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Biomedical subjects

N Pendleton

Publications and source records attributed to N Pendleton.

At least 19 recordsLinked to original sources
PubMed2000

New approach to risk determination: development of risk profile for new falls among community-dwelling older people by use of a Genetic Algorithm Neural Network (GANN).

BACKGROUND: Falls risk in older people is multifactorial and complex. There is uncertainty about the importance of specific risk factors. Genetic algorithm neural networks (GANNs) can examine all available data and select the best nonlinear combination of variables for predicting falls. The aim of this work was to develop a risk profile for operationally defined new falls in a random sample of older people by use of a GANN approach. METHODS: A random sample of 1042 community-dwelling people aged 65 and older, living in Nottingham, England, were interviewed at baseline (1985) and survivors reinterviewed at a 4-year follow-up (n = 690). The at-risk group (n = 435) was defined as those survivors who had not fallen in the year before the baseline interview. A GANN was used to examine all available attributes and, from these, to select the best nonlinear combination of variables that predicted those people who fell 4 years later. RESULTS: The GANN selected a combination of 16 from a potential 253 variables and correctly predicted 35/114 new fallers (sensitivity = 31%; positive predictive value = 57%) and 295/321 nonfallers (specificity = 92%; negative predictive value = 79%); total correct = 76%. The variables selected by the GANN related to personal health, opportunity, and personal circumstances. CONCLUSIONS: This study demonstrates the capacity of GANNs to examine all available data and then to identify the best 16 variables for predicting falls. The risk profile complements risk factors in the current literature identified by use of standard and conventional statistical methods. Additional data about environmental factors might enhance the sensitivity of the GANN approach and help identify those older people who are at risk of falling.

Accidental Falls↗
PubMed1999

A study of infection in elderly nursing/residential home and community-based residents.

It is commonly believed that patients admitted to hospital from nursing homes/residential homes (NHRH) with infections are less likely to respond to treatment and have a higher fatality rate than counterparts admitted from their own homes ('the Community'). It is also believed that NHRH's harbour a reservoir of unusual and resistant organisms. These preconceptions may influence how these patients are managed. A database of 10593 sequential admissions to a Geriatric Medical unit over a three-year period was used to identify NHRH and community populations with a principal diagnosis of infection. They were investigated using the Department of Microbiology's database. The admission rate in the NHRH group was twice that of the community group. There were no significant differences in length of stay (LOS) [16 +/- 2 vs 17 +/- 2 days (s.e.m.)], or mean survival time (ST)(61 days (37-84) vs 48 days (25-72): 95% confidence intervals) between the two groups. Subgroups of the NHRH group did have significantly different survival times. Fatality rate was not significantly different between the NHRH (40%) or Community (35%) groups. Both the NHRH and community group underwent very similar levels of investigation (189 vs 200 investigations performed). The types and frequencies of pathogen seen in the two groups were very similar.

Aged↗
PubMed1999

The effect of aging on skeletal muscle capillarization in a murine model.

Capillarization of skeletal muscle has been reported to be both maintained and reduced with advancing age. This conflict may represent methodological differences between biopsy studies. We have examined capillarization throughout two muscles, soleus and extensor digitorum longus (EDL), from a well-established colony of aging mice, and related this to fiber number (C/F ratio) and type. Labeling of muscle capillaries was performed with the biotinylated Griffonia (Bandeiraea) simplicifolia lectin (GSL 1) using immunochemistry. The results showed a significant increase in the C/F ratio in the aged mice when compared with the younger (6-month mice soleus = 1.296, 95% CI 1.226-1.366 vs 28-month mice soleus = 1.530, 95% CI 1.488-1.572, p <.001; 6-month mice EDL = 0.881, 95% CI 0.751-1.011 vs 28-month mice EDL = 1.124, 95% CI 1.028-1.220, p = .017). These differences could not be accounted for by changes in fiber type but may reflect loss of fibers. Alternatively, there may be increased angiogenic drive or a failure of downregulation of angiogenesis.

Aging↗
PubMed1998

Assessment of vascularity in histological sections: effects of methodology and value as an index of angiogenesis in breast tumours.

The aims of this study were to (a) determine how the quantification of blood vessels in histological sections (vascularity) is affected by the methodology used and (b) assess the value of vascularity as an index of angiogenesis by comparing tumour and normal breast tissue. Archival specimens of breast, lung and oral carcinoma, oral dysplasia and normal breast tissue were used to test the effects of the following experimental variables on vascularity: pretreatment of the sections (enzymatic digestion, heating), endothelial markers (von Willebrand factor and CD31 antibodies), method of quantification (highest microvascular density, average microvascular density and microvascular volume) and interobserver variations. All the variables examined significantly affected the estimated vascularity; this depended on the type of tissue and method used. The pretreatment of the sections before staining was the most important variable, altering the vascularity ranking of the tumours. Vascularity in breast tumours was similar to that of the normal breast intralobular stroma, suggesting that an area of high microvascular density in the tumour does not necessarily represent tumour-induced angiogenesis. Contradictory results have been published regarding the value of vascularity as a tumour prognostic factor. Our results suggest that statistically significant differences in vascularity values are most likely to arise from failure to optimize the staining protocol and from the method used to assess vascularity.

Blood Vessels↗
PubMed1998

Heterogeneity in microvascular density in lung tumours: comparison with normal bronchus.

The aim of this study was to test the hypotheses that (a) microvascular density (MVD) measured in histological sections of resected non-small cell lung carcinomas is an index of angiogenesis and (b) the measurement of MVD in a single block is representative of the overall MVD of the tumour. MVD was quantitated in one block per specimen of 60 lung tumours and nine normal lung tissues, and in 47 blocks taken from different regions of four tumours. Blood vessels were stained with antibody to von Willebrand Factor and MVD was quantitated using two methods: average density throughout the section (a-MVD) and density in the most vascularized area or 'hot spot' (h-MVD). Similar h-MVD values were found in tumours and in normal bronchus, whereas a-MVD was greater in the latter (P < 0.01). When 47 blocks from four tumours were analysed, inter-tumour variation was significant (P < 0.001) in spite of significant intra-tumour variation. The highest MVD value was not necessarily found in the periphery of the tumour. The four tumours were ranked into either two or four tiers according to their overall MVD. In 50 random selections of one block per tumour, the correct ranking was achieved in 68-74% of cases with the two-tier ranking and in 6-16% of cases with the four-tier ranking (h-MVD and a-MVD values respectively). These results suggest that elevated MVD values do not necessarily represent angiogenesis in non-small cell lung carcinomas. When only one block per tumour is examined, the chance of obtaining an accurate estimate of the vascularity of that tumour may be lower than 68%.

Adenocarcinoma↗
PubMed1998

Prediction of hemorrhagic blood loss with a genetic algorithm neural network.

There is no established method for accurately predicting how much blood loss has occurred during hemorrhage. In the present study, we examine whether a genetic algorithm neural network (GANN) can predict volume of hemorrhage in an experimental model in rats and we compare its accuracy to stepwise linear regression (SLR). Serial measurements of heart period; diastolic, systolic, and mean blood pressures; hemoglobin; pH; arterial PO2; arterial PCO2; bicarbonate; base deficit; and blood loss as percent of total estimated blood volume were made in 33 male Wistar rats during a stepwise hemorrhage. The GANN and SLR used a randomly assigned training set to predict actual volume of hemorrhage in a test set. Diastolic blood pressure, arterial PO2, and base deficit were selected by the GANN as the optimal predictors set. Root mean square error in prediction of estimated blood volume by GANN was significantly lower than by SLR (2.63%, SD 1.44, and 4.22%, SD 3.48, respectively; P < 0.001). A GANN can predict highly accurately and significantly better than SLR volume of hemorrhage without knowledge of prehemorrhage status, rate of blood loss, or trend in physiological variables.

Algorithms↗
PubMed1998

Evolution of artificial neural network architecture: prediction of depression after mania.

Artificial neural networks (ANNs) are compared to standard statistical methods for outcome prediction in biomedical problems. A general method for using genetic algorithms to "evolve" ANN architecture (EANN) is presented. Accuracy of logistic regression, a fully interconnected ANN, and an EANN for predicting depression after mania are examined. All methods showed very good agreement (training set accuracy, chi-square all p < 0.01). However, significant differences were found for stability (test set accuracy); logistic regression being the most unstable and EANN being significantly more stable than a fully interconnected ANN (McNemar p < 0.01). We conclude that the EANN method enhances ANN stability. This approach may have particular relevance for biomedical prediction problems, such as predicting depression after mania.

Algorithms↗
PubMed1997

Comparison of a genetic algorithm neural network with logistic regression for predicting outcome after surgery for patients with nonsmall cell lung carcinoma.

BACKGROUND: Neural networks have been used to predict outcome in cancer patients. Their accuracy compared with standard statistical methods has not been fully assessed. METHODS: In this study, the authors examined the ability to predict the outcome of surgery in 620 patients with nonsmall cell lung carcinoma (NSCLC) by a genetic algorithm neural network (GANN) using Bayes' theorem compared with logistic regression, and the predictive value of tumor volume measures in addition to standard indices such as histologic type and stage. Predictive methods were compared by examining accuracy of classifying target outcome of patients living or dead at 6, 12, 18, and 24 months after surgery. RESULTS: GANN was a significantly better predictor of outcome than logistic regression at all time points (McNemar, P < 0.01). Measures of tumor volume produced significant improvement in the prediction of 12-, 18-, and 24-month time points with GANN, and at 18- and 24-month time points with logistic regression (Wilcoxon matched pairs signed rank test, P < 0.02). CONCLUSIONS: In this study of surgically treated NSCLC patients, outcome predictions were significantly improved by including measures of tumor volume. For predicting individual patient outcome, GANN was found to be highly accurate and significantly better than logistic regression.

Aged↗
PubMed1997

Relationship between vascularity, age and survival in non-small-cell lung cancer.

Lung tumours in the elderly show reduced growth potential; impaired angiogenesis may contribute to this phenomenon. Recent studies have suggested that the angiogenic potential of a tumour may be inferred by the vascularity measured in histological sections. The purpose of this study has been to determine whether vascularity is related to age, survival or other clinical parameters in resected non-small-cell lung cancer (NSCLC). A group of 88 consecutive patients with a follow-up period of at least 5 years was selected. The group exhibited a wide age range (37-78 years) and similar survival characteristics to those of the general NSCLC population. Tumour sections were stained with a pan-endothelial antibody (vWF) and vascularity was quantitated, without knowledge of the clinical details, by three methods: highest microvascular density; average microvascular density; and average microvascular volume. The results were analysed by non-parametric statistical tests. A correlation was found between all three methods of quantitation. Vascularity was not associated with age, sex, tumour type, stage, volume, size (TNM-T) nodal status (TNM-N) or survival. However, survival time was generally longer for patients with higher vascularity, reaching borderline significance (P = 0.06) for the average microvascular density values. Higher tumour volume (P = 0.02) and stage (P = 0.05) were associated with lower survival times. Using multivariate survival analysis, tumour volume was the only factor related to survival. We conclude that vascularity is not associated with age and has no significant prognostic value in NSCLC.

Adult↗
PubMed1997

Older people's perceptions about symptoms.

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.

Aged↗
PubMed1996

Expression of markers of differentiation in normal bronchial epithelium and bronchial dysplasia.

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.

Aged↗
PubMed1996

'Tumour volume' as a predictor of survival after resection of non-small-cell lung cancer (NSCLC)

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.

Carcinoma, Non-Small-Cell Lung↗
PubMed1996

Correlates of tumor size, gender, cell type, and metastasis of resected non-small cell lung cancer and age.

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.

Adenocarcinoma↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗