High technology medical interventions: what do older people want?
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Biomedical subjects
Publications and source records attributed to N Pendleton.
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BACKGROUND: Little is known of the nature and origins of the attitudes that older people have towards ageing, disease, and medical treatments. Several studies on older people in the community have suggested under-reporting of symptoms. There may be several reasons for this, including the possibility that some older people regard disease processes as a natural feature of ageing and, consequently, feel that medical intervention may have little to offer. AIM: To investigate the perceptions of older people about the significance of symptoms and what action they would take in response to particular symptoms. METHOD: Thirty-three men and 77 women attending social clubs (median age 78 years) were opportunistically selected and assessed using a supervised questionnaire. RESULTS: Many symptoms classically associated with common diseases were often considered to represent disease as well as to be normal for old people. Most would consult a doctor if they were to experience them. Some important symptoms, such as blackouts or paralysis of a limb, were not considered to be normal. Non-specific symptoms of psychiatric disturbances were also frequently considered normal but were not considered to represent disease. Whether or not a doctor would be consulted was often, but not always, related to whether a symptom was thought to represent a disease. Consulting a pharmacist was seldom considered appropriate. CONCLUSIONS: Doctors working with elderly people need to consider how beliefs about health and disease might affect what is reported to them. Specific enquiry needs to be made about symptoms of psychiatric disturbances. These findings suggest that there is a case for increased health education at retirement age.
Bronchial epithelial dysplasia is a non-invasive cellular change often associated with physical or chemical injury and considered a pre-neoplastic lesion in the formation of lung cancer. A series of 39 bronchial dysplasias associated with both neoplastic and non-neoplastic lesions were assessed for expression of markers of differentiation by immunocytochemistry and compared with samples of normal bronchial epithelium. The normal bronchial epithelium studied expressed cytokeratins (CKs) 4, 6, 7, 8, 18, and 19 in all cases; CK 13 in 13 cases; and peanut agglutinin (PNA) in seven cases. Involucrin, CK 10, and CK 14 were not observed in the normal bronchial samples. In the dysplastic bronchial biopsies, epithelial staining was observed with epithelial CKs 7, 8, 18, and 19 in all cases; CK 13 was seen in 26 cases; CK 14 in 13 cases; CK 6 in 11 cases; and CK 10 in five cases. In 13 cases of dysplasia, only simple epithelial antigens were identified. Involucrin expression was observed in 17 dysplastic biopsies and PNA in 12. By Fisher's exact test, a significant association between non-severe histological grade of dysplasia and CK 6 expression (P = 0.018) was found. Comparison of the results using the same analysis showed significant correlations between the loss of CK 6 expression (P < 0.001) and the expression of CK 14 (P = 0.008) and involucrin (P = 0.0018) with bronchial dysplasia. These data show that the pattern of differentiation antigen expression in bronchial dysplasia is significantly different from that of the normal bronchial epithelium, but the phenotypic heterogeneity of these lesions is similar to that of bronchial carcinomas.
Many factors have been individually related to outcome in populations of non-small-cell lung cancer (NSCLC) patients. Factors responsible for the outcome of an individual after surgical resection are poorly understood. We have examined the importance of 'tumour volume' in determining prognosis of patients following resection of NSCLC in a multivariate model. Cox's proportional hazard analysis was used to determine the relative prognostic significance of stage, patient age, gender, tumour cell-type, nodal score and estimated 'tumour volume' in 669 cases with NSCLC treated with surgical resection, of which 280 had died. All factors (except tumour cell-type, P = 0.33) were individually related to survival (P < 0.05). When examined together, survival time was significantly and independently related to 'tumour volume' and stage (P < 0.001), and other factors ceased to be significant. In cases with stage I or II tumours, risk of death was found to increase significantly with increasing estimated 'tumour volume' (23.8% relative increase in hazard to death per doubling of 'tumour volume', 95% confidence interval 13.2-35.2%, P < 0.001 stage I; P < 0.006 stage II). In cases with stage IIIa tumours this factor alone was the significant prognostic variable. In conclusion, an estimate of 'tumour volume' significantly improves prediction of prognosis for individual NSCLC patients with UICC stage I or II tumours.
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The purpose of this retrospective study was to examine the relationship between tumor volume and age in resected non-small cell lung cancer (NSCLC). Differences exist in the behavior, growth rate, and metastatic potential of solid tumors in both aged humans and experimental animal models. Data from 669 cases of NSCLC resected between 1980 and 1992 were reviewed (445 males; 224 females; median age 67 years, range 16-86). Measurements of the resected tumor in-situ were made in three dimensions, and these were multiplied to give an estimate of the tumor volume. Multiple regression analysis was used to examine the relationship between the tumor volume, age, gender, histological cell type, and TNM nodal score. No direct relationship existed between patient age and tumor volume or nodal score. However, there was a significant relationship between patient gender and tumor volume, i.e., smaller volume tumors in female patients (p = .02). Considering all variables, two relational subgroups were identified: younger male patients with large adenocarcinomas and older female patients with small squamous cell carcinomas (p = .05). We conclude that the relationship between tumor volume and age is complex and dependent on patient gender and tumor cell type.
An important role in differentiation and proliferation has been demonstrated for the 20 cytokeratin (CK) polypeptides. The serum of 24 patients with biopsy-proven non-small cell lung cancer (NSCLC) and a similar number of controls was examined for evidence of CK8 and CK18. Using enzyme-linked immunosorbent assay (ELISA), all the control sera were negative, but 9 of the 24 patients were positive (mean 2.62 ng/ml; range 1.4-5.8; P = 0.0036). Western blotting confirmed the results of the ELISA in all cases, and indicated full size CK polypeptides. Advanced stage disease patients were more likely to be seropositive (P = 0.00024). Biopsy specimens showed CK8 expression in all 24 cases by immunochemistry and CK18 in 22 cases. This is the first study to demonstrate that a subgroup of NSCLC patients have intact CK8 and CK18 peptides in their serum, and their detection may correlate with advanced disease.
Bronchial epithelial dysplasia is thought to be a premalignant stage in the evolution of lung cancers. Using the CM-1 polyclonal antibody, we have examined the expression of the p53 protein in a larger series of bronchial dysplasias (n = 60) than hitherto investigated. The p53 protein was detected in 14% of mild, 25% of moderate and 59% of severe dysplasias; increased p53 expression correlated with the severity of dysplasia. p53-positive dysplasias had greater PCNA indices than p53-negative dysplasias. p53 expression in dysplastic tissues was compared with that in two groups of histologically normal epithelium: 14 bronchial biopsies from non-cancer patients of which all but one were negative and 32 bronchial margins from resected carcinomas, of which 17 showed infrequent solitary cells with p53-positive nuclei in predominantly basal locations scattered throughout the epithelium. These results for resection margins were confirmed by use of a second antibody, DO-1. Sixty-nine per cent of the corresponding carcinomas were p53 positive, but in 15 cases the p53 reactivity differed from resection margins. No correlation between p53 expression and any of the clinicopathological characteristics of these tumours was found. This study supports the observation that abnormal p53 expression may be an early but not obligatory event in malignant transformation in lung.
Forty-eight patients with intermediate and high-grade NHL were treated with an intensive weekly six-drug regimen of methotrexate, doxorubicin, prednisolone, etoposide, cyclophosphamide and vincristine (MAPECO) between 1982-1988 and now have a median follow-up of 4.8 years. Nineteen of these patients received an intensified derivative of this regimen with the incorporation of bleomycin. Histological sub-type showed intermediate grade in 28 and high grade in 20 patients. Forty-five patients received the 4 planned cycles, and all patients achieved an objective response, of whom 36 (75%) entered complete remission. At 5 years, the actuarial survival of the 48 patients was 50%. Of the 36 patients achieving complete remission, the relapse-free survival at 5 years was 62%. The 5-year time to treatment failure was 48% for the whole group and 40% for the 22 stage III+IV patients. Histological sub-type had no effect on survival and time to failure curves. Neutropenic fever occurred in 15 patients and grade 3/4 mucositis was seen in 25. The MAPECO combination is an effective intensive regimen with acceptable toxicity for intermediate and high-grade lymphoma.
Proliferating cell nuclear antigen (PCNA) is expressed in cells in the cell cycle and has been studied as a marker of proliferation in lung and other tumours. We have noted immunocytochemical differences in PCNA expression between normal and neoplastic bronchial cells. As bronchial dysplasia is considered preneoplastic, we have examined PCNA expression in this condition. PCNA staining in 47 cases of bronchial dysplasia and 32 samples of normal bronchial epithelium was compared. Of the dysplasias, three were mild, 11 moderate, and 33 severe. A significant increase in PCNA counts over normal epithelium was seen only in moderate and severe dysplasias. In dysplasia, mitotic indices showed a significant positive correlation with the percentage of PCNA-positive cells. We conclude that in moderate and severe dysplasias there is an increase in the number of cells expressing PCNA and undergoing division, indicating abnormal growth control.
A microbiological survey was undertaken on the eight patients in the Liverpool District who have a humidifier attachment on their oxygen concentrator. All but one of the humidifiers were contaminated with potentially pathogenic bacteria.
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Intracerebroventricular (ICV) infusions of the selective mu receptor agonist morphiceptin produce a dual effect on lordosis behavior in ovariectomized, steroid-primed rats. Low doses of morphiceptin (20 ng) inhibit lordosis whereas higher doses (2000 ng) facilitate this behavior. The present experiment tested whether naloxone, an antagonist of both high- and low-affinity mu receptors, or the long-acting high-affinity mu receptor antagonist naloxazone could block the dual effect of morphiceptin on lordosis. Ovariectomized rats primed with estrogen and progesterone received naloxone, naloxazone, or a control solution prior to ICV infusions of either 0, 20, or 2000 ng of morphiceptin. Naloxone reversed both the inhibition and facilitation of lordosis produced by morphiceptin, but had no effect on lordosis when administered before control infusions. In contrast, naloxazone reversed the inhibition but not the facilitation of lordosis. These results indicate that the inhibitory effect of morphiceptin on lordosis reflects the activation of high-affinity mu receptors whereas the facilitatory effect reflects either the activation of low-affinity mu receptors or other opioid receptor subtypes. The failure of naloxone or naloxazone to affect lordosis in rats receiving control infusions of saline further suggests that endogenous opioid systems do not exert a tonic inhibitory or facilitatory action on lordosis behavior.
BACKGROUND: As more people survive into old age, a greater number are becoming eligible for dialysis treatment for end-stage renal failure. In the UK the elderly have previously been excluded from treatment programmes, and continuing financial constraints are unlikely to improve this situation. There are few data on the views of elderly subjects on renal replacement treatment. We have, therefore, explored the views of elderly subjects in this study. METHODS: 50 subjects were selected from hospital geriatric wards and nursing homes. A short clinical vignette about a 75-year-old patient with renal failure was presented, and the subjects were asked to give their opinion on choices made by the patient to different treatment options. The subjects were then asked what choice they would make if in the same situation. They were asked what level of symptoms they would tolerate and for their views on cost and treatment allocation. Important contributors to quality of life were also determined for each subject using visual analogue scales. RESULTS: 84% of the subjects would choose dialysis treatment, and 78% of all elderly would attend hospital as necessary, if their symptoms could be relieved. 54% of the in-patient elderly and 83.3% of nursing home elderly even when physically disabled and living in a nursing home would want dialysis for end-stage renal failure. 74% of all elderly preferred to have home dialysis treatment. Only 36% of the subjects thought cost was important when allocating dialysis to the elderly. Being independent and free from major symptoms was regarded as important for a good quality of life. CONCLUSIONS: In this survey, elderly subjects wanted dialysis treatment. Neither age nor cost were considered important determinants for resource allocation. Symptom relief and maintaining independence were considered the main goals of treatment.
Tumour growth is accompanied by angiogenesis and reduced apoptosis in experimental animals. The aim of this study was to examine the prognostic value of apoptosis and the association between apoptosis and vascularity in non-small cell lung cancer (NSCLC). Following in-situ end-labelling of DNA, apoptotic cells were quantified by three different indices: as a percentage, either counting total cells (AI-tc) or point-counting (AI-pc), or as cells per area (AI-area). Blood vessels were stained with vWF antibody and vascularity was quantified by three methods. Median values for AI-tc, AI-pc and AI-area were 0.38, 0.32 and 10.7, respectively. High values were associated with improved survival, reaching statistical significance for AI-area (p < 0.05). All three apoptotic indices were significantly correlated with each other, but no correlation was found between indices of apoptosis and vascularity. As previously reported, vascularity had no prognostic value. These results indicate that, in NSCLC, vascularity is not informative, but apoptotic index may be a useful prognostic factor.
Microvascular density has been put forward as an independent prognostic factor in breast cancer, with high levels indicating poorer prognosis. However, various studies have failed to confirm its prognostic value. The reasons for the contradictory results are not known, but it is believed that methodological differences are responsible. To test this hypothesis, we have used four different methods of assessing vascularity (average and highest microvascular density, microvascular volume and image analysis of vascular area) and related them to known prognostic factors in 51 cases of breast cancer NOS. All four methods showed a significant correlation with each other, with the exception of image analysis vs microvascular volume. The average microvascular density was significantly lower in p53 positive compared to negative tumours (median 38.4 and 66.2; IQR 31.1 and 49.4, respectively, p < 0.05). Vascularity, measured by the four methods, was not associated with nodal status or any other parameter examined.