signal and error control signals from a ground station to a mobile station in a full duplex mode. Fundamental transmission characteristics were measured in a fixed station. Finally, experiments of medical data transmission were conducted with a navigating ship and an aircraft flying an international route. The measured threshold values of C/N(o) to guarantee satisfactory data reception were well below the lower boundary of C/N(o) of munication link. Consequently, the feasibility of this technique was verified. |
8070810 | The detection of the onset of electrode-electrolyte interface impedance nonlinearity: a theoretical study. | The equivalent series resistance and reactance of the electrode-electrolyte interface impedance have both been used to detect the onset of signal amplitude induced nonlinearity. Using a theoretical model, it is shown that the choice of the most sensitive indicator depends on the phase angle of the "polarization" impedance and on the applied frequency. |
8070811 | Signal detection theory and reconstruction algorithms--performance for images in noise. | In many noisy image processing situations, decision making is the ultimate objective. In this paper, we show using signal detection theory how direct optimal processing of the projection data yields a considerable gain in the decision making performance over that obtained by first using image reconstruction. The problem is formulated in the framework of a two hypotheses detection problem. Optimal processors based on the likelihood ratio approach have been presented for two cases. The first considers direct processing of the projection data. The second applies optimal decision theory to the reconstructed data. Results based puter simulation are presented in the form of receiver operating curves (ROCs) for different signal-to-noise (SNR) ratios. Early results indicate that large performance gains can be achieved by direct optimal processing of the projection pared with optimal processing of reconstructed data. Results for the latter case can be interpreted as providing an upper bound on all postreconstruction decision rules. We hope to extend this approach to a number of different aspects of the image decision making problem. |
8070813 | The genetic basis of chronic granulomatous disease. | Chronic granulomatous disease is a serious clinical entity. The disease is caused by the failure of NADPH oxidase in phagocytic leukocytes to generate superoxide, needed for the killing of micro-organisms. The patients need careful management aimed at prevention and aggressive treatment of infections. CGD is a heterogeneous syndrome, both clinically and genetically. This disease is caused by a diversity of mutations, and multiple genes are affected. In fact, in the A22 and X91 subtypes of CGD, in which the alpha subunit and the beta subunit of cytochrome b558 are affected, respectively, the mutations are virtually unique for each CGD family tested. The results of these studies provide a better understanding of the mechanism of action of the ponents of the superoxide-generating enzyme. Although treatment of CGD patients has improved considerably over the past 30 years, death caused by overwhelming infections is still a serious threat. Prenatal diagnosis now provides the relatives of a CGD patient with the possibility to choose for first-trimester abortion of an affected fetus. Moreover, genetic correction of the disease is now a goal within reach. |
8070815 | Molecular basis of the motheaten phenotype. | Mice homozygous for the autosomal recessive motheaten (me) or the allelic viable motheaten (mev) mutations manifest a unique immunological disease associated with severe immunodeficiency and autoimmunity. Over the past few years, our group has used the motheaten mouse as a model system for elucidating the genetic and cellular events that contribute to expression of normal hematopoietic and immune cell function. To this end, we have sought to identify the gene responsible for the motheaten phenotype. In our initial studies, our general approach involved the use of subtractive hybridization to identify genes that were differentially expressed in the mutant versus control mice and which might thus provide clues as to the primary gene defect. Using this approach, we showed that genes encoding stefin A cysteine proteinase inhibitors are markedly overexpressed in bone marrow cells of me and mev pared to bone marrow cells of normal congenic animals. However, the motheaten mutation has been mapped to mouse choromosome 6 while the stefin A gene cluster was localized to mouse chromosome 16. Stefin gene therefore does not represent the primary gene defect. Our second strategy aimed at identifying the primary gene defect underlying the motheaten phenotype was prompted by the recent localization of a protein tyrosine phosphatase gene to human chromosome 12p12-p13, a region containing a large segment of homology with the region on mouse chromosome 6 where the motheaten locus has been mapped. We have shown that abnormal Hcph transcripts are expressed in me and mev bone marrow cells and that the generation of these altered transcripts is due to RNA splicing defects caused by single basepair changes in the Hcph genes of the mutant mice. These mutant mice thus provide a valuable model system for elucidating the biological roles of HCP in vivo and defining the mechanism whereby defective function of a hematopoietic cell phosphatase leads to expression of the motheaten phenotype of severe immunodeficiency and systemic autoimmunity. |
8070818 | The molecular basis of X-linked severe combined immunodeficiency: the role of the interleukin-2 receptor gamma chain as a common gamma chain, gamma c. | X-linked bined immunodeficiency is characterized by severe and persistent infections from early life resulting from profound impairment of both cellular and humoral immune function. XSCID is characterized by an absence or diminished number of T cells and histologic evidence of hypoplastic and abnormal differention of the thymic epithelium. The discovery that this disease results from the mutations of the IL-2R gamma chain was surprising since IL-2-deficient mice and human SCID patients had milder phenotypes. This led to the speculation that IL-2R gamma would prove to be mon gamma chain, gamma c, which would play important roles in other cytokine receptors in addition to the IL-2 receptor. There is pelling evidence to support a role in at least two other cytokine receptors, namely the IL-4 and IL-7 receptors. Thus, with inactivation of gamma c, multiple cytokine systems are simultaneously affected, resulting in the profoundly impaired phenotype of XSCID. It is possible and even likely that gamma c will be found to be a ponent of additional receptors as well. These findings have resulted in a significant improvement in our understanding of the pathophysiologic development of the defects in XSCID and also have important ramifications for prenatal and postnatal diagnosis, carrier female identification, and gene therapy for XSCID. |
8070817 | X-linked agammaglobulinemia: new approaches to old questions based on the identification of the defective gene. | The identification of a cytoplasmic tyrosine kinase, Btk, as the defective protein in human XLA and xid in the mouse, supports the hypothesis that both disorders are due to defects in B-cell activation or differentiation. Phenotypic analysis of B-lineage cells and studies on X-chromosome inactivation patterns in both mice and human patients suggest that mutations in Bth do not affect entry of stem cells into the B-lineage pathway but they do inhibit progression at multiple steps along that pathway. Although the exact function of Btk in signal transduction is not yet known, it is probable that studies which correlate specific mutations in different patients with alterations in Btk function will provide clues about critical sites in the molecule. Diagnosis and genetic counseling for families at risk of carrying the gene for XLA will be improved almost immediately by the identification of the responsible gene. Improvements in therapy e more slowly. The possibility of curative gene therapy is attractive; however, there are several features of Btk that suggest that this will be a challenging undertaking. Overexpression or expression in inappropriate cell lineages may carry unacceptable risks. Mutant proteins may interfere with the function of wild-type proteins provided by gene therapy. However, it is likely that a better understanding of Btk function and regulation will benefit not only patients with XLA but also other patients with defects in B-cell function. |
8070823 | Enalapril for prevention of restenosis after coronary angioplasty. | We have evaluated the effect of enalapril in the prevention of restenosis after percutaneous transluminal coronary angioplasty by a randomized trial conducted on 95 patients. The treatment group (n = 46) received enalapril 10 mg/day besides aspirin with calcium blockers, beginning 24 hours before coronary angioplasty. The conventional medical treatment group (n = 49) received only aspirin and calcium blockers. Enrollment required the presence of angina pectoris and successful dilatation of all significant coronary narrowings. All patients were followed up for at least 6 months. Restenosis was identified by symptoms and exercise testing and confirmed by angiography. The incidence of angiographic restenosis was 34% in the enalapril group and 31% in the conventional treatment group. Long term angiotensin converting enzyme inhibition with enalapril in a dose of 10 mg per day does not prevent restenosis after coronary angioplasty. |
8070821 | Retrograde non-transseptal balloon mitral valvuloplasty--an initial experience. | Eleven patients with symptomatic isolated non-calcific mitral stenosis were treated with retrograde nontransseptal balloon mitral valvuloplasty. This new technique utilizes a specifically designed steerable catheter to enter the left atrium retrogradely via the left ventricle thus avoiding transseptal puncture, an essential step in other methods of balloon mitral valvuloplasty. Technical success was obtained in ten (91%) patients. Mitral valve area increased from 0.8 +/- 0.2 to 1.8 +/- 0.4 cm2 and the transmitral gradient decreased from 23.9 +/- 7.7 to 8.2 +/- 2.8 mmHg. There were no plications such as cardiac perforation, embolic events, cardiac tamponade or severe mitral regurgitation. This early experience, the first outside Greece (centre of origin) indicates that retrograde nontransseptal balloon mitral valvuloplasty is a simple, effective and safe technique with parable with other techniques of mitral balloon dilatation which require transseptal catheterisation. Further experience involving multicenteric trials, is required to determine the overall efficacy of this technique for percutaneous balloon mitral valvuloplasty. |
8070827 | Enhanced lipid peroxidation in patients during coronary artery bypass grafting. | Lipid peroxidation products were measured at various time intervals in 20 patients with coronary artery disease, who underwent coronary artery bypass graft (CABG) surgery. Post-operative blood lipid peroxides were found to be significantly higher (p < 0.001) than the preoperative value. Lipid peroxides raised to a peak value of 46.42 +/- 12.86 n mol/g Alb at 5 min of reperfusion pared to the basal value and afterwards the level declined to 41.02 +/- 7.09 at 2 hrs and remained in that level even at 24 hrs of reperfusion. This increase implies an enhancement in free radical mediated oxidation of membrane lipids during bypass surgery and thus provides evidence for free radical generation during myocardial reperfusion. |
8070824 | Early experience with the two patch technique for complete atrioventricular septal defect. | A total of 12 cases underwent repair plete atrioventricular (AV) septal defect utilising the two-patch technique. There were 4 males and 8 females. The mean age at repair was 9.6 months (range, 3 to 49 months). The average weight was 5.4 kg (range, 3.5 to 13 kg). Five had associated patent ductus arteriosus. A Gore-Tex patch and glutaraldehyde preserved pericardium was utilised for the ventricular and atrial portions of the defects respectively in all patients. Four of these were done under hypothermic circulatory arrest. There were no intra-operative deaths. Early prised of 2 patients (2/12, 16.6%). One due to a pulmonary hypertensive crisis and the other to septicemia. The mean duration of ventilatory support was 62 hours (range, 24 to 192 hours). The mean duration of inotropic support was 57 hours (range, 24 to 192 hours). Primary repair of AV septal defects using the two-path of technique can be plished with a low early mortality in carefully selected patients. |
8070825 | Surgical correction of aneurysms of sinus of Valsalva--a report of 22 cases. | Twenty two cases of aneurysm of sinus of Valsalva managed during a 12 year period are analysed. The right coronary sinus was involved in 14 and the non-coronary sinus in eight cases. It had ruptured in 20 patients while in the other two it had produced right ventricular outflow tract (RVOT) obstruction. Six patients had associated ventricular septal defect (VSD), and eight had aortic regurgitation (AR), five of these requiring aortic valve replacement (AVR). Aortocameral approach was preferred and was used in 18 patients. Recurrence had occurred in one. Surgical management and results are discussed. |
8070828 | Can common exercise indices determine peak exercise oxygen consumption and anaerobic threshold during stress testing in patients with chronic congestive heart failure? | Maximal oxygen consumption (VO2 max) is one of the most important predictors of prognosis in chronic heart failure and is now used to define degree of heart failure. While most centres can routinely do treadmill exercise testing (TMT), VO2 max measurements are not widely available. We, therefore, analysed the ability to predict VO2 max mon TMT variables: Peak exercise heart rate, exercise time, and METS achieved in 26 patients with chronic congestive heart failure (NYHA II-III, ejection fraction 43 +/- 2%) in whom exercise VO2 studies were simultaneously done by breath to breath expiratory gas analysis using a metabolic cart. METS achieved during exercise and exercise time correlated reasonably well although not perfectly (r = 0.78 & 0.73 respectively, tail critical value +/-0.41). Resting ejection fraction did not correlate at all (r = 0.0004). The regression equation (2.7) (METS) + 5.8 defined VO2 max with SE of 0.47. Although in unvariate analysis, exercise time, METS achieved & peak heart rate predicted VO2 max, only METS achieved was predictive in step wise regression. None of the parameters predicted the anaerobic threshold accurately although there was a modest relation between AT and peak exercise VO2. We conclude that most exercise variables do not accurately predict VO2 max in patients with chronic congestive heart failure. METS achieved is the best predictor and the VO2 max can be predicted using a regression equation. Anaerobic threshold cannot be predicted without tests involving expiratory gas analysis. |
8070833 | Modulation of Fc and C3b receptor activity of mouse peritoneal macrophages elicited by preformed immune complexes. | A study was undertaken to reveal the role of Fc and C3b receptor of mouse peritoneal macrophages (MPM) in the uptake of radiolabelled plexes. Large latticed plexes consisting of human serum albumin (HSA)-anti HSA at equivalence (IC-Eq) and with antibody excess (IC-Ab) were observed to be avidly taken up by resident macrophages unlike small plexes with antigen excess (IC-Ag). Macrophages elicited by thioglycollate (Tg) showed higher IC-binding capacity while IC-elicited MPM showed reduction in the same pared to the resident cells. plement plexes were significantly taken up by these IC-elicited macrophages. Uptake studies were further extended to determine the expression of Fc and C3b receptor activity in MPM when elicited with preformed IC. Tg-elicited MPM were observed to bind greater number of IgG-coated erythrocytes (E-IgG) than resident MPM whereas IC-elicited MPM bound E-IgG poorly. When Fc receptors were blocked by in vitro IC treatment, poor binding plement coated E-IgG [E(IgG)C] was recorded in resident MPM. The plement medicated rosetting data tends to show enhanced expression of C3b receptors on IC-elicited macrophages. |
8070822 | Subcutaneous nodules in acute rheumatic fever--an analysis of age old dictums. | It is assumed that subcutaneous nodule (SCN), one of the major criteria in acute rheumatic fever (ARF), is rare and whenever these nodules appear, they are invariably associated with carditis. Further large number of nodules appear in crops and they are evanescent. This prospective study of 42 cases of ARF with SCN attempts to analyse the accuracy of such statements. The prised of 12.5% of 336 consecutive cases of ARF. Other major criteria associated with SCN were carditis in 38 (90.4%), arthritis in 33 (78.5%) and chorea in two (4.7%). No evidence of carditis could be found in 4 (9.5%). When a detailed study of SCN was done the average number of nodules found in the group was 18 (range 4-49). Thirteen (30.9%) had less than 10 nodules and 5 (11.9%) had only 4-5 nodules. With initiation of treatment SCN disappeared within 4 weeks in 29 (69%), within next 5-8 weeks in 8 (19%) and within 9-12 weeks in 3 (7.1%). In two cases (4.7%) multiple nodules were observed 12 weeks later when all other evidences of activity had disappeared. The study shows parative high incidence of SCN in ARF, not all being associated with carditis. Number of nodules appearing in ARF might be quite small and they could persist for long inspite treatment. |
8070826 | Prophylactic lidocaine hydrochloride does not reduce ventricular arrhythmias after coronary artery bypass grafting in patients with poor left ventricular function. | Prophylactic lidocaine hydrochloride infusion followed by oral mexiletine hydrochloride was administered in the early post operative period to patients with poor left ventricular function undergoing coronary artery bypass graft surgery, to determine whether this decreased the incidence of ventricular arrhythmias and sudden death due to arrhythmias. Patients were randomly allocated to two groups of 50 each, the lidocaine prophylaxis group and the placebo infusion group. In the lidocaine prophylaxis group bolus dose of 1.5 mg/kg lidocaine hydrochloride was administered just before release of aortic cross clamp followed by an infusion at the rate of 2 mg/min. Oral mexiletine hydrochloride 150 mg 8 hourly was started after 24 hours and continued till discharge. The results showed that 17/50, patients developed ventricular arrhythmias in the lidocaine prophylaxis group and 22/50, in the placebo group in the first postoperative week. The incidence of ventricular arrhythmias apart from ventricular fibrillation was almost similar in both groups, 13/50, and 14/50, in the lidocaine prophylaxis and placebo infusion groups respectively. The incidence of ventricular fibrillation was 4/50, in the placebo infusion group and 2/50, in the lidocaine prophylaxis group (p < 0.05). Total number of deaths were 3 in each group. We concluded that this antiarrhythmic regimen in patients with poor left ventricular function did not decrease the incidence of ventricular arrhythmias or death due to arrhythmias in the early post operative period. |
8070834 | Antitumor effect of cisplatin against murine ascites Dalton's lymphoma. | Cisplatin treatment brings plete regression of ascites Dalton's lymphoma in mice. In the present study various steps involved during the tumor regression are examined using some biochemical and morphological parameters. During tumor regression, ascites fluid volume decreases sharply and there is an increase in carbohydrates and decrease in protein contents in the ascites supernatant after cisplatin treatment in vivo. Cisplatin treatment brings about definite changes in the arrangement/movement of surface membrane ruffles/blebs of tumor cells and causes infiltration of leukocytes (neutrophils, monocytes, lymphocytes) towards tumor cells. Membrane vesicles and vacuoles are also formed before the disintegration and lysis of tumor cells. |
8070831 | Non-surgery related aspergillus native valvular endocarditis: report of two cases. | Two unusual cases of aspergillus valvular endocarditis without any history of cardiovascular surgery found at autopsy are reported. As there is a chance of dissemination, early diagnosis is important. Clinical awareness can lead to early recognition and effective treatment of this potentially lethal condition. |
8070835 | Detection of tuberculous IgG antibodies using Mycobacterium tuberculosis H37Ra, excretory secretory antigen and tuberculin-purified protein derivative. | Different antigen preparations, viz. excretory-secretory antigen (ES Ag), phosphate buffer saline soluble antigen (PBS-S Ag) and sodium dodecyl sulphate soluble antigen (SDS-S Ag) of M. tuberculosis (M.tb) H37Ra strain along with tuberculin purified protein derivative (PPD) were employed in stick indirect ELISA to detect IgG antibodies in sera of sputum positive pulmonary tuberculosis cases. Sera from healthy individuals and individuals with diseases other than tuberculosis (cross-reacting diseases) were used as controls. ES antigen and PPD showed higher antibody titres in tuberculosis cases (GMT-1378 pared to PBS-S Ag (GMT-454) and SDS-S Ag (GMT-974). Thereafter, an extensive study was done analysing higher number of sera in each group for the detection of tuberculous IgG antibodies using ES Ag and PPD. The ES Ag showed better sensitivity (87%) and specificity pared to the sensitivity (73%) and specificity (78%) achieved with PPD. The ES Ag also showed higher IgG antibody titre (GMT-1068) than PPD (GMT-721). From the present study it can be envisaged that ES Ag has high diagnostic potential in tuberculosis. |
8070836 | Dopamine receptor mediated antidepressant action of B-HT 920 in mice. | Possible involvement of dopaminergic (DAergic) system in forced swimming-induced immobility (despair behaviour) was investigated in mice. B-HT 920 (0.05 and 0.1 mg/kg), a post-synaptic DAergic agonist, produced a dose dependent reduction in immobility period, which was sensitive to blockade by haloperidol (0.5 mg/kg) and sulpiride (100 mg/kg). This effect was also blocked by alpha 2 antagonist yohimbine (5 mg/kg). SKF 38393 (5 mg/kg), a D1-DA agonist potentiated the action of B-HT 920. Reserpinization (2 mg/kg, 24 hr prior) produced despair immobility in mice. When a low dose of B-HT 920 (0.05 mg/kg) was given to reserpinized animals, the duration of immobility period was further increased. But on the other hand, a higher dose (0.1 mg/kg) of it reduced reserpine-induced immobility. Desipramine (5 and 10 mg/kg), elicited a dose dependent reduction in the immobility period, which was sensitive to blockade by sulpiride (100 mg/kg). Desipramine (10 mg/kg) showed a diphasic response bination with B-HT 920, i.e., a potentiation of the response due to a low dose of B-HT 920 (0.05 mg/kg) and an antagonism of the response due to a higher dose of B-HT 920 (0.1 mg/kg), respectively. SKF 38393 (5 mg/kg), potentiated the action of desipramine (5 mg/kg). SKF 38393 (5 mg/kg) further potentiated the action of desipramine (5 mg/kg) and B-HT 920 (0.05 mg/kg). These observations suggests that B-HT 920 reduces behavioural immobility by DAergic mechanism and desipramine also modulates D2-DA receptors in its anti-depressant action. |
8070838 | Protective effect of Rubia cordifolia on lipid peroxide formation in isolated rat liver homogenate. | Rubia cordifolia Linn. (Rubiaceae) is an ponent of the ayurvedic system of medicine. It has a variety of uses such as blood purifier, immunomodulant, antiinflammatory and anti-PAF. In this report the anti-peroxidative property of the solvent free alcoholic extract of R. cordifolia has been studied in rat liver homogenate. It prevents the cumene hydroperoxide induced malondialdehyde formation in the dose and time dependent manner. This effect is panied by the maintained reduced glutathione level even in the presence of above toxin. |
8070837 | On the characterization of dopamine-induced contractile response of rat anococcygeus muscle preparation. | Presence of specific dopamine (DA) receptors and their characterization was attempted in rat anococcygeus muscle preparation. Dopamine (10(-6) M) and B-HT 920 (10(-6) M) produced concentration dependent contractions of the rat anococcygeus muscle preparation. The response of DA was shifted towards right in presence of haloperidol (10(-6) M; pA2 = 6.8) and sulpiride (10(-4) M) in petitive manner. Alpha 2 antagonists yohimbine (10(-5) M) and idazoxan (10(-5) M) blocked the response to DA in petitive manner, while alpha 1 antagonist prazosin (10(-5) pletely blocked the response to DA. SCH 23390 (10(-5) M), a D1 DA antagonist potentiated the response to DA. Reserpinization (5 mg/kg, 24 hr prior) brought about a shift towards the right, and this response was similarly blocked by haloperidol, sulpiride and yohimbine without affecting the maximum response. Desipramine (10(-5) M) blocked the response of DA in a petitive manner. Pretreatment of animals with desipramine (10 mg/kg) followed by reserpine, brought about a reversal of action of reserpine. The response to B-HT 920 (10(-6) M), was blocked similarly by haloperidol and yohimbine. However, the effect of desipramine was more pronounced pared to DA per se. SKF 38393, a D1 DA agonist, potentiated the response to B-HT 920. The findings suggest the presence of both D1 and D2 DA receptors in rat anococcygeus muscle and that DA also acts on adrenergic receptors to produce a contractile response of this muscle preparation. |
8070839 | Effect of gestational undernutrition and chlordiazepoxide treatment on black/white discrimination learning and retention in young rats. | Effects of prenatal undernutrition and chlordiazepoxide treatment on learning acquisition, and subsequent retention, of a black/white discrimination task, was assessed in the offspring. Undernutrition of the dams was induced by restricting food intake to half, throughout the period of gestation, whereas chlordiazepoxide (2.5 mg/kg, ip) treatment was given from day 13 to 20 of gestation, this being the critical period for neural development in this species. The pups born were subjected to brightness discrimination learning, and retention of the learning acquisition after an interval of one week, in a single unit black/white T-maze, at 8-9 weeks of age. The results indicate that prenatal undernutrition induces significant learning and retention deficits in the offspring. Prenatally administered chlordiazepoxide induced significant deficits in learning acquisition and subsequent retention of the discrimination problem. Chlordiazepoxide induced similar learning and retention deficits in the normal and undernourished rats, and exaggerated the learning and retention deficits induced by undernutrition. The results indicated that the prenatal insults in the form of undernourishment and anxiolytic pounds, leave a lasting imprint on cognitive behaviour of the offspring. |
8070840 | Effect of alkaloidal extract from Clerodendron colebrookianum on hematological parameters and hepatorenal functions in mice. | Effects of multiple weekly (20, 40 and 80 mg/kg) and daily therapeutic (2, 4 and 8 mg/kg) ip doses of C. colebrookianum leaf extract on liver and kidney functions and hematological parameters in mice were studied. No alteration in hematological and biochemical parameters at low and moderate dose level of daily and low dose level of weekly treatment of alkaloidal extract was observed. However, alkaloidal extract at moderate dose in weekly treatment increased significantly serum alanine aminotransferase, alkaline phosphatase, nonprotein nitrogen, blood urea, plasma protein and erythrocyte sedimentation rate. High dose of alkaloidal extract increased all the above parameters of weekly treated mice including serum aspartate aminotransferase and plasma cholesterol and decreased significantly serum bilirubin and clotting time. Whereas, in high dose daily treatment erythrocyte count and hemoglobin content were increased and serum bilirubin was decreased. The present study reveals that the high dose (above 40 mg/kg body weight) of alkaloidal extract of C. colebrookianum affects liver and kidney functions and metabolism and also alters only clotting time and ESR whereas the therapeutic dose level (hypotensive action at 2 to 8 mg/kg, i.v., dose level) did not exhibit any toxic action on the above mentioned system; the toxic action may be due to overdose. Hepatorenal dysfunction and alteration of hematological parameters were noted at moderate and high dose in a dose dependent manner. |
8070841 | Effect of homeopathic drugs plumbum and opium on experimentally induced lead toxicity in rats. | Homeopathic drugs plumbum 1M and Opium 30 were partially effective in the recovery of delta ALAD activity of the lead (150 mg% lead acetate) intoxicated rats. Plumbum 1M did not exhibit protective effect when dietary lead at high concentrations (> 25 mg% lead acetate) were given concurrently as assessed by blood delta ALAD activity and hemoglobin concentration. However it was partially effective in the recovery of delta ALAD activity and relieving anemia caused by chronic exposure of low doses of lead (below 15 mg% lead acetate). |
8070842 | On mechanism of action of ethanol-induced contraction of frog rectus abdominis. | Ethanol in low doses (0.5 to 4 M) causes contraction of isolated frog rectus abdominis muscle. Higher concentration did not produce any further increase in maximum response. Pretreatment with dantrolene produced partial but equal inhibition of acetylcholine (Ach) induced as well as ethanol-induced contraction in equieffective doses. Pretreatment with pancuronium produced right and downward shift of ethanol induced contraction. Pretreatment with succinylcholine produced persistent contraction of tissue and this response remained unaffected on subsequent treatment with Ach as well as ethanol. Pretreatment with hemicholinium abolished ethanol induced contraction, although tissue remained viable as confirmed on addition of Ach. The contraction induced by ethanol decreased on pretreatment with dantrolene as well as in Ca2+ free ringer. The results indicate that ethanol induced contraction may be due to release of Ach or Ach like neurotransmitter at neuromuscular junction and calcium acts as mediator to produce these effects. |
8070843 | Antioxidant potential in serum and liver of albino rats exposed to benzene. | Administration of benzene (ip, 0.5 ml/kg body wt or sc, 1 ml/kg body wt) consecutively for 10 days to male and female rats resulted in decrease in antioxidant potentials in serum. Serum uric acid and albumin showed significant decrease in all groups exposed to benzene. alpha-Tocopherol levels did not exhibit significant change in any of the groups pared to control. Increase in liver lipid peroxidation and decrease in content of free sulphydryl group were observed in rats exposed to benzene. Serum ferroxidase activity, total iron content (TIC) and total iron binding capacity (TIBC) in female rats exposed to benzene showed significant decrease in ferroxidase activity without any change in TIC or TIBC pared to control. The decrease in antioxidant potentials observed may be due to oxidation reactions exhibited by benzene metabolites, particularly, hydroquinone and 1, 2, 4-benzenetriol, resulting in oxidative stress in treated rats. |
8070844 | Multiple antibiotic resistance among gram negative bacteria isolated from poultry. | Gram negative bacteria, including species of Salmonella, Escherichia, Pseudomonas and Klebsiella, isolated from poultry, were screened for their resistance to monly used antibiotics: ampicillin, chloramphenicol, gentamycin, kanamycin, neomycin, polymyxin B, streptomycin and tetracycline. Of the 500 bacteria screened, 351 were found to be resistant to one or more antibiotics at the level of 50 micrograms/ml. Various patterns of antibiotic resistance observed during these studies have been reported. |
8070845 | Effect of GABA analogues on various components of maximum electroshock-induced seizures in mice. | Out of pounds reported here only four [N-valproyl GABA (V.GABA), N-phthaloyl GABA (P.GABA), gamma-phthalimido N-amyl butyramide (PGA) and gamma-phthalimido N-phenyl butyramide (PGP)] gave significant protection to all the ponents of maximal electroshock-induced seizures (MES) in mice. It appeared that substitution of either amino or carboxylic or both groups of gamma-aminobutyric acid (GABA) with bulkier groups like aliphatic or aromatic carbons usually produced effective anticonvulsant GABA derivatives. V.GABA and P.GABA were the most effective anticonvulsant GABA derivatives in protecting all ponents of MES-induced seizures. They were 2.3 and 1.5 times potent than sodium valproate in molar ratio, but P.GABA has low therapeutic index pared to V.GABA. The observed anticonvulsant activity may be due to enhanced GABA concentration in the CNS. Probably, the pound (V.GABA) crossed the blood brain barrier and hydrolysed to GABA and valproic acid to bring about its anticonvulsant action. |
8070847 | Modulation of antigen-presenting capacity of human monocytes by HIV-1 GP120 molecule fragments. | The two fragments of HIV-1 gp120 molecule were synthesized to study their interaction with human monocytes. Previous observations indicated that binant gp120 fragment (aa residues 410-511) passing CD4 binding region (rp120cd) induced tumour necrosis factor alpha (TNF) production in monocytes, while a similar fragment (rp120) not containing the CD4 binding sequence (aa 446-511) was inactive. This paper shows that rp120cd depressed monocyte ability to present antigen (PPD) to autologous T lymphocytes while rp120 was noninhibitory. The rp120cd interacted with monocytes but not T lymphocytes. Anti-TNF receptor type A antibody (utr-1) prevented the depression of antigen presentation caused by rp120cd, which suggested a role for TNF and its receptor. The depression of antigen presentation was seen only when monocytes were treated with rp120cd before, but not after, pulse with antigen. Parallel changes were observed in PPD-induced IL-6 production. Thus, induction of TNF by gp120 may be associated with impairment of antigen-presenting capacity of monocytes seen in AIDS patients. |
8070848 | Dituftsin and polytuftsin induce an anti-peptide IgG response to non-immunogenic peptides in mice. | The effect of covalently attaching multiple forms of the immunomodulating tetrapeptide tuftsin to normally non-immunogenic peptides was studied in BALB/c and C57Bl/6 mice. The peptides: (NANP)3 from the Plasmodium falciparum circumsporozoite protein and peptides 136-152 and 205-213 derived from the capsid protein of foot-and-mouth disease virus were coupled to polytuftsin or dituftsin. Anti-peptide IgG titers were determined after two immunizations. All of these three non-immunogenic peptides coupled to polytuftsin or dituftsin induced anti-peptide antibody production in mice while peptides alone did not elicit IgG. In addition, a conjugate of (NANP)3 and polytuftsin with built-in glycopeptide adjuvant elicited an anti-peptide parable in magnitude with that of a peptide-KLH conjugate. The data suggest that when non-immunogenic peptides are synthesized in tandem with dituftsin or conjugated to polytuftsin a significant immune response to the peptides may be elicited. This approach may be employed in synthetic vaccine design. |
8070849 | IL-6 mediated isotype specific suppression of hapten specific IgE in serum of BPO-KLH sensitized mice: role of IFN alpha in maintainance of hapten specific IgE responses. | The ability of IL-6 or IFN alpha or antibodies to these cytokines to regulate serum levels of hapten specific immunoglobulins (IgM, IgG1, IgE, IgA) was studied in BPO-KLH (benzylpenicilloyl-keyhole limpet hemocyanin) sensitized BALB/c mice at the peak of a hapten specific IgE antibody forming cell (AFC) response. To induce peak IgE responses, mice were injected intraperitonealy (i.p.) with BPO-KLH (10 micrograms) in aluminum hydroxide gel (alum) on days 0, 21, and 42. On day 44, mice were injected s.c. with IL-6 (100-1000 U), IFN alpha (1000-10,000 U), anti-IL-6 (100-1000 neutralizing units [NU]), or anti-IFN alpha (1000-10,000 NU). On day 46, levels of BPO specific IgM, IgG1, IgE and IgA in serum were determined (ELISA). Data are expressed as micrograms/ml. IL-6 suppressed BPO specific IgE in serum in isotype specific fashion (to > 90%), increasing IgA (approximately 3 fold), and leaving IgM and IgG1 unchanged. Since removal of endogenous IL-6 with anti-IL-6 increased serum IgE, and suppressed IgG1 (approximately 50%), with IgM and IgA unchanged, this suggests that IL-6 is an isotype specific suppressor of peak IgE responses and as such may be useful in the therapeutic management of atopic disease. IFN alpha treatment increased serum IgE levels (60%), and potentiated IgA responses (> 30 fold), with IgM and IgG1 unchanged. Since removal of endogenous IFN alpha with anti-IFN alpha decreased IgE levels (approximately 50%), increasing IgA, with IgM and IgG1 unchanged, this suggests a role for IFN alpha as an isotype specific helper of peak IgE responses and in maintenance of IgA responses. |
8070850 | Electroeluted outer membrane proteins as immunogens. | Electroeluted outer membrane proteins [(EOmp), (35-37 KDa, porins)] were highly immunogenic in New Zealand White rabbits. An ELISA peak titer of 51,200 to EOmp pared to 6,400 for non-eluted outer membrane protein (Omp) was demonstrated. EOmp enhanced the antigenicity of Omp possibly due to epitopes which were masked in the non-eluted antigen. Non-eluted, partially purified, Omp elicited high anti-lipopolysaccharide (LPS) titers (25,600); however, electroelution diminished LPS contamination (non detection of LPS chemically and on immunoblots) and greatly reduced the anti-LPS titer (400). It is biologically significant that anti-EOmp antibodies cross-reacted with wild-type urinary pathogens. Specificity for Omp reactivity was demonstrated by ELISA and on immunoblots with absorbed EOmp (LPS-free) antisera. These findings strengthen the rationale for exploring the protective potential of anti-Omp antibodies. |
8070851 | Immunomodulators in clinical practice. | Immunomodulators have opened new vistas in the management of the promised patient. They have been shown to enhance the efficacy of vaccines in infections, head and neck malignancy, the immunosuppressed and recently in AIDS. The mechanism of their action is discussed. They hold promise of further advances in immunotherapy. |
8070852 | Role of metronidazole in radiation therapy (a review of 717 cancer cases). | The presence of Hypoxic cells in a tumor decreases their radiosensitivity; which blocks the efficacy of external tele cobalt irradiation. So a study was undertaken in various cancer patients to observe the role of metrnidazole as a selective radiosensitizer. 717 cancer cases were enlisted and were divided into a study and control group. The study group were given metronidazole at a dose of 2 grams orally, 4 hours before each irradiation, (5 days in a week) for 6-7 weeks. The control group were devoid of it. pletion of the treatment, as well as, after 3 years follow-up, it was observed that the patients receiving metronidazole had better treatment response and more number of recurrence free years. Since it is a cheaper drug it can be used freely in the form of a potential radiosensitizer, for external irradiation therapy. |
8070855 | Characterization of the human cytochrome P450 isozymes responsible for styrene metabolism. | The rate of formation of styrene glycol from styrene pared in human, rat and mouse liver microsomes. At a low styrene concentration (0.085 mM), the rates decreased in the order, mouse > rat > human; at a high concentration (1.85 mM), the order was rat > mouse > human. The forms of cytochrome P450 that are responsible for transforming styrene to styrene glycol were determined by vaccinia virus-mediated cDNA expression of individual P450 forms in cultured cells. Of the 10 human P450 forms studied, CYP2B6 was the most effective in forming of styrene glycol, followed by CYP1A2, CYP2E1 and CYP2C8; the human P450s CYP3A3, CYP3A4 and CYP3A5 also catalysed metabolism, but were much less active; and CYP2A6, CYP2C9 and CYP2D6 had little detectable activity. CYP1A1 from mouse liver was more active in forming styrene glycol than mouse CYP1A2; the latter was less active than human CYP1A2. CYP2B1 from rat liver was more active than rat CYP2B2 or CYP2B6 from human liver. The rate of styrene glycol formation was higher in lung microsomes from smokers than in those from current nonsmokers. |
8070856 | 32P-postlabelling of DNA adducts in styrene oxide-modified DNA and in workers exposed to styrene. | Lamination workers are exposed to large amounts of styrene. A postlabelling method was developed in order to detect DNA adducts in white blood cells from such workers. First, styrene oxide was reacted with DNA, and the adducts were characterized by the nuclease P1 version of the 32P-postlabelling technique. The adducts in human samples were transferred magnetically during chromatography. The 2'-deoxyguanosine 3'-monophosphate (dGMP) adduct standards, including N2 and O6 adducts, were shown to be resistant to the action of nuclease P1. The O6 adducts were detected in the femtomole range at about 10% labelling efficiency. In lamination workers, the level of O6 adducts, adjusted for adduct recovery, was 5/10(8) nucleotides, which was five times the level in controls. |
8070858 | Use of haemoglobin adducts for biomonitoring exposure to 1,3-butadiene. | Measurement of specific adducts to haemoglobin can be used to establish the dosimetry of pounds and metabolites in experimental animals and in man. Adducts of 1,2-epoxybutene with the N-terminal valine in haemoglobin were determined in male B6C3F1 mice and Sprague-Dawley rats following exposure by inhalation to low concentrations of 1,3-butadiene (0, 2, 10 or 100 ppm, 6 h/day, 5 days/week, 4 weeks; animals killed within 1 h after the last exposure). The adduct level increased linearly with butadiene concentration in the mice, whereas a deviation from linearity was observed in the rats. After exposure to 100 ppm butadiene, the adduct levels were four times higher in mice than in rats; at lower concentrations of butadiene, the species difference was less pronounced. Adduct levels of about 1-3 pmol/g globin were recorded in human subjects (nonsmokers) who worked in a production area where butadiene levels of about 1 ppm had been recorded in a survey conducted three to nine months prior to this study. Increased adduct levels were also observed in cigarette smokers (two subjects) who were not exposed occupationally to butadiene. Although preliminary, the data suggest that the adduct levels, and consequently the doses of epoxybutene per parts per million-hour of butadiene are lower in humans than in mice and rats. The adduct levels are much lower than those seen after occupational exposures to corresponding air levels of ethylene oxide and are lower than those seen after exposure to ethylene. |
8070859 | Biological monitoring of 1,3-butadiene: species differences in haemoglobin binding in rat and mouse. | The adduct formed by the reaction of 1,3-butadiene monoxide, a major metabolite of the mutagen and carcinogen 1,3-butadiene, with the N-terminal valine of haemoglobin was used as a dosimeter for the bioavailability of reactive metabolites. The dose-dependence of adduct formation was studied in female CB6F1 mice and female Wistar rats exposed to 0, 50, 200, 500 or 1300 ppm butadiene in an open inhalation chamber for 6 h per day for five consecutive days. Globin was isolated 18 h after the last exposure, and N-terminal valine was obtained by a modified Edman degradation procedure. Adduct levels were five times higher in mice than in rats (17 and 3.5 nmol/g globin, respectively, at 500 ppm), which may partially explain the greater susceptibility of mice to tumour formation. Adduct levels increased linearly with dose in rats, whereas in mice this slope of the curve became flatter at 500 ppm and increased with higher doses. Similar results were obtained in male and female C3H x 101/EL mice. |
8070860 | Biomonitoring of exposure to 1,3-butadiene: detection by high-performance liquid chromatography and 32P-postlabelling of an adenine adduct formed by diepoxybutane. | 1,2-Epoxy-3-butene and 1,2:3,4-diepoxybutane, the two oxidative metabolites of 1,3-butadiene, are considered to be involved in some of the carcinogenicity of the pound. Diepoxybutane is a bifunctional alkylating agent and reacts with DNA to form monoadducts and cross-links. We investigated DNA alkylation after exposure to diepoxybutane in order to develop a method for human biomonitoring. After reacting dAMP and then poly(dA-dT) (dA-dT) with diepoxybutane, we identified a major adenine adduct. Preliminary mass spectrometry indicated an adenine adducted by diepoxybutane at the N6 position. A high-performance liquid chromatography/32P-postlabelling method was developed, and the adduct was detected in calf thymus DNA and in DNA from Chinese hamster cells after exposure to diepoxybutane. The labelling efficiency, the amount of the adduct and its stability suggest that it could be a suitable indicator of exposure to butadiene. |
8070861 | The occupational scene of styrene. | Styrene readily undergoes homopolymerization as well as copolymerization with other monomers, such as acrylonitrile and butadiene. In closed polymerization processes, exposure of workers to styrene is generally lower than current reference values (20-50 ppm), but high peaks of exposure may occur during the cleaning, filling and maintenance of reaction vessels and during transport of liquid styrene. Styrene is used not only in styrene polymers but also as a reactive solvent in the manufacture of unsaturated polyester resins. During the lamination process, when resins are applied manually or by spraying in open moulds, workers are exposed to styrene at concentrations that are on average two or three times higher than the 8-h time-weighted average hygienic standard, 20 ppm. Further, exposures during the open mould process tend to fluctuate widely, so that short-term exposures are often twice the short-term reference value (100 ppm; 15-min time-weighted average). These processes also involve exposure to styrene oxide, which is a suspected carcinogen. Use of low-emission resins reduces exposure during curing but not during lamination itself. The exposure of laminators can be reduced by use bined, carefully planned, general and local ventilation, adequately designed work places and promotion of safe working habits. The best way of controlling exposures to styrene in the reinforced plastic industry in general would be to automate the processes and to use closed moulds. |
8070862 | Neurotoxicity in workers exposed to styrene. | Quantitative electroencephalography (EEG) for 99 workers exposed to styrene in the reinforced-plastics industry was analysed pared with exposure parameters. The work places and factories from which the subjects were selected had been evaluated previously, and exposure levels were known relatively accurately. That information and data on individual exposures bined to create an exposure index, which reliably reflected long-term exposure to styrene in various occupational settings. All of the subjects underwent careful medical and neurophysiological examinations. Quantitative EEG was recorded on 19 channels and analysed for absolute and relative power, asymmetry, coherence, frequency distribution, and statistical normative data parisons (neurometrics). When the workers were divided into three groups on the basis of exposure, workers with the highest exposure had significantly more EEGs classified as abnormal and had higher absolute EEG power in alpha band in the fronto-temporal regions of the brain. The findings indicate that abnormalities can occur in cerebral function even after relatively low mean exposures. We conclude that the efforts to lower regulatory hygienic levels of styrene are justified. |
8070863 | Effects of styrene on the reproductive health of women: a review. | Styrene has been shown to cross the placenta. Studies in animals suggest that styrene and styrene oxide have embryotoxic or fetotoxic effects early in pregnancy, but there is no evidence with regard to teratogenicity. This paper is a review of epidemiological investigations on the effects of occupational exposure to styrene on the reproductive health of women. The results of these studies are contradictory. Some early reports suggested that exposure to styrene induces menstrual disturbances, spontaneous abortions and congenital malformations. In more recent studies, no risk was observed among workers exposed to styrene in the reinforced-plastics industry. An excess of spontaneous abortions was, however, indicated by one investigation in women whose work included the processing of polystyrene. Two studies also suggested associations between exposure to styrene and low birth weight and reduced fertility. Although some epidemiological studies suggest that exposure to styrene involves reproductive hazards, the validity of most of these studies is weakened by methodological ings. The available evidence cannot be used to draw any firm conclusions. |
8070864 | Male-mediated F1 effects in mice exposed to 1,3-butadiene. | We examined the effects on dominant lethality and the incidence of fetal abnormalities of acute and subchronic exposure of male mice by inhalation to the industrial monomer 1,3-butadiene. Investigation of the effect on tumour incidence in surviving offspring is still in progress. In the acute study, CD-1 mice were exposed to atmospheres containing 0 (n = 25), 1250 (n = 25) or 6250 ppm (n = 50) for 6 h, and each male was caged five days later for one week with two untreated virgin females. One of the females was killed humanely on day 17 of gestation. The other was allowed to deliver and rear her litter; the litters are being monitored for life. The killed female was examined for the number of live fetuses, the number of post-implantation deaths (early and late) and the number and type of any gross malformations. In the subchronic study, males were exposed to 0 (n = 25), 12.5 (n = 25) or 1250 ppm (n = 50) for 6 h per day on 5 days per week for 10 weeks and then mated immediately. Mating and observation were conducted as in the acute study. Acute exposure to butadiene resulted in only a small decrease in implantations; after 10 weeks' subchronic exposure to either the high or the low concentration, however, a wide variety of statistically significant effects was seen. At 1250 ppm, the number of implantations was reduced, dominant lethal mutations were induced, and the incidences of early and late deaths were increased; some of the live fetuses had abnormalities. The low dose also increased the frequency of abnormalities and late deaths, but it did not affect the number of early deaths. Thus, butadiene is mutagenic in the germ cells of male mice, as shown by the induction of dominant lethality at 1250 ppm, and the frequencies of late deaths and congenital abnormalities appear to be increased at the subchronic level of 12.5 ppm. |
8070865 | Genetic toxicity of 1,3-butadiene and styrene. | 1,3-Butadiene and styrene (vinyl benzene) are indirect genotoxins, which require metabolic activation to an epoxide form in order to bind covalently to DNA. Styrene 7,8-oxide, the active metabolite of styrene, is a carcinogen in rodents and has been shown to be genotoxic in most in-vitro test systems and at various genetic endpoints. The few studies available on the genotoxicity of styrene 7,8-oxide in vivo have yielded negative or (in mice) weakly positive results. Styrene is not usually genotoxic in vitro in assays employing a microsomal preparation from rat liver for metabolic activation, but positive effects have been obtained when other sources of metabolic activation, such as human erythrocytes, were provided. In vivo, styrene has been found repeatedly to be weakly genotoxic in the assay for sister chromatid exchange, especially in mice. Cytogenetic damage (usually chromosomal aberrations) has been reported in many studies of workers, mainly from the reinforced plastics industry where ambient concentrations of styrene may be high (50-100 ppm), while most negative findings are associated with exposure to lower levels. Butadiene is metabolized to two reactive forms, 1,2-epoxy-3-butene and further to 1,2:3,4-diepoxybutane, both of which are genotoxic in various test systems in vitro. The lowest effective dose of the latter is 1-2 orders of magnitude higher than that of the respective monoepoxide. Butadiene itself has not been tested extensively for genotoxicity in vitro. A species-specific difference in the responses of mice and rats at various cytogenetic end-points is seen in vivo, the lowest effective concentrations in rats being clearly higher than those in mice.(ABSTRACT TRUNCATED AT 250 WORDS) |
8070866 | Mutagenicity of 1,3-butadiene and its epoxide metabolites in human TK6 cells and in splenic T cells isolated from exposed B6C3F1 mice. | The mutagenic potential of 1,3-butadiene and its epoxide metabolites have been measured in a human lymphoblastoid cell line (TK6) and in splenic T cells from exposed B6C3F1 mice. TK6 cells were exposed for 24 h to 0-400 microM 1,2-epoxybutene, 0-800 microM 3,4-epoxy-1,2-butanediol or 0-6 microM diepoxybutane and plated to measure the frequencies of mutations at the hprt and tk loci. All three metabolites were mutagenic at both loci, but diepoxybutane was active at concentrations 100 times lower than epoxybutene or epoxybutanediol. Mice exposed to 625 ppm butadiene for two weeks had an average hprt mutation frequency of 6.2 x 10(-6) in splenic T cells, whereas that in controls was 1.2 x 10(-6). In mice given three daily intraperitoneal doses of epoxybutene at 60, 80 and 100 mg/kg or diepoxybutane at 7, 14 and 21 mg/kg, the average hprt frequencies were 5.4, 4.1 and 8.6 x 10(-6) in those given epoxybutene and 4.6, 9.4 and 13 x 10(-6) in those treated with diepoxybutane. DNA sequencing revealed that 50% of the mutations induced in vivo by butadiene, epoxybutene and diepoxybutane were transition and transversion mutations at AT and GC base-pairs and 50% were frameshift mutations. The mutational spectra obtained are very similar to that produced by ethylene oxide, suggesting that these epoxides act through a similar mechanism. |
8070867 | Cytogenetic studies of rodents exposed to styrene by inhalation. | Female B6C3F1 mice and Fischer 344 rats were exposed to styrene at nominal concentrations of 125, 250 and 500 ppm by inhalation for 6 h per day for 14 consecutive days. One day after the final exposure, murine peripheral blood lymphocytes, spleen and lungs were removed, and the cells were cultured for analysis of chromosomal aberrations, micronucleus induction (using the cytochalasin B-block method) and sister chromatid exchange. Peripheral blood smears were scored for micronucleus induction in normochromatic erythrocytes. For the rats, peripheral blood lymphocytes were cultured for analyses of sister chromatid exchange, chromosomal aberrations and micronuclei in cytochalasin B-induced binucleated cells and were also examined in the single-cell gel assay for analysis of DNA strand breakage under alkaline conditions. Bone-marrow smears were made from femurs of rats for analysis of micronucleus induction in normochromatic erythrocytes. Small but statistically significant concentration-related increases in the frequency of sister chromatid exchange were seen in both mice and rats in all cell types examined. No statistically significant concentration-related increase in chromosomal aberration or micronucleus induction frequencies were observed in either species, and there was no significant increase in DNA strand breakage in peripheral blood lymphocytes from exposed rats. These results indicate that styrene is a weak inducer of sister chromatid exchange in vivo when administration to rodents by inhalation. |
8070868 | Studies of the induction of chromosomal aberration and sister chromatid exchange in rats exposed to styrene by inhalation. | A large number of studies have been reported on the genotoxicity of styrene in vitro and in vivo and the potential effects on humans of occupational exposure. Because of a variety of technical problems and difficulties in data interpretation, it has not been clearly established whether styrene can induce chromosomal aberrations and/or sister chromatid exchange (SCE) in vivo in animals or humans. The importance of clarifying this situation led to the development of the study described in this paper. Male Fischer 344 rats were exposed to styrene at concentrations of 150, 500 or 1000 ppm for 6 h/day on 5 days/week for 4 weeks. A negative control (air) was included. An additional control (ethylene oxide, 150 ppm) group was included in an attempt to establish the usefulness of rat lymphocytes for cytogenetic analysis in this protocol of long-term exposure by inhalation. The choice of agent and of exposure was based on the expectation that they would produce a positive response for SCE and/or chromosomal aberrations under the assay conditions used. Peripheral blood samples were drawn at 1, 2, 3 and 4 weeks of exposure and at 4 weeks after the end of exposure. Cultures were established, and SCE (second mitosis) and chromosomal aberrations (first mitosis) were analysed. The frequency of chromosomal aberrations was not increased over that in the air controls in the animals exposed to styrene or ethylene oxide at any of the sampling times. Styrene did not induce SCE at any of the concentrations or sampling times; however, the frequency of SCE was increased following exposure to ethylene oxide at all sampling times, with a positive exposure-response relationship with time of exposure as the variable. The data pared with other, similar sets reported in the literature, and their significance for predicting responses in people occupationally exposed to styrene is discussed. |
8070869 | Use of transgenic mice for assessing the mutagenicity of 1,3-butadiene in vivo. | We have examined the mutagenicity of 1,3-butadiene in vivo in transgenic mice constructed with lambda phage shuttle vectors that contain either lacZ or lacI as transgenes. Thus far, we have shown that butadiene is mutagenic to the lung of lacZ mice (CD2F1, 625 ppm butadiene, 6 h/day, 5 days) and to the bone marrow of lacI mice (B6C3F1, 62.5, 625, 1250 ppm butadiene, 6 h/day, 5 days/week, 4 weeks) exposed by inhalation to the same concentrations used previously in bioassays of the carcinogenicity of butadiene. Analysis of the DNA sequences of lacI mutants from the bone marrow of lacI mice demonstrated a shift in the spectrum of mutation from G:C base pairs in the control group to mutation at A:T base pairs in the exposed group. In addition, analysis of DNA sequences of mutations in three animals exposed to butadiene showed evidence of mutant clonal expansion in vivo. These results indicate that butadiene induces mutation in mouse tissues. Analysis of mutations at the level of DNA sequences is useful for examining the relationship between mutation and mutant frequencies in vivo and the spectrum of mutation in transgenic animals after exposures to carcinogens. |
8070870 | DNA binding and stimulation of cell division in the carcinogenicity of styrene 7,8-oxide. | [7-3H]Styrene 7,8-oxide was administered by oral gavage to male CD rats at a dose of 1.3 mg/kg. After 4 h, the forestomach was excised, DNA was isolated, purified to constant specific radioactivity and degraded enzymatically to the 3'-nucleotides. High-performance liquid chromatography fractions with the normal nucleotides contained most of the radiolabel, but a minute level of adduct label was also detected. Using the units of the covalent binding index (micromoles adduct per mole DNA nucleotide)/(millimole chemical administered per kilogram body weight), a DNA binding potency of 1.0 was derived. parison of the covalent binding indices and carcinogenic potencies of other genotoxic forestomach carcinogens showed that the tumorigenic activity of styrene oxide is unlikely to be purely genotoxic. Therefore, styrene oxide pared with 3-t-butylhydroxyanisole (BHA) with respect to stimulation of cell proliferation in the forestomach. Male Fischer 344 rats were treated for four weeks at three dose levels of styrene oxide (0, 137, 275 and 550 mg/kg, three times per week by oral gavage) and BHA (0, 0.5, 1 and 2% in the diet); the highest doses had been reported to result in 84% and 22% carcinomas in the forestomach, respectively. Cell proliferation was assessed by incorporation of bromodeoxyuridine into DNA and immunohistochemical analysis. An increase in the labelling index was found in all treated animals. In the prefundic region of the forestomach, the labelling index increased significantly, from 42% (controls) to 54% with styrene oxide and from 41 to 55% with BHA.(ABSTRACT TRUNCATED AT 250 WORDS) |
8070871 | Elevated somatic cell mutant frequencies and altered DNA repair responses in nonsmoking workers exposed to 1,3-butadiene. | Epidemiological evidence indicates that 1,3-butadiene is a human carcinogen; however, the epidemiological studies reflect past levels of exposures in the work place, which in all likelihood were higher than present-day levels. Studies of the metabolism of butadiene suggest that there may be qualitative differences among species in this respect. The question therefore arises as to the mutagenic and carcinogenic effects of butadiene in humans. The biomonitoring study reported here was designed to determine whether current exposure to this chemical in the work place is sufficient to induce mutations and/or to alter DNA repair functions, and to determine further whether levels of urinary metabolites correlate with the effects of exposure to butadiene. Nonsmoking workers in a butadiene production plant, who were exposed to levels of 1-3 ppm butadiene, were evaluated for hprt mutant frequencies, cytogenetic effects, including a challenge test to detect DNA repair deficiencies, and formation of protein adducts. We report here the results of the initial study on hprt mutant frequencies and of the challenge assay and the correlation between the results of these assays and levels of butadiene metabolite in the urine. A single metabolite of butadiene, 1,2-dihydroxy-4-(N-acetylcysteinyl-S)butane, was detected in the urine of all subjects. The concentration of the metabolite in the highly exposed group of workers was significantly higher than that in the group exposed to low concentrations or that in outside control groups. The correlation between the level of the metabolite in urine and the frequency of hprt mutants was r = 0.85 (p < 0.0003). Initial observations from a newly developed cytogenetic assay intended to measure altered DNA repair capability (the challenge assay) indicate a statistically significant increase in the high-exposure group relative to the low-exposure group (p < 0.01). This study thus reinforces and extends the results of the epidemiological studies and indicates that present exposure levels may not be sufficiently low to protect workers. It also provides evidence that levels of the urinary metabolite that was considered to be indicative of insensitivity correlate with the frequencies of somatic mutations and exposure to butadiene. |
8070872 | Susceptibility to induction of chromosomal damage by metabolites of 1,3-butadiene and its relationship to 'spontaneous' sister chromatid exchange frequencies in human lymphocytes. | Occupational exposure to butadiene is associated with the occurrence of lymphohaematopoietic cancers. The mutagenicity of butadiene is thought to be mediated by its mono- and diepoxide metabolites, which are capable of binding to DNA. Diepoxybutane is the most potent genotoxic metabolite and is known to produce interstrand DNA cross-links. In order to study individual differences in response to the genotoxicity of diepoxybutane, we devised a human lymphocyte culture system that involves short-term culture of T lymphocytes and measurement of sister chromatid exchange (SCE) and chromosomal aberration frequency as genotoxic end-points. We observed that when lymphocytes from healthy individuals are exposed in vitro to 6 microM of diepoxybutane, the number of SCEs induced is distributed bimodally: about 20% of 173 healthy workers studied were twice as sensitive to the induction of SCEs as the remaining 80%. Cells from sensitive individuals also contain four times more diepoxybutane-induced chromosomal deletions and exchanges. Of particular interest is the observation that diepoxybutane-sensitive individuals have higher frequencies of baseline (i.e., uninduced) SCEs. We have now examined the sensitivity of individual lymphocytes to SCE induction by another DNA cross-linking agent (nitrogen mustard) and to monoepoxybutene. The results indicate that lymphocytes sensitive to diepoxybutane-induced SCEs have normal sensitivity to nitrogen mustard and a moderately increased response to the monofunctional agent monoepoxybutene. Measurement of diepoxybutane-induced SCEs is a potential biomarker of sensitivity to the genotoxic effects of butadiene and may be useful in occupational epidemiological studies. Such studies, bination with measures of butadiene metabolism, could be useful in ascertaining whether the sensitivity is mediated by enzyme polymorphisms. |
8070873 | Exposure to styrene in the general Canadian population. | As part of an environmental health assessment in Canada, estimates of the intake of styrene by the general population were derived. Concentrations of styrene reported in air, water, soil and foods in Canada were reviewed in detail. Data on ambient air, collected by Environment Canada, showed mean concentrations of 0.09-2.35 micrograms/m3 at 18 sites across the country. In a national pilot study of indoor air in 757 homes across Canada, the mean styrene concentration was found to be 0.28 microgram/m3. The range of mean concentrations of styrene in treated water from 80 supplies in Ontario's Drinking Water Surveillance Program was 0.050-0.250 microgram/L. In limited testing of uncontaminated urban soils in southern Ontario, the styrene levels were less than 10 micrograms/kg. In a small Canadian survey, pound was not detected (limits of detection, 1.0 microgram/L for liquids and 0.005 microgram/g for solids) posite samples of 34 groups of food purchased in Windsor, Ontario. On the basis of these monitoring data, daily intakes of styrene were estimated for the general population. Intakes from ambient air ranged from 0.004 to 0.17 microgram/kg body weight per day and those from indoor air from 0.07 to 0.10 microgram/kg body weight per day for various age groups: infants, toddlers, school-age children, teenagers and adults. Intake from food was calculated to range from < 0.11 to < 0.58 microgram/kg body weight per day. The estimated intakes from drinking-water and soil were negligible. Potential exposure from cigarette smoke, on the basis of the styrene reported in mainstream smoke (10 micrograms per cigarette) and a smoking rate of 20 cigarettes per day, was estimated to be 2.86 micrograms/kg body weight per day for adults. |
8070874 | Cytogenetic studies of workers exposed to styrene: a review. | In 17 of 50 cytogenetic studies (on chromosomal aberrations, micronucleus formation and sister chromatid exchange) in peripheral blood lymphocytes from a total of 667 workers in industries in which there is exposure to styrene, significant increases in the frequency of chromosomal damage have been reported pared with unexposed controls. The positive or negative e of these studies is, however, unrelated to the extent of exposure to styrene. Furthermore, in the 17 investigations in which positive results were found, there is no convincing evidence of a positive dose-response relationship, in spite of the wide ranges of exposure and different methods of measurement. There are also serious discrepancies between findings on the chromosomal damaging effects of styrene in human lymphocytes in vitro and the types of damage reported in exposed workers. The findings are not consistent with the interpretation that styrene is responsible for the observed effects in workers. Several other chemicals identified in the environment of styrene workers have been reported to induce chromosomal damage in vitro and/or in vivo. |
8070875 | Cancer mortality in an international cohort of workers exposed to styrene. | Increased risks for leukaemia and lymphoma have been suggested in studies of workers exposed to styrene in the rubber and plastics industry. A historical cohort study was conducted in Denmark, Finland, Italy, Norway, Sweden and the United Kingdom involving 40,683 workers employed in the reinforced plastics industry, where high exposure to styrene occurs. Exposure to styrene was reconstructed through job histories, environmental and biological monitoring data and production records of the plants in the study. Cause-specific national death rates were used as the reference. Among exposed workers, no excess was observed for mortality from all causes (2195 deaths, standardized mortality ratio [SMR], 95; 95% confidence interval [CI], 91-99), from all neoplasms, from lung cancer or from other major epithelial cancers. Mortality from neoplasms of the lymphatic and haematopoietic tissues was not elevated (50 deaths; SMR, 96; CI, 71-126) and was not consistently associated with length of exposure. The rate of mortality from leukaemias and lymphomas increased with time since first exposure. Among subjects who had been exposed for more than one year, a two-fold risk was observed 20 years after first exposure (eight deaths; SMR, 197; CI, 85-387). These results are inadequate to exclude the possibility that styrene causes leukaemia and lymphoma. |
8070876 | Industrial exposure to 1,3-butadiene in monomer, polymer and end-user industries. | Researchers from the National Institute for Occupational Safety and Health (NIOSH) of the Centers for Disease Control and Prevention conducted an extent-of-exposure study of 1,3-butadiene monomer, polymer and end-user industries to assess occupational exposure to butadiene and to evaluate control technologies. The findings of the exposure assessment are reported here. Walk-through surveys were conducted in 11 monomer, 17 polymer and two end-user plants; in-depth industrial hygiene surveys were conducted at four monomer, five polymer and two end-user plants. Airborne exposure concentrations of butadiene were determined for various job categories by personal sampling. The samples were analysed by a new method developed at NIOSH that is sensitive to 0.2 microgram per sample. A total of 687 personal (full-shift and short-term) and 232 area samples were taken. The results indicate that all exposures were well below the current permissible exposure limit of the US Occupational Safety and Health Administration of 1000 ppm. The US Occupational Safety and Health Administration (1990) has proposed a new standard that would reduce exposure to 2 ppm. Exposures ranged from less than 0.005 ppm to 374 ppm, and 3.7% of the samples contained more than 10 ppm, 7.8% more than 2 ppm but less than 10 ppm and 88.5% less than 2 ppm. We mend means for reducing exposure by the use of engineering controls. |
8070878 | 1,3-Butadiene induces cancer in experimental animals at all concentrations from 6.25 to 8000 parts per million. | 1,3-Butadiene, a chemical produced in large volumes, induces cancer in many organs in rats (at 1000 and 8000 ppm) and mice (at 6.25 to 1250 ppm); however, the sites of tumour induction (seven in rats and nine in mice) and the magnitudes of response differ between the two species. Particularly noteworthy in the studies of mice exposed by inhalation were the early, extensive induction of malignant lymphomas, the induction of mon as of the heart and the development of malignant lung tumours at 6.25 ppm, the lowest concentration ever used in a long-term carcinogenicity study of this gas. In order to account for the impact of early mortality on the expression of late development of tumours, survival-adjusted tumour rates puted for mice exposed to butadiene at 6.25-625 ppm. The results provide a more accurate characterization of concentration-dependent responses for butadiene-induced cancers. Stop-exposure studies revealed that the atmospheric concentration of butadiene was a greater contributing factor to the development of lymphomas than was duration of exposure. The studies in mice show a good correspondence with the reported associations between occupational exposure to butadiene and excess mortality from lymphatic and haematopoietic cancers; mice are thus a better experimental surrogate for humans. Although further work is needed to improve our understanding of the mechanisms of tumour induction by butadiene, pursuit of that research must not delay reduction of human exposure to this carcinogenic chemical. |
8070877 | Cancer incidence in the Danish reinforced plastics industry. | Increased occurrences of malignancies of the lymphatic and haematopoietic tissues have been reported from industries in which employees are potentially exposed to styrene. The aim of the study reported here was to describe cancer incidence in the reinforced plastics industry in Denmark. A total of 64,000 employees of 552 panies assessed to have produced reinforced plastics at any time since the 1960s were identified from a public administrative registry of all Danish employers and wage earners. Cancer incidence in the population pared with similar rates for the population at large. No excess risk for all neoplasms was observed. Among male employees, increased risks were found for cancer of the lung (396 cases; relative risk [RR], 1.15; 95% confidence interval, 1.04-1.27), of the pleura (20 cases; RR, 2.33; 1.42-3.60), of the nasal cavities (nine cases; RR, 1.55; 0.71-2.94), of non-Hodgkin's lymphoma (61 cases; RR, 1.27; 0.97-1.63) and for leukaemia (61 cases; RR, 1.15; 0.88-1.48). Among female employees, a reduced risk for non-Hodgkin's lymphoma was observed (one case; RR, 0.16; 0.00-0.88). Some support was thus found for previous reports of increased risk for respiratory cancers and for malignancies of the lymphatic and haematopoietic tissues. The results must be interpreted with caution, however, owing to ings in the design of the study. |
8070879 | Styrene and styrene oxide: results of studies on carcinogenicity in experimental animals. | Fourteen long-term toxicity studies were reviewed in an effort to evaluate the potential carcinogenic activity of styrene and styrene oxide in animals. Each study was reviewed and evaluated for detail and adequacy of design, adequacy of reported data and interpretation. The results of the review are: 1. There is no convincing evidence for a carcinogenic action of styrene in animals, even though it has been studied in several species and by several routes of exposure: inhalation, gavage, in the drinking-water and by intraperitoneal and subcutaneous injection. Most of the studies of styrene, however, have deficiencies in design and/or conduct. 2. Styrene oxide was carcinogenic to the forestomach of rats and mice of each sex after exposure by gavage at all doses tested, including one as low as 50 mg/kg per day. An increase in the incidence of liver neoplasms was observed in male mice in one study. No carcinogenic activity was observed in mice exposed by skin painting. The relevance to humans of the studies in which exposure was by gavage is limited because: (i) the route is less than ideal for extrapolating to human risk from exposure by inhalation or dermally; (ii) xenobiotics often cause neoplasms at this site when given at high concentrations; and (iii) neoplasms at sites distant from the site of exposure were found in only one sex of one species. 3. None of the studies of styrene or styrene oxide reported here is well suited for extrapolating to potential carcinogenic activity in humans, because all have deficiencies in design, conduct and/or interpretation. An up-to-date chronic inhalation study would have to be conducted in order to evaluate this aspect of hazard assessment. |
8070880 | Time-to-tumour risk assessment for 1,3-butadiene based on exposure of mice to low doses by inhalation. | The excess risk for cancer due to lifetime occupational exposure to 1,3-butadiene at the proposed US Occupational Safety and Health Administration standard of 2 ppm was estimated on the basis of a quantitative risk assessment. The risk assessment was based on a recent study by the US National Toxicology Program of the carcinogenicity of butadiene in B6C3F1 mice, using exposure concentrations ranging from 6.25 to 625 ppm butadiene and controls. Cancer risks were estimated using a multistage Weibull time-to-tumour model; the dose was based on the external butadiene concentration, owing to the low-dose linearity of butadiene metabolism. The parameters of the time-to-tumour model were estimated for seven tumour sites in male mice and nine in female mice. The risk estimates were extrapolated from mice to humans on the basis of body weight raised to the three-fourths power, and the median lifespan of mice was equated to a human lifespan of 74 years. Estimates of excess risk for lifetime occupational exposure (8 h/day, 5 days/week, 50 weeks/year, for 45 years) to 2 ppm butadiene ranged from 0.2 per 10,000 workers, based on female mouse heart as, to 600 per 10,000 workers, based on female mouse lung tumours. An analysis was performed to assess the effects of varying the modelling assumptions (incidental versus fatal tumours, inclusion or exclusion of the 625-ppm dose group, and basis for interspecies scaling) on the risk estimates from the female mouse lung tumour model. Depending on the assumptions, estimates of lifetime excess risk derived from the female mouse lung model ranged from 60 per 10,000 to 1600 per 10,000. These results suggest that exposures to butadiene in the work place should be reduced to the lowest feasible level. |
8070881 | Cancer mortality among workers at a butadiene production facility. | A cohort study was carried out of mortality among 2749 male workers who had been employed for at least six months between 1943 and 1990 at a 1,3-butadiene production facility. Most of the members of the cohort were covered in two earlier studies, both of which found a statistically significant deficit for all causes of death and lower than expected mortality from most of the main causes of death. Both also found a statistically significant excess risk for a, which was concentrated in workers who had been employed for fewer than 10 years, had first been employed before 1946 and had been employed in jobs with routine potential exposure. The purpose of the study reported here was to examine the patterns of mortality after addition of five years of follow-up, new eligible cohort members plete information on work histories. We were able to obtain information on the vital status of all but 1.4% of the cohort: 1051 deaths had occurred between 1943 and 1990. Death certificates were obtained for all but 15 of the deceased men (1.4%). The standardized mortality ratio (SMR) for all causes of death is 88, and this low figure is statistically significant; the SMR for all cancers, 87, is not statistically significant. The SMR for all lymphohaematopoietic cancers is 143 (95% confidence interval, 100-200). The SMR for leukaemia is 112 (11 deaths), that for a, 209 (nine deaths), that for other lymphomas, 126 (10 deaths) and that for Hodgkin's disease, 175 (four deaths). None of the latter SMRs is statistically significant. |
8070882 | Cancer epidemiology among styrene-butadiene rubber workers. | The standardized mortality ratios for some cancers of the lymphohaematopoietic system were high in an early cohort analysis. Since the presence of large numbers of unexposed workers could conceal risks within a cohort, a case-control study was designed to examine the relationship between estimated exposures and the occurrence of these cancers. The results suggested that the risk for leukaemia was associated with exposure to butadiene and with work in specific areas. Modelling, using rank scores, indicated an increase in the risk for leukaemia with increasing exposure score. Use of cases validated by review of hospital records and selection of a new set of controls did not change the findings. The data indicated parison of scores within the same time frame improved the model and increased the estimated odds ratio, suggesting that exposure time or dose rate may prove to be the important variable for risk. Exact measurements from panies involved showed significant correlations between assigned ranks and level of exposure derived from personal monitoring for butadiene but not for styrene. Thus, use of the measured values might be expected to show an association between leukaemia and exposure to butadiene. The standardized mortality ratio for leukaemia among long-term workers hired before 1960 who had worked in the three plants where the geometric mean butadiene level was three to five times higher than those in the other plants is 1.8 times higher than that of the US population. An appropriate algorithm paring cases and controls on the bases of the measured samples is being developed. |
8070883 | Interspecies differences in metabolism and kinetics of 1,3-butadiene, isobutene and styrene. | Investigations on the pharmacokinetics of inhalation of 1,3-butadiene and its primary reactive intermediate, epoxybutene, in mice and rats have demonstrated reasonably clearly that the species differences observed in the carcinogenicity of butadiene are panied by species differences in its metabolism. Mice metabolize butadiene to epoxybutene faster than rats but have a limited capacity for detoxification and accumulation of the reactive epoxide intermediate; these characteristics are viewed as major determinants of the greater susceptibility of mice to butadiene. The detection of alkylation products of epoxybutene and diepoxybutane with guanine residues in DNA of livers of mice exposed to butadiene indicate that eposybutene is further biotransformed to diepoxybutane in this species. This assumption is supported by the finding that butadiene induces cross-linking between DNA and proteins in mice, which can be attributed to the bifunctional alkylating diepoxybutane. Quantitative differences between rats and mice in butadiene metabolism and in the biological effectiveness of the reactive epoxide intermediates reflect the activities of different enzymes in butadiene metabolism. Epoxybutene is metabolized primarily via glutathione S-transferase-mediated pathways, resulting in glutathione depletion, increased toxicity at higher doses and covalent binding of reactive butadiene intermediates. A drastic depletion of non-protein sulfhydryl is observed in the tissues of mice but not of rats after acute exposure to butadiene. Isobutene (2-methylpropene) is converted by hepatic monooxygenase(s) to the epoxide, 2,2-dimethyloxirane. This epoxide, when appropriately tested, was mutagenic to Salmonellatyphimurium strains TA100 and TA1535. Addition of an exogenous metabolic system diminished the mutagenicity of 2,2-dimethyloxirane.(ABSTRACT TRUNCATED AT 250 WORDS) |
8070884 | Critical assessment of epidemiological studies on the carcinogenicity of 1,3-butadiene and styrene. | 1,3-Butadiene. The consistent finding in five epidemiological studies of workers occupationally exposed to butadiene is excess mortality from lymphohaematopoietic malignancy. This highly reproducible finding is noted despite methodological limitations in each of the published studies that tend to diminish the likelihood of observing an etiological association: (i) lack of detailed data on individual exposures to butadiene; and (ii) increasing longevity of many patients with lymphohaematopoietic malignancies, owing to treatment with modern therapeutic regimens, which results in their not being included in analysis of mortality. The observed excess in cancer mortality is most clearly evident in subpopulations heavily exposed to butadiene: production and maintenance workers as well as African-American workers. These epidemiological data strongly suggest an etiological association between exposure to butadiene and human cancer. The data amply fulfil all of Bradford Hill's criteria for causality. It is reasonable to conclude that there now exists convincing evidence for the carcinogenicity of butadiene to humans. Styrene. Epidemiological data on styrene suggest the possibility of an association with lymphohaematopoietic malignancy, although the finding has not been consistent. The most recent epidemiological study, an analysis of 35,000 European workers, suggests, however, an association between these malignancies and time elapsed since first occupational exposure to styrene. Preliminary data from a nested case-control study within the cohort also suggest an association with cumulative exposure to styrene. Although the current classification of the human carcinogenicity of styrene within the IARC Monographs programme appears to be reasonable, if the new findings are confirmed it may e necessary in the near future to revise the classification. Downgrading of the IARC classification is clearly contraindicated in light of current epidemiological and toxicological data. |
8070886 | Research strategy for assessing target tissue dosimetry of 1,3-butadiene in laboratory animals and humans. | 1,3-Butadiene is carcinogenic to rats and mice, although mice are more sensitive than rats. It is not known if butadiene poses a carcinogenic risk to humans. Butadiene requires metabolic activation to reactive epoxides that can bind to DNA to initiate a series of events that lead to tumour formation. Species differences in activation and detoxification must be considered in estimating human risks from exposure to butadiene. A research strategy for assessing the role of metabolic factors in the carcinogenicity of butadiene involves studies in laboratory animals in vivo, supplemented with studies in vitro with tissues from both laboratory animals and humans. In experiments conducted on liver and lung tissues from Sprague-Dawley rats, B6C3F1 mice and humans, we characterized the oxidation of butadiene and butadiene monoepoxide by cytochrome P450-dependent mono-oxygenases and the detoxification of butadiene monoepoxide by epoxide hydrolases and glutathione transferases. B6C3F1 mouse liver microsomes displayed a capacity for butadiene oxidation exceeding that seen in either human or rat liver microsomes. Except in mice, oxidation of butadiene occurred at rates significantly lower with lung than with liver microsomes. In general, human liver microsomes hydrolysed butadiene monoepoxide at higher rates than either rats or mice. The capacity for glutathione conjugation with butadiene monoepoxide was higher in mice than in humans or rats. The ratios of butadiene activation (P450):detoxication (hydrolysis and conjugation) are markedly different in mouse (74:1), rat (6:1) and human (6:1) liver tissues. The differences in the ratios between mice and rats are consistent with the higher carcinogenic sensitivity of mice than rats to butadiene. Factors in addition to metabolism, however, probably play a role in the carcinogenicity of butadiene in rats and mice. Metabolic rate constants for butadiene and butadiene monoepoxide oxidation and for butadiene monoepoxide hydrolysis and conjugation with glutathione, determined from physiological pharmacokinetic model simulations of butadiene-exposed rats and mice, were for the most part similar to the constants determined in vitro. The same trends that were noted in vitro were seen in vivo. The physiological dosimetry model for butadiene that includes in-vitro vitro metabolic constants can stimulate behaviour in vivo and can be used to predict blood and tissue concentrations of butadiene and its monoepoxide.(ABSTRACT TRUNCATED AT 400 WORDS) |
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