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Biomedical subjects

I E Smith

Publications and source records attributed to I E Smith.

At least 109 records · Page 6Linked to original sources
PubMed1996

Comparison of MIB-1 proliferation index with S-phase fraction in human breast carcinomas.

The MIB-1 antibody has been raised against recombinant parts of the Ki-67 antigen and, unlike Ki-67, has wider application to routinely fixed specimens. The aim of this study was to compare the usefulness of MIB-1 with S-phase fraction (SPF) as a measure of proliferation. A total of 75 patients with operable breast cancer were studied, 44 (median age 56 years) before any treatment and 31 (median age 68 years) after primary medical hormonal therapy. Sections from formalin-fixed paraffin-embedded tissue were stained with the MIB-1 antibody and a percentage score of positively stained cells obtained. SPF was measured by flow cytometry in fine-needle aspiration samples taken from the same lesion in each patient. Median MIB-1 score was 9% and median SPF was 11.1%. A close correlation was found between MIB-1 score and SPF (rho=0.59, P<0.0001). There was a difference in the strength of the correlation found between the no treatment group and the treatment group, however, 95% confidence intervals for the rho values overlapped, indicating that there was no significant statistical difference. When analysed for ploidy status a correlation was found only in aneuploid tumours. MIB-1 immunostaining can be used as an effective method of assessing proliferation in human breast carcinomas. This can be done using simple, widely available technology and provides the opportunity to perform large-scale retrospective analyses of archival materials.

Aged↗
PubMed1996

How should cancer presenting as a malignant pleural effusion be managed?

The objective of the study was to review the natural history of patients with a malignant pleural effusion but without obvious evidence of a primary, to assess the value of investigations used to look for a primary and to assess the response to palliative chemotherapy. This was done by a retrospective study of patients' notes at the Lung Unit, Royal Marsden Hospital, Sutton, Surrey. Improvement in tumour-related symptoms (and duration) on chemotherapy was assessed by the patient before the first course of chemotherapy and following each course using simple descriptive criteria as follows: (1) complete disappearance of symptoms (CR); (2) good improvement in symptoms (PR); (3) minor or no change in symptoms (NC); (4) worse symptoms (PD). Pleural effusion objective response (and duration) according to Hamed definition: success defined as a continued absence of reaccumulation of pleural fluid on all follow-up radiographs; any reaccumulation was regarded as a treatment failure. Overall survival was measured from the date of histological/cytological diagnosis to death. The study included 42 patients, 27 males and 15 females with a median age of 55 years. A primary was found in 15 patients (36%), and considered to be lung cancer. A total of 11/32 (34%) had a thoracic computed tomography (CT) scan with abnormalities compatible with a diagnosis of lung primary. When thoracic CT scan was negative, fibre optic bronchoscopy was always negative (0/13). Abdominal and pelvic CT scan, abdominal ultrasound, pelvic ultrasound and mammograms failed to reveal the primary. Twenty-three patients underwent local treatment and 37 received systemic chemotherapy. A total of 29/37 (78%) patients achieved symptomatic improvement (median duration, 6 months) and 32/37 (86%) an objective response of their pleural effusion on chemotherapy (median duration, 6 months). The median survival of the whole group was 12 months (3-60+ months). In this series the thoracic CT led to a diagnosis of lung primary in 34% of the cases. Other radiological examinations and bronchoscopy were unhelpful. Chemotherapy achieved symptom relief in 78% of patients.

Adult↗
PubMed1996

Phase II study of continuous infusional 5-fluorouracil with epirubicin and carboplatin (instead of cisplatin) in patients with metastatic/locally advanced breast cancer (infusional ECarboF): a very active and well-tolerated outpatient regimen.

Infusional 5-fluorouracil (F) with cisplatin (C) and epirubicin (E), so-called infusional ECF, is a highly active new schedule against locally advanced or metastatic breast cancer. Cisplatin, however, is a major contributor to toxicity and usually requires inpatient treatment. In an attempt to overcome this, we have investigated the effect of substituting carboplatin for cisplatin in our original infusional ECF regimen. Fifty-two patients with metastatic (n = 36) or locally advanced/inflammatory (n = 16) breast cancer were treated with 5-fluorouracil 200 mg m-2 day-1 via a Hickman line using an ambulatory pump for for 6 months, with epirubicin 50 mg m-2 intravenously (i.v.) and carboplatin AUC5 i.v. every 4 weeks, for six courses (infusional ECarboF). The overall response rate (complete plus partial) was 81% (95% CI 67%-90%), with a complete response rate of 17% (95% CI 6-33%) in patients with metastatic disease and 56% (95% CI 30-80%) in patients with locally advanced disease. Median response duration and survival for metastatic disease was 8 and 14 months respectively, and two patients with locally advanced disease have relapsed. These results are very similar to those previously achieved with infusional ECF. Severe grade 3/4 toxicity was low. Infusional ECarboF is a highly active, well-tolerated, outpatient regimen effective against advanced/metastatic breast cancer and now warrants evaluation against conventional chemotherapy in high-risk early breast cancer.

Adult↗
PubMed1996

Therapeutic effects of the aromatase inhibitor fadrozole hydrochloride in advanced breast cancer.

The endocrine and therapeutic effects of the aromatase inhibitor fadrozole hydrochloride have been assessed in 80 post-menopausal patients with recurrent breast cancer after tamoxifen failure. Treatment allocation was randomly 0.5, 1.0 or 2.0 mg orally b.d. Eight patients were not assessable for response. All patients were evaluated for toxicity (intent-to-treat analysis). In general, the patients' characteristics were well balanced between the three randomised groups. The endocrine data from this study previously reported suggest a dose-related suppression of oestrone, but not oestradiol or oestrone sulphate. The objective response rate was 17% (95% CI 8.9-27.3%) with no complete responders. Fifteen patients (21%) had stable disease (NC) and 45 patients (63%) had progressive disease (PD). The median duration of objective response was 36 weeks. The median time to treatment failure was 12.7 weeks. The log-rank test showed no statistical difference between the dosage groups. The main adverse events reported were mild to moderate severity: nausea in 11 patients (15%), hot flashes in four (5%) and somnolence in three (4%). No serious adverse events were reported. In conclusion, fadrozole is a clinically active aromatase inhibitor with a low incidence of side-effects and phase III clinical trials in post-menopausal women are currently under way.

Adult↗
PubMed1996

Chronic sputum production: correlations between clinical features and findings on high resolution computed tomographic scanning of the chest.

BACKGROUND: There are few published data on the correlation between the clinical findings in subjects with chronic sputum production and the appearances on high resolution computed tomographic (HRCT) scans of the chest. METHODS: HRCT scanning of the chest was performed on 40 subjects with chronic sputum production. Three readers independently reported the scans for the presence or absence of bronchiectasis and the extent of bronchiectasis on the basis of the percentage of involved bronchi in each lobe. Relationships were sought between these findings and the clinical history, physical examination, and laboratory investigations. RESULTS: HRCT scanning showed that 27 subjects had bronchiectasis. Of the clinical features only the continual production of purulent sputum and childhood pertussis were associated with bronchiectasis. There was a positive correlation between the extent of bronchiectasis and dyspnoea, and a negative correlation with forced expiratory volume in one second but not with forced vital capacity. CONCLUSIONS: These results indicate that, in subjects with chronic sputum production, only a few clinical features show any correlation with the presence or extent of bronchiectasis as visualised on HRCT scans.

Adult↗
PubMed1996

A laboratory comparison of four positive pressure ventilators used in the home.

Four brands of ventilator used for noninvasive positive pressure ventilation in the home were assessed to determine their performance on a patient simulator. We tested the tidal volume (VT) preset Companion 2801 (Puritan Bennett), minute volume preset Monnal D (Taema), and two pressure preset ventilators, the Nippy (Friday Medical) and the Bilevel Positive Airway Pressure (BiPAP) (Respironics). A patient simulator was employed to investigate the relationships between VT, peak airway pressure (PAP) and mean airway pressure (MAP), the responses to an additional leak in the circuit and patient effort of a variable duration, which was modelled using a negative pressure pump. For equivalent VTs, >300 mL, the Monnal D and Nippy generated a PAP up to 100% greater than the Companion 2801 and BiPAP. When an additional leak was introduced to the circuit, the VT of the Companion 2801 and Monnal D fell by >50%, while the Nippy and the BiPAP responded by increasing flow and maintained VT close to the level achieved with no leak. When the ventilators were triggered by a simulated patient effort of 0.25 s duration with a frequency 33% greater than that of the ventilator, the minute volume increased by 41% for the Companion 2801, by 18% for the Monnal D (no change expected), and by 17% for the Nippy (less than expected), and fell by 7% for the BiPAP due to irregular triggering. When patient effort was prolonged to 1.5 s, a similar length to the inspiratory time of the ventilators, there was no further change in the minute volume of the Companion 2801 and Monnal D, while that of the Nippy and of the BiPAP increased by 38 and 71%, respectively, compared to baseline. These results show that distinct brands of ventilator respond to changes in the patient and patient circuit in different ways, which are not always predictable from a simple description of their operating principles. This should be borne in mind when choosing a positive pressure ventilator for noninvasive ventilation.

Equipment Design↗
PubMed1996

Review article: imaging in bronchiectasis.

Bronchiectasis remains an important and relatively common cause of pulmonary disability. High resolution computed tomography has revolutionized imaging of the bronchi and has superseded the chest radiograph and bronchogram in the diagnosis of bronchiectasis. It has enabled a better understanding of the association between clinical features of the disease and structural abnormalities in the airways and has an important role to play in understanding the pathogenesis and natural history of bronchiectasis.

Bronchiectasis↗
PubMed1996

Kyphosis secondary to tuberculosis osteomyelitis as a cause of ventilatory failure. Clinical features, mechanisms, and management.

STUDY OBJECTIVES: To investigate the relationship of thoracic kyphosis following tuberculosis to the development of ventilatory failure and to assess the efficacy on nocturnal noninvasive ventilatory support. DESIGN: Retrospective consecutive case series with crossover from a phase without noninvasive ventilatory support to a phase with this treatment. SETTING: The Respiratory Support and Sleep Centre, Papworth, Hospital, Cambridge, England. PATIENTS: Seven patients with thoracic kyphosis following tuberculous osteomyelitis which had been contracted by the age of 4 years were studied. Their mean age was 53 (SD 7.1) years and the mean angle of kyphosis was 113.60. All patients were in ventilatory failure. INTERVENTIONS: The patients were treated with nocturnal noninvasive ventilation with either an individually constructed cuirass shell and a negative pressure pump or nasal intermittent positive pressure ventilation using a volume preset ventilator. MEASUREMENT AND RESULTS: Each patient underwent an initial clinical assessment along with radiologic studies of the spine, pulmonary function tests, daytime arterial blood gas tensions, and overnight recordings of arterial saturation, and transcutaneous carbon dioxide tension. They were reassessed in detail at a mean of 5 years after starting ventilatory support. Symptoms, vital capacity, daytime carbon dioxide tension, and overnight oximetry had all improved following treatment. Temporary withdrawal of ventilatory support led to severe sleep fragmentation in four patients and the appearance of central apneas and hypopneas in the other three. Six of the 7 patients were alive at a mean of 5.7 years after starting nocturnal ventilation. CONCLUSION: These results show that ventilatory failure may develop, after an interval of many years, in patients with a severe thoracic kyphosis due to tuberculosis in childhood. Noninvasive nocturnal ventilatory support can control the symptoms of ventilatory failure, improve the physiologic abnormalities, and is associated with prolonged survival.

Female↗
PubMed1996

The prognostic implications of chemotherapy in the treatment of breast cancer.

Randomized trials with long follow-up confirm the beneficial effect of adjuvant chemotherapy in most groups of patients with operable breast cancer. The use of chemotherapy in large tumours before surgery does not appear to jeopardize survival. High-dose chemotherapy and the use of taxoids may change the natural history of metastatic disease.

Breast Neoplasms↗
PubMed1995

Changes in estrogen receptor, progesterone receptor, and pS2 expression in tamoxifen-resistant human breast cancer.

Changes in estrogen receptor (ER) expression and function may explain the development of tamoxifen resistance in breast cancer. ER expression was measured by an immunohistochemical assay, validated for use in tamoxifen-treated tumors against a biochemical enzyme immunoassay, in 72 paired biopsies taken before treatment and at progression or relapse on tamoxifen. Progesterone receptor (PgR) and pS2 gene expression were also measured immunohistochemically as an indicator of ER function. Overall the frequency of ER expression was reduced from 37 of 72 (51%) pretamoxifen to 21 of 72 (29%) at progression or relapse, with a significant reduction in the quantitative level of ER (P < 0.0001; Wilcoxon signed rank sum test). Tumors treated with primary tamoxifen that responded but then developed acquired resistance frequently remained ER positive (ER+) at relapse: 16 of 18 (89%) were ER+ pretamoxifen (75% of these expressed either PgR or pS2) and 11 of 18 (61%) were ER+ at relapse (82% continued to express PgR or pS2). In contrast, only 3 of 20 (15%) tumors that progressed on primary tamoxifen with de novo resistance were ER+ pretamoxifen, and all tumors were ER- at progression. At progression, 6 of 20 (30%) of these tumors expressed high levels of PgR (mean H-score, 98) and/or pS2 (mean, 50% cells positive), despite being ER-. In tumors that recurred during adjuvant tamoxifen therapy, including locoregional and metastatic lesions, ER expression was significantly reduced from 18 of 34 (53%) in the original primary tumor to 10 of 34 (29%) at relapse (P = 0.002). PgR expression was likewise significantly reduced in this group (P = 0.001). This study confirms that expression of a functional ER in breast cancer is a strong predictor for primary response to tamoxifen. Although ER was reduced in tamoxifen-resistant tumors overall, the development of acquired resistance was associated with maintained ER expression and function in many tumors, whereas de novo resistance remained related to lack of ER expression. Recurrence during adjuvant tamoxifen was associated with development of an ER/PgR-negative phenotype in some tumors. These data imply that separate mechanisms of resistance may occur in these different clinical subgroups.

Aged↗
PubMed1995

Exon 5 deletion variant estrogen receptor messenger RNA expression in relation to tamoxifen resistance and progesterone receptor/pS2 status in human breast cancer.

The exon 5 deletion splice variant of estrogen receptor (delta 5 ER), which in vitro is constitutively active in the absence of estrogens, may have a role in conferring both tamoxifen resistance and ER-related phenotype in breast cancer. We have investigated the expression of this variant in vivo (at the level of mRNA) in relation to known tamoxifen resistance and expression of the estrogen-regulated genes progesterone receptor (PgR) and pS2. The amount of delta 5 ER mRNA relative to wild type (WT) ER mRNA (% delta 5/WT) was assayed in 70 tamoxifen-resistant and 50 primary breast carcinomas using reverse transcription/PCR. Both WT and delta 5 ER mRNA were detected in the majority of tumors, although delta 5 ER was detected only in the presence of WT ER. Overall no significant difference was seen in % delta 5/WT ER between tamoxifen-resistant and primary control tumors (medians, 13 and 15%, respectively). Tumors in both control and resistant groups which expressed PgR/pS2 in the absence of measurable ER protein (ER- PgR+ and ER- pS2+) had significantly higher delta 5 ER mRNA levels compared with other phenotypes (P < 0.002). This association with ER-/pS2+ tumors has not been demonstrated previously. In ER+ tumors which expressed pS2, significantly greater delta 5 ER mRNA expression was observed in tamoxifen-resistant compared with control tumors (P = 0.05). A similar although nonsignificant trend was observed in ER+ PgR+ tumors. While delta 5 ER mRNA is unlikely to be responsible for tamoxifen resistance in most breast cancers, elevated delta 5 ER mRNA levels may be important in some tumors, especially those which continue to express high levels of PgR/pS2.

Adult↗