Biomedical subjects
Publications and source records attributed to P Fraser.
We report two patients with systemic lupus erythematosus who subsequently developed thrombotic thrombocytopenic purpura. In each case the coexistence of these two conditions was confirmed by pathological findings. Both patients responded to treatment, but one eventually died. A review of the literature suggests a possible relationship between the two disorders.
The United Kingdom Atomic Energy Authority mortality study investigated the relation between mortality and recorded exposure to ionising radiation among employees working at the authority's seven establishments between 1946 and 1979. This report examines the design of the study and methods of data collection and validation. The completeness of the study population was deemed to be unsatisfactory at two establishments, where records of employment before 1965 had been destroyed. Assessment of the magnitude of the deficit led to the conclusion that the data from these establishments were too incomplete for inclusion in the mortality analysis. At the other establishments validation showed that the data collected were accurate and unbiased. Certain characteristics of the 39 546 employees included in the mortality analysis were identified which were relevant in interpreting the findings.
An analysis was conducted of 3373 deaths among 39 546 people employed by the United Kingdom Atomic Energy Authority between 1946 and 1979, the population having been followed up for an average of 16 years. Overall the death rates were below those prevailing in England and Wales but consistent with those expected in a normal workforce. At ages 15-74 years the standardised mortality ratios (SMRs) were 74 for deaths from all causes and 79 for deaths from all cancers. Mortality from only four causes was above the national average--namely, testicular cancer (SMR 153; 10 deaths), leukaemia (SMR 123; 35 deaths), thyroid cancer (SMR 122; three deaths), non-Hodgkin's lymphoma (SMR 107; 20 deaths)--but in none was the increase significant at the 5% level. Half of the authority's employees were recorded as having been monitored for exposure to radiation, their collective recorded exposure being 660 Sv (65 954 rem). Among these prostatic cancer was the only condition with a clearly increased mortality in relation to exposure. Of the 19 men who had a radiation record and died from prostatic cancer at ages 15-74 years, nine had been monitored for several different sources of exposure to radiation. The standardised mortality ratios were 889 (six deaths) in employees monitored for contamination by tritium, 254 (nine deaths) in those monitored for contamination by other radionuclides, and 385 (nine deaths) in those with dosimeter readings totalling more than 50 mSv (5 rem); but the same nine subjects tended to account for each of these significantly raised ratios. Because multiple exposures were common and other relevant information was not available the reason for the increased mortality from prostatic cancer in this population could not be determined and requires further investigation. Excess mortality rates of 2.2 and 12.5 deaths per million person years per 10 mSv (1 rem) were estimated for leukaemia and all cancers, respectively. The confidence limits around these estimates were wide, included zero, and made it unlikely that the International Commission on Radiological Protection's cancer risk coefficients were underestimated by more than 15-fold. Thus despite this being the largest British workforce whose mortality has been reported in relation to low level ionising radiation exposure, even larger populations will need to be followed up over longer periods before narrower ranges of risk estimates can be derived.
The HLA genetic region was studied in 51 patients with systemic onset juvenile rheumatoid arthritis: 35 with childhood onset and 16 with adult onset (adult Still's disease). HLA genotypes were established by including family members, 261 of whom were also typed in the study. The most marked difference between patients and controls involved the HLA-DR4 gene, which occurred with a frequency of 0.348 in the childhood onset patients and 0.170 in the controls (chi 2 = 8.97, P = 0.0028, adjusted P = 0.017). In contrast, the adult onset patients showed a marginal increase in HLA-DR7, but were similar to controls with respect to HLA-DR4. HLA-Bw35 was increased in children with systemic onset disease, in accordance with earlier findings. The results suggest that patients with systemic onset juvenile rheumatoid arthritis have complex HLA associations which are different in childhood onset and adult onset disease.
The results of hybridization analyses using cDNA probes for mouse and human alpha-spectrin mRNA indicate that a single gene encodes the alpha-subunit of erythrocyte spectrin. Sequencing of the cDNA clones showed that they code for 370 amino acids (aa) covering three repeat domains close to the C terminus of alpha-spectrin. The cloned cDNAs will now permit the isolation of the alpha-spectrin gene and should lead to the characterization of the genetic aspects in human hereditary anemias in which alpha-spectrin has been characterized as the site of the molecular defect.
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Morbidity and mortality statistics are routinely collected in many countries. These data may be arranged in a number of ways, for example, classified by area of residence, or occupation of the person concerned, or by the time-period during which the relevant event occurred. Judicious use of such data enables disease to be monitored and may draw attention to the adverse effects of harmful agents in the environment. This paper describes the different methods of analysing data for such purposes, giving examples of their application and discussing their relative merits. Particular reference is made to the data-collecting systems in England and Wales and to the statistical aspects of monitoring disease.
The hypothesis that high nitrate ingestion may increase the risk of stomach cancer has led to concern over rising levels of nitrate in drinking water, but with little consideration as to whether nitrate from water makes a major contribution to total nitrate intake. In order to investigate the relative importance of water and food as sources of nitrate, 404 adult well-water users completed a diet diary over a 48-hour period and provided a 24-hour urine specimen and a sample of their drinking water. Where the waterborne nitrate level is less than 50 mg/I, as recommended by the World Health Organization (WHO), 30% of ingested nitrate is from water. As the well-water nitrate concentration rises the contribution of water to daily intake increases; at levels between 50 and 100 mg/I, on average, nearly 70% of daily intake is from water, and above 100 mg/I over 80% of daily intake is waterborne. Thus it is only at levels above those currently recommended by the WHO that waterborne nitrate appears to be the major contributor to total nitrate intake.
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This study was designed to investigate whether exposure to nitrate-containing dust during fertiliser manufacture was associated with an excess of deaths from cancer in general or specifically from cancers of the digestive tract, liver, lung, and bladder. It was based on data extracted from census schedules by the Office of Population Censuses and Surveys, occupational characteristics recorded by fertiliser workers at the 1961 and 1971 censuses of England and Wales being related to subsequent mortality ascertained through the National Health Service Central Register. The 1961 cohort, followed up until 1978, showed a "healthy worker effect" and no evidence of excess mortality from cancer at any site. The 1971 cohort also showed below average mortality during 1971-7 for all causes of death and for circulatory diseases, but there were more deaths from cancer than expected, due mainly to an excess of cancers of the lung and digestive tract. The excess of cancer was more pronounced, but not statistically significant, when compared with other employed men. Though the numbers for comparison were small, there was weak evidence of an association between cancer mortality and frequency of exposure to nitrate-containing dust in this cohort. It is difficult to reconcile the excess cancer mortality in the 1971 cohort with the more favorable level in the earlier cohort, since industrial hygiene has improved and the cohorts showed a similar distribution by region and social class. To examine further these conflicting results the 1971 cohort will be followed for a longer period and re-examined when more deaths have accrued.
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Experience is reported of the hydrocortisone suppression test in 140 hypercalcaemic patients, comprising 98 new cases of hyperparathyroidism and 42 cases of non-parathyroid malignant disease. The diagnostic accuracy of the test was compared in 168 patients with that of discriminant analysis, the discriminant functions being derived from plasma inorganic phosphate, alkaline phosphatase, chloride, bicarbonate, and urea, and the erythrocyte sedimentation rate. The hydrocortisone test and discriminant analysis each achieved a diagnostic accuracy of about 93% in 148 patients with either non-parathyroid malignant disease or hyperparathyroidism without osteitis fibrosa. When both tests pointed to the same diagnosis, they were wrong in less than 1% of cases. The hydrocortisone test was not helpful in patients with osteitis fibrosa. Both tests can be performed in any hospital with reliable standard laboratory services. Used in combination they have a high predictive value in distinguishing hypercalcaemia of parathyroid origin from that due to non-parathyroid malignant disease and have not led to errors of clinical importance. They should continue to play a major role in the differential diagnosis of hypercalcaemia until a prompt and reliable service finally establishes parathyroid hormone assay as the definitive laboratory procedure.
Nitrites, derived mainly from ingested nitrates, may react in vivo with secondary nitrogen compounds occurring naturally in certain foods to form N-nitroso compounds, which are potent carcinogens in laboratory animals. This paper reviews the mechanism of their formation and the evidence from epidemiological studies that high nitrate ingestion is involved in the aetiology of human cancer.
This paper reviews briefly some industrial applications which may result in occupational exposure of the workforce to preformed N-nitroso compounds. It considers exposure to nitrate in more detail, discussing epidemiological evidence which lends support to the hypothesis that high nitrate ingestion is related to high mortality from gastric cancer, through the formation in vivo of carcinogenic N-nitroso compounds. It presents the preliminary findings in a census-based mortality study of industrial workers exposed to nitrate-containing dust in the manufacture of fertilizers.
Three formulae have been advocated for interpreting the blood-count when differentiating between iron deficiency and heterozygous thalassaemia: the discriminant function. M.C.V.-R.B.C.-(5 X Hb)-k, the M.C.V/R.B.C. ratio, and the (M.C.V.)2 X M.C.H. product. In a comparison of their diagnostic accuracy in microcytic adults from several countries, the discriminant function was the most satisfactory. 417 of 455 uncomplicated cases (91.6%) of iron deficiency, heterozygous alpha1- and beta- thalassaemia were correctly identified. The function was not able to distinguish heterozygous alpha2-thalassaemia from iron deficiency. A flow chart illustrates how the discriminant function can be used in haematological practice.
Although various factors have been implicated in the aetiology of oesophageal cancer, one factor common to many countries is the consumption of alcoholic beverages. In England and Wales mrtality from oesophageal cancer declined rapidly during the early part of this century but both mortality and incidence have increased in recent years. The generation of males born in 1906 had lower mortality than any preceding or succeeding generation. It is suggested that ages 20 to 30 may be critical in the development of oesophageal cancer and that the 1906 cohort was less exposed to alcohol than other generations. The international analysis suggests that ethyl alcohol itself rather than any specific alcoholic beverage is associated with this cancer.