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Biomedical subjects

N Pendleton

Publications and source records attributed to N Pendleton.

29 records · Page 2Linked to original sources

Simple cytokeratins in the serum of patients with lung cancer: relationship to cell death.

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.

Adenocarcinoma↗

p53 expression in normal and dysplastic bronchial epithelium and in lung carcinomas.

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.

Biopsy↗

A six-drug regimen (MAPECO) for intermediate or high-grade non-Hodgkin's lymphoma.

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.

Adolescent↗

Expression of proliferating cell nuclear antigen (PCNA) in dysplasia of the bronchial epithelium.

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.

Aged↗

Dual effect of morphiceptin on lordosis behavior: possible mediation by different opioid receptor subtypes.

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.

Analgesics↗

Opinions of elderly people on treatment for end-stage renal disease.

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.

Adaptation, Psychological↗

High levels of apoptosis are associated with improved survival in non-small cell lung cancer.

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.

Adenocarcinoma↗

Neural networks.

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Humans↗

Relationships between different measurements of vascularity and clinico-pathological parameters in breast cancer.

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.

Aged↗