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Biomedical subjects

David Webb

Publications and source records attributed to David Webb.

8 recordsLinked to original sources

Localization of the endothelin-B receptor using a transgenic approach.

The use of reporter genes such as beta-galactosidase and green fluorescent protein is a powerful molecular tool for the visualization of in-vivo gene expression. In this paper, we describe the generation of mice that possess a beta-galactosidase reporter gene introduced into the endothelin-B receptor locus by homologous recombination in embryonic stem cells. These mice express beta- galactosidase wherever endothelin-B is expressed and therefore provide a precise in-vivo localization profile of endothelin-B expression.

Animals↗

Long-term follow-up of relapsed childhood acute lymphoblastic leukaemia.

We have reviewed the outcome after relapse in a cohort of 505 children with acute lymphoblastic leukaemia (ALL) seen at a single institution. The majority of relapses (74%) occurred within 3 years from diagnosis, and most involved the bone marrow alone or with overt extramedullary relapse. Early relapse was more common in children with T-ALL and those with unfavourable cytogenetics. Factors influencing second remission included length of first remission and type of relapse. Children who had not received previous cranial irradiation had a superior survival. The German relapse score involving length of first remission, site of relapse and immunophenotype was highly predictive of outcome: event-free survival with 95% confidence intervals at 6 years for patients who received modern treatment [intensive chemotherapy or bone marrow transplantation (BMT)] was 78% (51-92%) for standard risk, 41% (33-49%) for intermediate risk and 19% (10-31%) for highest risk. Retrospective comparison of BMT with chemotherapy showed no difference in the intermediate-risk group but a possible advantage in the highest risk group. Follow-up of 235 patients who relapsed after chemotherapy and received a third course of treatment showed an extremely high early attrition rate, but a small number of patients survived in third remission. We conclude that new approaches are needed to individualize therapy in intermediate-risk patients and to improve the outcome for those in the highest risk group. Only a small number of children can be treated effectively in third remission.

Bone Marrow Transplantation↗

Parenteral antibiotics in a palliative care unit: prospective analysis of current practice.

All patients receiving parenteral antibiotics in a palliative care unit were prospectively monitored over a 13-month period. Of 913 consecutive admissions, 41 patients received 43 courses of parenteral antibiotics. On 27 of 43 occasions, the use of parenteral antibiotics was considered helpful (62%), in eight cases it was considered unhelpful (19%) and in a further eight cases the outcome could not be assessed (19%). The sites of infection for which parenteral antibiotics were prescribed included urinary tract infections (37%), lower respiratory tract infections (26%), soft tissue/skin or wound infections (16%), purulent terminal respiratory secretions (5%) and other (16%). In this sample, urinary tract infections were more commonly associated with a positive outcome than other indications combined (88% versus 48%, respectively). There appeared to be no association between outcome of use and age of the patient (median age 70, range 37-90), underlying diagnosis (HIV versus advanced malignancy) and reason for admission (symptom control versus respite care versus terminal care). However, outcomes appeared to vary in this sample according to the palliative care phase of the patient at the time parenteral antibiotics were administered. Positive outcomes were more common in terminal- (83%) and stable-phase (71 %) patients than deteriorating- (58%) or acute-phase (38%) patients. This survey demonstrates that in specific circumstances a beneficial role exists for the use of parenteral antibiotics in a palliative care setting. The establishment of appropriate guidelines is recommended.

Acquired Immunodeficiency Syndrome↗

Successful treatment of juvenile myelomonocytic leukemia relapsing after stem cell transplantation using donor lymphocyte infusion.

Juvenile myelomonocytic leukemia (JMML) is a rare pediatric malignancy. Hematopoietic stem cell transplantation (SCT) is the only curative approach. However, relapse after SCT remains the major cause of treatment failure. Unlike most other pediatric malignancies, JMML may be susceptible to a graft-versus-leukemia (GVL) effect, although, unlike chronic myeloid leukemia, reports of response to donor lymphocyte infusions (DLIs) remain scanty. This is the first report that describes the successful treatment of relapsed JMML with DLI in the absence of further chemotherapy and provides definite proof of a GVL effect in JMML.

Adult↗

Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation.

Hemophagocytic lymphohistiocytosis (HLH) comprises familial (primary) hemophagocytic lymphohistiocytosis (FHL) and secondary HLH (SHLH), both clinically characterized by fever, hepatosplenomegaly, and cytopenia. FHL, an autosomal recessive disease invariably fatal when untreated, is associated with defective triggering of apoptosis and reduced cytotoxic activity, resulting in a widespread accumulation of T lymphocytes and activated macrophages. In 1994 the Histiocyte Society initiated a prospective international collaborative therapeutic study (HLH-94), aiming at improved survival. It combined chemotherapy and immunotherapy (etoposide, corticosteroids, cyclosporin A, and, in selected patients, intrathecal methotrexate), followed by bone marrow transplantation (BMT) in persistent, recurring, and/or familial disease. Between July 1, 1994, and June 30, 1998, 113 eligible patients aged no more than 15 years from 21 countries started HLH-94. All had either an affected sibling (n = 25) and/or fulfilled the Histiocyte Society diagnostic criteria. At a median follow-up of 3.1 years, the estimated 3-year probability of survival overall was 55% (95% confidence interval +/- 9%), and in the familial cases, 51% (+/- 20%). Twenty enrolled children were alive and off therapy for more than 12 months without BMT. For patients who received transplants (n = 65), died prior to BMT (n = 25), or were still on therapy (n = 3), the 3-year survival was 45% (+/- 10%). The 3-year probability of survival after BMT was 62% (+/- 12%). HLH-94 is very effective, allowing BMT in most patients. Survival of children with HLH has been greatly improved.

Adolescent↗

Cross cultural research in palliative care.

Hospices within Australia, such as the Sacred Heart Hospice (SHH) at Darlinghurst, have over many years proven to be highly successful in meeting the needs of persons who require palliative care and addressing the concerns raised by their families. However, health professionals have increasingly recognised that caring for persons who are from a Non-English Speaking Background (NESB) and for their families requires giving them special consideration because of their different cultural needs. This project involved reviewing all inpatient files of the SHH over a three year period (1 October 1994 to 30 September 1997) and quantitatively reviewing all inpatient files of NESB inpatients during this period. Following this review, the researchers coordinated a focus group that comprised various health professionals from SHH and other health and community services and representatives of four non-English speaking countries--Greece, Italy, the former USSR, and China. These countries had the highest representation of inpatients during the three-year term covered by the research project. The project identified a number of specific strategies aimed at providing a more culturally sensitive health care service to NESB inpatients.

Attitude to Death↗

Valuing biodiversity: reality or mirage?

The objective of this paper was to consider the social value of biological diversity and explore if this value could be expressed in terms of a unidimensional metric in money. Economics distinguishes between use-values and non-use-values, which are critically evaluated for valuing biodiversity. It is shown that these utility-based valuations have severe limitations as they treat species in isolation from their ecological contexts. In contrast, ecosystem ecology regards ecosystems as an integrated non-linear and nonconvex system in which ecosystem functions can be understood as a four-component cycle; exploitation, accumulation of biomass, creative destruction and renewal. Within such a cycle, ecosystems can be seen to have two properties: stability and resilience. A good proxy for resilience is the probability of extinction of species, and social value of biodiversity can be expressed as a partial ordering with this probability as an index. This approach is consistent with decision theory, of which social choice is an important component, pioneered by Arrow.

Animals↗