Case-referent survey of young adults with mesothelioma: I. Lung fibre analyses.

OBJECTIVES: Our study aimed to determine the lung tissue concentration of asbestos and other mineral fibres by type and length in persons with mesothelioma aged 50 yr or less at time of diagnosis, compared to controls of similar age and geographical region. In this age group it was thought that most, but not all, work-related exposures would have been since 1970, when the importation of crocidolite, but not amosite, was virtually eliminated. METHODS: Eligible cases were sought from recent reports by chest physicians to the SWORD occupational disease surveillance scheme. Lung tissue samples were obtained at autopsy from 69 male and four female cases, and mineral fibres identified, sized and counted by electron microscopy. Fibre concentrations per microg dry tissue were compared with similar estimates from a control series of autopsies of sudden or accidental deaths. Unadjusted, and adjusted odds ratios calculated by logistic regression, assessed relative risk in relation to fibre type, length and concentration. RESULTS: Unadjusted and adjusted odds ratios increased steadily with concentration of crocidolite, amosite, tremolite and all amphiboles combined. There was also some increase with chrysotile, but well short of statistical significance. Incremental risk examined in a linear model was as highly significant for all amphiboles together as individually. Short, medium and long amphibole fibres were all associated with increased risk in relation to length. Mullite and iron fibres were significant predictors of mesothelioma when considered without adjustment for confounding by amphiboles, but, after adjustment, were weak and far from statistically significant. CONCLUSIONS: In this young age group, amosite and crocidolite fibres could account for about 80% of cases of mesothelioma, and tremolite for some 7%. The contribution of chrysotile, because of low biopersistence, cannot be reliably assessed at autopsy, but to the extent that tremolite is a valid marker, our results suggest that it was small. The steep linear trend in odds ratio shown by amphiboles combined indicates that their effects may be additive, with increased risk from the lowest detectable fibre level. Non-asbestos mineral fibres probably made no contribution to this disease. Contrary to expectation, however, some 90% of cases were in men who had started work before 1970; this was so whether or not amosite or crocidolite was found in lung tissue.

Case-referent survey of young adults with mesothelioma: II. Occupational analyses.

OBJECTIVES: Our study aimed to identify occupations at increased risk of developing mesothelioma in persons aged 50 yr or less, and to relate these occupations to lung tissue concentration of asbestos fibres by type. In this age group it was thought that most, but not all, work-related exposures would have been since 1970, when the importation of crocidolite, but not amosite, was virtually eliminated. METHODS: Eligible cases were sought from recent reports by chest physicians to the SWORD occupational disease surveillance scheme. Work histories were obtained for 115 men and 13 women, usually with the help of the chest physicians or coroners. Jobs were coded by the Office of National Statistics, so that the observed years spent in each occupation could be compared with expected values from census data, 1960-90. Lung tissue samples were obtained at autopsy from 69 male and four female cases, and mineral fibres identified, sized and counted by electron microscopy. RESULTS: Of 37 industrial occupations analysed, odds ratios were significantly raised in eight: five in the construction industry and the others in shipbuilding, the manufacture of cement products and the manufacture of non-metallic mineral products (including asbestos). The concentrations in lung of crocidolite and amosite fibres, which together could account for 80-90% of cases, did not differ between occupational categories; those for amosite were appreciably higher than for crocidolite. Tremolite fibres were rarely found. CONCLUSION: Mesothelioma in this young age group is dominated by carpenters, plumbers, electricians and insulators in the construction industry, and is mainly attributable to amphibole exposure. Work in shipbuilding and manufacture of mineral products was less important than in earlier studies. Contrary to expectation, however, some 90% of cases were in men who had started work before 1970.

Mood and cognitive performance improved by a small amount of alcohol given with a lunchtime meal.

Three drinks containing 0 g (no alcohol, NA), 8 g (low alcohol, LA) and 24 g (high alcohol, HA) of alcohol were formulated which were found to be indistinguishable from one another in sip-and-swallow triangle tests. In a second study, conducted according to a within-subjects design, 14 healthy human volunteers consumed these drinks as part of a small lunchtime meal, in counterbalanced order on 3 different days. They also completed a battery of cognitive tasks, together with mood ratings, before lunch and during the 4 h following lunch. Compared with NA, LA (approximately 0.12 g/kg) significantly increased hit rate on a difficult rapid information processing vigilance task. In contrast, HA (approximately 0.35 g/kg) tended to impair performance of this task. There were no reliable effects of alcohol on performance on less demanding tasks. The low dose of alcohol also improved mood (for example, it significantly reduced tension and uncertainty), suggesting that the improvement in task performance was mediated by the calming or sedative effects of the alcohol. Volunteers did detect alcohol in the HA, but not the LA drink, when they consumed the full drink, confirming the difficulty of disguising the administration of alcohol.

Acute effects on mood and cognitive performance of breakfasts differing in fat and carbohydrate content.

Sixteen subjects consumed low-fat/high-carbohydrate (LFHC), medium-fat/ medium-carbohydrate (MFMC), high-fat/low-carbohydrate (HFLC) iso-energetic breakfasts and no breakfast in a counterbalanced order on four separate days. The LFHC breakfast was similar in macronutrient composition, though not in meal size (more kcal) and types of foods offered, to the habitual breakfast of the subjects. A battery of cognitive performance tasks together with mood and appetite ratings were completed before and during the 3 h following breakfast. Results showed no clear differences in performance between the four dietary conditions, but significant effects on mood were observed. Mood improved (a decline in fatigue/dysphoria) following the LFHC breakfast compared to the other meals. The findings show that the macronutrient content of breakfast, independent of energy value and oro-sensory qualities, can exert small but reliable effects on subsequent mood, and suggest that deviation from habitual meal composition can produce a relative decline in mood state. These conclusions are supported by results from a previous study of the effects of lunch which found very similar relationships between meal composition, habitual choices and postprandial mood changes.

Psychosocial factors and adult onset rapidly progressive periodontitis.

On the basis of clinical observations, some periodontologists have suggested an association between psychosocial factors such as depression, stress and anxiety, and adult onset rapidly progressive periodontitis (RPP). This study investigated more formally possible associations between a number of relevant psychosocial factors and RPP. The significance of the psychosocial variables was assessed by comparing 3 groups: 50 patients with RPP, 50 patients with routine chronic adult periodontitis (RCAP), and 50 patients without significant periodontal destruction (controls). It was anticipated that the RPP group would show higher levels of psychosocial maladjustment than the RCAP and control groups. A between-subjects multivariate analysis of covariance indicated that the combined psychosocial variables were significantly related to the periodontal diagnosis. 2 psychosocial factors, depression and loneliness, were significant in distinguishing between groups. The RPP group presented significantly increased depression and loneliness compared to the RCAP and control groups. Future research is indicated to further clarify the significance of these psychosocial differences in relation to the onset and progression of RPP.

DNA synthesis by pituitary tumours, with reference to plasma hormone levels and to effects of bromocriptine.

BACKGROUND AND OBJECTIVE: In parathyroid adenomas and experimentally in the normal rat pituitary gland, cell replication and secretory activity were previously shown to be correlated. A similar relationship has now been investigated in human pituitary tumours, since this could have relevance to their growth and aetiology. The effect of bromocriptine on the two variables was examined. PATIENTS: Data were derived from 50 patients undergoing operation for pituitary tumour, including 15 with acromegaly and 11 with prolactinoma. MEASUREMENTS: Preoperative plasma levels of GH, PRL and gonadotrophins were measured by radioimmunoassay. DNA synthesis, an index of cell replication, was measured in vitro in freshly removed tumour tissue. Nuclear diameter of tumour cells was measured in histological sections and immunostaining for relevant hormones was carried out on tumour tissue. RESULTS: DNA synthesis was correlated (P < 0.05) with plasma hormone levels in cases of prolactinoma, both treated and not treated with bromocriptine, and in a group of putative FSH secreting tumours from male patients. The correlation was not significant in cases of acromegaly. Comparisons of mean values between groups treated and not treated with bromocriptine showed significantly lower DNA synthesis and mean nuclear diameter in prolactinomas under treatment but not in GH secreting tumours. CONCLUSIONS: The findings in prolactinomas suggest a close relationship between secretion and tumour cell replication dependent on still undefined agents, but including dopamine, affecting both variables, and isoforms of PRL, which may stimulate or inhibit replication of PRL secreting cells. The basis of the relationship in FSH secreting tumours is unknown. The relationship was absent in the non-homogeneous group of GH secreting tumours. When secretion and growth are correlated, the secretory process may be the site of the primary abnormality in the tumour cell. Evidence that bromocriptine inhibits tumour cell replication was obtained for prolactinomas but not for GH secreting tumours.

Barriers to the adoption of reduced-fat diets in a UK population.

OBJECTIVE: To assess perceived and actual barriers to dietary fat reduction. DESIGN: A 20-week intervention study was carried out to investigate the problems encountered by persons attempting to reduce their fat intake. SUBJECTS: Seventy subjects initially consuming moderately high-fat diets were recruited from the local area by newspaper advertisement. Sixty-one completed the study. INTERVENTION: Subjects were randomized into either a control or an experimental group. Subjects in the experimental group (n = 45) received instruction on reducing their intake of fat using current dietary recommendations. All subjects initially completed a questionnaire to assess their beliefs and attitudes regarding selected dietary changes, and the experimental group also completed a similar questionnaire at intervals during the study. Weighed diet records were completed by all subjects throughout the study. STATISTICAL ANALYSIS: Repeated measures analysis of variance was used to examine changes in nutrient intake. Univariate analysis of variance was used to examine differences in barriers encountered by most and least successful fat reducers. RESULTS: Perceived barriers reflected actual problems encountered. One of the most consistently reported problems was that of reduction in taste quality of the diet. Other problems included an increase in cost, decrease in convenience, lack of family support for certain changes, and an inability to judge the fat content of diets. APPLICATIONS/CONCLUSIONS: Strategies aimed at improving the taste of low-fat diets, increasing awareness of fat intake, and increasing family support may be most effective in promoting greater adherence to dietary guidelines intended to achieve reductions in fat consumption.

Mood and cognitive performance effects of isocaloric lunches differing in fat and carbohydrate content.

Eighteen subjects consumed low-fat/high-carbohydrate (LFHC) (29% fat, 54% carbohydrate, 15% protein), medium-fat/medium-carbohydrate (MFMC) (45% fat, 42% carbohydrate, 12% protein), and high-fat/low-carbohydrate (HFLC) (62% fat, 24% carbohydrate, 13% protein) isocaloric lunches in random order on 3 separate days. The MFMC lunch was similar in energy and macronutrient composition to the habitual lunchtime intake of the subjects. A battery of cognitive performance tasks together with mood and appetite ratings were carried out before and during the 3 h after lunch. Results showed longer reaction times following the LFHC and HFLC lunches compared to the MFMC lunch, which produced an improvement in performance on this task. In addition, subjects rated themselves as more drowsy, uncertain and muddled, and less cheerful after the LFHC and HFLC lunches compared to the MFMC lunch, and as less tense after the LFHC meal. These findings indicate that the macronutrient content of lunch can have significant acute effects on subsequent mood and performance. In particular, higher than usual proportions of fat or carbohydrate produced a relative impairment of cognitive efficiency.

Changing to a low fat diet: attitudes and beliefs of UK consumers.

A questionnaire on attitudes and beliefs regarding low fat diets was mailed to 2000 consumers throughout the United Kingdom. Information was also obtained about present fat intake by means of a food frequency questionnaire. A total of 665 (33%) questionnaires were returned of which 390 (20%) were completed correctly and used in the present analysis. Respondents were divided into tertiles for percentage energy from fat, allowing classification into low, medium and high fat intake groups, and no consistent differences emerged in the attitudes and beliefs of respondents. The majority of people were familiar with current guidelines concerning reduction of fat intake and accepted the putative health benefits of adopting lower fat diets. Regardless of actual fat intake, the majority of people felt that their diet was healthy and was not high in fat, and indicated that they had already reduced their fat intake. A major barrier to reducing fat intake in the UK may therefore be associated with a general failure to recognize what comprises effective dietary change.

Apoptosis in the anterior pituitary gland of the rat: studies with estrogen and bromocriptine.

Apoptosis was investigated by electron and light microscopy in the anterior pituitary gland of the male Fischer rat in which hyperplasia of prolactin-secreting cells had been induced by estrogen implanted subcutaneously for 6 weeks. Counts by light microscopy of apoptotic cells and cells containing phagocytosed apoptotic bodies increased during a period of 44 h after estrogen withdrawal. Necrosis was present but was not prominent. Administration of bromocriptine after estrogen withdrawal increased apoptotic counts to nearly double those in the absence of bromocriptine. Bromocriptine caused some increase in necrosis. Apoptosis occurred in prolactin-secreting cells identified by immunostaining and in other cells. Phagocytosed apoptotic bodies were seen in folliculo-stellate and not in other cells. It is concluded that apoptosis occurs in the anterior pituitary gland and is induced by bromocriptine. Phagocytosis of apoptotic bodies is a function of the folliculo-stellate cells.

Cell kinetics in parathyroid adenomas: evidence for decline in rates of cell birth and tumour growth, assuming clonal origin.

OBJECTIVE: We aimed to provide a cell kinetic explanation for the demonstrated lack of disease progression in most patients with mild, asymptomatic primary hyperparathyroidism. DESIGN: We compared cell birth rates, estimated at the time of adenoma excision, with the lowest birth rates needed to grow tumours of the observed size. PATIENTS: Sixty-three patients with primary hyperparathyroidism due to a single chief cell adenoma who had normal renal function were followed up for long enough to demonstrate cure after surgical excision. MEASUREMENTS: Fresh adenoma tissue was incubated with tritiated thymidine. The proportion of cells synthesizing DNA was determined directly by radioautography in 18 cases, and indirectly from the regression of label index on rate of DNA synthesis in 45 cases. The birth rate of new cells was calculated assuming the duration of S phase to be 12 hours. The number of cells in each adenoma was estimated both from parenchymal weight and from total DNA content, and the minimum birth rate needed to produce this number of cells from a single cell, beginning in utero, was calculated on an exponential model. RESULTS: The mean observed birth rate of new cells (mean (SD)) was 17.3 (11.1)%/year, and the minimum needed birth rate was 42.8 (21.6)%/year, significantly, (P less than 0.001) higher than the observed birth rate. CONCLUSIONS: The rate of mitosis had fallen substantially during the life span of most parathyroid adenomas. To account for this, we propose that the mutation implied by a clonal origin increases the secretory setpoint. Because proliferation, as well as hormone secretion, is influenced by calcium in parathyroid cells, the expected result would be rapid initial growth, slowing down as tumour size reached an asymptotic value corresponding to the total rate of hormone secretion needed to raise the plasma calcium to the new setpoint.

Multiple endocrine neoplasia type 2b: long-term follow-up of a case.

Multiple endocrine neoplasia type 2b is a rare inherited syndrome which comprises the association of medullary thyroid carcinoma, phaeochromocytoma, widespread neuromatous proliferation and a characteristic body habitus. In this report we present the late clinical course and autopsy findings of the first patient with this syndrome described in Australia. At presentation she was found to have a right adrenal phaeochromocytoma and medullary thyroid carcinoma which were resected in separate operations. No clinical or biochemical evidence of residual medullary thyroid carcinoma was identified in life. However, in spite of serial vanillylmandelic acid estimations, which showed normal or only mildly elevated levels, and normal results of urinary catecholamine studies, a left adrenal phaeochromocytoma was identified in a metaiodobenzylguanidine (MIBG) study performed 14 years after presentation. Her late clinical course was dominated by progressive dysphagia, intestinal dysmotility and megacolon associated with unrelenting malnutrition. After her death due to an intracerebral haemorrhage, an autopsy confirmed the presence of a left adrenal phaeochromocytoma and revealed diffuse intestinal ganglioneuromatosis to be the cause of her intestinal dysmotility. No residual medullary thyroid carcinoma was found. This case emphasises the propensity for multiple endocrine tumours in these patients and highlights the potentially significant role of intestinal ganglioneuromatosis in the natural history of this condition.

The parathyroid glands in chronic renal failure: a study of their growth and other properties made on the basis of findings in patients with hypercalcemia.

We investigated the growth of hyperplastic parathyroid glands removed at operation from 16 patients with chronic renal failure complicated by hypercalcemia, by incubating fresh tissue with tritiated thymidine. In each gland the proportion of cells synthesizing DNA was determined directly by counting labeled nuclei after autoradiography and indirectly from incorporation of label into DNA, and the mean diameter of chief cell nuclei was measured. Both DNA synthesis and mean nuclear diameter were positively correlated with plasma calcium level. Assuming the mean duration of S phase to be 12 hours, the birthrate of new cells (mean +/- SD) was 18.5% +/- 23.6% per year, significantly (p less than 0.05) greater than the 11.5% +/- 7.4% per year found in 63 parathyroid adenomas previously studied. On the basis of estimated disease duration, the minimum birthrate needed to grow glands of the observed weight was 23.4% +/- 16.5% per year. The similarity between observed and needed birthrates indicates that the glands were growing almost as fast as when renal failure began, and that parathyroid growth was no longer regulated in accordance with normal plasma calcium homeostasis. To account for this, we propose that the disordered growth is a consequence of an increase in secretory set point, which in turn is a consequence of calcitriol deficiency. Because the effectiveness of parathyroid hormone is impaired in renal failure, a large increase in total hormone secretion is needed to raise the plasma calcium level to the new set point, and the necessary increase in gland size can be achieved only by a sustained increase in the rate of cell division.

Intestinal pseudo-obstruction in pheochromocytoma.

Intestinal pseudo-obstruction is a rare complication of pheochromocytoma. We describe a 39 year old man with a large right adrenal pheochromocytoma and extremely high catecholamine levels, who developed pseudo-obstruction which responded promptly to intravenous phentolamine infusions. This case supports the concept that this complication is attributable to high circulating levels of catecholamines, acting by direct and indirect inhibition of gastrointestinal motility.

Immobilization-induced hypercalcemia and regional osteoporosis.

Immobilization hypercalcemia accompanied by unusual hormonal and bony changes complicated the Guillain-Barré syndrome in a 21-year-old woman. Metaphyseal rarefaction appeared in many sites and was severe in the lower limbs. A bone scan showed increased uptake of 99mTc methylene diphosphonate at these sites and throughout the axial skeleton. The literature on experimental metaphyseal rarefaction suggests that osteoclastic resorption and enhanced regional blood flow are associated with immobilization. Suppression of this osteoclastic component of the increased bone turnover, especially if it is widespread, was the rationale for treatment with calcitonin (CT). The patient also became amenorrheic, with low plasma gonadotropin and estrogen levels. Estrogen therapy coincided with a return of plasma calcium to normal.

Nuclear diameter in parathyroid carcinomas.

Nuclear diameter was measured and mean nuclear diameter calculated in 18 parathyroid carcinomas. In 11 of the 18 tumours mean nuclear diameter was above the range previously reported for 55 parathyroid chief cell adenomas and provides a useful discriminant in histological diagnosis.

Chronic lead nephropathy in Queensland: alternative methods of diagnosis.

Indices of past lead absorption were measured and compared in patients with chronic renal failure from many causes, including some with chronic lead nephropathy. X-ray fluorescence (XRF) yielded finger bone lead concentrations by a new in vivo method. These correlated significantly with excess urinary lead following calcium di-sodium EDTA (ethylenediamine tetra-acetate) and erythrocyte lead concentration. Discriminant function analysis demonstrated that the patients in the study could be separated into two groups without any reference to the EDTA lead excretion test using the following variables, all of which contributed significantly to the discrimination. In order of importance, these were: a childhood history of acute lead poisoning, a history of gout, a family history of gout and detectable XRF finger bone lead. Although the XRF finger bone lead measurement is convenient and non-invasive, its lack of sensitivity (48%) limits its usefulness as a screening test for chronic lead nephropathy.