Dental assistants: partners in dental health care.
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Biomedical subjects
Publications and source records attributed to J Ramsey.
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AIMS: To assess geographical variations in mortality and the relationship of socio-economic correlates to deaths from volatile substance abuse (VSA) in Great Britain. DESIGN: Analysis of the National Register of deaths from VSA by linking the addresses (postcode) of the deceased to census enumeration districts and hence wards and counties. SETTING AND PARTICIPANTS: All 775 deaths in Great Britain listed in the national register between 1985-91. Population counts from the 1991 census were used as denominators. MEASUREMENT: The Poisson heterogeneity test was used to test the null hypothesis that all standardized mortality ratios were from the same population. The t-test was used to compare differences in Townsend Deprivation scores between wards with and without VSA deaths. Multiple regression was used to assess the relationship between indices of deprivation and deaths from VSA. FINDINGS: One-third of all VSA deaths occurred in six regions of Great Britain which accounted for 17% of the at risk population. There was considerable variation in age standardized mortality ratios (ASMR) across regions. A ward level analysis indicated that wards with a VSA death had significantly higher levels of deprivation. The Townsend deprivation index showed mean deprivation scores of 2.8 and 0.2, respectively, for wards with and without a registered death (p < 0.0001). Multiple regression at county/region level found that 45% of the variation in ASMR was explained by the components of the Townsend deprivation index. CONCLUSIONS: Factors associated with deprivation are important in VSA deaths and this should be taken into account in planning public health measures to prevent mortality.
Tumor cells genetically modified to express immunostimulatory molecules can produce high levels of antitumor immunity in rodent models. Although a number of clinical trials are currently in progress to assess the value of the approach in human disease, almost all require ex vivo transduction of cultured tumor cells with retroviral vectors. This process is not feasible for many human malignancies, hampering clinical evaluation of the approach. We have used an E1a,1b/E3 deletion mutant of adenovirus containing either the lacZ or the human interleukin-2 (IL-2) gene to transduce human neuroblastoma cells. This vector transduces fresh neuroblastoma cells and neuroblastoma cell lines with an efficiency of 80-90%, compared to an efficiency of 0-14% obtained with retroviral vectors. Cells transduced with the IL-2 adenovector produce up to 12,000 pg of IL-2/10(6) cells/24 hr. IL-2 adenovector-transduced neuroblasts are immunostimulatory; when they are cultured with patient lymphocytes, they increase the proportion of DR+ T cells and generate major histocompatibility complex (MHC) unrestricted cytotoxic effector cells active against parental (nontransduced) tumor cells. We conclude that IL-2 adenovector can be used to transduce freshly isolated human tumor cells efficiently, which will then produce immunomodulatory quantities of the cytokine. The use of adenoviral rather than retroviral vectors facilitates preparation of human tumor "vaccines" and these vectors are now being used in our clinical study of neuroblastoma patients.
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Changes in extracellular pH (pHo) induce changes in the intracellular pH (pHi) of cardiac myocytes that are slow and attenuated. Little however is known about the effects of changing pHo on the pHi of the coronary smooth muscle cells. We have therefore directly compared the effects of altering pHo on pHi of both coronary and cardiac myocytes. Carboxy-SNARF was used in single cells to measure pHi. Alteration of pHo caused corresponding changes in pHi that were large (70-80% of pHo) and rapid in coronary myocytes compared to cardiac myocytes. In contrast, changes of pHi produced by weak acids or bases produced similar pHi responses in both types of cells. It is suggested that the differential effects of pHo on coronary and cardiac cells may be functionally significant, as it will allow rapid alteration of coronary perfusion to meet tissue needs, while maintaining cardiac output.
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A 9-year-old cat was evaluated for left-sided enophthalmos and protrusion of the third eyelid. A primary orbital fibrosarcoma was diagnosed. During the orbital exploration, normal periorbital fascia could not be identified in the lateral and ventral region, thus accounting for the enophthalmos.
OBJECTIVE: To examine the effects of volatile substance abuse on neuropsychological functioning. DESIGN: A sample of index children and matched controls were identified by a two stage procedure. Firstly, over 5000 secondary school pupils completed a screening questionnaire, and, secondly, a sample of those who acknowledged volatile substance abuse and a matched sample of those who denied the practice were assessed in detail by means of (a) individually conducted interviews and (b) toxicological examination of breath samples (to exclude those intoxicated at the time of testing). SETTING: 16 Local education authority secondary schools in London. SUBJECTS: 160 Pupils aged 13-16: 80 index children who had abused volatile substances to the point of intoxication at least once (confirmed by interview) and 80 controls (confirmed by interview) matched for school year, sex, and ethnic background. MEASUREMENTS AND MAIN RESULTS: Neuropsychological functioning tests provided 35 main outcome measures and were administered blind. Data on educational test performance before substance abuse began were obtained retrospectively. Information on potentially confounding social factors, such as number of siblings, tenure of housing, and parents' socioeconomic and employment state was also obtained. The index children performed significantly less well than the controls in tests of vocabulary, verbal intelligence quotient, full scale intelligence quotient, and a measure of impulsivity. When background social disadvantage was taken into account these differences were no longer significant. There were no significant associations between performance on psychological testing and frequency of abuse, and relations with other aspects of the children's history of abuse were generally weak or unsystematic. Comparisons between the results of these tests and of educational tests taken before substance abuse produced equivocal findings. CONCLUSION: Volatile substance abuse, as commonly practised by secondary school pupils, is unlikely to result in neuropsychological impairment.
1. Volatile substance abuse is largely a teenage practice; it is estimated that in the UK 3.5-10% of young people have at least experimented and that 0.5-1% are current users. 2. The products abused are many and varied but only about 20 chemical compounds, notably toluene, chlorinated solvents such as 1,1,1-trichloroethane, fuel gases such as butane and aerosol propellants, are commonly encountered. 3. The acute hazard varies with the compound, product and mode of abuse. Mortality in the UK is now about 100 per year, from all social classes, 90% of whom are male. 4. Chronic toxicity is difficult to assess, partly because of the diversity of products abused. However it is clear that some long-term abusers suffer permanent damage to the central nervous system, heart, liver and kidney. 5. Toxicological analysis may be relied upon for confirmation of diagnosis, providing attention is paid to the kinetics of excretion and stability in the sample. 6. Responses include codes of practice for the sale of products and educational strategies; legislation has also been enacted. There is little evidence that any of these measures have made a significant impact on the problem.
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A 4 year old boy developed a profound motor neuropathy after repeated deliberate inhalation of petroleum vapour. The condition was characterised by extreme slowing of the nerve conduction velocity. He made a gradual recovery over six months. The neuropathy was attributed to the N-hexane component of petroleum.
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We examined the formation of the early classical complement (C) pathway enzymes on sheep (Es), guinea pig (Egp), and human (Eh) erythrocytes (E). Each species' E were sensitized with sufficient IgM or IgG anti-E Ab to establish equal numbers of C1-fixing sites on all E. After sensitization with 100 C1-fixing sites of Ab and excess C1, uptake of C4 was equivalent on all three cell types, judged by anti-C4 binding (for guinea pig C4) or by direct uptake of radiolabeled protein (for human C4). With equal numbers of cell-bound C1 and C4, however, there were marked differences in C2 convertase activity on Es, Egp, and Eh. Sheep EAC14 utilized C2 at least 20 times faster than Egp and Eh bearing the same number of C1 and C4 molecules. C3 cleavage was even further depressed on Egp and Eh, and was not changed by the substitution of oxyC2 for normal human C2. In whole guinea pig serum (GPS), 300 times more C1-fixing sites were required on Egp than on Es to achieve similar amounts of lysis; however, equivalent C3 uptake on Egp and Es was associated with equal extents of lysis, demonstrating that GPS lysis of these cells was regulated by early steps in classical pathway (CP) activation. Incubation of E bearing radiolabeled C4b with Factor I demonstrated that C4b on Egp was highly resistant to cleavage compared to the same protein bound to Es or Eh. Studies with partially purified C3 convertase decay-accelerating factors from Eh stroma demonstrated that these membrane proteins could not account for the observed surface regulation of CP activity because these proteins do not affect the rate of C2 cleavage by EAC14. We conclude that E surface molecules have an important role in modulation of CP activation. This surface-associated CP regulation occurs at the level of cell-bound C4b.
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