Search PubMed⌕ Search

Biomedical subjects

A M Stewart

Publications and source records attributed to A M Stewart.

At least 37 records · Page 2Linked to original sources
PubMed1994

Mitochondrial DNA mutations in an outbreak of optic neuropathy in Cuba.

Since October 1991, nearly 51,000 Cubans have been afflicted in an outbreak of optic and peripheral neuropathies. To begin an investigation of the possible role of mitochondrial DNA (mtDNA) mutations in the outbreak, we studied mtDNA from 14 affected and two unaffected Cubans for the 12 mutations associated with Leber's hereditary optic neuropathy. Eleven probands (12 patients) had optic neuropathy and two had peripheral neuropathy only. We also studied two unaffected relatives of one proband. We identified two mtDNA mutations, at nucleotides 11778 and 3460, in two of the 11 probands with optic neuropathy. Although this data set is too small to reach statistically valid conclusions, it does suggest that mtDNA mutations might be contributing to the outbreak of optic neuropathy in Cuba.

Base Sequence↗
PubMed1993

Reanalysis of Hanford data: 1944-1986 deaths.

Reanalysis of Hanford data by a method, which is new only in the sense that it makes new uses of standard epidemiological procedures, has produced evidence of a cancer risk at low dose levels. By a conservative estimate, about three per cent of the pre-1987 cancer deaths of Hanford workers had occupational exposures to external radiation as the critical (induction) event. These radiogenic cancers were evenly distributed between five diagnostic groups, but as a result of there being much greater sensitivity to "cancer induction by radiation" after, rather than before, 50 years of age, they were concentrated among the cancers which proved fatal after 70 years of age. The reanalysis provides no support for the idea that radiation is more likely to cause leukemia than solid tumors, or the idea that there is reduced cancer effectiveness of radiation at low dose levels (dose rate effectiveness factor or DREF hypothesis), but the estimated proportion of radiogenic cancers was much higher for the 175 nonfatal cancers (which had other certified causes of death) than for the 1,732 fatal cases. Finally, according to the latest publication of the US Committee on Biological Effects of Ionizing Radiation (BEIR V), dose rate is more important than exposure age, and even a single exposure to 10 rem would only increase the normal cancer risk by four percent. Nevertheless, for all recorded exposures of Hanford workers, the estimated doubling dose was close to 26 rem; for exposures after 58 years, it was close to 5 rem, and for exposures after 62 years, it was less than 1 rem.

Age Factors↗
PubMed1993

A-bomb survivors: further evidence of late effects of early deaths.

Reanalysis of A-bomb survivor data has shown the following: a) in the high-dose (> 1 Gy) subgroups of the life span study cohort of 5-y survivors, there is a significant deficit of individuals who were < 10 y or > 50 y at the time of the bomb; and b) in the cohort on in utero children, there is a significant deficit of individuals who were < 8 wk of fetal age when exposed. This paper discusses how this selection bias has affected the perception of three effects of A-bomb radiation: marrow damage, carcinogenesis, and second-generation effects.

Age Factors↗
PubMed1991

Evaluation of delayed effects of ionizing radiation: an historical perspective.

It is widely assumed that after the bombing of Hiroshima and Nagasaki there were no lasting effects of the acute injuries (which included extensive damage to blood forming tissues by the radiation) or the massively high death rate (which was caused by environmental effects of the blast as well as personal injuries). However, close inspection of the dose response curves for non-cancer deaths has shown that this could be a false impression caused by one effect of marrow aplasia being confused with leukemia (defective erythropoiesis) and a second effect being confused with early selection in favor of general fitness (defective immune responses). Possible consequences of such confusion (for cancer risk coefficients) are discussed in relation to what is known about late effects of prenatal x-rays and occupational exposures to radiation.

History, 20th Century↗
PubMed1991

Changing interactions between astrocytes and neurons during CNS maturation.

The environments of the developing brain and injured adult brain differ in their abilities to support axonal growth. To determine if astrocytes contribute to this difference, neurons were plated onto astrocytes cultured from the neonatal rat cortex and from the injured adult brain. Two patterns of neurite growth were observed in these two astrocyte culture systems. Neurons contacting the neonatal astrocytes had neurites that were twice as long as those contacting the injured adult astrocytes. Furthermore, in cultures with neonatal astrocytes, neurites faithfully followed the astrocytic processes, maximizing their contact, while in cultures of injured adult astrocytes, the neurites had a tendency to cross the processes orthogonally, minimizing their interaction with the astrocytes. When neurons were grown suspended over either neonatal or injured adult astrocytes, no difference in neurite length or the pattern of neurite growth was observed, indicating that neurite growth was not differentially affected by soluble factors released from the two populations of astrocytes. The addition of fetal calf serum, which is known to contain protease inhibitors, did not alter neurite growth when compared to serum-free medium, suggesting that a substantial difference in protease activity does not account for the variations in neurite length observed. Based on these results, it appears that the molecular components of the external surface of injured adult astrocytes do not support neurite growth to the same extent as those found on neonatal astrocytes. The differing abilities of these two populations of cultured astrocytes to support neurite growth in culture may reflect a change in the functional role of these cells that occurs during the development of the central nervous system.

Age Factors↗
PubMed1991

A randomised study of outcomes in a defined group of acutely ill elderly patients managed in a geriatric assessment unit or a general medical unit.

The aim of this study was to identify differences in the medical management and clinical outcome in a group of elderly patients admitted to a designated geriatric assessment unit (GAU) or to two general medical units (GMUs). A prospective randomised controlled trial was undertaken in 267 patients aged 70 years and over (mean age = 78.3 years). Following discharge from hospital, patients were followed up at three monthly intervals for a total of 12 months. At the time of discharge, no significant differences were found in inpatient management, length of stay, mortality rates, discharge rates to institutional care or utilisation of community services in patients admitted to the GAU and the GMUs. Similarly, no significant differences were found at three, six, nine, and 12 month follow up in case fatality, activities of daily living indices, mental health status, rates of institutional referral and the level of community service support in patients admitted to the GAU and the GMUs studied. These findings do not show any advantage for the unselected 70+ acutely ill elderly patient who is admitted to a designated geriatric assessment unit rather than to a general medical unit. Therefore, an admission policy to GAU, based solely on age 70+ is medically inappropriate and cost-inefficient. Evidence from other sources suggests that an age cohort of acutely admitted patients beyond 80 years may well have returned more optimistic findings for the GAU. In future, GAUs will require a more selective admission policy to maximise the benefits of their rehabilitative and interdisciplinary approach.

Acute Disease↗
PubMed1990

A-bomb radiation and evidence of late effects other than cancer.

Cancer risk coefficients for ionizing radiation are currently based on the assumption that, after the bombing of Hiroshima and Nagasaki, there were no late effects of early selection (survival of the fittest) or acute marrow damage. These negative findings were the result of applying a linear model of relative risk to the deaths of 5-y survivors. By applying a linear-quadratic model to these deaths (i.e., a model with more than one degree of freedom), we have obtained evidence of longstanding competition between selection effects of the early deaths and other radiation effects, and also evidence that late effects of radiation include marrow damage as well as cancer. Consequently, the present method of risk estimation--by linear extrapolation of high dose effects--should no longer be used for estimating the cancer effects of occupational exposures or background radiation.

Humans↗
PubMed1987

Ten-day rule.

Explore the source record for details and available documents.

Child↗
PubMed1986

Immunizations against infectious diseases and childhood cancers.

A study based upon an unusually large series of childhood cancers and matched controls found a significant deficit of case/control pairs in which the cancer case had fewer immunizations against infectious diseases than the matched control. All types of immunizations and cancers were affected but the case/control differences were more pronounced for older cases with late immunizations than for younger cases with early immunizations, and more pronounced for solid tumours than leukaemia. Therefore there may be immune system responses to immunizations (or simulated infections) which make it difficult for small clones of cancer cells to enlarge and are more successful in preventing localised tumours in adolescents than childhood leukaemias.

Adolescent↗