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D Tait

Publications and source records attributed to D Tait.

At least 37 records · Page 2Linked to original sources
PubMed2001

Influence of a vac-fix immobilization device on the accuracy of patient positioning during routine breast radiotherapy.

Continued use of basic planning and treatment techniques, in contrast to the improved methods implemented at many other anatomical sites, has emphasized the need for improved breast dosimetry. Any future technique delivering a superior three-dimensional dose distribution will be of maximum benefit if set-up errors are minimized. To determine the influence of vacuum moulded bag (vac-fix) immobilization on routine breast radiotherapy, 17 patients received half their radiotherapy fractions using our standard breast board technique and half using a vac-fix device positioned on the breast board. Treatment accuracy and reproducibility were assessed for each technique using daily electronic portal imaging and were analysed in terms of random and systematic translational and rotational displacements of treatment fields with respect to corresponding simulation images. In addition, patients completed a short questionnaire aimed at determining which technique they preferred. Results showed that random errors for the two techniques did not differ significantly. Approximately 80% of random translations recorded were less than 3 mm and 80% of random rotations were less than 1.5 degrees. Systematic errors showed some improvement with the vac-fix system. In the anteroposterior direction, approximately 80% of systematic errors were less than 4 mm for both techniques, but in the superoinferior direction the 80% point was reduced from 5.0 mm for the standard set-up to 2.7 mm for treatment in vac-fix. For rotational systematic errors, the corresponding value dropped from 1.8 degrees for the standard set-up to 1.1 degrees in vac-fix. Therefore, for many patients, additional use of a vac-fix device improved the transfer of the planned set-up from simulator to treatment unit. Additionally, answers to the questionnaire indicated that patients generally favoured the vac-fix system over use of the breast board alone. In conclusion, however, introduction of vac-fix immobilization for all patients was not thought justified as the improvements demonstrated are not likely to be clinically significant with the present treatment technique.

Breast Neoplasms↗
PubMed2000

daf-12 encodes a nuclear receptor that regulates the dauer diapause and developmental age in C. elegans.

The daf-12 gene acts at the convergence of pathways regulating larval diapause, developmental age, and adult longevity in Caenorhabditis elegans. It encodes a nuclear receptor most closely related to two C. elegans receptors, NHR-8 and NHR-48, Drosophila DHR96, and vertebrate vitamin D and pregnane-X receptors. daf-12 has three predicted protein isoforms, two of which contain DNA- and ligand-binding domains, and one of which contains the ligand-binding domain only. Mutations cluster in DNA- and ligand-binding domains, but correspond to distinct phenotypic classes. DAF-12 is expressed widely in target tissues from embryo to adult, but is upregulated during midlarval stages. In the adult, expression persists in nervous system and somatic gonad, two tissues that regulate adult longevity. We propose that DAF-12 integrates hormonal signals in cellular targets to coordinate major life history traits.

Alleles↗
PubMed2000

Allogeneic blood and bone-marrow stem-cell transplantation in haematological malignant diseases: a randomised trial.

BACKGROUND: Autologous transplantation with peripheral blood stem cells (PBSC) results in faster haematopoietic-cell repopulation than with bone marrow. We prospectively compared bone marrow and PBSC for allogeneic transplantation. METHODS: Adult HLA-identical sibling donors provided bone marrow and lenograstim-mobilised PBSC. 39 patients with malignant haematological disorders were infused with either bone marrow (n=19) or PBSC (n=20) after standard conditioning regimens in a double-blind, randomised fashion. The identity of the infused products for all patients remained masked until 1 year after the last patient had received transplantation. FINDINGS: The PBSC group had significantly faster neutrophil recovery to 0.5x10(9)/L (median 17.5 vs 23 days, p=0.002), and platelet recovery to 20x10(9)/L (median 11 vs 18 days, p<0.0001) and to 50x10(9)/L (median 20.5 vs 27 days, p=0.02) than the bone-marrow group. PBSC patients were discharged from hospital earlier than were bone-marrow patients (median 26 vs 31 days, p=0.01). At 4 weeks after transplantation, absolute lymphocytes (0.48 vs 0.63, p=0.08) and CD25 cells (0.04 vs 0.08, p=0.007) were higher in the PBSC group, and the proportion of patients with absolute lymphopenia (74% vs 33%, p=0.03) and CD4 lymphopenia (59% vs 24%, p=0.05) was significantly higher in the bone-marrow group. There was no significant difference in the occurrence of acute or chronic graft-versus-host disease and overall survival. The probability of relapse was significantly higher in the bone-marrow group than in the PBSC group (p=0.01); all five relapses occurred among bone-marrow recipients. INTERPRETATION: Our small study indicates that PBSCs are better than bone marrow for allogeneic transplantation from HLA-identical siblings in terms of faster haematopoietic and immune recovery, and have the potential to reduce disease recurrence.

Adult↗
PubMed2000

Melphalan/TBI is not more carcinogeneic than cyclophosphamide/TBI for transplant conditioning: follow-up of 725 patients from a single centre over a period of 26 years.

As there is concern regarding the high carcinogenic potential of melphalan (Mel), 725 patients with haematological malignancies who received allogeneic (n = 714) or syngeneic (n = 11) transplants over the last 26 years were followed-up to evaluate if melphalan was more likely to result in secondary malignant neoplasms (SMNs) than cyclophosphamide (Cy). Three hundred and ninety-five were treated with Cy/TBI and 330 with Mel/TBI. Twelve patients developed non-haematological SMN. Median time to develop a SMN was 7 years (range 2-17 years). Age-adjusted rate was significantly higher than in the general population (observed 12 expected 1.2, risk 10; P < 0.0001). The cumulative overall risk of developing a SMN at 2, 5, 10 and 15 years post transplant was 0.4% (95% CI 0.1-2.6%), 1.7% (95% CI 0.6-4.4%), 6.4% (95% CI 2.8-10.8%) and 6.6% (95% CI 3.4-12.4%), respectively. Even though age-adjusted rates were higher than the general population melphalan/TBI was not associated with higher age-adjusted risk than Cy/TBI (increased risk 7.9 vs 11.4; P = NS). The cumulative overall risk of SMNs was not different with CY/TBI or Mel/TBI (8/393 vs 4/363; 10 year risk 4.4%, 95% CI 1.8-10.6 vs 8.4%, 95% CI 2.9-22.9; P = NS). The risk was significantly higher with use of additional cranial or cranio-spinal irradiation (17.5% vs 2.7% at 10 years; P = 0.0241). Transplants for acute lymphatic leukaemia resulted in a higher incidence of SMNs than did transplants for other diseases (ALL: 17.4%, 95% CI 6.3-42.6%; other diseases: 3.4% (95% 1.3-8.5%, P = 0.0469). The risk of SMN for patients with chronic GVHD was 8.4% (95% CI 3.7-18.7%) as compared to 3.5% (95% CI 1-11.1%) for patients without chronic GVHD (P = NS). No factor was associated with independently increased risk in multivariate analysis. Use of melphalan and TBI for transplant conditioning does not appear to be associated with higher risk of second malignant neoplasms than cyclophosphamide and TBI.

Adolescent↗
PubMed2000

Autologous bone marrow transplantation for childhood acute lymphoblastic leukaemia in second remission - long-term follow-up.

From 1984 to 1996, 31 consecutive children without sibling donors, aged 5-19 years (median 8) with acute lymphoblastic leukaemia (ALL) in second complete remission (CR), received unpurged autologous bone marrow transplantation (ABMT) after melphalan and single fraction total body irradiation (TBI). ABMT was performed using fresh unmanipulated marrow harvested after standard reinduction and consolidation therapy 2-11 months (median 5) after relapse. With a median survival of 2.9 years the probability of survival for all patients in continuing second CR was 45.1% (95% CI, 24%-62%) after 5 years. Regimen-related and non-leukaemia mortality was 7% (95% CI, 2%-26%). The longest time to second relapse from ABMT was 3.1 years. Pituitary and gonadal dysfunction requiring hormonal replacement therapy occurred in the majority of long-term survivors. Twelve patients developed cataracts. ABMT with melphalan/single fraction TBI has proved an effective anti-leukaemia treatment with low regimen-related mortality but significant long-term morbidity. The current approach of allogeneic BMT from an unrelated donor when no sibling donor is available, following conditioning with cyclophosphamide/ fractionated TBI has resulted in a reduced relapse rate and improved short-term overall survival in the treatment of relapsed childhood ALL. However, long-term results are awaited.

Adolescent↗
PubMed2000

A low CD34+ cell dose results in higher mortality and poorer survival after blood or marrow stem cell transplantation from HLA-identical siblings: should 2 x 10(6) CD34+ cells/kg be considered the minimum threshold?

We studied the effect of the CD34+ cell dose on transplant-related mortality (TRM) and survival in 39 patients randomized to receive lenograstim-mobilized PBSCT (n = 20) or BMT (n = 19) from HLA-identical siblings. Both marrow and blood were harvested, and one infused in a double-blind fashion. The median nucleated (7.0 vs 3.2 x 10(8)/kg; P < 0.0001), CD34+ (3.7 vs 1.5 x 10(6)/kg; P = 0.002), CFU-GM (42 vs 19 x 10(4)/kg; P = 0.002), and CD3+ (1.9 vs 0.3 x 10(8)/kg; P < 0.0001) cell doses with PBSCT were higher. Thirteen patients (6 BMT and 7 PBSCT) experienced TRM at 15-733 days (median 57); 10 of 20 receiving <2 x 10(6) CD34+ cells/kg compared with three of 19 receiving > or =2. Eight of 20 patients receiving <2 x 10(6) CD34+ cells/kg are alive compared with 14 of 19 receiving > or =2. In Cox analysis, CD34+ cell dose > or =2 x 10(6)/kg was associated with lower TRM (RR 0.2, P = 0.01), and higher overall (RR 3.7, P = 0.01) and event-free (RR 3.2, P = 0.02) survival. Other cell populations and the source of stem cells did not affect TRM or survival. We conclude that 2 x 10(6) CD34+ cells/kg may be the ideal minimum cell dose for allogeneic transplantation although lower doses do not preclude successful therapy. Since the likelihood of obtaining this threshold CD34+ cell number is significantly greater from blood than marrow, PBSCT may be preferable to marrow for allografts from HLA-identical siblings.

Adolescent↗
PubMed2000

A patient with 17 primary tumours and a germ line mutation in TP53: tumour induction by adjuvant therapy?

We report the case history of a woman with a germ line mutation in the TP53 gene who developed 17 separate primary tumours. The incidence of new tumours rose steeply after adjuvant tamoxifen treatment for breast cancer and adjuvant vaginal vault radiotherapy for endometrial cancer. This increase could be due to cumulative genetic damage from environmental agents and the fact that the patient lived to the relatively late age of 60 years, or to a high inherent deleterious somatic mutation rate, which could represent the inability of cells from patients with TP53 mutations to repair therapy-induced genetic damage.

Antineoplastic Agents, Hormonal↗
PubMed2000

Effectiveness of a bed positioning program for treating older adults with knee contractures who are institutionalized.

BACKGROUND AND PURPOSE: Although contractures in patients in long-term care institutions are an important issue, there have been only a few studies that have evaluated interventions for contractures. The purpose of this study was to determine the effectiveness of a bed positioning program (BPP) for the treatment of patients with knee flexion contractures. SUBJECTS: Sixteen patients with a high level of cognitive and functional impairment (mean age=82 years, SD=6.48, range=71-93) in a chronic care hospital participated in the study. METHODS: The BPP consisted of stretching a patient's knee into extension and then securing and maintaining the position for a period of 40 minutes, 4 times per week. Participants were randomly assigned to 2 groups (n=8 in each group). One group received a BPP for 8 weeks, followed by 8 weeks of no intervention. The other group received the intervention in the reverse order. Once a week, participants were assessed for range of knee extension, knee pain, and skin integrity. RESULTS: Twelve participants completed the study. There was no improvement in participants' range of knee extension during the intervention period. Overall, there was no difference in mean range of knee extension between the intervention period and the no-intervention period. CONCLUSION AND DISCUSSION: The results of this study do not support the use of a BPP for treating patients with knee flexion contractures.

Aged↗
PubMed2000

Metastatic paraganglioma causing spinal cord compression.

We describe two cases of metastatic retroperitoneal paraganglioma associated with extradural spinal cord compression. Both occurred in young men; one being metastatic at presentation, the other becoming metastatic 19 years after attempted surgical resection. Despite a long, relatively stable natural history after diagnosis (10 and 19 years, respectively) both had an acceleration of their disease once extradural disease was detected. These cases illustrate the potentially aggressive nature of this disease, the need for long-term follow-up and the effectiveness of a variety of therapies for palliation, and also raise the possibility of "prophylactic" treatment to prevent spinal cord compression.

Adolescent↗
PubMed1999

Comparison of radiation side-effects of conformal and conventional radiotherapy in prostate cancer: a randomised trial.

BACKGROUND: Radical radiotherapy is commonly used to treat localised prostate cancer. Late chronic side-effects limit the dose that can be given, and may be linked to the volume of normal tissues irradiated. Conformal radiotherapy allows a smaller amount of rectum and bladder to be treated, by shaping the high-dose volume to the prostate. We assessed the ability of this new technology to lessen the risk of radiation-related effects in a randomised controlled trial of conformal versus conventional radiotherapy. METHODS: We recruited men with prostate cancer for treatment with a standard dose of 64 Gy in daily 2 Gy fractions. The men were randomly assigned conformal or conventional radiotherapy treatment. The primary endpoint was the development of late radiation complications (> 3 months after treatment) measured with the Radiation Therapy and Oncology Group (RTOG) score. Indicators of disease (cancer) control were also recorded. FINDINGS: In the 225 men treated, significantly fewer men developed radiation-induced proctitis and bleeding in the conformal group than in the conventional group (37 vs 56% > or = RTOG grade 1, p=0.004; 5 vs 15% > or = RTOG grade 2, p=0.01). There were no differences between groups in bladder function after treatment (53 vs 59% > or = grade 1, p=0.34; 20 vs 23% > or = grade 2, p=0.61). After median follow-up of 3.6 years there was no significant difference between groups in local tumour control (conformal 78% [95% CI 66-86], conventional 83% [69-90]). INTERPRETATION: Conformal techniques significantly lowered the risk of late radiation-induced proctitis after radiotherapy for prostate cancer. Widespread introduction of these radiotherapy treatment methods is appropriate. Our results are the basis for dose-escalation studies to improve local tumour control.

Follow-Up Studies↗
PubMed1999

Intermediate term results of total lymphoid irradiation for the treatment of non-specific graft dysfunction after heart transplantation.

BACKGROUND: A proportion of heart transplant recipients develop poor graft function in the absence of cellular infiltrate in endomyocardial biopsies or transplant associated coronary artery disease. The condition has a poor prognosis and its aetiology is poorly understood. We report encouraging intermediate term results with total lymphoid irradiation (TLI) in the management of this condition. METHODS: Eleven adult cardiac transplant recipients who developed severe allograft dysfunction (NYHA class-4) at a median period of 4 months after orthotopic heart transplantation were successfully treated with TLI. Endomyocardial biopsies and coronary angiography were normal in each patient and biventricular failure developed in spite of immunosuppression with Cyclosporin-A, Azathioprine, oral Prednisolone, Cyclophosphamide and intravenous Methylprednisolone therapy. Total lymphoid irradiation was given with standard Mantle and inverted Y-fields over ten treatments to achieve a cumulative dose of 8 Gy. RESULTS: Each patient had a significant improvement in clinical response and in ventricular performance within 2 months of commencing TLI. Nine patients are currently well (four NHYA class-1, five NHYA class-2) at 4-48 (median 26) months following TLI. Two patients died; one from bacterial septicaemia and one as a consequence of chronic renal failure. Three patients developed opportunistic infection which was successfully treated with appropriate antimicrobial agents. An Ebstein-Barr virus associated lymphoproliferative disorder occurred in one patient and was successfully treated by reduction in immunosuppression and high dose Acyclovir. Two patients developed transient bone marrow suppression. CONCLUSION: The intermediate term results of TLI in the management of poor graft function in cardiac transplant recipients with normal endomyocardial biopsies and coronary angiography are encouraging. Although complications of opportunistic infection, bone marrow suppression and lymphoproliferative disorder occurred, treatment was successful in each case.

Adult↗
PubMed1999

Impact of previous high-dose therapy on outcome after allografting for multiple myeloma.

We describe a single centre experience of 33 patients allografted for multiple myeloma, of which 28 received matched sibling marrow, one haploidentical family donor marrow and four matched but unrelated donor marrow. Median follow-up after transplant is 27 months, and 13 patients are currently alive. One out of four patients with an unrelated donor survives and 12 out of 28 (42.8%) with matched sibling donors. Four patients were unevaluable because of early death (<day 21), and one patient experienced graft failure. The probability of overall survival is 35.7 % at 3 years. The probability of disease-free survival is 39% at 3 years, and the probability of treatment-related mortality is 54% at 1 year. Acute GVHD developed in 26 (78.8%) patients and was responsible for six deaths. Twenty-four patients (72.7%) developed renal dysfunction and 22 (66.7%) developed hepatic dysfunction. Seventeen patients (51.5%) died of transplant-related problems in the first 150 days, and one at 6 months. Among the 13 survivors, none has experienced disease progression at a median follow-up of 27 months (range 3-65 months). We conclude that since allogeneic bone marrow transplantation is the only potentially curative option in myeloma, it should be offered to younger patients early in the course of their disease, when procedure-related morbidity and mortality are likely to be at their lowest.

Adult↗
PubMed1999

Recombinant tissue plasminogen activator (rtPA) for the treatment of hepatic veno-occlusive disease (VOD).

Seventeen patients who developed hepatic veno-occlusive disease (VOD) following hematopoietic stem cell transplantation were treated with recombinant tissue plasminogen activator (rtPA) with or without heparin. rtPA was started a median of 13 days post transplant (range 4-35). All patients received rtPA at a dose of 10 mg/day as a starting dose, and 12 patients also received heparin (1500 U bolus; then 100 U/kg/day as a continuous i.v. infusion). The median number of days of rtPA therapy was 2.5 (1-12). The median total serum bilirubin level was 116 mmol/l (range 63-194) at the beginning of treatment. Six patients showed a response to rtPA treatment (29%). It was observed that by day 2 of rtPA therapy, bilirubin levels in responders showed a downwards trend as compared to those in nonresponders. In all except one patient this response was observed after two doses of rtPA. Seven out of the 11 non-responders had a past history of liver dysfunction, compared with none of the responders. There were no differences between the two groups in terms of day of onset of liver dysfunction, manifestations of disease, maximum bilirubin and creatinine levels, and day of commencing treatment. No patient experienced severe hemorrhagic complications during therapy. Four responders survived for more than 100 days compared to none of the non-responders. Probability of survival was 33% at day 100. It is difficult to unequivocally establish the role of rtPA in the treatment of VOD. The importance of bilirubin levels on days 2 or 3 of therapy in predicting outcome should be established, as should the optimum dose of rtPA and optimum duration of therapy.

Adult↗
PubMed1999

Comparison of proton therapy and conformal X-ray therapy in non-small cell lung cancer (NSCLC).

This study compares the performance of one proton and four conformal X-ray planning techniques in treating non-small cell lung cancer (NSCLC). The treatment volumes for 13 NSCLC patients undergoing radical radiotherapy were planned using the five different techniques and dose-volume histograms (DVH) were used extensively in the comparative analysis. The minimum dose to the phase 2 target volume was escalated to 90 Gy, or until the point at which pre-set tolerance limits of spinal cord or lung were exceeded. The proton plan could treat nine of the 13 patients up to a dose of 90 Gy. Among the four X-ray techniques, performance varied enormously. One of them could not treat any of the patients, even to the conventional 60 Gy level, without failing to meet one or more of the criteria, whilst another one could treat 10 out of the 13 patients, although with this technique only four were permitted to have the dose escalated to 90 Gy. It was also found that two of the 13 patients could not be treated by any of the proton or X-ray plans to the conventional level, and were therefore considered unsuitable for radical radiotherapy. Various issues in conformal NSCLC radiotherapy including organ movement, tumour control, other possible organs at risk etc., are also discussed.

Carcinoma, Non-Small-Cell Lung↗
PubMed1998

Ataxin-3 is transported into the nucleus and associates with the nuclear matrix.

It has been reported that the ataxin-3 protein containing a polyglutamine sequence in the pathological range (61-84Q) is localized within the nucleus of neuronal cells, whereas ataxin-3 with a normal repeat length (12-37Q) is predominantly a cytoplasmic protein. In this study, the subcellular localization of the full-length ataxin-3 protein with a glutamine sequence in the normal range (Q3KQ22) was analysed in two mammalian cell lines. Using two affinity-purified polyclonal antibodies raised against the N- or C-terminal portion of ataxin-3, the protein was detected predominantly, but not exclusively, in the nucleus of COS-7 as well as neuroblastoma cells by immunofluorescence and confocal laser scanning microscopy (CLSM). The distribution of the protein in these cellular compartments was confirmed by biochemical subcellular fractionations. Furthermore, CLSM revealed that the ataxin-3 protein present in the nucleus of neuroblastoma cells is associated with the inner nuclear matrix. Our results taken together with the finding of a nuclear localization signal in ataxin-3 indicate that the ataxin-3 protein per se translocates to the nucleus and that an expanded glutamine repeat is not essential for this transport.

Animals↗
PubMed1998

A comparison of conventional and conformal radiotherapy of the oesophagus: work in progress.

A retrospective treatment planning study was carried out in five patients to assess the effectiveness of conformal radiotherapy of the oesophagus. A two-phase conventional treatment plan was created for each patient, with a prescribed dose of 55 Gy. This plan was compared with a single-phase conformal plan consisting of the same field arrangement as the second phase of the conventional treatment, but with conformal blocks shaped to the beam's eye view of the planning target volume. A further comparison was made between the conventional plan and a two-phase plan using the same beam angles and weights as the conventional plan, but with conformal field shapes. The effectiveness of each treatment plan was assessed using dose--volume histograms and normal tissue complication probabilities for the lungs. On average, the single-phase conformal technique increased the mean lung dose from 22.5% (+/- 6.2 SD) of the prescribed dose to 29.5% (+/- 5.2 SD) compared with the conventional technique (p = 0.0001). This indicates that this technique did not offer any benefit in terms of reducing the risk of pneumonitis. However, the two-phase conformal technique reduced the mean lung dose from 22.5% (+/- 6.2 SD) of the prescribed dose to 19.8% (+/- 4.6 SD)(p = 0.03), showing that this technique should reduce the risk of pneumonitis. Further work is underway to study more patients and to investigate tumour control probability and dose escalation.

Antimetabolites, Antineoplastic↗