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The theory that increasing cancer incidence rates in developed countries are primarily the consequence of an expanding ageing population and improved diagnostic testing is widely held. In the United Kingdom the proportion of people aged 50 and over has increased by 45% since 1951 and this proportion is set to increase by a further 36% by the year 2031, so the United Kingdom does indeed have an expanding ageing population. However, the increase in cancer incidence affects people across the whole age spectrum. To test the hypothesis that the age of onset of cancer (overall and specific) in England and Wales is decreasing over time we have developed The Cancer Incidence Temporality Index (CITI), which gives a crude measurement of the portion of the population, in which cancer incidence is rising fastest over time: I=(SigmaO(a)/ SigmaE(a))/(SigmaO(a)/SigmaE(a)), where I is the CITI value, O is the observed number of cases and E is the expected number of cases; 'a' and 'b' refer to separate summation ranges for younger and older age groups. Population data and cancer incidence data in England and Wales, 1971-1999 were obtained from the UK Office for National Statistics. The trends in CITI values have been shown graphically for cancer overall and for specific tumour sites. The impact of diagnostic testing is also addressed. The results of this study suggest that the average age of onset of prostate, breast and cervical cancer is temporally decreasing. The study also suggests that for cancer overall the trend for the age of onset of cancer in males has stabilised since 1990 and has started to reverse in females from 1995 despite the expanding ageing population. A similar trend is observed for leukaemias. The CITI analysis for colon cancer shows that the age of onset in both males and females is increasing over time. The trend for ovarian cancer is similar to that for colon cancer. The CITI analysis for NHL in males is similar to that for colon cancer, however, in females the trend stabilised after 1990. The CITI may aid prediction of changes in the age of onset of cancer and thus aid targeted aetiological research. In addition, we suggest the need for a mathematical model, which may measure the changes in the age of onset of cancer in units of time.

Organophosphate (OP) pesticides are often used in combination with one another and with the components of formulations. Evidence already exists for interactions in the neurotoxic effects of OPs through interference with metabolism, but there is also potential for interactions related directly to cell damage. The purpose of this work was to investigate this possibility for OPs and the components of one of their common formulations in vitro. NB2a neuroblastoma cells were induced to differentiate in the presence of the OPs diazinon and chlorpyrifos, in combination with a commercial formulation (identified as Commercial Formulation 1) of the compounds and, independently, the components of that formulation. The compounds were tested in pairs in various proportions and the resulting inhibition of neurite outgrowth was measured by light microscopy and quantitative image analysis. Interactions were determined in terms of enhanced or reduced effects of the paired compounds in comparison with the expected additive effects estimated from the effects of each compound on its own. Synergism was detected between combinations of: 10 microM chlorpyrifos and 500 nM pyrethrum; chlorpyrifos and one of the solvents (regular spirit) found in Commercial Formulation 1. All other combinations of OPs and products were additive in their neurotoxicity. The data suggest that exposure to multiple OP-containing pesticide formulations may lead to synergistic neurotoxicity by a direct mechanism at the cellular level.

Organ development may be assessed by estimating the total number of functional units within an organ over time; the potential functional capacity of that organ may be represented by the total number of functional units present in the fully developed, mature organ. Relative development of the lung at birth is essential to provide sufficient oxygenation of body tissues and so maintain ex utero life. Estimation of the number of one type of functional unit of the lung – terminal bronchiolar duct endings – provides important information regarding development of the lung. This investigation used stereological techniques, specifically Cavalieri’s Principle and the “physical disector”, to estimate total number of terminal bronchiolar duct endings in the upper lobe of the right lung of a group of 14 control infants between 0 and 66 weeks post-natal age. Results demonstrate that total terminal bronchiolar duct ending number does not increase significantly over the first 24 weeks of post-natal life in normal infants ( P =0.997). The unbiased, design-based techniques used in this paper confirm previous model-based research that indicates that terminal bronchiolar duct ending development is completed before birth.

Summary A rat-specific mouse monoclonal antibody, exclusively reacting with a blood-brain and blood-nerve barrier protein, was employed to assess the post-natal, age-related changes in morphology and intraparenchymal distribution of barrier competent microvessels in normal rat forebrain. Antibody binding first appeared in single cells over the external surfaces of the brain between days 3 and 6 post-partum and increased progressively with age. In mature rats, the cerebral grey matter showed higher vascularization by barrier competent microvessels than white matter. Microvessels in the hippocampus were immunocytochemically more avid but less “networked” than the rest of the neocortex. These features may be related to morphological, metabolic and haemodynamic changes associated with brain growth and development.

Infection was induced in five rhesus monkeys (Macaca mulatta) by intravenous inoculation with a virulent strain of Plasmodium knowlesi. Approximately one week after inoculation, four of the exposed animals developed acute malaria and died or were killed when moribund after varying periods of illness. Post-mortem and light microscopical examination showed marked cerebral vascular congestion and widespread plugging of the brain capillaries and venules (microvessels) by heavily parasitized erythrocytes mixed with uninfected erythrocytes. Electronmicroscopically, the major changes seen were adherence of large numbers of parasitized erythrocytes and macrophages to swollen microvascular endothelial cells; increased numbers of fibroblasts and deposition of collagen bundles in the extracellular matrix around damaged and parasite-packed microvessels were also found in many areas. This animal model may prove useful for further investigation of the pathogenesis of cerebral malaria.