Passive smoking and dental caries in children.
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Child↗
Biomedical subjects
Michael Davies
Publications and source records attributed to Michael Davies.
Apoptotic gene expression in Paget's disease: a possible role for Bcl-2.
Paget's disease of bone is characterized by an increase in both the size and the number of bone-resorbing osteoclasts. An important regulator of osteoclast activity is the process of apoptosis, and any aberration in this process could lead to increased osteoclasis. Analysis using human apoptosis cDNA expression arrays revealed that the apoptotic suppressor, Bcl-2, showed a marked increase in expression in Pagetic bone. In situ hybridization (ISH) and computer-assisted image analysis confirmed that the levels of Bcl-2 transcripts were significantly (p<0.0001) increased in Pagetic osteoclasts. The Bcl-2:Bax transcript ratios were similarly elevated. These findings were confirmed by immunohistochemistry. The Bcl-2 gene promoter sequence from 20 Pagetic patients and controls was analysed. Single nucleotide mutations were identified in three of the Paget's patients and one of the controls. Luciferase reporter analysis showed that the mutations induced a basal 12-fold increase and hydrogen peroxide-induced 19-fold increase in luciferase expression, compared with the normal construct. It is concluded that in Paget's disease, there is an increase in the expression of genes that are involved in the inhibition of apoptosis, notably Bcl-2. The increase in Bcl-2 may be explained in some patients by mutations in the Bcl-2 gene promoter. These results provide a potential explanation for the dramatic increase in osteoclasis seen in patients with Paget's disease.
Apoptosis↗
A comparison of in situ hybridisation, reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ-RT-PCR for the detection of canine distemper virus RNA in Paget's disease.
Previous evidence implicating Paramyxoviruses in the aetiopathology of Paget's disease of bone has proved controversial. Whilst several groups have demonstrated Paramyxoviruses using techniques such as in situ hybridisation (ISH), reverse transcriptase-polymerase chain reaction (RT-PCR), and in situ-RT-PCR (IS-RT-PCR), others have found no evidence of viruses using only RT-PCR. To investigate this latter finding, we have now compared detection of canine distemper virus by ISH, RT-PCR (three different methods) and IS-RT-PCR, in 10 patients with Paget's disease, and samples of non-diseased bone from four patients. Canine distemper virus was detectable in six of the samples by ISH, but only in five of the samples by RT-PCR, using one of the methods. Neither of the other RT-PCR methods detected canine distemper virus. IS-RT-PCR demonstrated canine distemper virus in all 10 samples. There was no evidence of virus in the control samples. We have shown that the ability to detect canine distemper virus in bone is dependent on the technique used. IS-RT-PCR clearly showed that canine distemper virus was present in 100% of Pagetic samples, whereas canine distemper virus was only found in 60% by ISH and in 50% using one particular RT-PCR method. These results provide conclusive evidence that canine distemper virus is present within Pagetic bone, and provide a possible explanation for the failure of some groups to detect Paramyxovirus sequences. These findings also have wider implications for other studies investigating viral expression.
Distemper Virus, Canine↗
Association between vertebral fracture and increased mortality in osteoporotic patients.
UNLABELLED: Determinants of mortality were studied in a prospective study of 677 women and men with primary or secondary osteoporosis. Prevalent vertebral fractures were associated with increased mortality, but other known predictors of mortality explain a significant proportion of the excess risk. INTRODUCTION: In population studies, prevalent vertebral fractures are associated with increased mortality. It is unknown whether this excess mortality is related to low bone mineral density or its determinants or whether there is an additional component associated with fracture itself. METHODS: We studied 677 women and men with osteoporosis, 28-88 years old, of whom 352 had morphometrically determined vertebral fracture, to examine the risk and causes of mortality in patients with osteoporosis (defined densitometrically as a spine bone mineral density T-score < -2.5 and -3.0 for women and men, respectively, and/or one or more prevalent vertebral fractures without a history of significant trauma). The participants had enrolled in a double-blind placebo-controlled study in osteoporosis and were comprised of 483 women with postmenopausal osteoporosis, 110 women with secondary osteoporosis, and 84 men with osteoporosis of any cause. Demographics, medical history, and other measures of skeletal and nonskeletal health status were assessed at entry. RESULTS: During a median follow-up of 3.2 years, 37 (5.5%) participants died, with 31 of these deaths occurring in those with prevalent vertebral fractures. Compared with participants who did not have a prevalent vertebral fracture, those with one or more fractures had a 4.4-fold higher (95% CI, 1.85, 10.6) mortality rate. After adjustment for predictors for poor health--including number of medications, number of diseases, use of oral corticosteroids, alcohol intake, serum albumin and erythrocyte sedimentation rate (ESR), renal function, height, weight, gender, and age--the point estimate of risk remained elevated but was no longer statistically significant (hazard ratio, 2.4; 95% CI, 0.93, 6.23). CONCLUSIONS: Prevalent vertebral fractures in osteoporotic patients are associated with increased mortality. Other known predictors of mortality can explain a significant proportion of the excess risk.
Adult↗
Neurological sequelae in in-vitro fertilisation babies.
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Brain↗
Gestation and birthweight in dizygotic twins.
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Birth Weight↗
Nutrition before birth, programming and the perpetuation of social inequalities in health.
The need to explain social inequalities in health has led to the theory that chronic disease is due, in part, to a legacy of adverse experiences in early life. Epidemiological studies show consistently that individuals who are small at birth have an increased risk of cardiovascular disease in adulthood. There is growing consensus that this association reflects a causal relationship and is not simply the product of bias or confounding. The concept of programming is invoked as the biological mechanism; birth size is thus a proxy for fetal programming. Recent findings suggest that fetal programming interacts with the post-birth environment. The adverse exposures that are thought to underlie and potentiate programming cluster in socially patterned ways, thus creating substantial inequalities in health. Experiments in animals demonstrate that nutritional interventions before or during pregnancy can produce programming phenomena in the offspring, sometimes without an impact on birth size. However, the extent to which maternal nutrition contributes to programming in contemporary developed countries is uncertain.
Animals↗
Vitamin D metabolism, rickets, and osteomalacia.
Rickets in the growing child or adolescent and osteomalacia in the adult develop in a variety of clinical situations and have in common an absence or delay in the mineralization of growth cartilage and in newly formed bone collagen. Classically, deficiency of vitamin D, which is essential for the absorption of dietary calcium, has been the major cause. However, rickets is also seen as a result of hereditary defects in critical vitamin D signaling molecules. Disturbances of phosphate metabolism can also lead to signs of rickets and osteomalacia, notably X-linked hypophosphatemic rickets, and oncogenic osteomalacia. Extrarenal synthesis of 1,25-dihydroxyvitamin D, such as that associated with granulomatous disease, can also lead to disturbances in calcium metabolism, with associated skeletal and nonskeletal changes.
Calcium↗
Monitoring the progress of system integration.
As providers of health care face the multiple challenges of today's health care environment, many believe that integrated delivery systems promise the structure needed to provide high-quality, cost-efficient care. They make structural and process changes with the expectation that those changes will improve system performance. But few systems actually measure progress in creating an integrated system. This article describes one health care system's strategy for introducing organizational measures to create an integrated system scorecard and focuses on the development, results, and use of the staff survey. The survey provides reliable indicators of system integration. Linking the survey results with network performance measures, in turn, provides managers with tools for judging whether system integration is associated with improved system performance.
Data Collection↗