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Biomedical subjects

J F Robertson

Publications and source records attributed to J F Robertson.

At least 19 recordsLinked to original sources
PubMed1992

Tumour oestrogen receptor content allows selection of elderly patients with breast cancer for conservative tamoxifen treatment.

Immunocytochemical analysis was used to determine tumour oestrogen receptor (ER) content in elderly patients with primary operable breast cancer. Only those ER positive were selected for conservative treatment with tamoxifen alone. Initial response was compared with that of historical controls not selected according to ER status. Early progressive disease was markedly reduced at 6 months, from 30 per cent in the unselected control group to 2 per cent in the study group (P < 0.001). Immunocytochemical analysis is useful for the initial selection of elderly patients with breast cancer who may be treated with tamoxifen alone.

Aged↗
PubMed1992

Cellular effects of tamoxifen in primary breast cancer.

We have investigated the effect of tamoxifen on the biological characteristics of the primary tumour in 33 patients with breast cancer. All patients had pre-treatment biopsy of the primary breast cancer and subsequent trucut biopsy of the primary tumour after 1-4 months on tamoxifen therapy. The staining patterns in the primary tumour of each of the tumour antigens 115D8, DF3, NCRC-11, and carcinoembryonic antigen (CEA) were unaffected by tamoxifen therapy: there was 16%-31% change before vs. during tamoxifen therapy, but this did not reach significance for any of the four antigens. Comparison of the pattern of staining between the four antigens showed 115D8, DF3, and NCRC-11 to be similar to each other both before and during tamoxifen therapy. All three antigens were significantly different from the staining pattern shown by CEA before and during therapy. Tumour antigen expression pre-treatment did not correlate with therapeutic response for any of the four antigens. However, NCRC-11 staining during tamoxifen therapy did correlate with response (p = 0.004). There was no significant difference in oestrogen receptor status before and during tamoxifen therapy, both of which correlated with response. DNA ploidy of the tumour before tamoxifen did not correlate with response to therapy, but there was a weak correlation between response and DNA ploidy measured during tamoxifen therapy. In only a minority of tumours (up to 30%) did tamoxifen exert an effect on the biological characteristics studied. Changes in these biological markers were mainly in tumours which responded to tamoxifen, and the changes seen were a tendency to greater expression of differentiation antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Confirmation of a prognostic index for patients with metastatic breast cancer treated by endocrine therapy.

We have previously reported a retrospectively constructed index which can accurately predict survival at the time of diagnosis of symptomatic metastatic breast cancer. The index, derived from a Cox model, is scored: Index score = (4 x Grade)-(6 x ER) + (4 x SIMD)-(0.1 x DFI), where histological grade is scored 1-3 (good, moderate, or poor), oestrogen receptor (ER) is scored 0 (negative) or 1 (positive), site of initial metastasis (SIMD) is scored 1-4 for bone only, lung only, bone and lung, or visceral metastases, respectively, and disease-free interval (DFI) is measured in months. Patients were divided into three prognostic groups on the basis of index score. In the present study we have tested this index prospectively on a new group of 147 patients with metastatic breast cancer. The percentage of patients in each of the three groups was similar between the retrospective and prospective studies. In the prospective study the difference in survival between the 3 groups was highly significant (p less than 0.001), confirming our retrospective analysis. No single one of the four factors was as powerful in predicting survival as the index itself. We now use this index in our patient management.

Adult↗
PubMed1992

Mastectomy or tamoxifen as initial therapy for operable breast cancer in elderly patients: 5-year follow-up.

135 consecutive patients aged over 70 years with operable primary breast cancer (clinically maximum diameter 5 cm) were randomised to either wedge mastectomy or tamoxifen 20 mg twice daily as initial therapy. The mean time from randomisation is now 65 months. There was no difference between the two groups in terms of overall survival or cause of death. Likewise, the groups were similar for site of initial metastatic disease and the probability of developing metastatic disease. However, failure of locoregional control was significantly greater in the tamoxifen group. The optimum treatment for elderly patients with operable breast cancer includes mastectomy.

Aged↗
PubMed1992

Inhibition of gastrin-stimulated growth of gastrointestinal tumour cells by octreotide and the gastrin/cholecystokinin receptor antagonists, proglumide and lorglumide.

The rat pancreatic cell line, AR42J possessed high-affinity gastrin and somatostatin receptors and its growth was stimulated by physiological gastrin-17 concentrations between 5 x 10(-11) mol/l and 10(-9) mol/l as measured by [75Se]selenomethionine uptake. The somatostatin analogue, octreotide (2 x 10(-7) to 2 x 10(-11) mol/l), reduced this stimulated growth. Gastrin-stimulated AR42J growth was also inhibited by proglumide (3 x 10(-4) mol/l) and lorglumide (3 x 10(-5) mol/l) at maximal G17 concentrations of 5 x 10(-11) and 10(-10) mol/l, respectively, and the analogues competed with [125I] gastrin-17 (5 x 10(-10) mol/l) for binding to gastrin receptors on AR42J (50% inhibitory concentrations, less than or equal to 10(-3) mol/l and 4 x 10(-6) mol/l, respectively. Octreotide reduced the basal growth of the human gastric cell line, MKN45G, (which is associated with intracellular gastrin immunoreactivity) in serum-free medium to 73% of control at a concentration of 2 x 10(-8) mol/l, which was reversed by gastrin-17 (10(-10) mol/l). Lorglumide (3 x 10(-5) mol/l) also reduced the basal growth to 30% of control, which was reversed to 78% by 10(-5) mol/l gastrin. Proglumide had no effect on the basal growth of MKN45G.

Animals↗
PubMed1992

Comparison of two oestrogen receptor assays in the prediction of the clinical course of patients with advanced breast cancer.

We have examined two new oestrogen receptor (ER) assays--an enzyme immunoassay (EIA) and an immunocytochemical assay (ICA) in a large series of primary breast tumours to compare their potential as predictors of (1) response to endocrine therapy and (2) survival in patients developing advanced breast cancer. Response to endocrine therapy was categorised at 6 months (UICC criteria). ER-ICA appears the better predictor of response to endocrine therapy than ER-EIA. Combining ICA and EIA results did not improve the prediction of response. With both assays patients with ER positive tumours survived longer from the time of diagnosis of advanced disease than those with ER negative tumours. The predictive power of these assay for progression of disease appears slightly better for the ER-ICA.

Aged↗
PubMed1992

Therapeutic effect of the gastrin receptor antagonist, CR2093 on gastrointestinal tumour cell growth.

The gastrin receptor antagonist, CR2093, competed with 125I-gastrin-17 (5 x 10(-10) M) for binding to gastrin receptors on the rat pancreatic adenocarcinoma, AR42J (CR2093 concentration inducing 50% of 125I-gastrin-17 binding (IC50) was 8 x 10(-5) M), on the human gastric adenocarcinoma, MKN45 (IC50 5.5 x 10(-5) M) and the human colo-rectal adenocarcinoma C523 (IC50 greater than 10(-4) M). Intravenous administration of CR2093 (40 mg kg-1 day-1) reduced the gastrin-17 stimulated growth of AR42J xenografts in nude mice to below that of the original basal growth (P = 0.0166 from basal and P = 0.0109 from gastrin stimulated growth). CR2093 administration also reduced the gastrin-stimulated growth of MKN45 xenografts (P = 0.045) but failed to inhibit the gastrin enhanced proliferation of C523 xenografts. This may be related to the affinity (Kd) of the gastrin receptors present on the xenograft lines as the Kds of the two xenografts inhibited by CR2093 were 4.6 x 10(-10) M (AR42J) and 1.2 x 10(-9) M (MKN45) respectively whereas the Kd of C523 was of higher affinity (2.2 x 10(-10) M). GR antagonists may be a viable therapeutic option for gastrin receptor positive, gastro-intestinal tumours.

Amino Acids↗
PubMed1992

Silver-stained nucleolar organiser region counts are of no prognostic value in primary breast cancer.

The assessment of nucleolar organising regions have been reported to be of prognostic value both in a number of haematological and solid tumours. We have examined the relationship between the number of nucleolar organising regions (NORs) present in 75 primary breast cancers and various clinical and pathological features known to be associated with prognosis in patients with breast cancer. Formalin-fixed, paraffin-embedded tumour tissue was sectioned and stained by a one-stage argyrophil (AgNOR) method. Using light microscopy the mean number of AgNORs per cell was calculated. No correlation was observed between AgNOR counts and any of the prognostic variables studied, including oestrogen receptor (ER) status, histological grade of malignancy, lymph node stage or site of initial metastatic disease. Similarly there was no correlation between AgNOR counts and disease-free interval or survival. AgNOR counts do not appear to be a prognostic factor in primary breast cancer.

Adult↗
PubMed1991

Occult regional lymph node metastases from breast carcinoma: immunohistological detection with antibodies CAM 5.2 and NCRC-11.

Ninety-eight consecutive patients with primary operable breast cancer and an initial diagnosis of no regional lymph node metastases as assessed by conventional light microscopy were studied. Immunohistological staining of routine lymph node sections was assessed using two monoclonal antibodies: CAM 5.2 (Becton Dickinson) with specificity for low molecular weight cytokeratin, and NCRC-11 (CRC Laboratories, Nottingham) with specificity for epithelial mucin antigen. Positive staining for occult metastases was seen in nine patients with CAM 5.2 and in eight of these nine with NCRC-11. At a follow-up out to 14 years, there was no difference in overall survival, in recurrence-free survival, or in frequency of or time to presentation of local or regional recurrences between occult metastasis-positive and occult metastasis-negative patients. This study concludes that while immunohistological staining of routine lymph node sections increases the diagnostic yield of metastases, it is not to be recommended as this increase is of no useful clinical value.

Adenocarcinoma↗
PubMed1991

Prospective assessment of the role of five tumour markers in breast cancer.

Retrospective analysis previously identified significant elevation of five tumour markers, carcinoembryonic antigen (CEA), ferritin, orosomucoid. C-reactive protein and erythrocyte sedimentation rate (ESR), in patients with systemic breast cancer and showed that changes in each of these markers individually correlated significantly with therapeutic response. In this study we have prospectively tested these findings. None of the five markers was significantly elevated in primary breast cancer compared to normal control or benign breast disease groups. They therefore appear to have no role either in screening or in the differential diagnosis of breast cancer. There was a significant elevation of all five markers in patients with systemic breast cancer (P less than 0.0001: analysis of variance) but sequential changes in CEA and ESR only correlated significantly with the UICC-assessed response. Prospective confirmation of the correlation between changes in serum CEA and ESR provides the basis for using these markers in the assessment of response to therapy in patients with systemic breast cancer.

Adult↗
PubMed1991

Hormone sensitivity in breast cancer: influence of heterogeneity of oestrogen receptor expression and cell proliferation.

The percentage of oestrogen receptor (ER) positive cells in a series of 118 breast cancers has been examined by immunohistochemistry in relation to patients' response to endocrine therapy. Positive and negative predictive values have been used to calculate appropriate cut-off points. The rate of response to treatment was significantly higher in women with receptor positive tumours, especially where the tumours contained more than 70% positive cells. Tumours that were apparently negative for ER expression rarely responded to endocrine therapy. The hormone sensitivity of ER positive breast cancer was also influenced by the rate of tumour cell proliferation, with tumours expressing high levels of Ki67 immunostaining rarely responding to therapy.

Antibodies, Monoclonal↗
PubMed1991

c-erbB-2 oncoprotein expression in primary and advanced breast cancer.

Immunoreactivity for c-erbB-2 oncogene product expression has been investigated in patients with breast cancer using the polyclonal antibody 21N. Three series of patients were studied, 602 presenting with primary operable cancer, 57 with stage 3 and 123 with stage 4 disease. Representative tissue sections of each primary tumour were stained using a standard immunoperoxidase technique. Invasive tumour membrane immunoreactivity was assessed and identified in 15% of patients with primary operable cancer and 20% in the advanced breast cancer group. The results demonstrate a relationship between poorer survival and oncogene expression in all three patient groups. Patients in the primary operable cancer group with membrane oncoprotein expression had a poorer outcome, 35% 10-year survival, compared with those in which membrane expression was absent, 55% 10-year survival. The median survival of patients with stage 3 disease with c-erbB-2 membrane positivity was 17 months compared to 24 months with membrane negativity. In stage 4 disease median survival with membrane expression was 8.8 months compared to 19.7 months with no membrane expression. In addition in the series of primary cancers a correlation existed between histological grade and membrane immunoreactivity. Multivariate analysis showed histological grade to be a more powerful prognostic factor than c-erbB-2 protein expression. In conclusion, this study demonstrates, in a large series of patients presenting to one centre, that c-erbB-2 protein expression is a prognostic indicator in patients with primary operable and advanced breast disease.

Breast Neoplasms↗
PubMed1991

Failure of CA19-9 to detect asymptomatic colorectal carcinoma.

Serum CA19-9 levels have been measured in 34 patients with asymptomatic colorectal cancer, 39 age and sex matched subjects with healthy colons (as assessed at full colonoscopy) and 55 patients known to have liver metastases from primary colorectal cancers. In subjects with asymptomatic cancer the median CA19-9 was 12.75 U ml-1 (0.0-280.7 U ml-1), in the healthy controls the median CA19-9 was 12.80 U ml-1 (0.0-88.9 U ml-1) and in those with liver metastases was 62.5 U ml-1 (4.8-458.0 U ml-1). Levels were significantly higher in patients with metastatic disease than in patients with asymptomatic tumours or the healthy controls, however there was no significant difference between the asymptomatic group and the controls. Using an upper limit of normal of 37 U ml-1, the sensitivity of CA19-9 was 60.3% for the detection of colorectal cancer with liver metastases but only 17.6% for asymptomatic cancer. Serum CA19-9 estimation is of no value as a means of screening for asymptomatic colorectal cancer.

Adult↗
PubMed1991

Objective measurement of therapeutic response in breast cancer using tumour markers.

In 65 patients with systemic breast cancer, a biochemical response index using three tumour markers in combination, carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA 15-3) and erythrocyte sedimentation rate (ESR), allowed objective biochemical assessment of response to endocrine therapy. Changes in these three markers at 2, 4 and 6 months showed a highly significant correlation with UICC assessed response at 6 months. At 4 months, changes in these three markers resulted in a selectivity of 93%, with a sensitivity of 92% and a specificity of 82%. Survival of groups of patients assessed biochemically or by UICC criteria for non-progression or progression showed no significant difference. The advantage of the biochemical assessment are that it is objective and reproducible. The assessment gives similar information to the UICC assessment but can be carried out earlier. Changes in the three markers appears to reflect the dynamics of change in tumour mass in response to systemic therapy in contrast to the UICC criteria which reflect structural change.

Adolescent↗
PubMed1991

Airborne dust, ammonia, microorganisms, and antigens in pig confinement houses and the respiratory health of exposed farm workers.

This study investigated the environmental conditions on pig farms and the respiratory health of pig farmers and their immunological response to airborne contaminants. Airborne concentrations of dust and ammonia were measured in 20 pig houses; viable microorganisms, endotoxins, and aeroallergens were measured in 6 of these houses, chosen to represent the range in dustiness. The 29 farmers employed on the farms completed a questionnaire and underwent lung function tests; 24 of them provided blood samples for the measurement of specific IgE and IgG antibody to extracts of pig squames and urine, feed components, and bacterial isolates. Mean airborne dust and ammonia concentrations in the pig houses ranged from 1.66 to 21.04 mg/m3 and from 1.50 to 13.23 ppm, respectively. Factors affecting these concentrations include time of year, feed systems used, and levels of ventilation. There was no direct relationship between airborne dust and ammonia concentrations. Airborne microorganisms ranged from 10(5) to more than 10(7) colony-forming units (cfu)/m3; most were bacteria, with few fungi or thermophilic actinomycetes isolated. Gram-positive bacterial genera (Staphylococcus, Micrococcus, and Bacillus spp.) predominated. Concentrations of endotoxin in collected airborne dust were low. Work-related respiratory symptoms, typically chest tightness/wheeze and nasal and eye irritation, were reported by 23 of the 29 workers. Three farmers had specific IgE to pig squames or urine and eight to feed components but none to the microbial extracts. Specific IgG to pig squames or urine and to feed components was demonstrated in 14 and 9 workers, respectively. Specific IgE responses occurred mainly in subjects with chest tightness or wheeze, although specific IgG responses were not related to symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Agricultural Workers' Diseases↗
PubMed1991

Promoting health among the institutionalized elderly.

1. Although health promotion is a current focus of nursing practice, the institutionalized elderly have not been a target of health promotion research by nurses. 2. Health promotion research in nursing home settings by other disciplines has shown that institutionalized elderly benefit from humanistic approaches and that lifestyle enhancement is possible in nursing home settings. 3. Long-term care nurses are in a unique position to empirically investigate the benefits and efficacy of health promotion interventions in institutionalized settings.

Aged↗