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Biomedical subjects

S Ashley

Publications and source records attributed to S Ashley.

179 records · Page 10Linked to original sources

Changing patterns of relapse in Hodgkin's disease.

The patterns of early and late relapses (those occurring later than 3 years after diagnosis) in 432 patients achieving complete remission after treatment for stage I and II Hodgkin's disease at the Royal Marsden Hospital between 1964 and 1983 were studied to identify factors predicting for late relapse. The incidence of early relapse has fallen progressively in recent treatment eras as staging procedures and management have improved but in contrast there has been no decrease in the risk of late relapse. The incidence of late relapse was greater in patients treated with radiotherapy rather than combined modality therapy (P less than 0.05). However, patients who were clinically staged and treated with combined modality therapy retained as high a risk of relapse between 3 and 6 years as in years 2 and 3. The risk of late relapse was also greater in patients with stage II disease and in those without B symptoms at presentation. Patients falling into the higher risk categories for late relapse require continued close follow-up beyond 3 years to monitor for possible relapse.

Adolescent↗

Treatment of advanced Hodgkin's disease with high dose melphalan and autologous bone marrow transplantation.

Twenty patients with Hodgkin's disease which had relapsed at least once after chemotherapy, were treated with melphalan 140-220 mg/m2 i.v. followed by reinfusion of non-cryopreserved autologous bone marrow. Four patients (20%) remain alive and disease-free 28, 45, 52, and 96 months after treatment respectively. There were no treatment-related deaths. This appears to be the only reported series of patients treated with a single agent in this situation. The results are comparable to those achieved by multi-agent regimens with autologous or allogeneic bone marrow transplantation.

Adult↗

Patterns of breast relapse after local excision +/- radiotherapy for early stage breast cancer.

One hundred patients with breast recurrence have been identified from patients at the Royal Marsden Hospital, treated by local excision +/- radiotherapy for early stage primary invasive breast cancer between 1961 and 1985. The mean follow-up was 58 months (range 1 month - 19 years). In 74/100 patients, breast recurrence occurred within the breast parenchyma, was not associated with systemic relapse and carried a relatively good prognosis with a median survival of 77 months from the time of breast relapse. In 67 patients with parenchymal relapse in whom the site of relapse could be reliably compared with that of the original tumour, 60 (90%) patients developed recurrent tumours at or close to the primary site. In 24/100 patients, breast recurrence occurred in the overlying skin and in only two of these patients (2% of total) did recurrence actually occur within the scar tissue. Skin relapse was associated with systemic relapse and carried a relatively poor prognosis with a median survival of 36 months from the time of recurrence. The pattern of breast relapse was similar in irradiated and unirradiated patients. Skin relapse appears to be a manifestation of metastatic disease while parenchymal relapse may represent regrowth of primary tumour. This pattern of breast relapse questions the requirement for radiotherapy to the whole breast after local excision for early stage breast cancer.

Adult↗

c-erbB-2 expression in benign and malignant breast disease.

An antibody, 21N, raised against a synthetic peptide from the predicted sequence of the c-erbB-2 protein has been used immunocytochemically in a retrospective study of formalin fixed paraffin embedded breast biopsies. Fourteen out of 103 infiltrating ductal carcinomas exhibited positive membrane staining. Fifty-four of these tumours had lymph node involvement of which nine contained stained cells. These were all cases where the primary tumour was positive. In this series there was no correlation between c-erbB-2 overexpression and lymph node status. In five of the positive cases studied there was an associated in situ component which was also positively stained. Ten out of 24 pure intraduct carcinomas showed membrane staining, but none of the 149 benign conditions studied, which included 22 radial scars and 13 cases of atypical ductal proliferation, demonstrated the pattern of staining associated with overexpression. It is concluded that the c-erbB-2 protein is overexpressed in a minority (approximately 14%) of infiltrating ductal carcinomas and only in cells that are cytologically malignant. Overexpression of c-erbB-2 is considered in relation to pathogenesis.

Breast Neoplasms↗

High dose BCNU chemotherapy with autologous bone marrow transplantation and full dose radiotherapy for grade IV astrocytoma.

In a series of 22 patients, high dose BCNU (800-1,000mg m-2) with autologous bone marrow transplantation was given as the first post-surgical treatment for grade IV astrocytoma and followed by full dose radiotherapy. When compared to historical experience and matched to control patients in national studies, there appeared to be a small prolongation of survival but no increase in the proportion of long survivors. Acute myelosuppression was mild but toxicity to lung and liver was substantial and limited further dose escalation. Late bone marrow failure was seen in 4 patients. Pharmacokinetic studies were performed and suggested that the late marrow failure was due to persistence of BCNU at the time of marrow return. Despite the suggestion of a prolongation of survival this approach is not routinely recommended and a randomised trial is probably not justified.

Adult↗

Immunohistochemical localization of c-erbB-2 in human breast carcinomas.

This study was carried out to assess the utility of antibodies raised to synthetic peptides of the predicted sequence of the c-erbB-2 gene product to identify immunocytochemically those tumours overexpressing this putative transmembrane receptor. Staining with rabbit antiserum 21N gave the best correlation with gene amplification and did not stain the membrane of any of the normal tissues at the dilution which strongly stained the membrane of any of the normal tissues at the dilution which strongly stained the amplified tumours. No significant correlation was found with lymph node involvement, epidermal growth factor receptor status or with oestrogen receptor levels. Of the 12 out of 34 cases which demonstrated c-erbB-2 gene amplification in the primary tumour, two had lymph node metastases which were also positive immunocytochemically. Fourteen other cases which had lymph node metastases were negative in the primary tumour and in the metastases. These tumours all showed strong membrane positivity. A comparison of modified methacarn and formol saline fixation demonstrated an increased sensitivity with the former, but the staining pattern was unaltered. This small but extensively studied group of cases has indicated that increased c-erbB-2 protein can be identified routinely in fixed tissue sections, making it possible to carry out extensive studies to look for clinical correlates, but also to assess the stage in tumour progression at which the increased expression occurs and whether it correlates with any potentially premalignant condition.

Breast Neoplasms↗

Linkage of Pep-2 and Apk on mouse chromosome 10.

An ethylnitrosourea (ENU)-induced electrophoretic variant of mouse PEP-2, a tripeptidase, has been used to determine the location of the structural gene on chromosome 10. Gene order and recombination frequencies were estimated as Apk-21.8 +/- 3.9%-Pep-2-3.7 +/- 2.1%-Sl. Methods for rapid determination of Apk and Pep-2 alleles by cellulose acetate electrophoresis and a valuable linkage testing stock carrying the unique Apkm and Pep-2b alleles are described.

Acid Phosphatase↗

An analysis of possible prognostic features of long term and short term survivors of metastatic breast cancer.

Factors influencing the extremes of survival in disseminated breast cancer were analysed. From a pool of 1066 patients with distant metastatic breast cancer, the 41 patients who had survived 5 yr or more from first distant recurrence were matched with the 41 patients with the shortest survival times. Both groups were compared with the pool and, where relevant, with each other. There were no differences with respect to presentation clinical stage, histological subtype, adjuvant therapy or the likelihood of menopause during the disease-free interval. There were significant differences in age, menopausal status, primary treatment, grade, pathological node involvement, time to recurrence, situation and number of sites of metastatic involvement, and response to treatment. The interpretation of these relationships as causal or casual is uncertain; however, given the magnitude of the survival differences, we expected the associated differences to be much greater than we found.

Adult↗

High-dose oral medroxyprogesterone acetate in heavily pretreated patients with metastatic breast cancer.

Fifty heavily pretreated postmenopausal patients with advanced breast cancer were treated with oral medroxyprogesterone acetate (1 g) daily for 1-18 months. Eight patients (16%) responded to treatment for periods up to 18 months and in an additional eight patients (16%) the disease stabilized for up to 10 months. Thirty-two patients (64%) developed adverse effects and eight (16%), all of whom had extensive pulmonary metastases, died a respiratory-related death thought possibly to have been brought on or accelerated by treatment. Only eight patients (16%) experienced increased appetite, weight gain, feeling of wellbeing, or improved performance status. We conclude that medroxyprogesterone acetate is useful in patients with advanced metastatic disease but should be restricted to carefully selected patients and used only with extreme caution in patients with underlying cardiovascular or respiratory disease. Its major application probably lies in the benefit it confers earlier in the disease.

Adult↗

The modulating effects of flurbiprofen on adriamycin plus vincristine or vindesine in the treatment of advanced breast cancer.

To assess the modulating effects of a non-steroidal anti-inflammatory drug on chemotherapeutic agents, 183 patients with advanced breast cancer have been treated in a randomised study with flurbiprofen or placebo and adriamycin plus a vinca alkaloid. To assess the efficacy of the new vinca alkaloid, vindesine, in breast cancer, patients were further randomised to receive vindesine or vincristine. The overall response rate in evaluable patients was 57%, and the median duration of response in the different treatment groups varied from 6 to 10 months. Response rates and toxicity in vindesine- and vincristine-treated patients were similar, although with vindesine neurotoxicity was slightly lower. Flurbiprofen did not improve the response rate or reduce the toxicity of adriamycin plus vinca alkaloid.

Adult↗

Treatment of disseminated breast cancer with tamoxifen, aminoglutethimide, hydrocortisone, and danazol, used in combination or sequentially.

222 patients with disseminated breast cancer have been randomised to receive either a combination of hormone therapies using tamoxifen, aminoglutethimide with hydrocortisone, and danazol (TAD), or tamoxifen alone. The response to the combination was significantly better (43%) than that to tamoxifen alone (31%). Patients who relapsed after response or failed to respond to tamoxifen were subsequently treated with aminoglutethimide and then, if possible, with danazol. Some patients who received TAD were subsequently treated with alternative endocrine therapy, which was usually medroxyprogesterone acetate. Of the 111 patients who initially received tamoxifen, 43 responded to the tamoxifen and/or subsequent endocrine therapy. Of the 111 patients who initially received TAD, 50 responded. Although the duration of response to TAD was the same as for tamoxifen, the TAD patients achieved remission more quickly. The total time in endocrine remission for patients receiving TAD is 303 months to date, compared with 264 months for patients receiving tamoxifen. Survival for patients randomised to receive TAD or tamoxifen is the same.

Aminoglutethimide↗

Does the Kensey catheter keep a coaxial position inside the arterial lumen? An in-vitro angioscopic study.

Angioscopy was used to evaluate the "self-centering" ability of three Kensey catheters (KC) with different flexibility: one 8Fr "peripheral" and two 5Fr "coronary" (I & II). Angioscopic observations were made inside arteries, 5-18 mm in diameter. There was a good correlation between flexibility and self-centering of the KC [r = 0.83, p less than 0.05]. Increasing the flow rate of rinsing solution from 18 to 60 ml/min prolonged coaxial position from 8.9 +/- 3.3 to 36 +/- 2.2 sec/min of activation [p less than 0.001]. A smaller effect on coaxial position was exerted by increasing cam speed from 5.2 +/- 0.7 to 19.2 +/- 1.6 sec/min (p less than 0.001). In conclusion, angioscopy showed that the KC has a limited ability to maintain a coaxial position inside the arterial lumen and operators cannot rely on its self-centering property.

Angioplasty, Balloon, Coronary↗

Randomized prospective study comparing preoperative epidural and intraoperative perineural analgesia for the prevention of postoperative stump and phantom limb pain following major amputation.

BACKGROUND AND OBJECTIVES: Acute stump pain and phantom limb pain after amputation is a significant problem among amputees with a reported incidence of phantom limb pain in the first year following amputation as high as 70%. Epidural analgesia before limb amputation is commonly used to reduce postamputation acute stump pain in the immediate postoperative period and phantom pain in the first year. We investigated whether immediate postamputation stump pain and phantom pain in the first year is reduced by preoperative epidural block with bupivacaine and diamorphine compared with intraoperative placement of a perineural catheter infusing bupivacaine. METHODS: In a randomized prospective trial, 30 patients scheduled for lower limb amputation were randomly assigned epidural bupivacaine at the standard rate used in our hospital (0.166%, 2 to 8 mL/h) and diamorphine (0.2 to 0.8 mg/h) for 24 hours before and during operation (14 patients; epidural group) and 3 days postoperatively, or an intraoperatively placed perineural catheter (16 patients; perineural group) for intra and postoperative administration of bupivacaine (0.25%, 10 mL/h). All patients had general anesthesia for the amputation and were asked about stump and phantom pain in the first 3 days and then at 6 and 12 months by an independent examiner. Study endpoints were rate of stump and phantom pain, intensity of stump and phantom pain, and consumption of opioids. The groups were well matched in baseline characteristics. RESULTS: Stump pain scores in the first 3 days were significantly higher in the perineural group compared with the epidural group (P <.01). After 3 days, 4 (29%) patients in the epidural group and 7 (44%) in the perineural group had phantom pain (P =.32). Numbers of patients with phantom pain for epidural versus perineural group were: 5 (63%) versus 7 (88%) (P =.25) at 6 months; 3 (38%) versus 4 (50%) (P =.61) at 12 months. Stump pain and phantom sensation were similar in both groups at 6 and 12 months. CONCLUSIONS: Using our regimen, perioperative epidural block started 24 hours before the amputation is not superior to infusion of local anaesthetic via a perineural catheter in preventing phantom pain, but gives better relief of stump pain in the immediate postoperative period.

Aged↗