Biomedical subjects
Publications and source records attributed to R Newton.
Looks at management development at Ashworth Hospital as part of a continuing programme of professional development. This programme is innovative and revolutionary. It puts control of learning in the hands of the participants who are responsible for driving the programme and share the responsibility for supporting and motivating colleagues.
Details the results of an attempt to identify the impact of a comprehensive management development programme on organizational effectiveness within the health service public sector. Concludes that management development programmes must have a prespecified set of strategically linked outcomes, identifying the benefits to the organization, and a set of critical success factor measures to determine their achievement or otherwise. Programmes which do not result in managers feeling empowered will be criticized in not impacting positively on the organization.
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OBJECTIVE: To determine whether the prevalence of schizophrenia among the homeless population of Edinburgh resident in hostels has changed between 1966 and 1992. DESIGN: Comparison of two cross sectional surveys. SETTINGS: Hostels for homeless people in Edinburgh. SUBJECTS: In 1966 a random sample of 98 residents of three common lodging houses. In 1992 a random sample of 198 residents of nine hostels. MAIN OUTCOME MEASURE: Prevalence of schizophrenia. RESULTS: The prevalence of schizophrenia in 1992 was 12/136 (9%) compared with 20/79 (25%) in 1966 (odds ratio 0.29; 95% confidence interval 0.13 to 0.62; P = 0.001). Adjustment for confounding by age, current hostel, and duration of unemployment by means of logistic regression produced an adjusted odds ratio of 0.22 (0.08 to 0.58). CONCLUSIONS: The prevalence of schizophrenia was lower in 1992 even after other changes in the population resident in hostels occurring between 1966 and 1992 were taken into account. The findings are not consistent with an increase in the prevalence of schizophrenia among homeless people despite a 66% reduction in adult psychiatric beds in the region during 1966-92.
The onset of labor in humans is associated with an increase in prostaglandin production. One of the key steps is the conversion of arachidonic acid to prostaglandin E2 by cyclo-oxygenase (Cox). Cox has been found to exist as two distinct genes, Cox-1 and Cox-2. We have used RT-PCR to study the relative abundance of mRNA from each Cox gene in amnion at term. Quantitation of PCR efficiency indicated an approximate 100 fold excess of Cox-2 messenger RNA over that for Cox-1. These data point to the importance of Cox-2 in the increased prostaglandin synthesis associated with labor. Further studies should therefore focus on the control mechanisms for Cox-2.
Various polymorphic markers with a random distribution along the X chromosome were used in a linkage analysis performed on a family with apparently X-linked recessive inheritance of neural tube defects (NTD). The lod score values were used to generate an exclusion map of the X chromosome; this showed that the responsible gene was probably not located in the middle part of Xp or in the distal region of Xq. A further refining of these results was achieved by haplotype analysis, which indicated that the gene for X-linked NTD was located either within Xp21.1-pter, distal from the DMD locus, or in the region Xq12-q24 between DXS106 and DXS424. Multipoint linkage analysis revealed that the likelihood for gene location is highest for the region on Xp. The region Xq26-q28, which has syntenic homology with the segment of the murine X chromosome carrying the locus for 'bent tail' (Bn), a mouse model for X-linked NTD, is excluded as the location for the gene underlying X-linked NTD in the present family. Thus, the human homologue of the Bn gene and the present defective gene are not identical, suggesting that more than one gene on the X chromosome plays a role in the development of the neural tube.
Three microsatellites and five restriction fragment length polymorphisms (RFLPs) have been detected at loci DXS275, DXS97, DXS11 and DXS100. All of the reported polymorphisms are in linkage equilibrium with existing polymorphisms at these loci. However, two RFLPs at DXS275 and two at DXS97 appear to be in linkage disequilibrium with each other. Increased informativity at these loci have enabled exclusion of Xq22-q25 as a candidate region for X-linked spina bifida and anencephaly, and should aid in the mapping of other genes in the region.
The accuracy of self-report of herpes zoster was investigated in the Duke Established Populations for Epidemiological Studies of the Elderly, a longitudinal study of 4162 community-dwelling elderly persons residing in North Carolina, 1986-1993. The authors compared self-reports of zoster with physician diagnosis of zoster and with a zoster verification questionnaire (ZVQ). Compared to physician diagnosis, 3.2% (95% confidence interval 0-61%) of self-reports of zoster (n = 31) were false-positive and no denials of zoster (n = 63) were false-negative. The agreement of self-reports to physician diagnosis was 98.9%, the sensitivity and negative predictive value were 100%, the specificity was 98.4% and the positive predictive value was 96.7%. The ZVQ comparisons were similarly high. These data suggest that the frequency of false-positive and false-negative reports of zoster is low in this elderly population. Zoster self-reports appear to be accurate and suitable for epidemiological investigations.
We report here the findings of a linkage analysis, involving numerous markers from the human X chromosome, in an attempt to localise a putative gene causing apparent X-linked spina bifida and anencephaly (SBA) in a large Icelandic pedigree. Two-point linkage analysis was performed using markers from 62 informative loci in this family. Although small positive lod scores were found at a number of these loci, none reached the significance level for linkage. Haplotypes were extensively analysed and found to exclude linkage to the X chromosome.
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A single dose pharmacokinetic study with modified human Interleukin-1 Beta (IL-1 beta or DuP 118) was performed by injecting 5 micrograms/kg of drug into the jugular vein of three beagle dogs. Serial 5-ml plasma samples were removed from the dogs over a 120-minute period. DuP 118 plasma levels were measured using a sandwich ELISA technique capable of measuring concentrations ranging from 0.25 to 2 ng/ml with accuracy and precision constraints of less than +/- 20% variability. DuP 118 stored at -20 degrees C in dog plasma was stable for at least 1 month. Pharmacokinetic parameters were determined for the three dogs by standard model independent or non-compartmental methods. DuP 118 was rapidly distributed in the dog. The volume of distribution was approximately two-fold higher than the total body water of a lean dog. The terminal half-life was short, less than 30 minutes. Within approximately an hour after dosing, DuP 118 plasma levels were reduced 20-fold and were below the quantifiable limit of the assay.
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Cytokines have been implicated in the regulation of eicosanoid synthesis and synovial cell proliferation. To further define these mechanisms, we have compared the effects of basic fibroblast growth factor and platelet-derived growth factor on cell growth, prostaglandin E2 (PGE2) production and phospholipase A2 enzyme activity in long-term cultures of synovial cells from rheumatoid arthritis (RA) patients capable of proliferating in serum-free medium. Compared with serum-free medium alone, RA synovial cell growth was significantly enhanced by adding either basic fibroblast growth factor (bFGF) or platelet-derived growth factor (PDGF) to the culture medium. Growing RA synovial cells for 14 days in serum-free medium plus bFGF caused them to spontaneously release significant amounts of PGE2, an effect not seen if cells were grown in serum-free medium alone, or serum-free medium plus PDGF. Enhanced release of PGE2 occurred when arachidonic acid was added to bFGF but not PDGF-treated RA synovial cells, suggesting that bFGF increased cyclooxygenase enzyme activity in these cells. Moreover, phospholipase A2 (PLA2) enzyme activity was found to be significantly greater in RA synovial cells grown for 14 days in serum-free medium containing bFGF alone, or bFGF plus interleukin 1 beta (IL-1 beta) compared with cells grown in either serum-free medium alone, or serum-free medium plus PDGF. Similarly, bFGF plus IL-1 beta-stimulated release of PLA2 activating protein, a novel mammalian phospholipase stimulator found in high concentrations in RA synovial fluid.(ABSTRACT TRUNCATED AT 250 WORDS)
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The interaction of salmeterol with model membranes has been studied with regard to equilibrium and kinetic behavior, including determination of the membrane-based partition coefficient, the rate of dissociation of salmeterol from membranes, and the rate of association. These data were obtained in various membrane preparations and under various conditions (e.g., temperature, cholesterol content). The compound is very lipophilic, compared with other beta 2 agonists such as salbutamol, and has a rapid association rate and a moderate dissociation rate. The equilibrium data support the assertion that the salmeterol action measured in perfused tissue involves an exo-site for nonspecific binding that may be identified with or related to the lipid bilayer. The kinetic data in unilamellar and multilamellar liposomes of synthetic lipids further suggest that the approach to the exo-site and the active site may involve components in the native system other than the lipid bilayer in which the beta 2 receptor is located. These additional components may explain the slow onset and the extraordinarily long duration of action.
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