Prenatal sonographic diagnosis of unilateral fetal renal agenesis.
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Biomedical subjects
Publications and source records attributed to B Armstrong.
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Lung tissue samples from 78 cases from autopsy of mesothelioma in Canada, 1980 through 1984, and from matched referents were examined by optical and analytical transmission electron microscopic study. Concentrations of amosite, crocidolite, and tremolite fibers, and of typical asbestos bodies discriminated sharply between cases and referents. The distributions of chrysotile and anthophyllite/talc fibers and of all other natural and man-made inorganic fibers (greater than or equal to 8 microns) in the two series were quite similar. Relative risk was related to the concentration of long (greater than or equal to 8 microns) amphibole fibers with no additional information provided by shorter fibers. The proportion of long fibers was much higher for amphiboles than chrysotile and, except for chrysotile, systematically higher in cases than referents. Amphibole asbestos fibers could explain most mesothelioma cases in Canada and other inorganic fibers, including chrysotile, very few. Fibrous tremolite, contaminant of many industrial minerals including chrysotile, probably explained most cases in the Quebec mining region and perhaps 20% elsewhere.
A case-control study was undertaken of the family histories of colorectal cancer in 128 patients with colorectal cancers and those of 61 patients with colorectal adenomas and matched surgical control patients who were attending a regional surgical service in Western Australia. One family with multiple polyposis of the colon was excluded from the study. A history of colorectal cancer in one or more first-degree relatives was associated with a relative risk of colorectal cancer of 2.5 (95% confidence interval, 0.8 to 8.0), of adenoma of 2.0 (95% confidence interval, 0.5 to 8.0) and of any colorectal neoplasm of 2.3 (95% confidence interval, 0.9 to 5.6). Four patients with colorectal cancer and one patient with colorectal adenoma had more than one first-degree relative with colorectal cancer, whereas no control subject gave this history. The five families that were represented by these cases each showed some other features of non-polyposis familial colorectal cancer. It was estimated that familial factors could explain 60% of colorectal cancer in persons with a family history of the disease in a first-degree relative and 5% of colorectal cancer in the population as a whole. Haemoccult II tests were posted to 629 living first-degree relatives of the patients with colorectal cancers and adenomas; 44% of these relatives returned the completed tests. Four relatives with positive results of tests both before and after dietary restriction were investigated; all four subjects had colorectal adenomas. In addition, one subject had a short segment of ulcerative colitis. A further mailing of Haemoccult II tests one year later gave a 39% response rate; no further cases of colorectal neoplasia were found. One relative developed carcinoma of the caecum 10 months after a negative result in the first round of Haemoccult screening. Persons with two or more first-degree relatives with colorectal cancer, with or without other features of non-polyposis familial colorectal cancer, are at a high risk of the development of colorectal cancer. The comparatively-poor response to an offer of Haemoccult II testing and its known insensitivity and lack of specificity suggest that it is not a satisfactory method of screening these high-risk subjects.
Findings from a survey of 56,067 women in Montreal on maternal occupation and pregnancy outcome have been reported. Paternal occupation recorded in the same survey was analysed for spontaneous abortion in 24 occupational groups retaining the six main sectors of maternal occupation and allowing, by means of logistic regression, for seven potentially confounding variables. In only one of the 24 fathers' occupational groups was there a statistically significant excess of spontaneous abortions--mechanics, repairers, and certain assemblers (O/E = 1.10, 90% CI = 1.02-1.20); subdivision of this group suggested that this excess was mainly attributable to the large group of motor vehicle mechanics (O/E = 1.17). No significant excess of known chromosomally determined defects was found in any of the 24 occupational groups. An association of developmental defects was found with food and beverage processing (18 defects observed compared with 8.02 expected; p less than 0.05); however, there was no specificity in type of food, beverage, or congenital defect, and no obvious explanatory mechanism.
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Sonographic prenatal diagnosis and management of a twin pregnancy complicated by acardius anceps of one twin and acute polyhydramnios is presented. To our knowledge, this is the first case of an acardiac twin gestation in which Doppler umbilical arterial velocimetric studies were obtained. These studies, performed at 29 weeks' gestation, demonstrated markedly different umbilical artery systolic to end-diastolic (S/D) ratios in the twins. This difference is explained by the vascular resistance reflected in the umbilical artery S/D ratios obtained on each twin. The healthy twin's S/D ratio represented the vascular resistance of the placenta and the perfused acardiac twin. Because of the reversed direction of blood flow in the acardiac twin's umbilical artery, this S/D ratio represented the vascular resistance of the acardiac twin. Planned preterm delivery resulted in survival of the healthy normal twin.
Responses to a standardized respiratory symptom questionnaire, spirometry, and cross-shift decreases in lung function between 70 current employees of a polyvinylchloride (PVC) fabrication plant and a control group consisting of 48 men employed in a vegetable packing plant were compared. FEV1/FVC was significantly lower in the PVC workers. Cross-shift drops in Vmax75 of 15% or more were also more prevalent in the exposed group (p = .01). When examining the association between months of work within the exposed workforce and spirometric indices of airway obstruction, no relationship could be demonstrated. However, an inverse dose-response relationship was seen between level of FVC and duration of employment, suggesting a restrictive impairment. While the specific exposures have not been identified, it appears that employment in PVC fabrication may be associated with both obstructive and restrictive ventilatory effects.
We have studied the progression of breast tumors induced by N-methyl-N-nitrosourea in Wistar/Furst rats during serial passages through isogeneic animals, using characteristic markers previously defined. The tumors contained various types of structure, which evolve from intraductal nodes to duct-like structures and then to invasive strands or cells. Most primary tumors were not invasive but became so in subsequent transfers. The distribution of invasive and noninvasive tumors in the various lineages was not random, implying that the tumors differed from their inception in the propensity toward invasion. In different lineages invasive structures appeared repeatedly and independently but with different frequencies, suggesting that they were produced by a stochastic mechanism with different probability of occurrence. The possible nature of this mechanism is discussed. This experimental system is useful for further studies of tumor invasion; the results obtained are relevant for understanding and evaluating the evolution of human breast cancer.
To work toward an understanding of the mechanisms of cancer progression, we have followed the changes in expression of several genes in rat mammary carcinomas during the development of invasion. Tumors were induced by N-methyl-N-nitrosourea and serially transplanted to isogeneic rats. Gene expression in individual cells was followed by immunofluorescence microscopy. We show that invading cells do not express the same genes as the primary tumor or normal adult mammary gland but are similar to the primitive mammary duct cells present in late embryos. In the most advanced tumors, the most fundamental epithelial characteristic, polarity, is lost. Relative to the mechanism of invasion, we observe that the basal lamina, often thinner than normal, always coats the strands of invading cells and may be entirely absent from single invasive cells only. These observations suggest that the basal lamina ultimately disappears because of reduced expression of the genes or the failure to assemble the components. In these tumors it is the progressive alteration in gene expression rather than the enzymatic breakdown of the basal lamina that leads to invasion. These results show that the most important aspect of cancer progression is the progressive alteration of gene expression. They also raise questions about the mechanism that causes tumor cells to retrace the steps in their differentiation.
A criterion for eligibility to compensation is sought for bladder cancer cases among workers in the aluminum smelting industry. Probability that a case of bladder cancer was caused by occupational exposure can be estimated from a relationship derived from results of epidemiologic studies. Because the effects of occupational exposure and smoking apparently combine multiplicatively, this probability is independent of whether a case patient smoked. Estimated probabilities of causation have been used in a criterion for eligibility to compensation by the Quebec workers' compensation board. Workers with cancer for whom the upper 95% confidence limit of the probability of causation is at least 50% are compensated. This implies a minimum cumulative exposure to benzo[a]pyrene (concentration in micrograms per cubic meter times duration in years) of 19 micrograms/m3 years. Possible alternative approaches to compensation are discussed.
The frequency of low birth weight (less than or equal to 2500 g) and of preterm birth (less than 37 weeks) was studied in 22,761 single live births in relation to maternal employment, taking account of 11 nonoccupational confounding factors. There was some increase of low statistical significance in both types of prematurity in service and manufacturing sectors of industry. A substantial excess of preterm births was seen in women employed in food and beverage service (O/E = 1.29, p = 0.03) and psychiatric nursing (O/E = 2.47, p less than 0.01) and of low birth weight in food and beverage service (O/E = 1.30, p = 0.02), in chambermaids and cleaners (O/E = 1.42, p = 0.03), and in those employed in the manufacture of metal and electrical and certain other goods (O/E = 1.57, p less than 0.01). Heavy lifting and long hours of work were consistently related to both outcomes, changing shift work less consistently. Noise was associated with low birth weight in the health and manufacturing sectors. The findings of this study are unlikely to have resulted from subject or observer bias but the role of unidentified factors related to selection for work are difficult to assess.
The relation between spontaneous abortion (n = 5010), stillbirth without congenital defect (n = 210), and working conditions was analysed in 22,613 previous pregnancies of 56,067 women interviewed, 1982-4, immediately after termination of their most recent (current) pregnancy. The 22,613 previous pregnancies were those in which at time of conception the women were employed 30 or more hours a week. Ratios of observed (O) to expected (E) fetal deaths after allowance by logistic regression for seven non-occupational confounding variables were calculated at four stages of pregnancy in 60 occupational groups and six main sectors for women whose work entailed various physical demands, environmental conditions, and exposure to chemicals. The O/E ratios for abortion were raised in the sales sector (1.13, p less than 0.05) and services sector (1.11, p less than 0.01) and for stillbirth in the sales sector (1.50, p less than 0.1). Substantially increased O/E ratios for late but not early abortion were found in operating room nurses (2.92, p less than 0.05), radiology technicians (3.82, p less than 0.01), and employees in agriculture and horticulture (2.40, p less than 0.05); in all categories the O/E ratio for stillbirth were also raised but only significantly (5.55, p less than 0.01) in the latter group. The O/E ratio for stillbirth was also raised in leather manufacture (3.09, p less than 0.01). In both individual and grouped analysis (the latter undertaken to minimise the possible effect of recall bias) significantly increased O/E ratios for abortion were found in women exposed to various high levels of physical stress, particularly weight lifting, other physical effort, and standing (p less than 0.01). Increased ratios for stillbirth at this level of significance (p less than 0.01) were found for other physical effort and vibration. Noteworthy chemical exposure was identified only in the health, services, and manufacturing sectors; the O/E ratio for stillbirth approached two in women exposed to solvents, almost all in manufacturing (p less than 0.01). In the latter sector exposed to solvents was also associated with an approximately 20% increase in abortion ratio at similar probability level.
Data from the Montreal survey on occupational factors in pregnancy were used to test the hypothesis that visual display units (VDUs) constitute a hazard to reproduction. Use of a VDU was recorded in 4712 current and 2164 previous pregnancies of women in full time employment at time of conception. After allowance for seven confounding variables, the risk of spontaneous abortion in current pregnancies relative to all working women was 1.19 (90% CI 1.09-1.30) and in previous pregnancies, 0.97. In an analysis by occupational title, in which 60 occupational groups were aggregated into eight categories according to use of VDUs, the relative risk for spontaneous abortion was 1.06 (90% CI 0.8-1.4) in current pregnancies and 1.01 (90% CI 0.7-1.3) in previous pregnancies. This suggests that the small excess of spontaneous abortions among individual women reporting the use of VDUs in current pregnancies may have been due to recall bias. Relative risks for stillbirth, preterm birth, and low birth weight all had 90% confidence limits which included unity. In an analysis of congenital defects the number of pregnancies was increased to include women who worked 15 or more hours a week. In all but one of nine groups of congenital defect examined confidence limits for the relative risk included unity in both current and previous pregnancies. The relative risks for the renal urinary group of defects were raised in both current (1.84, 90% CI 1.07-3.15) and previous pregnancies (1.66, 90% CI 0.82-3.25). There being no prior reason to suspect a causal link with this type of defect, interpretation remains open to question.
The risk of congenital defect was examined in 47,913 pregnancies of women employed for 15 hours a week or more at time of conception. The rate of defects of all types per 1000 births in this series was 25.0; 1.8 from defects classified as chromosomal (group A), 10.8 as developmental (group B), and 12.5 as musculoskeletal (group C). Some evidence of an excess in the risk ratio (p less than 0.05) was found in the services sector and in four occupations--agriculture and horticulture (2.61), telephone and postal clerks (1.74), a miscellaneous group of service jobs (1.68), and receptionists and information clerks (1.47); excesses of lower statistical significance (p less than 0.1) were found in those engaged in plastics and rubber manufacture (2.02) and in child minders (1.84). There were two cases of tracheo-oesophageal fistula--a rare defect--among eight defects (1.32 expected) in agriculture and horticulture. Overall, the distribution of risk ratios in the 60 occupations examined was not significantly heterogeneous. Analysis of chemical exposure profiles for each occupational group showed no evidence of any increased risk, perhaps due to lack of sensitivity and discrimination in this method of exposure estimation. In 152 pregnancies of doctors and nurses who had administered antineoplastic drugs in the first month eight defects, miscellaneous in type, were observed compared with 4.05 expected (p = 0.05). Special study of musculoskeletal defects and work demands showed some evidence of an association with a long working week (greater than or equal to 46 hours) but no other ergonomic factor. With these few exceptions the survey failed to identify appreciable risk of congenital defect related to occupation.
Numerical concentrations of asbestos bodies (AB) were measured by light microscopy both in samples of bronchoalveolar lavage (BAL) fluid and in samples of lung parenchyma from 69 patients with suspected asbestos-related diseases who had had lavages and later open lung biopsies or autopsies. Objectives were to study the recovery of pulmonary AB by BAL and the ability of BAL concentrations to predict parenchymal concentrations. BAL and parenchymal concentrations were both spread over 6 orders of magnitude and were positively correlated (r = 0.74 between logarithmic values). It is believed that, by a process of progressive elution, AB firmly adherent to the alveolar wall become suspended in BAL fluid; such suspended bodies represent roughly 2% of all the bodies stored in the portion of lung lavaged. Recovery is associated with great interindividual variations. When a measured BAL concentration exceeds 1 AB/ml, it can be quite confidently predicted, however, that the parenchymal concentration is in excess of 1,000 AB/g and that the patient has experienced a nontrivial asbestos exposure.
In planning simple cohort mortality studies, researchers need to know what size of relative risk may be confidently detected with the projected size of the cohort and length of follow-up. Although methods for the calculation of such minimum detectable risks have been devised for case-control studies and for cohort studies where internal comparisons are the focus, this has not been explicitly done for cohort studies using external comparisons. This paper describes a simple procedure designed explicitly for investigating the adequacy of cohort size at the planning stage of a study. An example is presented of a retrospective cohort study of men in a Canadian factory. A method is shown for estimating the minimum detectable underlying relative risk for lung cancer in this cohort.
The purpose of this study was to determine the diagnostic accuracy of knee extensor muscle torque tracings in patients suspected of having damage to the anterior cruciate ligament of the knee joint. The knee extensor torque tracings of 30 patients suspected of having anterior instability of the knee joint were reviewed independently for abnormalities believed to be associated with anterior cruciate ligament damage. These results were compared blindly with an arthroscopic evaluation. The diagnostic accuracy of the torque tracing approach was determined by calculating the prevalence, sensitivity, specificity, and positive and negative predictive values. The sensitivity and specificity were calculated to be 25.0% and 85.7%, respectively. These results suggest that the curve patterns examined in this article have poor diagnostic accuracy and are of little benefit as a clinical diagnostic aid.
Over a two year period, 1982-4, 56067 women, delivered or treated for a spontaneous abortion in 11 Montreal hospitals covering 90% of such admissions, were interviewed in detail regarding their occupational, social, and personal characteristics in their most recent and past pregnancies--104,649 in all. These data were analysed in relation to four main adverse outcomes--spontaneous abortion, stillbirth (without defect), congenital defect, and low birth weight (less than or equal to 2500 g). For comparison with observed numbers, expected figures were calculated by logistic regression using up to eight potentially confounding variables. Sixty occupational groups in six main industrial sectors were examined in current and previous pregnancies, with tests for heterogeneity between these two estimates of risk. Women in managerial, health, and clerical sectors had little evidence of excess of any of the four outcomes, by contrast with those in sales, service, and manufacturing sectors. Substantial and statistically significant excesses of spontaneous abortion were observed in nursing aides, women in sales occupations and food and beverage service; of stillbirth in agriculture and horticulture, leatherwork, and certain sales occupations; of congenital defects in women in child care, certain service occupations, and the manufacture of metal and electrical goods; and of low birth weight in chambermaids, cleaners, and janitors, and in women employed in the manufacture of food and drink, metal and electrical goods, and clothing.