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Biomedical subjects

D A Cameron

Publications and source records attributed to D A Cameron.

At least 37 records · Page 2Linked to original sources
PubMed2000

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

UNLABELLED: 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/m2 on day 1, 10 mg/m2 on days 2 and 3 and oral cyclophosphamide 250 mg/m2 (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.

Administration, Oral↗
PubMed2000

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

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.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

A cardiac evoked response algorithm providing threshold tracking: a North American multicenter study. Clinical Investigators of the Microny-Regency Clinical Evaluation Study.

The purpose of this study was to evaluate a pacing system using the recognition of cardiac evoked response for the automatic adjustment of pacing output. Patients were prospectively followed after primary implantation of VVIR pacemakers using AutoCapture (St. Jude Medical CRMD). Sensing and pacing thresholds, polarization signal, evoked response, and AutoCapture performance were evaluated with serial visits and 24-hour Holter monitoring. Three hundred ninety-eight patients (mean age 71 +/- 15 years) were followed for an average duration of 1 year (3 days-1.75 years) with the algorithm functional in > 90% of patients. Backup pacing in the event of exit block was confirmed in all patients. Pacing thresholds remained stable at 0.89 +/- 0.34 V with a pulse width of 0.31 ms (with chronic output autoset at 0.3 V above the actual threshold). Evoked response exhibited a small but statistically significant increase with time (8.92 mV at implant, 9.60 mV at 12 months), however, this finding did not result in any change in AutoCapture function during our follow-up period. The polarization signal remained stable with minimal variation (1.12 mV at implant, 1.18 at 12 months). No clinical adverse events were observed using the AutoCapture algorithm. In this initial experience with the AutoCapture algorithm the evoked response and polarization measurements remained adequate, allowing the system to function in the majority of patients with safe, low output pacing. High energy backup pacing provided an added safety feature over fixed output devices in cases of unexpected threshold rises. Longer follow-up is required for continued long-term validation of the algorithm.

Aged↗
PubMed1999

Morphological, physiological, and biochemical changes in rhodopsin knockout mice.

Mutations in rod opsin, the visual pigment protein of rod photoreceptors, account for approximately 15% of all inherited human retinal degenerations. However, the physiological and molecular events underlying the disease process are not well understood. One approach to this question has been to study transgenic mice expressing opsin genes containing defined mutations. A caveat of this approach is that even the overexpression of normal opsin leads to photoreceptor cell degeneration. To overcome the problem, we have reduced or eliminated endogenous rod opsin content by targeted gene disruption. Retinas in mice lacking both opsin alleles initially developed normally, except that rod outer segments failed to form. Within months of birth, photoreceptor cells degenerated completely. Retinas from mice with a single copy of the opsin gene developed normally, and rods elaborated outer segments of normal size but with half the normal complement of rhodopsin. Photoreceptor cells in these retinas also degenerated but did so over a much slower time course. Physiological and biochemical experiments showed that rods from mice with a single opsin gene were approximately 50% less sensitive to light, had accelerated flash-response kinetics, and contained approximately 50% more phosducin than wild-type controls.

Animals↗
PubMed1999

Locally advanced breast cancer: the outcome of primary polychemotherapy based on infusional 5 fluorouracil.

Over a 5-year period, 75 patients with locally advanced breast cancer presenting to the Edinburgh Breast Unit were managed with a policy of infusional primary chemotherapy. For 65 patients, the regimens comprised infusional 5 fluorouracil with anthracycline and/or either cyclophosphamide or cisplatinum (AcF, CAF or ECF) whilst 10 older patients had CMF-inf. The overall activity and tolerability for the regimens was good with a 76% objective response rate including 15% clinical complete responses. Surgery was possible in 64% and pathological complete responses confirmed in 7 (9.3%). Median disease free survival (DFS) is 5.23 years. Factors predicting for DFS or Overall Survival (OS) were assessed in this small group and ER positive patients did better than ER negative although there was surprisingly no negative DFS or OS association with inflammatory disease or advancing age. We found a paradoxical interaction with use of post-chemotherapy tamoxifen which was significantly associated with poorer DFS and OS overall and in the ER negative subgroups.

Journal Article↗
PubMed1999

Lessons from the use of aromatase inhibitors in the neoadjuvant setting.

Postmenopausal patients with oestrogen receptor-positive locally advanced T4b, N0-1, M0 and large operable breast cancers T2>3 cm, T3, T4, N0-1 and M0 have been treated with 2.5 mg letrozole (12 patients), 10 mg letrozole (12 patients), 1 or 10 mg anastrozole (24 patients) and 20 mg tamoxifen (65 patients). There was no apparent difference in response rate between 2.5 and 10 mg letrozole. Only 17 patients with anastrozole have so far completed the 3-month treatment period. Median clinical, mammographic and ultrasound reductions in tumour volumes for patients treated with letrozole were 81% (95% confidence interval (CI) 66-88), 77% (95% CI 64-82) and 81% (95% CI 69-86) respectively and for anastrozole, values were 87% (95% CI 59-97), 73% (95% CI 58-82) and 64% (95% CI 52-76) respectively. This compares with a median reduction in tumour volume for tamoxifen-treated patients as assessed by ultrasound of 48% (95% CI 27-48). There were seven complete clinical responses (CR), sixteen patients who achieved 50% or greater reduction in tumour volume (PR) and one no change (NC) for letrozole and four CRs, twelve PRs and one progressive disease for anastrozole. Best radiological responses were one CR, twenty PRs and three NCs for letrozole and one CR, fifteen PRs and one NC for anastrozole. This study has shown that the new aromatase inhibitors, letrozole and anastrozole, are highly effective agents in the neoadjuvant setting and they should now be compared with tamoxifen as first-line treatment in a randomised study.

Aged↗
PubMed1998

Pilot study of a semi-flexible intra-oral appliance for the control of snoring.

OBJECTIVE: To determine the effectiveness and acceptability of an intra-oral appliance in the reduction of snoring, with construction and fitting as a 1-visit process. DESIGN AND SETTING: This was a prospective study. Patients were attending a hospital sleep breathing disorders clinic and appliances were made at a dental hospital. This work was carried out in the UK during 1996 and 1997. SUBJECTS AND METHODS: Patients were selected from those referred to a sleep breathing disorders clinic with socially disruptive snoring. MAIN OUTCOME MEASURES: Patients were assessed by means of limited sleep studies and by questionnaires before and after fitting of the appliances. The sleep studies consisted of monitoring respiratory variables (principally oronasal airflow and nocturnal oxygen saturation). A respiratory disturbance index was assigned. Questionnaires were completed by both patients and sleep partners, with many of the responses being marked on visual analogue scales. RESULTS: 16 male patients, mean age 49 years, were included in the trial. 14 were able to wear the appliance and their level of snoring, as assessed by their sleep partners, reduced from a mean of 8.8 out of 10 to 4.2 out of 10 (P = 0.0003, paired t-test). CONCLUSION: It is concluded that the semi-flexible intra-oral appliance is effective in the control of snoring.

Adult↗
PubMed1997

Visual pigment assignments in regenerated retina.

Retinas of adult teleost fish can regenerate after injury. Two important issues regarding this phenomenon are the assembly of the regenerated retina and the neuronal images of the visual scene that the regenerated retina produces. Here we report experiments in which the visual pigment content of photoreceptors derived from native and regenerated sunfish retinas was determined by microspectrophotometry. In native retina, there is an apparently perfect correspondence between cone morphology and visual pigment content; all rods contain a middle-wavelength pigment, all single cones contain a different middle-wavelength pigment, and all double cone members contain a long-wavelength pigment. The visual pigments in regenerated rods and double cones were the same as in native retina; however, triple cones, a morphology never observed in native retina, contained the long-wavelength pigment. Moreover, although approximately 60% of regenerated single cones contained the expected middle-wavelength pigment, all other single cones contained the long-wavelength pigment. This mismatch between morphology of regenerated single cones and their visual pigment assignment indicated the following: (1) There is a degree of independence between the mechanisms that establish cone morphology and pigment content during regeneration, which suggests that cone photoreceptor regeneration is not a straightforward recapitulation of the normal cone photoreceptor developmental plan. (2) Although anomalous, the long-wavelength single cones may enable regenerated retina to restore the native spectral sampling of the visual scene.

Animals↗
PubMed1997

The split-post lock: an alternative lock for hinge clasps and swing-lock removable partial dentures.

When the locking component of a prosthesis loses its effectiveness, the solution has been to replace the component. This article describes a procedure for the production of a split-post lock. This lock can be used as an alternative in the construction of custom-made hinge clasps or for swing-lock dentures. If a loss or reduction in lock strength occurs through wear of components, then this split-post lock can be reactivated. A procedure in which this lock can be used to replace a worn swing-lock latch is also described.

Dental Clasps↗
PubMed1997

CHOP-based chemotherapy is as effective as alternating PEEC/CHOP chemotherapy in a randomised trial in high-grade non-Hodgkin's lymphoma. Scotland and Newcastle Lymphoma Group.

The aim of this study was to test whether survival for patients with high-grade non-Hodgkin's lymphoma (NHL) can be improved with a non-cross-resistant regimen as compared to a CHOP-based regimen. This is a multicentre study comprising 325 adult patients, median age 58 years, with high-grade non-Hodgkin's lymphoma: patients of any age and performance status were eligible provided they were able to receive the drugs in the regimens. Patients were randomised to either B-CHOP-M (bleomycin, cyclophosphamide, doxorubicin, vincristine, prednisolone and methotrexate) or PEEC-M (methylprednisolone, vindesine, etoposide, chlorambucil and methotrexate) alternating with B-CHOP-M. At a median follow-up of 9 years, there was no significant difference in overall survival or disease-free survival between the two arms. Toxicities for the two regimens were equivalent. This study confirms that for relatively unselected patients with high-grade non-Hodgkin's lymphoma, an alternating multidrug regimen does not improve upon the results obtained with B-CHOP-M.

Adult↗
PubMed1997

The expression of Ki-S1 and BCL-2 and the response to primary tamoxifen therapy in elderly patients with breast cancer.

Ki-S1, a marker of proliferation, and bcl-2, the gene product of which is an antagonist of apoptosis, have been measured in 51 ER-positive primary breast cancers before and during tamoxifen treatment and then related to clinical response. Both markers were detected in the majority of tumours before treatment and, quantitatively, initial expression of Bcl-2 protein, but not Ki-S1, was significantly related to the percentage reduction in tumour volume as assessed by ultrasound. Staining for both markers was lower in post treatment samples than in those taken prior to treatments, but concordant decreases in staining indices were seen in only 11 of the 51 tumours. The results demonstrate, using clinical material, that the response to tamoxifen may involve changes in proliferation and/or susceptibility to cell-death.

Aged↗
PubMed1997

Tamoxifen induced apoptosis in ZR-75 breast cancer xenografts antedates tumour regression.

The ZR-75-1 ER positive breast cancer cell line, xenografted in female nude mice, has been used to determine the effect of tamoxifen on cell proliferation (as measured by mitosis) and cell death (as evidenced by apoptosis and necrosis). After 2 days treatment, there was a significant rise in apoptosis (p < 0.05), whereas a fall in mitosis was not apparent until 7 days (p < 0.05). Furthermore there was an increase in the apoptotic:mitotic ratio on day 7 (p < 0.05). These changes antedated tumour regression, which did not reach not significance until day 14. Tamoxifen did not increase necrosis (which significantly decreased in treated tumours once they had regressed (p < 0.01). In contrast tamoxifen treatment of xenografted MDA-MB-231 ER-negative breast cancer cells produced no significant effects on growth, apoptosis, or mitosis. This study presents clear evidence for tamoxifen inducing apoptosis in ZR-75-1 xenografts (but not MDA-MB-231 tumours). Since changes in apoptosis and mitosis antedate tumour regression, their assessment may provide the potential by which to predict tumour response to tamoxifen therapy.

Animals↗
PubMed1997

Primary systemic therapy for operable breast cancer--10-year survival data after chemotherapy and hormone therapy.

Between 1984 and 1990, 94 women presenting to the Edinburgh Breast Unit with operable breast cancer of 4 cm or greater in diameter (T2, T3, N0, N1, M0) were given preoperative systemic therapy. Initially, all women received hormone therapy, with CHOP (cyclophosphamide 1 g m(-2), doxorubicin 50 mg m(-2), vincristine 1.4 mg m(-2) to a maximum of 2 mg and prednisolone 40 mg per day orally for 5 days) chemotherapy being administered to those who failed to respond by 3 months. After April 1987, first-line hormone therapy was only offered to women with oestrogen receptor (ER)-moderate/-rich (> 20 fmol mg(-1) protein) tumours, and CHOP was reserved for those women whose tumours failed to respond to hormone therapy and for those with ER-negative/-poor tumours. Response data have been published previously (Anderson et al, 1991). After a median follow-up of 7.5 years, there is no difference in survival between those women given initial hormone therapy and those given chemotherapy, with neither group having yet reached its median survival. The two key factors that predicted for a poor survival were the number of involved axillary nodes after preoperative systemic therapy (P < 0.00001) and a lack of response to preoperative therapy (P < 0.05). These data suggest that many women with ER-moderate/-rich tumours will have a good prognosis after preoperative hormone therapy alone. However, it is possible to identify, by their post-systemic therapy axillary node status, a group of women who still have an appalling prognosis after preoperative chemotherapy or hormone therapy.

Adult↗
PubMed1996

Properties of a custom-made hinge clasp compared with a conventional circumferential clasp.

The use of the hinge clasp in removable partial denture design, together with the design of a custom-made hinge unit, is discussed in this article. Tests of the retention provided by these custom-made hinge clasps were made, together with conventional clasps, and the results were compared. Six custom-made hinge clasps were constructed and attached to blocks of acrylic resin. The forces required to open these clasps and the effect of wear on the clasps were measured. Six conventional cast clasping units were also constructed and tested. The results indicated that the average force required to open the hinge clasps was 8.13 N (SD 1.99). After a period of simulated wear, the mean value of force required was 7.70 N (SD 2.33) and there was no statistically significant deterioration caused by wear. The mean forces required to withdraw these clasps vertically from a tooth were 30.25 N (SD 6.51) for the conventional clasps and 49.67 N (SD 18.69) for the hinge clasps. It was also found that the hinge clasps had to be withdrawn further from their seated position than the conventional clasps before retention was finally lost. However, neither of these differences were statistically significant.

Dental Clasps↗
PubMed1996

The case for high-dose adjuvant chemotherapy in breast cancer: (II) clinical experience.

Recent Phase II studies on the use of myelo-ablative chemotherapy in breast cancer have confirmed that this approach is associated with low mortality and apparent efficacy. In a preceding article the theoretical arguments were presented for testing this approach in the high-risk adjuvant setting; in the current article the clinical data justifying the present approaches for this type of treatment are reviewed. The evidence suggests that peripheral blood stem cell supported myelo-ablative chemotherapy should be tested against conventional regimens in order to determine whether or not the increased expense and toxicity of such an approach is associated with improved survival for women whose axillary node status places them at high risk of disease relapse and subsequent death.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

The case for high-dose adjuvant chemotherapy in breast cancer: (I) theoretical considerations.

Adjuvant systemic therapy of breast cancer is now a well-established treatment resulting in improved survival. However, the available evidence suggests that it is most unlikely that an individual woman will be cured as a consequence of such treatment. There is, therefore, a pressing need for more effective therapy, particularly for younger women whose degree of axillary nodal involvement indicates a high risk of subsequent relapse. The case for using myelo-ablative chemotherapy for such women is presented in this article. In a subsequent publication we will discuss the clinical data to suggest that such an approach is not only possible with acceptable toxicity, but also could actually offer the increased cure rate sought by clinicians and patients alike.

Antineoplastic Agents↗