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Biomedical subjects

David Webb

Publications and source records attributed to David Webb.

18 recordsLinked to original sources
PubMed2007

Adolescents with acute lymphoblastic leukaemia: outcome on UK national paediatric (ALL97) and adult (UKALLXII/E2993) trials.

BACKGROUND: Adolescents with acute lymphoblastic leukaemia (ALL) have languished in the shadow of success of the outcome of therapy in childhood ALL. Their treatment has always been incorporated into either paediatric or adult clinical trials depending on the mode of referral and hence there is a need to address an age and risk specific strategy for improving the outcome of this neglected group of patients. This article has summarised the recent and updated retrospective comparative analysis of adolescents treated on the Medical Research Council (MRC) trials. This analysis adds further emphasis to the treatment approach and the merits and limitations of treatment of adolescents on paediatric and adult trials. METHODS: A retrospective comparative analysis of adolescents aged 15-17 years, treated on either MRC ALL97/revised 99 (n = 61), a randomised paediatric trial or UKALLXII/E2993 (n = 67), an adult trial, between 1997 and 2002 was undertaken. RESULT: Results suggest a trend towards a superior outcome on paediatric trials. The 5-year EFS on ALL97 was 65% (95% CI = 52-78%) and on UKALLXII/E2993 was 49% (95% CI = 37-61%; P = 0.01). Multivariate analysis allowing for age and Ph status, diminished the EFS difference, but confirmed a reduced rate of death in remission in patients managed on the paediatric protocol. CONCLUSIONS: Despite limitations in the methodology, comparative studies including our MRC study suggest a consistent advantage for adolescents managed intensively on paediatric trials. Redefining age limits with risk-based strategy and multi-centre collaboration should be considered to improve the survival of young adults.

Adolescent↗
PubMed2007

HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis.

In HLH-94, the first prospective international treatment study for hemophagocytic lymphohistiocytosis (HLH), diagnosis was based on five criteria (fever, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, and hemophagocytosis). In HLH-2004 three additional criteria are introduced; low/absent NK-cell-activity, hyperferritinemia, and high-soluble interleukin-2-receptor levels. Altogether five of these eight criteria must be fulfilled, unless family history or molecular diagnosis is consistent with HLH. HLH-2004 chemo-immunotherapy includes etoposide, dexamethasone, cyclosporine A upfront and, in selected patients, intrathecal therapy with methotrexate and corticosteroids. Subsequent hematopoietic stem cell transplantation (HSCT) is recommended for patients with familial disease or molecular diagnosis, and patients with severe and persistent, or reactivated, disease. In order to hopefully further improve diagnosis, therapy and biological understanding, participation in HLH studies is encouraged.

Diagnosis, Differential↗
PubMed2006

The cyclic nucleotide-gated calmodulin-binding channel AtCNGC10 localizes to the plasma membrane and influences numerous growth responses and starch accumulation in Arabidopsis thaliana.

Cyclic nucleotide gated channels (CNGCs) that are regulated by calmodulin (CaM) have been shown to play essential roles in signal transduction, metabolism, and growth in animals. By contrast, very little is known about the subcellular location and the function of these channels in plants. Here we report on the effects of antisense suppression of the expression of AtCNGC10, a putative K+ channel, and the immunolocalization of the protein using an AtCNGC10-specific antiserum. In Arabidopsis thaliana leaves, AtCNGC10 was localized to the plasma membrane of mesophyll and parenchyma cells. Antisense AtCNGC10 plants had 40% of the AtCNGC10 mRNA levels and virtually undetectable protein levels relative to wild type plants. Antisense expression of AtCNGC10 did not affect the mRNA levels of AtCNGC13, the most closely related CNGC family member in the genome. Relative to wild type Columbia, antisense AtCNGC10 plants flowered 10 days earlier, and had a 25% reduction in leaf surface area, thickness and palisade parenchyma cell length. Their roots responded more slowly to gravitropic changes and the chloroplasts accumulated more starch. We propose that AtCNGC10, through interactions with CaM and cGMP, modulates cellular K+ balance across the plasma membrane, and that perturbations of this K+ gradient affect numerous growth and developmental processes.

Arabidopsis↗
PubMed2006

Adolescents with acute lymphoblastic leukaemia: emerging from the shadow of paediatric and adult treatment protocols.

Adolescents and young adults (AYA) with acute lymphoblastic leukaemia (ALL) constitute a distinct population from children and older adults. Based on patterns of referral, they may be treated by either paediatric or adult oncologists. As a group, AYA with ALL have a worse survival and event-free survival (EFS) compared to that achieved by younger children. A systematic review of all published clinical trials, which provide data on treatment and outcome of adolescents with ALL, has been summarised in an effort to determine whether they should be treated on paediatric or adult type protocols. Adolescents appear to have a consistent survival advantage when treated on paediatric regimens.

Adolescent↗
PubMed2006

Rapid diagnosis of cannula migration by cerebral oximetry in neonatal arch repair.

Although it has gained much interest in other surgical specialties, the application of near-infrared spectroscopy to assess cerebral perfusion during cardiac surgery is relatively new. Regional cerebral oxygen saturation (rSO2) is a function of cerebral oxygen supply and demand. Continuous monitoring of the rSO2 permits early detection of cerebral ischemia allowing for prompt intervention. The following is a description of a repair of truncus arteriosus with type A interrupted aortic arch during which continuous cerebral oximetry assisted with the positioning of the arterial cannula avoiding a prolonged episode of cerebral ischemia.

Aorta, Thoracic↗
PubMed2005

Congenital insensitivity to pain--review and report of a case with dental implications.

Pain is a protective mechanism for the body. Absence of pain is a symptom in several disorders, both congenital and acquired. The congenital types are present at birth and affect the number and distribution of types of nerve fibers. At present, 5 types of hereditary sensory and autonomic neuropathies have been identified. The various disorders within this group are classified according to the different patterns of sensory and autonomic dysfunction and peripheral neuropathy and the presence of additional clinical features such as learning disability. However, the field is currently moving away from classification based on clinical presentation toward classification based on underlying genetic abnormality. In the absence of pain, patients are at risk of late presentation with illnesses or injuries, and have an increased incidence of traumatic injury. Self-mutilation is an almost invariable feature of these disorders. We report the case of a patient with congenital insensitivity to pain that presented with self-mutilation injuries to his hands and oral tissues caused by biting. The severe nature of these injuries necessitated serial extraction of his primary teeth soon after eruption, which led to a cessation of the problem. The mutilation has not returned following the eruption of the first of his permanent teeth, suggesting that he has learned not to bite himself, even though to do so causes him no discomfort.

Bites, Human↗
PubMed2005

Stem cell transplantation with reduced-intensity conditioning for hemophagocytic lymphohistiocytosis.

Allogeneic stem cell transplantation (SCT) is curative for hemophagocytic lymphohistiocytosis (HLH). However, patients frequently have significant morbidity before transplantation and there is high transplant-related mortality (TRM). Because first-degree HLH is caused by immune dysregulation, a reduced-intensity conditioned (RIC) regimen might be sufficient for cure while decreasing the TRM. Twelve patients with HLH underwent RIC SCT from a matched family/unrelated or haploidentical donor. Eleven were conditioned with fludarabine/melphalan with additional busulphan for haploidentical grafts. One received fludarabine and 2-Gy total body irradiation (TBI). All patients showed engraftment at a median of 14 days. Nine of 12 (75%) are alive and in complete remission (CR) a median of 30 months (range, 9-73 months) after SCT. Two patients died from pneumonitis and one from hepatic rupture. Four patients developed acute graft-versus-host disease (GVHD) and 3 have chronic GVHD. Three of 9 survivors have mixed chimerism but remain free of disease. In summary, RIC compares favorably to conventional SCT with long-term disease control in surviving patients despite a significant incidence of mixed chimerism.

Adolescent↗
PubMed2005

A case study on easing an institutional bottleneck in aged care.

This is a case study about a cross-sector Interim Health Care Strategy (IHCS) developed by a Victorian metropolitan health service in partnership with a private residential facility and a community agency to provide a range of transitional or interim care initiatives for public hospital patients awaiting permanent residential care after completing acute or subacute treatment, Australia. The aims were to improve access to emergency and acute inpatient services, while meeting the needs of residential care clients in the metropolitan suburbs. The components included care within a residential care facility, community-based interim care and a subsequent Extended Rehabilitation Program. This IHCS has shown how a cross-sector initiative can improve care and outcomes of patients awaiting residential care placement. The case study shows how a multifaceted strategy that built upon existing relationships with strong planning, organisational commitment and a facilitating structure was successful in improving care integration.

Aged↗
PubMed2005

Haematopoietic stem cell transplantation in haemophagocytic lymphohistiocytosis.

Haemophagocytic lymphohistiocytosis (HLH) poses major therapeutic challenges, and the primary inherited form, familial haemophagocytic lymphohistiocytosis (FHL), is usually fatal. We evaluated, including Cox regression analysis, survival in 86 children (29 familial) that received HLH-94-therapy (etoposide, dexamethasone, ciclosporin) followed by allogeneic stem cell transplantation (SCT) between 1995 and 2000. The overall estimated 3-year-survival post-SCT was 64% [confidence interval (CI) = +/-10%] (n = 86); 71 +/- 18% in those patients with a matched related donor (MRD, n = 24), 70 +/- 16% with a matched unrelated donor (MUD, n = 33), 50 +/- 24% with a family haploidentical donor (haploidentical, n = 16), and 54 +/- 27% with a mismatched unrelated donor (MMUD, n = 13). After adjustment for potential confounding factors, estimated odds ratios (OR) for mortality were 1.93 (CI =0.61-6.19) for MUD, 3.31 (1.02-10.76) for haploidentical, and 3.01 (0.91-9.97) for MMUD, compared with MRD. In children with active disease after 2-months of therapy (n = 43) the OR was 2.75 (1.26-5.99), compared with inactive disease (n = 43). In children with active disease at SCT (n = 37), the OR was 1.80 (0.80-4.06) compared with inactive disease (n = 49), after adjustment for disease activity at 2-months. Mortality was predominantly transplant-related. Most HLH patients survived SCT using MRD or MUD, and survival with partially mismatched donors was also acceptable. Patients that responded well to initial pretransplant-induction therapy fared best, but some persisting HLH activity should not automatically preclude performing SCT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

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↗
PubMed2003

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↗
PubMed2003

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMed2002

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↗
PubMedDate not supplied

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↗