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Biomedical subjects

A Burton

Publications and source records attributed to A Burton.

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

Prospective randomized comparison of dacarbazine (DTIC) versus DTIC plus interferon-alpha (IFN-alpha) in metastatic melanoma.

Dacarbazine (DTIC) has been the mainstay of chemotherapy for metastatic melanoma for over two decades, but only 15%-20% of patients respond and benefit is usually transient. Randomized studies combining DTIC with interferon-alpha (IFN-alpha) in advanced disease have so far been inconclusive in terms of response and survival. We report a randomized prospective pilot Phase III trial of DTIC +IFN-alpha in patients with metastatic melanoma. The primary endpoint was death. A total of 61 patients were randomized between April 1995 and April 1998. Differences in survival between groups were assessed using log-rank analysis. Quality of life was measured using the European Organization for Research on Treatment of Cancer QLQ C30 (+3) questionnaire. Fifty-seven patients died during the study. The median survival for patients receiving DTIC was 7.2 months (95% confidence interval (CI) 4.4-9.0); it was 4.8 months for DTIC + IFN-alpha (95% CI 2.0-8.0). There was no significant difference in survival between the two treatment arms (chi2 unadjusted = 0.15, P = 0.70; chi2 adjusted = 0.01, P = 0.91). The 6-month survival of those patients randomized to DTIC alone was 58% compared with 40% for those patients randomized to DTIC + IFN-alpha. There were no differences in quality of life between treatment groups. This study failed to demonstrate a survival benefit for patients receiving IFN-alpha in combination with DTIC. These results are inconclusive primarily owing to the small size of the trial. A meta-analysis is required to determine whether there is a role for the addition of IFN-alpha to DTIC in the treatment of this disease.

Adult↗
PubMed2001

A pharmacy discharge plan for hospitalized elderly patients--a randomized controlled trial.

OBJECTIVES: to investigate the effectiveness of a pharmacy discharge plan in elderly hospitalized patients. DESIGN: randomized controlled trial. SUBJECTS AND SETTINGS: we randomized patients aged 75 years and older on four or more medicines who had been discharged from three acute general and one long-stay hospital to a pharmacy intervention or usual care. INTERVENTIONS: the hospital pharmacist developed discharge plans which gave details of medication and support required by the patient. A copy was given to the patient and to all relevant professionals and carers. This was followed by a domiciliary assessment by a community pharmacist. In the control group, patients were discharged from hospital following standard procedures that included a discharge letter to the general practitioner listing current medications. OUTCOMES: the primary outcome was re-admission to hospital within 6 months. Secondary outcomes included the number of deaths, attendance at hospital outpatient clinics and general practice and proportion of days in hospital over the follow-up period, together with patients' general well-being, satisfaction with the service and knowledge of and adherence to prescribed medication. RESULTS: we recruited 362 patients, of whom 181 were randomized to each group. We collected hospital and general practice data on at least 91 and 72% of patients respectively at each follow-up point and interviewed between 43 and 90% of the study subjects. There were no significant differences between the groups in the proportion of patients re-admitted to hospital between baseline and 3 months or 3 and 6 months. There were no significant differences in any of the secondary outcomes. CONCLUSIONS: we found no evidence to suggest that the co-ordinated hospital and community pharmacy care discharge plans in elderly patients in this study influence outcomes.

Aged↗
PubMed2001

The effects of specific retrieval instruction on social problem-solving in depression.

OBJECTIVES: We examine the proposal that social problem-solving in depression may be improved with the retrieval of specific autobiographical memories. DESIGN AND METHODS: Social problem-solving was assessed with the Means-End Problem-Solving task (MEPS; Platt & Spivack, 1975a). Depressed and non-depressed participants were required either to retrieve a specific memory prior to generating a MEPS solution (primed condition) or to report on the memories retrieved during MEPS performance after giving their MEPS solution (non-primed condition). Participants also judged whether the memories retrieved had been helpful or unhelpful for the process of solution generation. RESULTS: In both depressed and non-depressed individuals, priming increased specific memory retrieval but did not improve MEPS performance. An interaction between depression and priming revealed that priming increased the retrieval of helpful memories in the depressed sample. CONCLUSIONS: Specificity is not, in itself, a sufficient retrieval aim for successful social problem-solving. However specific memory priming may be beneficial in depression because it facilitates the recognition of memories which are helpful for problem-solving.

Adult↗
PubMed2000

Phase II clinical trials of cisplatin-then-paclitaxel and paclitaxel-then-cisplatin in patients with previously untreated advanced epithelial ovarian cancer.

PURPOSE: To examine the activity and safety of two sequentially scheduled chemotherapy regimens comprising four cycles of paclitaxel (pctx) 200 mg/m2/3 hours then four cycles ofcisplatin (cisDDP) 100 mg/m2, and vice versa, in patients with previously untreated advanced ovarian cancer. PATIENTS AND METHODS: Between January 1994 and February 1996, we recruited 30 patients to the pctx-then-cisDDP regimen and 29 to cisDDP-then-pctx, in parallel phase II trials. RESULTS: Both regimens were predictably active with responses seen in 22 of 30 patients (OR 74%; CR 27%, PR 47%) treated with pctx-then-cisDDP, as against 13 of 21 patients (OR 62%; CR 38%, PR 24%) treated with cisDDP-then-pctx. The OR rate to four cycles of pctx (induction) was 43%, with 27% disease progression; the OR to four cycles of cisDDP (induction) was 57%, with 5% progression. However, progression rates across both induction and consolidation phases were 16% (pctx-then-cisDDP) and 29% (cisDDP-then-pctx). Both regimens were unacceptably neurotoxic. II patients suffering grade 3 sensory neurotoxicity (5 on pctx-then-cisDDP, 6 on cisDDP-then-pctx) and 20 having grade 3 deafness (9 on pctx- then-cisDDP, 11 on cisDDP-then-pctx). CONCLUSION: The activity of these sequential regimens justifies their further development using the less neurotoxic platinum analogue carboplatin, perhaps combining paclitaxel with other platinum non-cross resistant drugs.

Adult↗
PubMed2000

A randomised, prospective, phase III clinical trial of primary bleomycin, ifosfamide and cisplatin (BIP) chemotherapy followed by radiotherapy versus radiotherapy alone in inoperable cancer of the cervix.

BACKGROUND: Phase II studies have shown primary (neo-adjuvant) chemotherapy with bleomycin, ifosfamide and cisplatin (BIP) is active against inoperable cervical cancer. We present here results of a randomised phase III multicentre trial comparing radical radiotherapy with neo-adjuvant BIP chemotherapy followed by radical radiotherapy in patients with inoperable cervical cancer, designed to discover whether this combination might improve survival. PATIENTS AND METHODS: Patients with inoperable cervical carcinoma were randomised to pelvic radiotherapy alone [RT] or two to three cycles of bleomycin 30 units/24-hour infusion, ifosfamide 5 g/m2/24 hours, and cisplatin 50 mg/m2) chemotherapy followed by pelvic radiotherapy (BIP + RT). Randomisation was stratified by stage and radiotherapy centre. RESULTS: One hundred seventy-two eligible women were randomised into this trial; eighty-six to RT and eighty-six to BIP + RT. A total of 190 cycles of chemotherapy were given. Median follow-up for the 47 patients still alive is 9 years with a minimum follow-up of 3 years. Complete or partial response occurred in 51 of 86 (59%) of those randomised to RT and 60 of 86 (69%) of those randomised to BIP + RT. The difference between response rates does not reach statistical significance (chi2 = 2.06, P = 0.15). Median survival is two years with an actuarial survival at five years of 32% (95% confidence interval (95% CI): 25%-39%). There is no significant difference between the treatment groups (chi2log-rank = 0.11, P = 0.74). CONCLUSIONS: This study does not show any survival benefit from the use of neo-adjuvant BIP chemotherapy in advanced cervical cancer.

Adult↗
PubMed2000

Bcl-2 expression identifies patients with advanced bladder cancer treated by radiotherapy who benefit from neoadjuvant chemotherapy.

OBJECTIVE: To assess the prognostic significance of Bcl-2 expression on the clinical outcome after radiotherapy for muscle-invasive bladder cancer, and to determine if it is possible to identify a subgroup of patients to whom neoadjuvant chemotherapy can be targeted to improve survival. PATIENTS AND METHODS: Immunohistochemical staining for Bcl-2 and p53 was performed on the tumours of 51 patients with stage T2-T4a NXM0 transitional cell carcinoma of the bladder who had been included in a randomized clinical trial of radiotherapy with or without neoadjuvant cisplatin. The association between positive staining and salvage cystectomy rate and overall survival was examined, with a median follow-up of 12 years. RESULTS: Bcl-2 and p53 expression was positive in 31 (61%) and 39 (76%) of the tumours, with no association between either, or with tumour stage or grade. There was no difference according to Bcl-2 positivity in the salvage cystectomy rate (P = 0.83) or survival (P = 0.68) for the 51 patients as a whole, but Bcl-2-negative patients receiving neoadjuvant cisplatin had a significantly better prognosis, with a median survival of 72 months compared to 17 months in Bcl-2-positive patients, and a 5-year survival rate of 55% (P = 0.03). CONCLUSIONS: Quantifying Bcl-2 in patients undergoing radiotherapy for advanced bladder cancer identifies those who may benefit from neoadjuvant chemotherapy. Further studies of other members of the Bcl-2 family and other proteins controlling both cell proliferation and apoptosis are warranted, to define the roles and the interactions between them that may contribute to oncogenesis and resistance to standard treatments. This may allow the targeting of specific treatments to patients known to be sensitive to them, and aid the future development of novel therapies for bladder cancer.

Adult↗
PubMed1999

Apoptotic and proliferative activity in the neoplastic progression of Barrett's oesophagus: a comparative study.

The balance between proliferation and apoptosis within a tissue is important in controlling its overall growth. When either or both are altered, uncontrolled cell proliferation can contribute to cancer. The aim of this study was to investigate apoptosis and proliferation in the progression from Barrett's oesophagus to adenocarcinoma. Fifty-one paraffin sections of Barrett's mucosa with both intestinal and gastric-type Barrett's mucosa, dysplasia, and adenocarcinoma, from 28 patients, were examined for apoptosis using haematoxylin and eosin (H&E)-stained sections counterstained immunohistochemically with CD45 to distinguish leucocytes from apoptotic bodies. Proliferation was detected by immunohistochemistry using the MIB-1 (Ki-67) antibody. There was an increase in proliferation in dysplastic and carcinomatous tissue compared with metaplastic tissue (p=0.0001). In dysplasia, proliferation was distributed throughout the basal-luminal axis, whereas in metaplasia, cell division was compartmentalized to the lower crypt (p<0.001). Conversely, there was a decrease in apoptosis in the upper crypt and luminal surface in dysplasia and adenocarcinoma compared with metaplasia (p<0.0008). There was a significant increase in apoptotic activity in intestinal-type Barrett's mucosa compared with gastric-type. There was a highly significant increase in the glandular proliferation to apoptosis ratio (GPAR) in the progression of metaplasia to dysplasia to adenocarcinoma (p=0.001). The shift in the GPAR in the progression of neoplastic change suggests that it may be a useful and sensitive marker of neoplastic change in Barrett's oesophagus, especially if the assessment of both apoptotic and proliferative activity in the mucosa can be made easier by more sophisticated technical methods.

Adenocarcinoma↗
PubMed1999

CD40 expression in bladder cancer.

The CD40 receptor is expressed in many immune cell types and is known to play a central role in both humoral and T-cell-mediated immunity, being a subject of intense research interest in recent years. It is also expressed on a variety of carcinomas and may therefore be of biological significance in the development and treatment of cancer. The expression of CD40 was examined immunohistochemically in a series of 131 bladder transitional cell carcinomas and the correlation with known prognostic markers and clinical outcome assessed. Seventy-eight per cent of the tumours were CD40-positive, with a highly significant association with both lower stage and lower grade (p<0.001). Ta and T1 tumours expressed CD40 in 89 per cent of specimens compared with 62 per cent seen in T2-T4 tumours and in contrast to normal urothelium, which was mainly CD40-negative. CD40 expression was not related to any other clinicopathological variable including Bcl-2 and p53 expression, nor was it an independent prognostic marker. The lack of the relationship with Bcl-2 staining which is normally seen in basal epidermal cells may indicate alternative or abnormal CD40-mediated cell differentiation mechanisms. The diffuse expression seen in Ta bladder tumours may account for its clinically less aggressive behaviour and is likely to be an important factor in the excellent clinical response seen to BCG immunotherapy. It also raises the possibility of the future development of CD40/CD40 ligand-based immunotherapy for bladder cancer.

Adult↗
PubMed1999

Prospective, double-blind, placebo-controlled randomized trial of cimetidine in gastric cancer. British Stomach Cancer Group.

Cimetidine is thought to inhibit suppressor T-lymphocyte function and preliminary evidence from a randomized trial indicated that it might prolong survival for patients with operable and inoperable gastric cancer. The British Stomach Cancer Group conducted a randomized, double-blind, placebo-controlled trial examining the effects of cimetidine (400 mg or 800 mg twice a day) on the survival of patients with early (stages I, II and III: n = 229) and advanced (stages IVa and IVb: n = 201) gastric cancer. The primary end point was death. A total of 442 patients were randomized by 59 consultants in 39 hospitals between February 1990 and March 1995. Log-rank survival analysis was used to assess differences between the groups. Three hundred and forty patients died during the study: 166 (49%) in the cimetidine treatment groups and 174 (51%) in the placebo groups. Median survival for patients receiving cimetidine was 13 months (95% confidence interval (CI) 9-16 months) and 11 months in the placebo arm (95% CI 9-14 months). There was no significant difference in survival between the two treatment groups (P = 0.42) or between different doses of cimetidine tablets (P = 0.46). Five-year survival of those patients randomized to cimetidine was 21% compared to 18% for those patients randomized to placebo. Cimetidine at a dose of 400 mg or 800 mg twice a day does not have a significant influence on the survival of patients with gastric cancer compared to placebo.

Adult↗
PubMed1999

Phase II trial of radical surgery for locally advanced pelvic neoplasia.

BACKGROUND: Reported operative mortality and survival rates following total pelvic exenteration (TPE) for recurrent pelvic neoplasia are now as good as those for many primary treatments. The currently accepted primary treatments for these tumours are, however, still either radiotherapy alone or radiotherapy and chemotherapy. The primary aim of this study was to evaluate the safety and tolerability of TPE and secondarily to ascertain survival after TPE. METHODS: This was a phase II study of 50 patients with locally advanced pelvic tumours who underwent TPE. RESULTS: Thirty-two patients (64 per cent) underwent TPE for recurrent carcinoma of the cervix, seven (14 per cent) for rectal cancer, three (6 per cent) for vulval carcinoma, three (6 per cent) for vaginal carcinoma, two (4 per cent) for prostate cancer and three (6 per cent) for other tumours. The 30-day mortality rate was 8 per cent with an in-hospital mortality rate of 16 per cent. The crude morbidity rate was 62 per cent, with 23 patients (46 per cent) having grade III or IV toxicity. A complete response was achieved in 63 per cent and a partial response in 37 per cent of patients. The overall median survival time was 86 weeks; it was 111 weeks in patients in whom a complete response was achieved. CONCLUSION: The survival and operative mortality rates that are now attainable with TPE are comparable to those achieved with chemoradiotherapy in advanced pelvic neoplasia. TPE should no longer be reserved for salvage therapy and should perhaps be compared with chemoradiotherapy as first-line treatment in a phase III randomized trial in patients with these tumours.

Adult↗
PubMed1999

Quality assurance of CFU-GM assays: inter-laboratory variation despite standard reagents.

To investigate the hypothesis that commercial kits for CFU-GM (colony forming unit granulocyte-macrophage) assay will reduce the interlaboratory variation noted by many workers, we carried out a quality assurance exercise in 2 parts. There were 8 participants in the first study and each performed CFU-GM assays using their in-house method and a commercial kit (Stem Cell CFU Kit, Gibco) in parallel. In the second exercise there were 10 participants and each performed CFU-GM with in-house methods and with a different commercial medium (Methocult GF H4534, Stem Cell Technologies). Twelve samples of cryopreserved peripheral blood progenitor cells (PBPC) were analysed by each participant in each part of the study. A very wide range of results was found for the different in-house methods, but standardizing the clonogenic assay with the commercial kits did not reduce the variation seen. To improve the reproducibility of CFU-GM assays between laboratories, scrupulous attention should be paid to all the steps involved in the assays, as little progress will be made by using commercial medium in isolation from efforts to reduce other sources of variation.

Colony-Forming Units Assay↗
PubMed1998

Everyday planning difficulties following traumatic brain injury: a role for autobiographical memory.

The present study examines the role of autobiographical memory in describing how to perform both open-ended and closed everyday activities in 12 patients suffering traumatic brain injury and 12 aged-matched controls. The frequency (high versus low) of performing the activities was also manipulated. Patients seemed less well able to benefit from using specific autobiographical memories; they reported using significantly fewer specific autobiographical memories for describing how to perform low-frequency activities and significantly more such memories for high-frequency activities compared with controls. The quality of their descriptions was also significantly poorer for the open-ended activities. Finally, significant correlations were found between the quality of the descriptions and the retrieval of specific autobiographical memories for the controls only. The importance of the retrieval of specific autobiographical memories for everyday problem-solving is discussed.

Activities of Daily Living↗
PubMed1998

Gender differences in the dual-task effects on autobiographical memory retrieval during social problem solving.

A dual-task paradigm was used to explore the effects of cognitive load on social problem solving and autobiographical memory retrieval. The role that gender may play in mediating the relationship was also examined. Participants performed a secondary task concurrently with two primary tasks: (a) a cueing task, and (b) the Means-End Problem-Solving (MEPS) Task, during which they were required to attend to the memories retrieved during solution generation. Two dual-task conditions were employed in order that two levels of secondary task difficulty could be explored. Level of difficulty proved to be an important factor in the effects of resource reduction on the two primary tasks. Retrieval during the MEPS was effected by both the easy and difficult secondary task whereas retrieval on the cueing task was affected by the difficult task only. The results also showed that females (in contrast to males) favoured a more detailed SPS style using a specific memory database. Consequently, under central executive pressure, females' performance was significantly affected while males' performance remained largely unchanged.

Adult↗
PubMed1997

Lateral advantages in same-different comparison of two-note, dichotically presented chords to a successively-presented probe.

An experiment is reported which examines same-different comparison of dichotically presented, two-tone chords to a probe. A prediction of a fast 'same' response indicative of holistic processing was tested. Stimuli and probes were systematically related by similarity relationships established in a previous experiment. No evidence was found for fast 'same' responding overall or on either ear, but a right ear advantage for the making of difficult 'different' decisions was found for accuracy. It is argued that the concepts of analytic and holistic processing may require some redefinition and a preliminary account is offered in terms of Krueger's [23] noisy operator model.

Acoustic Stimulation↗
PubMed1997

Social problem solving and autobiographical memory in non-clinical depression.

OBJECTIVES: We examine the proposal that specific autobiographical memories may play a major role in successful social problem solving (SPS). DESIGN AND METHODS: Depressed and control students report on the types of memories they retrieve while performing an SPS task and a cueing task. RESULTS: The retrieval of specific memories on the cueing task and during SPS was found to be positively related to SPS skill. CONCLUSIONS: Specific memories are important for successful SPS. However, the relationship between a specific memory deficit and poor SPS is mediated by severity of depression.

Adult↗
PubMed1997

Current status of the global eradication of poliomyelitis.

Substantial progress towards the global eradication of poliomyelitis by the year 2000 has been achieved since May 1988 when WHO Member States adopted this goal at the Forty-first World Health Assembly. Virtually all polio-endemic countries have begun to implement the WHO-recommended strategies to eradicate polio and it is expected that, by the end of 1997, all endemic countries in the world will have conducted full National Immunization Days (NID), providing supplemental oral polio vaccine (OPV) to nearly two-thirds of all children < 5 years. In contrast, although globally acute flaccid paralysis (AFP) surveillance was being conducted in 126 (86%) of 146 countries where polio is or recently was endemic, surveillance remains incomplete and untimely. A global network of polio laboratories, capable of detecting wild poliovirus when and where it occurs, has been developed. Furthermore, in countries where polio virus circulation has been limited to focal areas, and surveillance is adequate, mopping-up campaigns are being conducted to eliminate the final chains of transmission. The process for certification of polio eradication has been established in each WHO region as well as at the global level. The impact of the eradication initiative is evident, with an 88% decrease in the number of reported cases globally since 1988. In order to achieve the goal of eradication, the rapid development of complete and timely AFP surveillance and the continuation of effective NIDs constitute an urgent priority. This is of particular relevance in the remaining polio-endemic countries, especially in those that are affected by war or politically isolated and are important remaining reservoirs from where wild poliovirus continues to spread into bordering or even distant polio-free countries. External support will continue to be required by those countries and regions where the incidence of polio has reached low levels to ensure that final chains of poliovirus transmission are interrupted and to permit the eventual certification of eradication. The year 2000 objective for achieving poliomyelitis eradication remains a feasible target.

Adolescent↗
PubMed1996

Electrocardiographic changes during cesarean section: a review.

Recently, various authors have noticed and studied the phenomenon of ST segment depression during cesarean section. We have undertaken a review of the various postulated etiologies including venous air emboli, hormonal influences, autonomic nervous system influences tachycardia, postural influences, hypokalemia, hyperventilation, and myocardial ischemia. It appears that ST segment depression during cesarean section is almost certainly a multifactorial phenomenon. There is evidence that some myocardial dysfunction occurs during these episodes. Additionally, the hormonal milieu, tachycardia, and the postural component probably contribute to the phenomenon. Venous air emboli, hypokalemia, and hyperventilation probably have a minimal role. The sympatholysis produced by regional anesthesia is of unclear significance. It is important to note the apparent lack of morbidity associated with these changes.

Journal Article↗