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Biomedical subjects

J Cavenagh

Publications and source records attributed to J Cavenagh.

17 recordsLinked to original sources

Mental health and other clinical correlates of euthanasia attitudes in an Australian outpatient cancer population.

A majority of patients with cancer have been reported to endorse euthanasia and physician assisted suicide (PAS) in general and a substantial proportion endorse these for themselves. However, the potential influence of mental health and other clinical variables on these decisions is not well understood. This study of 228 outpatients attending an oncology clinic in Newcastle, Australia used a cross-sectional design and logistic regression modelling to examine the relationship of demographic, disease status, mental health and quality of life variables to attitudes toward euthanasia and PAS. The majority reported support for euthanasia (79%, n=179), for PAS (69%, n=158) and personal support for euthanasia/PAS (68%, n=156). However, few reported having asked their doctor for euthanasia (2%, n=5) or PAS (2%, n=5). Three outcomes were modelled: support for euthanasia was associated with active religious belief (adjusted odds ratio (AOR) 0.21, 95% CI: 0.10-0.46); support for PAS was associated with active religious belief (AOR 0.35, 95% CI: 18-0.70) and recent pain (AOR 0.87, 95% CI: 0.0.76-0.99); and personal support for euthanasia/PAS was associated with active religious belief (AOR 0.26, 95% CI: 0.14-0.48). Depression, anxiety, recent suicidal ideation, and lifetime suicide attempt were not independently associated with any of the three outcomes modelled.

Adolescent↗

Neuropathic pain: are we out of the woods yet?

Patients suffering from neuropathic pain continue to pose challenges in clinical practice. This descriptive review discusses the continuing debate on the definition and concerns about increasing incidence of neuropathic pain. The clinical features of neuropathic pain are outlined, and the current understanding of the possible mechanisms of neuropathic pain is highlighted. Current management strategies are reviewed, and future advances in our understanding of the mechanisms, accurate clinical diagnosis and more effective treatment strategies are eagerly awaited.

Analgesics↗

Management of chronic myeloid leukaemia in relapse following donor lymphocyte infusion induced remission: a retrospective study of the Clinical Trials Committee of the British Society of Blood & Marrow Transplantation (BSBMT).

Donor lymphocyte infusion (DLI) can restore remission in a high percentage of patients with chronic myeloid leukaemia (CML) who relapse after allogeneic stem cell transplant (SCT). Subsequent relapses after a DLI-induced remission do occur and the optimal management of these patients is not defined. A retrospective study of the practice of UK transplant centres was conducted. In all, 13 patients from seven centres were identified: all were treated for relapse post allogeneic SCT with DLI and achieved either a complete cytogenetic (n=5) or molecular (n=8) remission. All patients subsequently had a second relapse, at molecular (n=7), cytogenetic (n=4) and haematological (n=2) levels. Further DLI was used in the treatment of 11 patients, imatinib mesylate in three and chemotherapy in two. The two patients with haematological relapse died of blastic disease. The remaining 11 patients achieved either a complete cytogenetic (n=2) or molecular (n=9) remission. Nine patients remain in molecular remission at a median follow-up of 29 months, seven of whom had received DLI alone as treatment for second relapse, one DLI plus imatinib and one imatinib alone. Toxicity following DLI for second relapse was low. Longer follow-up will be required to see if these second DLI-induced remissions will be durable.

Adult↗

Analysis of outcome following allogeneic haemopoietic stem cell transplantation for myeloma using myeloablative conditioning--evidence for a superior outcome using melphalan combined with total body irradiation.

We have undertaken a retrospective multicentre analysis of 139 patients (median age 44.4 years) undergoing allogeneic haematopoietic stem cell transplantation (HSCT) for multiple myeloma using myeloablative conditioning. The majority of patients received total body irradiation (TBI) combined with either melphalan (56.9%) or cyclophosphamide (28.5%). Overall, transplant-related mortality (TRM) was 37.9% at 1 year and was not significantly different for patients receiving melphalan/TBI compared with cyclophosphamide/TBI. The overall complete remission (CR) rate, including patients in CR at the time of transplant, was greater for patients receiving melphalan/TBI (64.7%) compared with cyclophosphamide/TBI (47.2%)(P = 0.085). A significantly higher proportion of patients with continuing disease at the time of transplant achieved CR post-transplant following melphalan/TBI conditioning compared with cyclophosphamide/TBI (52.9% and 33.4% respectively, P = 0.009). Relapse/progression rates at 5 years were significantly lower for melphalan/TBI (36.7%) compared with cyclophosphamide/TBI (80.8%, P < 0.0001) and remained significant in multivariate analysis. This resulted in an overall survival at 5 years of 44.1% and 28.1% for melphalan/TBI and cyclophosphamide/TBI, respectively (P = 0.059). These results demonstrate that the type of conditioning for sibling allogeneic HSCT for myeloma has a major effect on transplant outcome.

Adult↗

Hepatitis-associated aplastic anaemia treated successfully with antilymphocyte globulin.

Aplastic anaemia may occur following an acute attack of hepatitis. This is a rare condition, which if not recognized and promptly treated, may be fatal. Antilymphocyte globulin and allogeneic bone marrow transplantation have been used in the treatment of this condition. We report the case of a young man who developed severe aplastic anaemia following nonviral hepatitis.

Adult↗

Effects of opioids and sedatives on survival in an Australian inpatient palliative care population.

AIMS: To assess whether opioid and sedative medication use affects survival (from hospice admission to death) of patients in an Australian inpatient palliative care unit. BACKGROUND: Retrospective audit. Newcastle Mercy Hospice--a tertiary referral palliative care unit. All patients who died in the hospice between 1 February and 31 December 2000. METHODS: Length of survival from hospice admission to death, and the median and mean doses of opioids and sedatives used in the last 24 h of life. Comparison of these with published studies outside of Australia. RESULTS: In this study, the use of opioids, benzodiazepines and haloperidol did not have an association with shortened survival and the only statistical significant finding was an increased survival in patients who were on 300 mg/day or more of oral morphine equivalent (OME). The proportion of patients requiring greater than or equal to 300 mg OME/day (at 28%) was higher than published studies, but the mean dose of 371 mg OME/day was within the range of other studies. The proportion of patients receiving sedatives (94%) was higher than other studies, but the median dose of parenteral midazolam equivalent of 12.5 mg per 24 h was lower than other studies from outside Australia. CONCLUSIONS: There was no association between the doses of opioids and sedatives on the last day of life and survival (from hospice admission to death) in this population of palliative care patients.

Aged↗

An UK myeloma forum phase II study of thalidomide; long term follow-up and recommendations for treatment.

Myeloma remains incurable with conventional treatment in the vast majority of patients. The introduction of thalidomide in 1999 for the treatment of relapsed disease offers the opportunity to treat patients who have developed myelotoxicity or who are refractory to conventional chemotherapy. The optimal schedule remains unresolved and only two studies have reported long term follow-up data. We report a phase II low dose escalation study of thalidomide with long term follow-up showing overall survival (OS) of 19 months and progression free survival (PFS) of 14 months. In addition we report on the side effects and toxicity and give recommendations for the use of thalidomide in the relapsed setting based upon these findings.

Adult↗

Anti-D immunoglobulin treatment for thrombocytopenia associated with primary antibody deficiency.

AIMS: To review our experience of anti-D immunoglobulin for immune thrombocytopenia (ITP) in patients with primary antibody deficiency. METHODS/PATIENTS: A retrospective case notes review of four Rhesus positive patients with ITP and primary antibody deficiency, treated with anti-D. Patients were refractory to steroids and high dose intravenous immunoglobulin (IVIG). Two patients were previously splenectomised. RESULTS: All patients responded to anti-D immunoglobulin. Improved platelet counts were sustained for at least three months. Side effects included a fall in haemoglobin in all cases; one patient required red blood cell transfusion. Two patients had transient neutropenia (< 1 x 10(9)/litre). CONCLUSION: Anti-D immunoglobulin may be an effective treatment for antibody deficiency associated thrombocytopenia, even after splenectomy. Anti-D immunoglobulin may have considerable clinical advantages in this group of patients, where treatments resulting in further immunosuppression are relatively contraindicated.

Adult↗

Myositis, polyserositis with a large pericardial effusion and constrictive pericarditis as manifestations of chronic graft-versus-host disease after non-myeloablative peripheral stem cell transplantation and subsequent donor lymphocyte infusion.

The clinical features of chronic graft-versus-host disease (cGVHD) following a non-myeloablative peripheral blood stem cell (PBSC) transplant may differ from those that occur after a conventional allograft. We describe a man with Hodgkin's disease refractory to chemotherapy and radiotherapy who was transplanted from an HLA-identical brother, who developed cGVHD characterised, in particular, by polymyositis, polyserositis with a large pericardial effusion and constrictive pericarditis, 1 month after donor lymphocyte infusion for relapsed disease. Constrictive pericarditis has not been previously reported after a conventional allograft, and none of these features have been reported after a non-myeloablative transplant. The course of cGVHD necessitated potent immunosuppression leading to the presumed loss of graft-versus-lymphoma (GVL) effect.

Adult↗

Interferon alpha and zidovudine therapy in adult T-cell leukaemia lymphoma: response and outcome in 15 patients.

Adult T-cell leukaemia lymphoma (ATLL) is an aggressive disease caused by the human T-lymphotropic virus 1 (HTLV-I) with a short survival. Responses to interferon alpha (IFN-alpha) and zidovudine (AZT) have been documented but not with long-term follow-up. We treated 15 ATLL patients with IFN and AZT. Eleven patients had acute ATLL, two had lymphoma and two smouldering ATLL, with progression. The main features were: organomegaly (14), skin lesions (10), high white blood cell (WBC) count (11) and hypercalcaemia (9). Eleven patients had previously received chemotherapy and one had received an autograft. At the time of the study, seven patients had progressive disease and eight were in partial or complete clinical remission. Responses (PR) lasting 2+ to 44+ months were seen in 67%; 26% did not respond (NR) and one patient was not evaluable. Hypercalcaemia predicted a poor outcome but differences were not significant. Eight of the 15 patients have died 3-41 months from diagnosis. Median survival for the 15 patients was 18 months. Survival of the NR ranged from 4 to 20 months; six PR patients are alive 8-82 months from diagnosis. The differences in survival between NR (median: 6 months) and PR (55% of patients alive at 4 years) were statistically significant (P = 0.002). In conclusion, IFN and AZT improves the outcome of ATLL patients and helps maintain responses.

Adult↗

Optimising testing for phospholipid antibodies.

AIM: To compare anticardiolipin (ACL) and anti-beta2 glycoprotein 1 (beta2gp1) enzyme linked immunosorbent assays (ELISAs) in the diagnosis of antiphospholipid syndrome (APS) and to incorporate these results into a meta-analysis of published data. METHOD: Three representative commercial ACL ELISAs and an in house beta2gp1 assay were optimised and then assessed on 124 sera from normal donors, patients with infection, or patients with APS. A Medline search was screened for papers meeting defined criteria to conduct a meta-analysis. The performance of the assays used in this study was included. RESULTS: A non-quantitative ACL assay performed at least as well as the anti-beta2gp1 assay in the diagnosis of APS. Meta-analysis confirmed that neither assay is perfect, although the anti-beta2gp1 assay had a higher specificity and lower sensitivity than the ACL assay. CONCLUSIONS: The pooled data suggest that the ACL assay is used to investigate thrombosis without overt underlying pathology and that the improved specificity of the anti-beta2gp1 assay is exploited where infection, connective tissue disease, or atheroma are present.

Antibodies, Anticardiolipin↗

Heterogeneous spectrum of mutations in the Fanconi anaemia group A gene.

Fanconi anaemia (FA) is a genetically heterogeneous autosomal recessive disorder associated with chromosomal fragility, bone-marrow failure, congenital abnormalities and cancer. The gene for complementation group A (FAA), which accounts for 60-65% of all cases, has been cloned, and is composed of an open reading frame of 4.3 kb, which is distributed among 43 exons. We have investigated the molecular pathology of FA by screening the FAA gene for mutations in a panel of 90 patients identified by the European FA research group, EUFAR. A highly heterogeneous spectrum of mutations was identified, with 31 different mutations being detected in 34 patients. The mutations were scattered throughout the gene, and most are likely to result in the absence of the FAA protein. A surprisingly high frequency of intragenic deletions was detected, which removed between 1 and 30 exons from the gene. Most microdeletions and insertions occurred at homopolymeric tracts or direct repeats within the coding sequence. These features have not been observed in the other FA gene which has been cloned to date (FAC) and may be indicative of a higher mutation rate in FAA. This would explain why FA group A is much more common than the other complementation groups. The heterogeneity of the mutation spectrum and the frequency of intragenic deletions present a considerable challenge for the molecular diagnosis of FA. A scan of the entire coding sequence of the FAA gene may be required to detect the causative mutations, and scanning protocols will have to include methods which will detect the deletions in compound heterozygotes.

Base Sequence↗

Paraproteins and monoclonal expansion of CD3+CD8+ CD56-CD57+ T lymphocytes in a patient with HIV infection.

An expansion of CD8+ lymphocytes associated with a monoclonal rearrangement of the T-cell receptor gamma locus was found in a woman with HIV-1 infection. A subpopulation of HIV-positive patients display an unusual response to HIV infection characterized by a persistent marked CD8+ lymphocytosis, the presence of which appears to be associated with an improved long-term prognosis. This condition is thought to represent a florid immune response to an ongoing viral infection which may be HIV itself, and suggests that monoclonal proliferation of CD8+ lymphocytes does not imply the presence of an underlying malignant process.

Antigens, CD↗