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Biomedical subjects

J Harrison

Publications and source records attributed to J Harrison.

At least 145 records · Page 8Linked to original sources
PubMed1994

Prevention of hepatitis B infection: a survey of surgeons and interventional cardiologists.

Hepatitis B immunization and the use of protective measures against blood contamination were assessed in a group of clinicians associated with invasive procedures. A self-administered confidential questionnaire was sent to 140 surgeons and interventional cardiologists, of whom 105 (75 per cent) replied. Ninety-five respondents (90 per cent) were immunized against hepatitis B, most (63 per cent) by an occupational health department and the majority within 5 years of this study. Only 80 per cent had had their immunity tested after immunization. Barrier protective techniques were used infrequently, with 30 per cent of respondents wearing impermeable gowns, 14 per cent wearing visors and 9 per cent using double-gloving for all procedures. Department of Health guidelines on protection from hepatitis B were published after this survey and the implementation of these guidelines in an NHS trust hospital is discussed.

Cardiology↗
PubMed1994

The role of orthotopic liver transplantation in the management of sclerosing cholangitis.

Our recommendations are to manage asymptomatic patients with biannual clinical and biochemical follow-up examinations. Symptomatic non-cirrhotic patients who have diffuse SC should be enrolled in trials addressing the efficacy of medical therapy such as UDCA. Patients with diffuse disease and cirrhosis of the liver should be considered for liver transplantation. Symptomatic patients with a dominant stricture should first undergo rigorous investigation to rule out CCA. Disease in those noncirrhotic patients who are deemed to have benign strictures should initially be managed by means of dilation or surgical excision, although careful monitoring and review will be needed because most will continue with progressive disease, eventually showing signs of portal hypertension and cirrhosis. Patients with dominant strictures and cirrhosis should be considered for orthotopic liver transplantation. Liver transplantation in experienced units now offers more than 80% of patients a full and effective rehabilitation, with more than 75% alive at 5 yr. A progressive, advancing decompensating cholestatic disorder with an increasing risk of underlying malignancy can be stopped, giving the patient a high quality of life. More than half of patients report an improvement in the symptoms of their inflammatory bowel disease.

Cholangitis, Sclerosing↗
PubMed1994

Novel delivery of antioxidant enzyme catalase to alveolar macrophages by Fc receptor-mediated endocytosis.

Excessive production of reactive oxygen species by alveolar macrophages (AMs) in response to inhaled toxic substances is a major cause of oxidative lung injury. Therapeutic approaches designed to protect the lungs from oxidative injury by administering native antioxidant enzymes such as catalase and superoxide dismutase have been suggested. However, problems associated with poor penetration of these enzymes to the intracellular target sites have limited their effective use. The present study reports a drug targeting method based on receptor-mediated endocytosis of the antioxidant enzyme catalase to the AMs. This method employs molecular conjugate consisting of a cognate moiety, in this case IgG which recognizes the macrophage Fc receptor, covalently linked to the enzyme catalase via the reversible disulfide linkage. The uptake efficiency of the enzyme conjugate and its protection against oxidative injury were evaluated microfluorometrically using the intracellular oxidative probe dichlorodihydrofluorescein BSA: anti BSA antibody complex (DCHF-IC), and the cell viability indicator propidium iodide. The DCHF-IC-stimulated macrophages exhibited a dose- and time-dependent increase in intracellular fluorescence with a half maximal response dose of approximately 120 micrograms/ml. Free catalase (50-500 U/ml) failed to inhibit the DCHF-IC-induced oxidative burst and had only a marginal protective effect on AM injury. In contrast, the catalase-IgG conjugate (50-500 U/ml) strongly inhibited both the DCHF-IC-induced oxidation and injury in a dose-dependent manner. Effective inhibition was shown to require both the antioxidant catalase moiety ant the cognate moiety for the cell surface receptor. Specific internalization of the conjugate through the Fc receptor was also investigated by competitive inhibition using free IgG.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Splicing variability in HIV type 1 revealed by quantitative RNA polymerase chain reaction.

A quantitative RNA-polymerase chain reaction (PCR) method able to detect the majority of mRNAs produced by human immunodeficiency virus type 1 (HIV-1) was developed and used to study expression of different HIV-1 clones in human cells. Amplified mRNAs were compared to known cDNA standards. This comparison permitted the optimization of PCR conditions and eliminated the generation of artifactual PCR bands. The use of RNA and cDNA standards demonstrated that the RNA amplification is linear within the tested range and suggested that it can be used to quantitate individual mRNAs. The results demonstrate the overall conservation of splicing in different HIV-1 clones. Although, in general, splicing was conserved, extensive qualitative and quantitative variability was observed in different HIV-1 clones. This variability is likely one determinant of the biological characteristics of the different HIV-1 clones, and demonstrates a great plasticity of the HIV-1 genome. The described RNA-PCR methodology was used for the study of HIV-1 expression in unstimulated peripheral blood mononuclear cells (PBMCs) of infected individuals. In general, the same mRNAs were identified in HIV-infected cultured cell lines and in unstimulated PBMCs. Analysis of a variant band found after amplification of PBMC RNA from an HIV-infected individual revealed a new splice site for the generation of Rev/Nef-encoding mRNAs. The availability of a sensitive, rapid, and essentially quantitative method to examine the major HIV-1 mRNAs will facilitate the detailed analysis of HIV-1 expression in human cells.

Base Sequence↗
PubMed1994

Beyond the business plan.

Acknowledges that business planning in the NHS frequently disappoints. Reasons for this are found in the tendency for managers to view the production of a plan as an end rather than a means. A further difficulty resides in the perception managers have of their world. Argues that marketing is the most appropriate paradigm for understanding and structuring this world at present. However, an adaptive cognitive style is necessary to allow constant reframing within the dominant paradigm or even reframing of the paradigm itself. In adopting these approaches, the probability of achieving competitive advantage is heightened. If they are ignored, however, it is likely that training and development techniques, however sophisticated, will have little lasting impact.

Administrative Personnel↗
PubMed1994

Expectations of general practice: gateways and bridges.

Looks at the role of the GP in today's Service and examines some of the organizational and motivational problems which have to be overcome before general practice can be confident of delivering to the strategic expectations of the NHS. They are designed to raise the level of debate for more long-term, practical support for general practice organizations. The issues involved have been researched both qualitatively and quantitatively and are grounded in a context of change. Includes excerpts from general practice profiles developed during research projects, consultancy projects and case study development work--large and small partnerships, single-handed practices, established and "bidding" fundholders, and significantly different practice populations. These are supported by the results of questionnaires circulated to over 2,500 doctors and practice managers and the views and work of others researching and practising in primary care.

Administrative Personnel↗
PubMed1994

Managing people: the breakfast menu.

Discusses an exploratory study of the impact of NHS reforms on the management of staff. Argues that "management" has moved from a view that staff should be provided with a secure and comfortable working environment to "labour" being viewed simply as a factor of production. The result seems to be an unprecedented sense of alienation among significant numbers of NHS staff. Proposes possible ways forward. The first focuses on the "means", accepting that the "ends" of the NHS will, for the foreseeable future, be dominated by the market. The second examines more closely the market-driven, business "end" or purpose and challenges the unitary view of the NHS Trust as a coherent business entity. Beyond these short- to medium-term responses, concludes that a return to a somewhat more flexible and less hard-edged human resources philosophy is a longer-term investment as the labour market tightens and skilled staff become scarcer in the later 1990s.

Focus Groups↗
PubMed1994

GPs: principles and practice.

Defines the role of GPs and explores their possible involvement in practice management and planning, which authorities are trying to encourage. Suggests that there would be a conflict of interest between management and doctors' relationships with patients, and that they could risk becoming public scapegoats as they are in the most exposed position. Raises points to consider, such as should GPs contemplate becoming involved in practice planning.

Family Practice↗
PubMed1994

A biomechanical evaluation of three forms of internal fixation used in ankle arthrodesis.

A biomechanical study was undertaken to evaluate the relative stability of three types of internal fixation used for ankle arthrodesis. Crossed screw fixation, RAF fibular strut fixation, and T-plate fixation were tested in 30 cadaver ankles using an MTS machine. T-plate fixation consistently provided the stiffest construct when compared with the other types of fixation. Failure occurred by distraction of bony surfaces, posterior to the plane of fixation, in the crossed screw and RAF groups. In contrast, failure in the T-plate group occurred through compression of bone anterior to the midcoronal plane of the tibia. Although the stability of fixation is only one factor in determining the success or failure of ankle arthrodesis, the results of this study would support T-plate fixation over the other forms tested.

Ankle Joint↗
PubMed1994

Predictors of psychiatric morbidity in cancer patients.

BACKGROUND: A significant proportion of cancer patients experience psychiatric morbidity in association with diagnosis and treatment. If this morbidity is to be reduced, a better understanding is needed of the factors which influence adjustment to cancer. METHOD: A review of the literature was carried out to explore those factors associated with poor psychological adjustment to cancer. These are described under four heading: characteristics of the patient; disease and treatment variables; the interaction between patient and illness; and environmental factors. RESULTS: A number of risk factors for psychiatric morbidity can be identified from each of the four areas. Methodological limitations are highlighted, in particular the preponderance of cross-sectional study designs. CONCLUSIONS: Increased awareness of the risk factors for psychiatric morbidity should lead to earlier detection and more appropriate treatment. Future research should focus on those risk factors which are potentially modifiable.

Adaptation, Psychological↗
PubMed1993

Additive effect of erythropoietin and heme on murine hematopoietic recovery after azidothymidine treatment.

The ability of combination treatment with erythropoietin (Epo) and heme to rescue hematopoietic activity in mice from the suppressive effect of azidothymidine (AZT) was determined. Exposure of mice to AZT for 5 weeks produced marked anemia, thrombocytopenia, neutropenia, and weight loss, whereas mice that received Epo and heme for 3 subsequent weeks showed significant alleviation of AZT cytotoxicity. Treatment with Epo (10 U for 5 times/week) stimulated hematopoietic recovery in the AZT-treated animals and reduced the severe anemia and thrombocytopenia by 3 weeks. Administration of a lower Epo dose (1 U Epo) resulted in only a modest retardation of AZT-induced anemia, although, when combined with heme, there was a great improvement in recovery of erythropoiesis. The combination of heme with Epo (10 U) produced the optimum response, resulting in almost normal recovery of bone marrow cellularity as well as recovery of burst-forming units-erythroid (BFU-E) and splenic hematopoietic progenitor content (colony-forming unit-spleen [CFU-S]) by the end of 3 weeks of post-AZT treatment. Treatment with heme alone markedly enhanced the recovery of BFU-E and CFU-S, as well as body weight post-AZT; however, this recovery was not to the extent seen in combination with Epo (10 U). Long-term bone marrow cultures (LTBMCs) established from mice exposed to AZT for 8 weeks showed a marked reduction in cellularity and this was completely alleviated when mice received heme and Epo (10 U) for 3 weeks after 5 weeks of AZT administration. The additive effect of heme and Epo was seen in BFU-E production, as well as in CFU-S production, in LTBMCs. Thus, heme exerts a significant protective effect on hematopoietic progenitors in vivo and may be of potential clinical use in combination with Epo to promote effective erythropoiesis in the setting of AZT therapy.

Anemia↗
PubMed1993

The hematopoietic stromal microenvironment promotes retrovirus-mediated gene transfer into hematopoietic stem cells.

In this study we report on the establishment of novel conditions which permit efficient retrovirus-mediated gene transfer of human adenosine deaminase (ADA) into murine hematopoietic progenitors. Using Southern blot analysis and an ADA probe, we demonstrated that prestimulation of bone marrow cells over an in vitro culture of adherent stromal cell layers (ACLs) for two days provides favorable conditions for gene transfer in the absence of exogenous growth factors. In bone marrow transplant recipients reconstituted with retrovirally-marked cells, ADA was detected in spleen, thymus and bone marrow cells of the recipients eight months after transplantation. These observations were also seen in transplants of embryonal hematopoietic stem cells. By using different incubation protocols, it was found that the developmental fate of hematopoietic stem cells varied with the presence of exogenous growth factors or an ACL in the prestimulation phase. Polyclonal hematopoiesis with multiple clones appearing simultaneously was revealed in mice reconstituted with growth factor-stimulated cells four months after transplantation. This was detected by multiple integration patterns of ADA integration into the genomes of individual colony forming units-spleen (CFU-S) in transplantation recipient mice. In contrast, two to five months after transplantation, polyclonal hematopoiesis was not observed in mice reconstituted with cells infected in the absence of growth factors. It appears that utilization of the bone marrow microenvironment through the use of an ACL results in a narrower spectrum of integration patterns, suggesting that a type of oligoclonal or monoclonal hematopoiesis is occurring. These studies demonstrate that an ACL provides novel conditions for successful gene transfer and stable integration of the vector into the genome. Use of an ACL may be advantageous for successful hematopoietic stem cell gene therapy.

Adenosine Deaminase↗