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Biomedical subjects

S Ashley

Publications and source records attributed to S Ashley.

At least 163 records · Page 9Linked to original sources
PubMed1991

Treatment of skeletal disease in breast cancer with clodronate.

Complications of breast cancer involving the skeleton include hypercalcaemia, bone pain and fracture. These complications arise because of progressive osteolysis which is in turn dependent on the activation of osteoclasts by tumour and host tissues. Clodronate is a powerful inhibitor of osteoclastic bone resorption which led us to evaluate its potential in metastatic breast cancer. When given intravenously it lowers serum calcium in the majority of hypercalcaemic patients. A convenient regimen is 600 mg iv as a single dose infused over several hours. We have additionally shown in a double-blind cross-over study that this regimen also has a significant effect on bone pain. This had led us to assess the longer term effects of clodronate by mouth in a prospective double-blind study of patients with established skeletal metastases. These studies are not yet complete but the agent appears to prevent hypercalcaemia and trends are emerging which indicate that the incidence of bone pain and fractures may also decrease.

Administration, Oral↗
PubMed1991

Hodgkin's disease of the liver; prognosis and possible indications for radiotherapy.

A retrospective analysis of 56 patients presenting with Hodgkin's disease involving the liver between 1970 and 1984 revealed a 10-year survival probability of 44%. The actuarial 10-year continuous progression free survival was 42%. Presentation variables predicting for relapse in the liver included hepatomegaly (P less than 0.025) or focal lesions on isotope, ultrasound or CT scan (P less than 0.01). These factors may define a context for investigation of adjuvant hepatic irradiation following chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

A randomised comparative trial of mitozantrone/methotrexate/mitomycin C (MMM) and cyclophosphamide/methotrexate/5 FU (CMF) in the treatment of advanced breast cancer.

Mitozantrone (Novantrone) has recently been incorporated into a new combination chemotherapy regimen with mitomycin-C and methotrexate (MMM) against advanced breast cancer. We have compared MMM (mitozantrone 8 mg m-2 i.v. q 3 weekly, methotrexate 35 mg m-2 i.v. q 3 weekly, mitomycin-C 8 mg m-2 i.v. q 6 weekly) with CMF (cyclophosphamide 100 mg orally, days 1-14, methotrexate 35 mg m-2 i.v., days 1 and 8, 5-FU 1,000 mg i.v., days 1 and 8, q 4 weekly), each regimen with folinic acid rescue, in a randomised trial, 29/57 evaluable patients treatment with MMM achieved an objective response (51%) compared with 33/55 treated with CMF (60%). Overall median survival was 16 months for MMM and 12 months for CMF. Subjective toxicity was low for both regimens and the only significant difference was in incidence of diarrhoea (50% for CMF vs 21% for MMM). Haematological toxicity was similar, leading to treatment delays and/or dose reductions in 35% patients with CMF vs 43% with MMM. Thrombocytopenia was significantly increased in MMM (34% vs 14%). No clinical cardiotoxicity was seen, but a significant reduction in left ventricular ejection fraction occurred in four patients on CMF vs 2 on MMM. MMM is an active, well tolerated new chemotherapy regimen for advanced/metastatic breast carcinoma with an efficacy and toxicity spectrum very similar to CMF.

Adult↗
PubMed1991

Rapid VAC high dose melphalan regimen, a novel chemotherapy approach in childhood soft tissue sarcomas.

Forty-three children with malignant soft tissue sarcomas (IRS Groups II-IV) were treated with rapid dose delivery chemotherapy protocol comprising six courses of vincristine, adriamycin and cyclophosphamide, given in most cases within 8 weeks (Rapid VAC). This was followed in 36 patients by high dose melphalan with autologous bone marrow rescue. Twenty-six patients also received irradiation to the site of primary tumour. The Rapid VAC regimen was well tolerated and largely administered as an out-patient. There was one toxic death which occurred 2 months after high dose melphalan due to a combination of infection and possible anthracycline cardiomyopathy. Stages were, (Intergroup Rhabdomyosarcoma Study (IRS) system) Group, Group II--four patients. Group III--27 patients and Group IV--12 patients; International Society of Paediatric Oncology (SIOP) staging, Stage I--11, Stage II--13, Stage III--7, Stage IV--12. Actuarial survival at 5 years for all stages is 57% and event free survival 44%. For patients with non-metastatic diseases, 62% and 53% respectively. This treatment strategy utilises the philosophy of rapid drug delivery with high dose consolidation and enables all chemotherapy to be finished within a 4 month period. In general, a conservative approach was applied to both radiation and surgery to minimise late sequelae related to these treatment modalities. Although the small number of high risk patients in this study limits conclusions regarding efficacy in these subgroups the overall results with this regimen appear to be comparable to that with other approaches.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Fine needle aspiration cytodiagnosis as a pre-requisite for primary medical treatment of breast cancer.

The accurate non-surgical diagnosis of breast lumps allows assessment of breast cancer patients for conservation or neoadjuvant primary treatment before surgical intervention. We have analysed the accuracy of clinical assessment, fine needle aspiration cytology (FNAC), and mammography in over 868 women seen in a symptomatic breast clinic. Clinical examination by an experienced breast physician, together with FNAC, detected over 99% of the cancers with a 12% false positive rate. A cytological diagnosis of definite carcinoma was obtained in 69% of women with breast cancer with no false positive result from the women with benign conditions producing a 100% positive predictive value. These results indicate that it would be acceptable to give pre-surgical systemic endocrine or chemotherapy to women with positive cytology which is therefore a prerequisite for a neoadjuvant therapy programme.

Biopsy, Needle↗
PubMed1990

Thermal characteristics of sapphire contact probe delivery systems for laser angioplasty.

Contact probes made from synthetic sapphire crystal, designed for general laser surgery, are currently being evaluated for use in laser angioplasty. Their mode of action and safety in the context of arterial recanalisation is unknown, particularly with respect to the degree of probe and catheter heating. Infrared thermal imaging was used to investigate the surface temperature rise of various rounded sapphire probes during emission of continuous wave Nd-YAG (1,064 nm) laser energy. Catheter safety was addressed by analyzing the temperature of the metal interface between the optical fiber and sapphire, as well as the catheter proximal to this junction. Transmission of Nd-YAG energy through each probe was also measured. Five rounded probes of 1.8-3.0 mm diameter (three supplied by Surgical Laser Technologies [SLT], two by Living Technology [LT]), along with their respective optical catheters, were compared. There was a large temperature gradient between the front and rim of the probes. The maximum surface temperature rise of the sapphire (at 20 W, 5-second exposure) was 314-339 degrees C (SLT) and 90-108 degrees C (LT) [P less than 0.001, 3-way ANOVA]. The reason for this difference may be related to "crazing" of the front surface of the SLT sapphires. At all energy levels sapphire temperatures were considerably lower than attained by metal laser thermal angioplasty probes. Forward transmission was slightly higher in the SLT probes (75-85%) than the LT sapphires (54-69%). With fiber perfusion at 2 ml/minute, a minor degree of heating of the metal sapphire holders was recorded (maximum rise 35 degrees C), but heating of the catheter proximal to this was negligible. Therefore, it would appear that the risk of tip detachment or arterial injury due to heating of the connecting metal interface is extremely low. Without perfusion, however, there was a greater degree of interface heating in the LT delivery system suggestive of more laser backscattering by these sapphires compared with the SLT probes [P less than 0.001, one-way ANOVA]. The SLT system is, therefore, potentially safer in this respect. These results suggest that some degree of surface heating of contact probes due to energy absorption within the sapphire does occur, but is localised to the front of the probe. This effect may contribute to the process of arterial recanalisation with this device. However, variation in the thermal and optical properties of sapphires from different sources has been demonstrated. The influence of these properties on plaque ablation, and ultimately the clinical performance of different contact probe systems, requires further investigation.

Humans↗
PubMed1990

Immunohistochemical distribution of c-erbB-2 in in situ breast carcinoma--a detailed morphological analysis.

An immunohistochemical study of c-erbB-2 expression was carried out on in situ (non-invasive) breast carcinoma, using antibody 21N, raised to the intracytoplasmic domain of the c-erbB-2 oncogene product. Strong membrane staining was observed in 44 out of 74 (59 per cent) cases of ductal carcinoma in situ (DCIS), but none of 48 lobular carcinoma in situ (LCIS) lesions. A detailed comparative morphological evaluation using several different parameters, including histological subtypes, was performed within the DCIS group. The results showed that there was a significant correlation between c-erbB-2 expression and the presence of large cell size, periductal lymphoid cell infiltration, marked nuclear pleomorphism, multinucleation, and a high mitotic rate. Of these, cell size appears to be the most important predictor of c-erbB-2 status, followed by the presence of periductal lymphoid cell infiltration. These results indicate, firstly, that LCIS and DCIS are biologically (as well as histologically) different and, secondly, that a subgroup of DCIS, which is associated with c-erbB-2 over-expression, exists and appears to have distinct histological features. The subgroup of DCIS cases which over-express c-erbB-2 may be a biologically definable category with prognostic importance. These results may therefore have relevance to breast screening programmes, but a larger study incorporating clinical data would be necessary to correlate these findings with clinical outcome.

Analysis of Variance↗
PubMed1990

Aneurysm formation after dynamic catheter assisted balloon angioplasty.

A male patient underwent recanalisation of a symptomatic popliteal artery occlusion using a dynamic angioplasty catheter, followed by balloon dilatation. A small subintimal dissection lead to an acute reocclusion. Repeat balloon angioplasty reopened the occlusion but was complicated by a distal embolus which was successfully treated by thrombolytic therapy followed by oral anticoagulation. Angiography 9 months later, demonstrated an aneurysm at the site of initial dissection. The artery remained patent and the patient free of claudication. A causal relationship between dynamic angioplasty and subsequent aneurysm formation is suggested and the possible predisposing factors discussed.

Aneurysm↗
PubMed1990

A new catheter to simplify portal vein cannulation for adjuvant cytotoxic liver perfusion following resection of rectal cancer.

Evidence from randomised clinical trials suggests that adjuvant cytotoxic liver perfusion with 5-fluorouracil following resection of colorectal carcinoma may improve survival in some patients. Various methods of cannulating the portal vein or a tributary at the time of surgery have been described. We describe a simple method of accessing the portal venous circulation via a tributary in the small bowel mesentery, employing a new type of polyurethane catheter. The technical details are discussed with reference to previous literature.

Catheterization, Peripheral↗
PubMed1990

Dual tracer technique to measure salvaged red cell survival following autotransfusion in aortic surgery.

The survival of autotransfused red cells was measured for two salvage devices used in 12 elective aortic reconstructions. Six patients underwent cell salvage with the Solco-trans device and six with the Haemonetics cell saver. A double tracer technique was used to take account of post-operative blood loss and fluid replacement. Comparison was made with the results of a group of normal volunteers. A comparison was made of the labelling efficiency of damaged and undamaged red cells using chromium to check that red cells damaged during autotransfusion can be labelled. No significant difference was seen. There was no significant difference in red cell survival between the volunteer group and either of the two salvage device groups. These results suggest that red cell survival is not compromised by the autotransfusion process using these two devices.

Aortic Diseases↗
PubMed1990

Experimental analysis of sapphire contact probes for Nd-YAG laser angioplasty.

Laser angioplasty may offer percutaneous recanalization of occluded vessels where conventional guidewire and balloon techniques fail. Metal laser thermal angioplasty probes may, however, cause excessive thermal damage due to high tip temperatures (greater than 400.C). Therefore, contact probes made from artificial sapphire crystal designed for general laser surgery are currently being evaluated for use in laser angioplasty with continuous wave Nd-YAG energy. The sapphire modifies the laser energy in various ways, and this paper examines the physical characteristics of five types of rounded sapphire probe (SMTR, MTR, MTRL, OS, LT) and how these properties are affected by clinical usage. The laser beam profile emitted by these probes demonstrates a focal spot 1-2 mm in front of the tip. However, the forward transmission of Nd-YAG energy through the sapphires varied (SMTR, 85%; MTR, 83%; MTRL, 75%; OS, 54%; LT, 69%). Probe heating occurs owing to energy absorption within the sapphire. The surface temperature of the sapphires was measured in air by infrared thermography and the hottest region within the probes localized by an isothermographic technique. At energy settings used clinically (20 J, 10 watts for 2 s) the SMTR, MTR, and MTRL probes exhibited higher temperature rises (94-112.C) than the OS and LT probes (30.C), and heating was localized to the front surface of the former probes. Peak sapphire temperatures remained lower than those of metal probes even at higher energies. After clinical use, the MTR probe demonstrated reduced transmission, beam defocusing, and increased heating, due to surface pitting. Thus, recanalization with sapphire probes occurs by a combination of photothermal and contact thermal effects that are localized to the probe tip and may reduce the degree of thermal injury associated with metal probes. Understanding these basic properties is important to the application and development of contact probes for laser recanalization.

Aluminum↗
PubMed1990

Hypercalcaemia in patients with disseminated breast cancer.

Ninety-three patients with breast cancer and elevated serum calcium (Ca) had a median survival of 8.5 months from the diagnosis of hypercalcaemia. The presence of symptoms, visceral disease and level of serum Ca were independent prognostic indicators for survival on multivariate analysis. Patients without symptoms, no evidence of visceral disease and Ca less than or equal to 3.0 mmol/l had the best prognosis (median survival 3.5 years) when compared to patients with one adverse prognostic feature (median survival 16 months); two or more unfavourable features identified the worst prognostic category (median survival 2.5 months). Future studies of hypercalcaemia in malignancy should assess the influence of treatment on survival as well as symptom control and should take into account disease related prognostic factors in addition to the level of serum calcium.

Adult↗
PubMed1989

Clinical, radiological and cytological diagnosis of breast cancer in young women.

In women over the age of 35 years, an accurate diagnosis of breast cancer can be made in over 95 per cent of patients using a 'triple assessment' system collating information from clinical examination, mammography, sonomammography, and fine-needle aspiration cytology. These methods have not been specifically evaluated in women aged 35 years or less, hence a study was undertaken on 30 such patients. Clinical examination was unreliable in predicting malignancy with a sensitivity of only 37 per cent. Thirty per cent of patients presented with a lump which had the clinical features of a fibroadenoma. Radiological methods were less sensitive in detecting malignancy in this age group than in older patients. The sensitivity of aspiration cytology was 78 per cent which was higher than that for breast cancer at all ages. Histology showed that there were fewer low grade tumours and fewer scirrhous tumours in this age group than in a control group of women aged over 35 years. This study indicates that cytological confirmation of apparently benign focal breast lesions in young women is essential, especially when these are managed conservatively.

Adult↗
PubMed1989

Stage III Hodgkin's disease--long-term results following chemotherapy, radiotherapy and combined modality therapy.

215 patients with stage III Hodgkin's disease (HD) were treated at the Royal Marsden Hospital between 1963 and 1985 (median follow-up 9 years). The actuarial 5- and 10-year survival was 77 and 65%, respectively with 55 and 48% 5 and 10 year disease-free survival. Of 13 variables tested, age was the only independent prognostic indicator for survival on multivariate analysis. Patients aged under 40, 40-59 and over 60 years had a 10-year survival of 76, 41 and 8%, respectively (p much less than 0.001). Ninety-one patients were initially treated with combined chemotherapy and radiotherapy (combined modality therapy, CMT), 73 patients with radiotherapy (RT) and 51 patients with chemotherapy (CT) alone. Patients under 40 years treated with CMT achieved the best disease-free survival (10 year disease-free survival: CMT 68%; RT 38%; CT 45%). The observed survival advantage for CMT was not statistically significant. In patients aged greater than 40 there was no survival or disease-free survival advantage following CMT. Analysis of recurrence pattern confirmed that CMT improves initial disease control both at previously involved and uninvolved sites. Recurrences at previously uninvolved sites continued up to 6 years following CT, up to 8 years following CMT and up to 14 years after RT alone. These results indicate that only long-term follow-up gives the true picture of stage III HD.

Adolescent↗
PubMed1989

Percutaneous video angioscopy in peripheral vascular disease.

Percutaneous video angioscopy was performed using high resolution thin angioscopes in 12 peripheral arteries in 10 patients with peripheral vascular disease, to study the intraluminal appearance before and after dynamic, laser and conventional balloon angioplasty. Clear blood free views of the whole length of artery instrumented were obtained in 10 arteries with the remaining two arteries being partially visualised. The angioscopic appearances were compared to angiography. Clinically significant findings were detected in all the arteries by angioscopy that were not found by angiography. These included thrombus in the artery and vascular sheath, intimal flaps and fractured atheroma. The angioscopic findings helped to assess the effects of angioplasty in different types of occlusion. The findings demonstrate the potential of percutaneous angioscopy as an aid to percutaneous angioplasty as well as being a powerful diagnostic procedure.

Aged↗