Biomedical subjects
Publications and source records attributed to A Wall.
The government should sort out the inconsistencies in its health policies. NHS managers have a good record on implementing government policy. The health secretary needs to clarify his attitude to managers and address the loss of top people.
Tyrosinase has been suggested as a prodrug-converting enzyme for the treatment of melanoma. We hypothesized that tyrosinase expression in transfected nonmelanotic cells can be used in a gene therapy paradigm of prodrug activation. To verify our hypothesis, we used the following tyrosinase variants: (a) a full-length human tyrosinase clone (T); (b) a mutant lacking the COOH-terminal cytoplasmic domain (TdeltaC); (c) a mutant lacking the COOH-terminal transmembrane and cytoplasmic domains (TdeltaTC); and (d) a fusion with the eight COOH-terminal amino acids of lysosome-associated membrane protein-1 (TL). Expression of mutant and wild-type tyrosinases was induced by transfection in nontumorigenic human cells of epithelial origin (293HEK, MCF-10A adenoma, and NHDF-Ad human dermal fibroblasts) as well as in tumor cells (9L gliosarcoma, MCF7 adenocarcinoma, and HT-1080 fibrosarcoma). When compared with the wild-type tyrosinase transfectants, truncated mutant expression resulted in higher mRNA levels that paralleled higher enzyme activity of the truncated mutants. Two model tyrosinase prodrugs, hydroxyphenyl-propanol (HPP) and N-acetyl-4-S-cysteaminylphenol (NAcSCAP) inhibited proliferation and caused cell death of transfected cells in a dose-dependent manner. Effects of prodrug treatment were compared for tumorigenic cells and their nontumorigenic counterparts. Two truncated mutants (TdeltaC and TdeltaTC) showed low endogenous cytotoxicity and efficiently suppressed proliferation and induced cytotoxicity in transfected tumor cells in the presence of NAcSCAP. Overall, these results indicate that the developed tyrosinase mutants hold promise as prodrug activation systems for tumoral gene therapy.
At least 40 chief executives have had their contracts terminated early in the past five years. Very few, if any, have gone through a disciplinary procedure. The most commonly stated reasons have been poor financial control and disagreements with chairs. This trend represents a considerable waste of talent. The experience required of a chief executive cannot be acquired overnight. The 'sudden death' of people at the top corrupts organisations and deprives them of continuity.
The present study compared the effects of chronic treatment (21 days) with (+)-nicotine and (-)-nicotine on exploratory behaviours and body temperature in rats. Chronic treatment with either (+)- or (-)-nicotine induced tolerance in exploratory behaviours. A cross-tolerance between the two stereoisomers was also observed. Body temperature was differentially affected by chronic (+)- and (-)-nicotine, but cross-tolerance was still observed. In addition, nicotinic acetylcholine receptor (nAChR) and N-methyl-D-aspartate (NMDA) receptor binding in rats treated with (+)- and (-)-nicotine were measured by receptor autoradiography. Chronic treatment with (+)- and (-)-nicotine significantly increased nAChR binding in different brain regions. Furthermore, significant differences in the induction of nAChR binding by chronic (+)- and (-)-nicotine were detected in several brain regions. Chronic treatment with (+)-nicotine significantly increased NMDA receptor binding in the CA1 region of the hippocampus. However, (-)-nicotine had no effect on NMDA receptor binding in any of the regions analysed. These results demonstrate differences between chronic treatment with (+)- and (-)-nicotine in physiological responses such as body temperature and biochemical changes such as changes in nAChRs and NMDA receptor binding, although a cross-tolerance between the two enantiomers in behaviour and body temperature is also observed.
Middle managers are essential to organisations but are often unsupported by those above them and reviled by those they supervise. Effective middle managers keep top managers in touch with reality and reinterpret policy and strategy so operational staff understand the point. Organisations should reassure middle managers about the validity of their work and provide continuing education.
Hallux valgus is still an open problem consists of many unexplained questions related to, not only its etiopathogenesis and biomechanics but also to treatment of this deformity. The purpose of investigation: 1) To find out hallux valgus predisposing factors; 2) To recognise anatomic features of the foot in hallux valgus patients, basing on orthopaedic physical examination as well as to find out the frequency of the occurrence of foot skeleton disorders in rentgenometric and plantoconturographic (foot prints) measurements. 335 feet in 173 patients (females) treated operatively due to hallux valgus in Orthopaedic Department of Wrocław Medical Academy in years 1980-1994 were examined. Those patients were operated on according to Keller, Dega and McBride method. All the patients underwent preoperative orthopaedic physical examination as well as rentgenographic and plantoconturographic one. Such factors as heredity and Egyptian shape of the foot as well as metatarsal index "plus" were recognised as hallux valgus predisposing factors. Most of the parameters evaluated in orthopaedic, rentgenographic and plantocontourographic examination presented pathologic values that indicated pathology within foot in hallux valgus patients.
The selected epidemiological data concerning revisional hip arthroplasties analysis is presented. The data were collected at 25 Polish orthopaedic centers (some 27% of all centers performing primary THR) during the year 1998. Survival time of the artificial joint (the time between primary and revisional hip replacement) appears as the main criterion of THR result. Failed cemented THR dominate over cementless ones. Septic complications constitute 4.55% complications demanding revisional arthroplasty. Distinct increase in revisional THR is found 7 years after primary operation. An average survival time for arthroplasty was 10.3 years, a little longer for acetabular component.
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A hierarchical structure in organisations reflects the natural order. A hierarchy does not have to denote an authoritarian management style. People need to know who their boss is. Lines of accountability on many hospital wards are unclear.
Successful chair-chief executive relationships depend on a 'no surprises' rule. The fact that a chair can terminate a chief executive's contract with little reference to anyone else is a weakness in the system. When a relationship breaks down it is usually for personal rather than formal reasons.
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The proposed size of primary care groups may prove problematic. Their creation will have bureaucratic consequences. Primary care groups' proposed accountability to three different organisations may lead to conflict. Their establishment will compound existing problems: increasing organisational complexity and conflicts between local discretion and central control.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.