Showing papers by "David Cameron published in 2000"

Swallowing disorders following acute stroke: prevalence and diagnostic accuracy.

Abstract: We prospectively examined 128 patients with acute first-ever stroke to determine the prevalence of swallowing disorders, the diagnostic accuracy of our clinical assessment of swallowing function compa

Reduced MLH1 Expression in Breast Tumors After Primary Chemotherapy Predicts Disease-Free Survival

Abstract: PURPOSE: Loss of function or expression of the mismatch repair protein MLH1 and the tumor suppressor protein p53 have been implicated in acquired resistance to anticancer drugs. We have compared the expression of MLH1 and p53 in tumors from women with clinically node-positive breast cancer before and after primary (neoadjuvant) chemotherapy. Further, we have assessed the value of these markers as predictors of response to therapy by correlation with disease-free survival. PATIENTS AND METHODS: Immunohistochemistry scores of MLH1 and p53 expression were made on 36 tru-cut prechemotherapy biopsies and 29 paired postchemotherapy tumor samples. The significance of the change in scores and their correlation with disease-free survival were evaluated by the Wilcoxon signed rank sum test and Cox proportional hazards regression analysis, respectively. RESULTS: Primary chemotherapy results in a significant reduction in the percent of cells expressing MLH1 (P = .010). This change in MLH1 expression after chemotherap...

The effect of nitrogen partial pressure on the bonding in sputtered CNx films : implications for formation of β-C3N4

Abstract: An investigation of the bonding structure in carbon nitride films deposited by DC magnetron sputtering using a Penning-type opposed target system has been carried out. The changes in the valence band structure have been measured by XPS, UPS and EELS. The density of unpaired electrons has been measured by ESR. As the nitrogen partial pressure and the nitrogen content of the films is initially increased, the structure shows a greater degree of sp 2 bonding compared to the pure carbon samples. However, with further increases in the nitrogen partial pressure up to 100% of the sputtering gas pressure, which has very little effect on the nitrogen content of the films, the bonding becomes more sp 3 -like in character and there is evidence for a reduction in the network terminating CN bonding. Under these circumstances the sp 3 -like nature becomes comparable to or greater than that for un-nitrogenated films. These results point to the reasons why crystalline β-C 3 N 4 material has been found in these films only with high nitrogen partial pressure even though the nitrogen content is not significantly enhanced in this situation.

Idarubicin and cyclophosphamide--an active oral chemotherapy regimen for advanced breast cancer

Abstract: Between October 1993 and September 1994, 33 women with metastatic breast cancer aged between 29 and 74 years with a median age of 58 were entered into a study of oral chemotherapy from three UK centres. Patients by definition had metastatic disease and were fit and well with performance status 0 or 1 in 23 cases, 2 in seven cases and 3 in two cases (one missing). Five patients had received prior adjuvant CMF chemotherapy, nine first line non-anthracycline containing chemotherapy for relapse, eight patients second line non-anthracycline containing chemotherapy and all patients had had hormone therapy either as adjuvant or for relapsed disease. Adjuvant radiotherapy had been given to 17 and palliative radiotherapy to 12 patients. In nine patients there was one site of disease at start of therapy, in 10 two sites, in 11 three sites and in three patients four or more sites. The regimen comprised oral idarubicin 15 mg/m 2 on day 1, 10 mg/m 2 on days 2 and 3 and oral cyclophosphamide 250 mg/m 2 (maximum 400 mg) on days 1, 2 and 3. Treatment was continued until disease progression or toxicity. Results : Overall 25% of 32 evaluable patients responded objectively including one complete response; 50% of patients had stable disease and 25% of patients progression. Among patients who had had no prior chemotherapy the objective response rate was 37.5%; 45% of patients had symptomatic improvement. The most common severe toxicity was granulocytopenia WHO grade 3 or more in 69.7% of patients. Thrombocytopenia grade 3 or 4 was seen in four patients. Six patients had documented infections and all but four patients had alopecia. All patients complained of mild or moderate fatigue. Nausea and vomiting occurred in 75% of patients but only four individuals had grade 3 toxicity. Two patients stopped therapy after myocardial infarction and one after impaired cardiac function was noted. The median time to progression was 2.7 months (1–11.5 months) and median survival time 8.8 months (1–13+ months). Conclusion : The combination chemotherapy is active in heavily treated patients with manageable toxicity but there are problems in heavily pre-treated patients. There was good compliance in taking medication and at the doses chosen the drugs appear to be suitable for younger fitter patients.

Identification of long-term survivors in primary breast cancer by dynamic modelling of tumour response.

Abstract: Although clinical response to primary chemotherapy in stage II and III breast cancer is associated with a survival advantage, it is the degree of pathological response in the breast and ipsilateral axilla that best identifies patients with a good long-term outcome. A mathematical model of the initial response of 39 locally advanced tumours to anthracycline-based primary chemotherapy has been previously shown to predict subsequent clinical tumour size. This model allows for the possibility of primary resistant disease, the presence of which should therefore be associated with a worse outcome. This study reports the application of this model to an additional five patients with locally advanced breast cancer, as well as to 63 patients with operable breast cancer, and confirms the biological reality of the model parameters for these 100 breast cancers treated with primary anthracycline-based chemotherapy. The tumours that responded to chemotherapy had higher cell-kill (P < 0.0005), lower resistance (P < 0.0001) and slower tumour regrowth (P < 0.002). Furthermore, ER-negative tumours had higher cell-kill (P < 0.05), as compared with ER-positive tumours. All patients with a pathological complete response had zero resistance according to the model. Furthermore, the long-term implication of chemo-resistant disease was demonstrated by survival analysis of these two groups of patients. At a median follow-up of 3.7 years, there was a statistically significantly worse survival for the 37 patients with locally advanced breast cancer identified by the model to have more than 8% primary resistant tumour (P < 0.003). The specificity of this putative prognostic indicator was confirmed in the 63 patients presenting with operable disease where, at a median follow-up of 7.7 years, those women with a resistant fraction of greater than 8% had a significantly worse survival (P < 0.05). Application of this model to patients treated with neoadjuvant chemotherapy may allow earlier identification of clinically significant resistance and permit intervention with alternative non-cross-resistant therapies such as taxoids.

Modelling the Effects of Paclitaxel and Cisplatin on Breast and Ovarian Cancer

Abstract: The two drugs, Paclitaxel and Cisplatin, have important roles in the treatment of breast and ovarian cancer, with the combination currently considered the optimum first line chemotherapy of epithelial ovarian cancer. There has been a variety of experimental and clinical studies to try to determine the most effective method to deliver these drugs. These studies consistently show that giving Paclitaxel prior to Cisplatin is the more effective regimen. However, the reasons why are not fully understood. Therefore, we have developed a mathematical model to describe and predict the effects of these two drugs. This model takes into account the cytotoxic effects of the drugs on the cell-cycle and the pharmacodynamic and pharmacokinetic effects of the drugs on each other. The model agrees with the experimental and clinical studies which show that Paclitaxel given prior to Cisplatin is the better combination and, in addition, the model also predicts more effective treatment regimens. These include conditions on the time between doses and the dosing of each of the drugs.