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Biomedical subjects

J Leigh

Publications and source records attributed to J Leigh.

At least 19 recordsLinked to original sources

Silica-induced apoptosis in alveolar and granulomatous cells in vivo.

Silica is a toxicant that can stimulate cells to produce various cellular products such as free radicals, cytokines, and growth factors. Silica and its induced substances may induce apoptosis to regulate the evolution of silica-induced inflammation and fibrosis. To examine this hypothesis, groups of Wistar male rats were intratracheally instilled with different doses of Min-U-Sil 5 silica (Silica, Berkeley Springs, WV). Ten days after the instillation, we obtained cells by bronchoalveolar lavage and placed them on slides by cytospin preparation. The slides were stained with Diff-Quik (Lab Aids, Sydney, NSW, Australia) and examined under oil immersion. A substantial number of cells with apoptotic features were identified in all silica-instilled rats and the apoptosis was confirmed by agarose gel electrophoresis. The number of apoptotic cells was clearly related to silica dosage. Engulfment of apoptotic cells by macrophages was also noted. Neutrophil influx in silica-instilled rats could be saturated with the increase of silica dosage and the number of macrophages in different dose groups changed in parallel with the proportion of apoptotic cells. Fifty-six days after instillation, morphologically apoptotic cells could be identified in granulomatous cells of lung tissue from silica-instilled rats. We conclude that intratracheal instillation of silica could induce apoptosis in both alveolar and granulomatous cells, and the apoptotic change and subsequent engulfment by macrophages might play a role in the evolution of silica-induced effects.

Administration, Inhalation

Health status and exposure of workers at a pilot brown coal liquefaction plant in Australia, 1985-1991.

In 1985, Brown Coal Liquefaction (Victoria) Pty Ltd (BCLV) commenced operation of a pilot plant that investigated the feasibility of producing oil from brown coal. The plant operated for five years. This study aimed to use exposure and health information routinely collected by the company to characterize various health parameters of the workforce and to investigate whether any adverse health measures were exposure-related. About 1680 persons were employed at some time or other by BCLV, and the primary study population consisted of 408 workers who had a medical examination at the end of employment and who consented to being in an epidemiological study. Reported photosensitivity was associated with higher cumulative skin exposure (RR = 1.85; 95% CI = 1.22-2.78), with an exposure-response relationship of increasing risk with increasing skin exposure being suggested. There was no consistent evidence that chemical exposure at BCLV had any negative effect on the haematological, biochemical, endocrine or lung function of workers at the plant. However, the maximum follow-up period of less than eight years limits the ability of the study to detect any emerging chronic effects.

Adult

Quantitative relation between emphysema and lung mineral content in coalworkers.

The relation between quantified emphysema and measured lung content of coal and silica was investigated in the lungs of 264 deceased underground coalworkers who had been exposed to mixed coal and silica dust. Lung specimens obtained at postmortem and inflated and fixed under standard conditions were used to quantify the extent of emphysema and then to measure the amount of coal and silica present in the lungs at the time of death. These data were combined with clinical and other pathological information from the subjects. Multiple regression analysis showed that the extent of emphysema (E score) had a strong positive quantitative relation with coal content of the lungs (p < 0.0003), age (p < 0.0001), and smoking (p < 0.0001). There was a significant negative interaction of uncertain biological importance between coal content of the lungs and smoking (p < 0.004; E score = -1.79 + 0.62 coal + 0.06 age + 0.21 smoking -0.17 coal x smoking; adjusted R2 = 0.25). In lifelong non-smokers emphysema was particularly strongly related to coal content and age (coal: p < 0.001; age: p < 0.002; E score = -1.56 + 0.78 coal + 0.06 age; adjusted R2 = 0.66). The relation was basically unchanged by adding a lung silica content term. Emphysema score was highly negatively correlated with forced expiratory volume in one second (FEV1; % predicted, obtained within five years of death) (r = -0.44, p < 0.0001). Degree of lung fibrosis was highly positively associated with lung silica content (chi 2(1) = 12.9, p < 0.0003). These results provide strong evidence that emphysema in coalworkers is actually related to lung coal content. The role silica in development of emphysema, however remains unclear.

Coal Mining

Simultaneous in vivo measurements of HbO2 saturation and PCr kinetics after exercise in normal humans.

Simultaneous measurements of phosphocreatine (PCr) and oxyhemoglobin (HbO2) saturation were made during recovery from exercise in calf muscles of five male subjects. PCr was measured using magnetic resonance spectroscopy in a 2.0-T 78-cm-bore magnet with a 9-cm-diam surface coil. Relative HbO2 saturation was measured as the difference in absorption of 750- and 850-nm light with use of near-infrared spectroscopy. The light source and detectors were 3 cm apart. Exercise consisted of isokinetic plantar flexion in a supine position. Two 5-min submaximal protocols were performed with PCr depletion to 60% of resting values and with pH values of > 7.0. Then two 1-min protocols of rapid plantar flexion were performed to deplete PCr values to 5-20% of resting values with pH values of < 6.8. Areas of PCr peaks (every 8 s) and HbO2 saturation (every 1 s) were fit to a monoexponential function, and a time constant was calculated. The PCr time constant was larger after maximal exercise (68.3 +/- 10.5 s) than after submaximal exercise (36.0 +/- 6.5 s), which is consistent with the effects of low pH on PCr recovery. HbO2 resaturation approximated submaximal PCr recovery and was not different between maximal (29.4 +/- 5.5 s) and submaximal (27.6 +/- 6.0 s) exercise. We conclude that magnetic resonance spectroscopy measurements of PCr recovery and near-infrared spectroscopy measurements of recovery of HbO2 saturation provide similar information as long as muscle pH remains near 7.0.

Adult

The role of alcohol in work-related fatal accidents in Australia 1982-1984.

This paper describes the role of detectable blood alcohol in fatal work injuries. An attempt was made to identify all work-related fatalities that occurred throughout Australia in the period 1982-1984. A research team examined coroners' records and classified 1737 fatal injury cases as being work-related according to study definitions. The following were also extracted from data in coroners' records: (i) whether or not the description of the fatal event indicated that inebriation was likely to have been a factor; (ii) whether or not there was documentation of blood alcohol concentration (BAC), and if so, what it was. The likelihood of inebriation was assessed without knowledge of the victim's BAC. In 1030 (59 per cent) of the 1737 fatal work injury cases, a BAC determination was documented. Zero levels were detected in 867 fatalities (84 per cent), and 163 cases (16 per cent) had non-zero BAC. In the latter group the median BAC was 104 mg%. Sixty-five per cent of measurable BAC cases had BAC greater than 50 mg%. Fatality risk in the non-zero BAC group relative to that of the zero BAC group was elevated for the following factors: marital status--single (risk ratio (RR) = 1.7, 95 per cent confidence interval (CI) 1.1-2.8) or separated/divorced (RR = 2.4, CI 1.5-3.8); occupation as manager, executive or administrator (RR = 2.5, CI 1.5-5.8); and commuting (RR = 1.6, CI 1.2-2.0).(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents, Occupational

Clinical aspects of malignant mesothelioma in Australia.

Australia is currently experiencing an epidemic of malignant mesothelioma. The clinical aspects of malignant mesothelioma were investigated in 295 Australian patients as part of a national study of the disease. Most patients were male (91%), with the mean age at diagnosis being 64 years. The predominant cell type was epithelial (38%) and the majority of primary tumours arose from the pleura (94%). Mean survival was poor (17.6 months from first symptom; 11.8 months from diagnosis). Patients with a pleural primary tumour were more likely to present with dyspnoea, chest pain and cough; to have a pleural effusion diagnosed radiologically; and to have metastatic spread. Patients with a peritoneal primary tumour were more likely to present with weight loss, loss of appetite, abdominal pain and ascites; to have radiologic evidence of asbestos exposure; and to have spread along a needle track created during a diagnostic tap. A minority of patients had past thoracic conditions, or radiologic findings, specifically related to previous asbestos exposure. About one fifth of patients had no known asbestos exposure. Forty-one per cent of subjects received some form of chemotherapy, radiotherapy and/or surgery, but no formal disease staging had been documented for any patient. Proper controlled trials of secondary and tertiary treatments in malignant mesothelioma are now needed.

Aged

Work-related agricultural fatalities in Australia, 1982-1984.

Work-related agricultural fatalities were examined as part of a larger population-based study of all work-related fatalities in Australia in the period 1982-1984. A total of 257 farm-related fatalities were identified, of which 223 were deaths of persons in the employed civilian labor force (19.4 deaths per 100,000 persons per year) and 34 were deaths of children less than 15 years of age. The fatality incidence was higher among men, older age groups, and nonmanagers in general and in certain occupations in particular. Mobile mechanical equipment (particularly tractors) was the main fatal agent, roll-overs accounting for many of the fatalities. Better provision of information to agricultural workers, improvements in compliance to and enforcement of legislation, and changes in farming work practices are recommended to improve the safety of farms and farm work.

Accidents, Occupational

Prediction of silicosis and lung cancer in the Australian labor force exposed to silica.

Empirical models for risk, based on recently published epidemiologic data, and simple prediction formulas were used to predict the occurrence of silicosis and lung cancer in the Australian labor force currently exposed to crystalline silica dust. As a result of an 0.9 (range 0.4-1.9)% average lifetime risk, approximately 1010 (range 380-2410) silicosis cases were predicted for the next 40 years among the estimated 136,400 men exposed at current silica dust levels [0.01-0.8 (average 0.094) mg.m-3]. Approximately 630 extra lung cancer cases (95% confidence interval 120-1320) would appear with an average excess risk of 0.5 (interval 0.1-1.1)%, the proportion of silica-induced lung cancer cases being about 15%. Currently 77% of the at-risk labor force is exposed to silica dust levels of < or = 0.1 mg.m-3. With this level as the limit, about 440 (range 140-1210) silicosis cases and 410 (interval 90-780) extra lung cancer cases would occur in 40 years. Adopting this level as the national exposure standard would reduce the risk of silicosis cases by 52% and the excess risk of lung cancer by 36%.

Adult

Lung asbestos fiber content and mesothelioma cell type, site, and survival.

All ascertainable cases of malignant mesothelioma in Australia were notified to a national surveillance program in the period January 1, 1980 to December 31, 1985. There were 854 cases obtained and 823 confirmed on clinical (77) or histologic (746) ground. Tumor site was known in 759 cases (685 pleural and 74 peritoneal). Lung fiber content analyses by light microscopy and analytic transmission electron microscopy with energy-dispersive x-ray analysis were done on 226 cases in which postmortem material was available, using the method of Rogers. Cell type was determined by a five-member expert panel of pathologists appointed by the Royal College of Pathologists of Australasia. There was a statistically significant trend between lung fiber content (fibers/g dry lung) and cell type from epithelial (low fiber content) through mixed to sarcomatous (high fiber content). This trend was most apparent for total uncoated fibers (chi-square = 6.8, df = 1, P less than 0.01) and crocidolite (chi-square = 6.7, df = 1, P less than 0.01). Lung fiber content also was associated with tumor site; higher lung fiber content being associated with peritoneal tumors. This relationship was significant for all fiber content measures except chrysotile and was independent of the fiber content-cell type relationship (log-linear analysis). Survival from time of provisional diagnosis was significantly longer for epithelial (mean, 13 months; standard deviation [SD], 12.8) and mixed (mean, 10.2 months; SD, 8.7) types than sarcomatous cell types (mean, 5.8 months; SD, 6.5; P less than 0.0001, by analysis of variance on log10 survival time). Survival time was significantly greater for pleural tumors (mean, 11.4 months; SD, 13.4) than peritoneal tumors (mean, 8.6 months; SD, 12.5) (P less than 0.005, by Student's t test on log10 survival time).

Asbestos

Relationship between lung asbestos fiber type and concentration and relative risk of mesothelioma. A case-control study.

Lung tissue from 221 definite and probable cases of malignant mesothelioma reported to the Australian Mesothelioma Surveillance Program from January 1980 through December 1985 and from an age-sex frequency matched control series of 359 postmortem cases were examined by light microscopic (LM) and analytical transmission electron microscopic (TEM) analysis and energy dispersive x-ray analysis (EDAX). Concentrations of total fibers (coated and uncoated) (LM), crocidolite, amosite, chrysotile, and unidentified amphibole (TEM) (fibers/g dry lung tissue) were measured. Fiber concentrations less than 10 microns in length and greater than or equal to 10 microns in length were separately quantified. By comparing cases (221) and controls (359 LM, 103 TEM), odds ratios for increasing fiber concentrations compared with less than 15,000 fibers/g (LM) and less than 200,000 fibers/g (TEM) (the respective detection limits) were calculated. Univariate analyses showed statistically significant dose-response relationships between odds ratio and fiber concentration for all fiber concentration measures. The relationship between log(odds ratio) and log(fiber concentration) was linear. Multiple logistic regression analysis showed that a model containing crocidolite greater than or equal to 10 microns, amosite less than 10 microns, and chrysotile less than 10 microns as explanatory variables best described the data. The odds ratios for a X10 increase in fiber concentration (fibers/micrograms) were as follows: crocidolite greater than or equal to 10 microns, 29.4 (95% confidence interval [CI], 3.6 to 241); chrysotile less than 10 microns, 15.7 (95% CI, 6.1 to 40); amosite less than 10 microns, 2.3 (95% CI, 1.0 to 5.3). An additive risk model gave similar results. In a subgroup of cases and controls with only chrysotile in the lungs, a significant trend in odds ratio with increasing fiber content was found.

Adult

The incidence of malignant mesothelioma in Australia 1982-1988.

From 1980 to 1985, the Australian Mesothelioma Surveillance Program, and since 1986, the Australian Mesothelioma Register, have been collecting data on all cases of malignant mesothelioma that could be ascertained in Australia. Incidence rates were calculated on 854 Program and 696 Register cases (total 1271) diagnosed in Australia between January 1, 1982 and December 31, 1988. Australia has one of the highest national rates of mesothelioma in the world (15.8 cases per million of population aged 20 years and older), and the rate is rising. The rate is far higher in males (28.3) than females (3.3). The Western Australian rate (28.9) is the highest among the states, as may be expected because of the crocidolite mine at Wittenoom; however, the largest numbers of cases occur in the more populous and industrial New South Wales. The high incidence rate, its expected continuing increase, and absence of a history of exposure to asbestos in approximately 28% of cases, demand consideration of potential environmental factors other than asbestos in the causation of this tumor, as well as continued surveillance.

Adult

Quantitation of time- and frequency-resolved optical spectra for the determination of tissue oxygenation.

The recent development of near-infrared time- and frequency-resolved tissue spectroscopy techniques to probe tissue oxygenation and tissue oxygenation kinetics has led to the need for further quantitation of spectroscopic signals. In this paper, we briefly review the theory of light transport in strongly scattering media as monitored in the time and frequency domains, and use this theory to develop algorithms for quantitation of hemoglobin saturation from the photon decay rate (delta log R/delta t) obtained using time-resolved spectroscopy, and from the phase-shift (theta) obtained from frequency-resolved, phase-modulated spectroscopy. To test the relationship of these optical parameters, we studied the behavior of delta log R/delta t and theta as a function of oxygenation in model systems which mimicked the optical properties of tissue. Our results show that deoxygenation at varying hemoglobin concentrations can be monitored with the change in the photon decay kinetics, delta delta log R/delta t in the time-resolved measurements, and with the change in phase-shift, delta theta, in the frequency-resolved technique. Optical spectra of the adult human brain obtained with these two techniques show similar characteristics identified from the model systems.

Algorithms

Vaginal birth after cesarean or repeat cesarean section: medical risks or social realities?

Despite the known medical safety and success of vaginal birth after cesarean section, rates of planned repeat cesarean sections remain high. The process involved in women's decisions to choose vaginal birth after cesarean section or repeat cesarean section was investigated by a questionnaire study at a private and a public hospital. Women were questioned regarding timing, influence of others, reasons for their choice, satisfaction with the decision, etc. Results from 160 respondents showed that over half the women identified themselves as the primary decision maker. Physicians exerted more influence on the decisions of patients at the public hospital than on the patients at the private hospital. Overall, social exigencies appeared to play a more important role than an assessment of the medical risks in making these decisions.

Cesarean Section