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Biomedical subjects

M Heatley

Publications and source records attributed to M Heatley.

18 recordsLinked to original sources
PubMed2005

The heart and the oesophagus: intimate relations.

The close anatomical relations of the heart and oesophagus, and the similarity of symptoms attributable to disorders of either organ, often lead to diagnostic difficulty in patients with chest pain. A definitive diagnosis of non-cardiac chest pain attributable to oesophageal reflux or spasm is hampered, both by the need for prolonged ambulatory monitoring of pH, manometry, and endoscopy, and by the common occurrence of asymptomatic reflux and spasm, and the corresponding difficulty in linking an episode of reflux or spasm with an episode of pain. Moreover, some patients with non-cardiac chest pain and normal tests of oesophageal structure and function have centrally mediated hypersensitivity, both within and without the oesophagus. Rather than proceed with investigations, in the absence of symptoms to suggest structural disease of the oesophagus, it would be reasonable to attempt symptomatic treatment with a proton pump inhibitor or an antidepressant.

Antidepressive Agents, Tricyclic↗
PubMed1998

Is the measurement of placental protein-14 and CA-125 in plasma and uterine flushings useful in the evaluation of peri-menopausal and post-menopausal bleeding?

In this prospective study, we examined the possible diagnostic value of the measurement of two endometrial proteins, placental protein-14 (PP14) and CA-125, in the evaluation of pre- and post-menopausal bleeding. Concentrations of these two proteins were measured in plasma and uterine flushings obtained from 139 pre- and post-menopausal women with bleeding problems, and 26 normal post-menopausal control women without bleeding. Endometrial biopsy samples were also obtained for histological study. Concentrations of PP14 in both the plasma and uterine flushings in post-menopausal women were significantly lower (P < 0.001) than those of control pre-menopausal women. In post-menopausal women, the concentrations of PP14 (mean +/- SEM) in both plasma and flushing were significantly higher (P < 0.001) in women with endometrial adenocarcinoma (46.9+/-7.5 ng/ml plasma; 3350+/-1711 ng/ml flushing) than in the controls (7.6+/-1.3 ng/ml plasma; 125+/-27 ng/ml flushing) or in women with post-menopausal bleeding and atrophic endometrium (20.4+/-2.1 ng/ml plasma; 453+/-167 ng/ml flushing). In contrast CA-125 concentrations in plasma and flushings were similar in post-menopausal and pre-menopausal women. Plasma concentrations of CA-125 were higher in post-menopausal women with adenocarcinoma (29.1+/-7.4 IU/ml) than in those with post-menopausal bleeding and atrophic endometrium (21.8+/-2 IU/ml) (P < 0.05) or control post-menopausal subjects (16.1+/-2.1 IU/ml) (P < 0.01). CA-125 concentrations in uterine flushings were not significantly different in any group of post-menopausal women. The results show that concentrations of PP14 are correlated more strongly to endometrial histopathology than those of CA-125 in pre- and post-menopausal women. Elevated PP14 concentrations are also associated with the presence of endometrial adenocarcinoma and may have a potential to be used as a marker for this disease.

Adenocarcinoma↗
PubMed1995

Cytokeratin intermediate filament expression in benign and malignant breast disease.

AIM: To carry out a comprehensive study of cytokeratin expression in benign and malignant breast epithelium and breast myoepithelial cells; to examine changes in the cytokeratin profile in malignant and benign epithelium and in carcinomas of increasing histological grade. METHODS: Frozen sections from fibroadenomas (19 cases), fibrocystic disease (19 cases), and infiltrating ductal (68 cases), lobular (seven cases), and mucinous carcinomas (three cases) were examined using a panel of monoclonal antibodies. RESULTS: The luminal epithelium in all fibroadenomas and all cases of fibrocystic disease, as well as tumour cells in most carcinomas, reacted with the specific antibodies to cytokeratins 7, 8, 18, and 19 and to antibodies which included these cytokeratins in their specificities (Cam 5.2, AE1, AE3, RCK102, and LP34). In a few ductal carcinomas none of the tumour cells reacted for cytokeratins 7, 8, or 18. Three ductal carcinomas expressed cytokeratin 14. Only occasional cases expressed cytokeratins 3, 4, 10, and 13. Antibodies which included cytokeratins 5 and 14 in their specificities detected myoepithelial cells less efficiently than antiactin antibodies. CONCLUSION: The cytokeratin profiles in the luminal epithelium in benign breast disease and in tumour cells in most carcinomas are similar in most cases. Some carcinomas, however, are negative for cytokeratins 7, 8, or 18. This may provide a means of predicting the biological behaviour of a histologically borderline lesion.

Antibodies, Monoclonal↗
PubMed1995

Vimentin and cytokeratin expression in nodular hyperplasia and carcinoma of the prostate.

AIM: To assess the value of vimentin and cytokeratin (CK) intermediate filament proteins (IFPs) in distinguishing between nodular hyperplasia and carcinoma of the prostate and in predicting prognosis in prostatic cancer. METHODS: Fifteen carcinomas and 49 cases of nodular hyperplasia were studied using frozen sections and monoclonal antibodies to CK and vimentin IFPs. RESULTS: There was no statistically significant difference in vimentin expression between nodular hyperplasia and carcinoma. The luminal epithelium in both also reacted with antibodies which detect CK8, 18 and 19. CK 7 expression was found in 57% of cases of nodular hyperplasia and was not identified in any carcinoma. There was a reaction with antibodies to CK1, 2, 3, 4, 10, 11, and 13 in only a minority of cases. There was no statistically significant difference in vimentin and CK reactivity in high and low grade carcinomas. CONCLUSION: Neither vimentin nor CK expression assists in establishing whether a prostatic lesion is benign or malignant or in predicting the biological behaviour of a prostatic carcinoma.

Diagnosis, Differential↗
PubMed1995

Distribution of cervical intraepithelial neoplasia: are hysterectomy specimens sampled appropriately?

AIM: To determine whether sampling the anterior and posterior cervical lips in hysterectomy specimens provides the best opportunity for detecting unsuspected cervical intraepithelial neoplasia (CIN). METHODS: The frequency with which CIN was identified at a range of positions on the anterior and posterior lips and left and right lateral aspects of the cervix was assessed in 100 cone biopsy specimens. RESULTS: CIN affected one or other cervical lip in all 100 cases studied and involved the midline positions (12 and 6 o'clock) in 94. The lateral edges of the cervical canal were also involved in 38 cases. CONCLUSION: CIN is more likely to be identified on the anterior and posterior lips than on the lateral aspect of the cervical os. The findings support the continuation of the established practice of taking blocks from the midline in these areas.

Biopsy↗
PubMed1994

Jass' classification revisited.

BACKGROUND: In 1986, Jass and colleagues claimed to have improved on Dukes' classification of prognosis for carcinoma of the colon and rectum. To have clinical relevance, such results should be reproducible and confirmed by other institutions. STUDY DESIGN: Retrospective clinicopathologic study of 312 carcinomas of the colon and rectum to determine whether or not Jass' classification is superior to that of Dukes' as assessed by their relative reproducibility and prognostic significance. RESULTS: Dukes' classification had excellent intraobserver and interobserver reproducibility (kappa values of 0.86 and 0.93, respectively). In contrast, the reproducibility of variables assessed by Jass showed only slight to fair agreement (lymphocytic infiltration: intraobserver and interobserver kappa values of 0.08 and 0.05, respectively, growth pattern: intraobserver and interobserver kappa values of 0.37 and 0.41, respectively). Dukes' stage and patient age were the most important prognostic variables on multivariate regression analysis. Tumor differentiation, nuclear polarity, tubule configuration, and lymphocytic infiltration remained significantly related to survival in the presence of Dukes' stage and age. The model which best predicted prognosis was a combination of Dukes' stage, patient age and tumor differentiation. Further addition of the variables assessed by Jass to this model did not significantly improve the prediction of prognosis. CONCLUSIONS: Dukes' classification is of greater prognostic value and more reproducible than the components of Jass' classification. The continued use of Dukes' classification is, therefore, warranted for prognostic and therapeutic decisions in patients with carcinoma of the colon and rectum.

Colonic Neoplasms↗
PubMed1994

Colorectal carcinoma: importance of clinical and pathological factors in survival.

A series of clinicopathological variables was assessed on 312 patients undergoing surgical resection for primary colorectal cancer. Although the presence of venous invasion was related to mortality (P = 0.02), classifying invasion into involvement of thick-walled or thin-walled veins did not produce a variable of prognostic value. Intestinal obstruction (P = 0.04) and the macroscopic appearance of the tumour (P = 0.04) were related to mortality from colorectal cancer, but not from all causes of death. Duke's stage, increasing patient age and poorly differentiated tumours were the variables which were individually most significantly related to poor prognosis (P < 0.001 for each analysis). Cox's regression analysis identified these three variables as independent predictors of outcome in colorectal cancer. This study confirms that Duke's stage, patient age and tumour differentiation are still the most important clinicopathological variables in colorectal cancer.

Adult↗
PubMed1993

Morphometric analysis of colorectal cancer.

Thirteen nuclear and cellular morphometric variables were measured in 312 cases of colorectal adenocarcinoma. All variables, except nuclear shape factors, differed significantly (P < 0.001) between normal colorectal and tumor tissue. In adenocarcinomas, epithelial nuclei in well-differentiated mucosa tended to be elliptic, while those in poorly differentiated mucosa were more spheric. Increasing values of maximum nuclear and elliptic diameter were associated with progression from none to simple tubule configuration (P < 0.001), none to easily discerned nuclear polarity (P < 0.001), and expanding growth pattern (P < 0.001). Univariate survival analysis revealed that none of the morphometric variables was significantly related to patient survival. Multivariate regression analysis showed that no morphometric variable could add significantly to a model containing the variables of patient age, Dukes stage, and tumor differentiation. Morphometry may be useful in distinguishing malignant from normal tissue and degrees of differentiation, but it is of little prognostic value in colorectal adenocarcinoma.

Adenocarcinoma↗
PubMed1993

C-erbB-2 oncogene product expression depends on tumour type and is related to oestrogen receptor and lymph node status in human breast carcinoma.

Although over-expression of the C-erbB-2 oncogene product can be detected on formalin-fixed, paraffin-embedded sections from tumours of the human breast, fixation results in a considerable loss of immunostaining for this protein. In this study, C-erbB-2 expression was studied immunohistochemically on frozen sections in 63 infiltrating carcinomas, 3 phyllodes tumours, 15 fibroadenomas and 16 cases of fibrocystic disease. The value of C-erbB-2 expression as a prognostic indicator in ductal carcinomas was examined by seeking an association with known prognostic indicators. C-erbB-2 over-expression was confined to ductal carcinomas of the breast and was positively correlated with tumour size, grade, oestrogen receptor status and the presence of metastatic deposits in axillary lymph nodes. Only the association with lymph node and oestrogen receptor status were statistically significant. No evidence of a correlation between C-erbB-2 expression and growth fraction (as assessed with the Ki-67 antibody) was demonstrated in the cases studied. Formalin fixation was associated with the loss of immunoreactivity in all cases studied. 75% of cases which were positive on frozen sections were negative in paraffin sections. These results highlight the significance of the method of fixation used in studying C-erbB-2 expression. They confirm the association between C-erbB-2 expression and known prognostic indicators.

Breast Neoplasms↗
PubMed1993

DNA densitometry of colorectal cancer.

DNA analysis was assessed by densitometry for 281 cases of colorectal adenocarcinoma. Detection of aneuploidy in a single case rose from 65% if one, to 92.5% when three or more sections, were analysed. Although aneuploid tumours had significantly larger nuclear areas than near diploid tumours (p = 0.009), densitometric measurements showed no association with clinicopathological variables. DNA content determined by densitometry was compared with that from flow cytometry on 465 tissue sections from 241 cases. Aneuploidy assessed by flow cytometry was significantly associated with that determined by densitometry (p < 0.01 for all comparisons), ploidy state being similar in 381 sections (82%, kappa = 0.63, p < 0.001), and 187 cases (77.6%, kappa = 0.57, p < 0.001). Univariate survival analysis showed that DNA densitometric variables had no significant association with survival in (a) all cases, (b) cases without lymph node metastases, or (c) cases without distant metastases. Multivariate regression analysis of densitometric and clinicopathological variables identified Dukes's stage, patient age, and tumour differentiation as the combination of variables most closely related to survival. Densitometric measurement of DNA content could not significantly improve on the prognostic model containing these three variables. It is concluded that, although the assessment of DNA content by densitometry is comparable with that of flow cytometry, conventional histological variables remain the best predictors of prognosis in colorectal cancer.

Adenocarcinoma↗
PubMed1993

Vimentin expression in benign and malignant breast epithelium.

AIMS: To determine vimentin expression in epithelial cells in benign breast disease and malignant breast tumours; to assess the value of vimentin expression as a prognostic indicator in breast carcinoma. METHODS: Frozen and formalin fixed, paraffin wax embedded sections from 78 carcinomas, three phyllodes tumours, 19 fibroadenomas and 19 cases of fibrocystic disease were examined with a monoclonal antibody from the V9 clone. A correlation between vimentin expression and known prognostic indicators was sought in ductal carcinomas. The intracellular localisation of vimentin was examined in benign and malignant lesions. RESULTS: Vimentin expression was identified on frozen section in the cells of ductal (53%), lobular (86%), and mucinous (33%) carcinomas and in the luminal epithelium of fibroadenomas (68%), cases of fibrocystic disease (47%), and a malignant phyllodes tumour. Formalin fixation reduced the percentage of carcinomas and cases of benign disease in which vimentin was detected. This reduction was more pronounced in fibroadenoma and fibrocystic disease than in ductal carcinoma. Associations were identified between vimentin expression as detected on frozen section and tumour grade, size, number of lymph nodes affected, oestrogen receptor content and growth fraction. Only the association with grade was significant (p = 0.045). There was no significant correlation between any of these prognostic variables and vimentin expression on paraffin wax sections. There was no difference in the intracellular localisation of vimentin staining between benign and malignant lesions, or between low and high grade ductal carcinomas. CONCLUSION: There is some loss of vimentin immunoreactivity after formalin fixation. Vimentin expression does not assist in differentiating between benign and malignant breast disease, but is correlated with tumour grade in ductal carcinoma.

Adenofibroma↗
PubMed1993

The role of flow cytometry in carcinoma of the colon and rectum.

Flow cytometry was performed upon 312 patients with adenocarcinoma of the colon and rectum, satisfactory results being obtained with 275 (108 diploid, 130 aneuploid and 37 tetraploid). The proportion of nondiploid instances increased from 28 percent if one, to 80 percent when six specimens were assessed per patient. Reproducibility of the technique showed substantial agreement in the assessment of deoxyribonucleic acid ploidy (Kappa value equals 0.74). Increasing values of cells in the diving (G2/M) phase of the cell cycle were associated with little lymphocytic tumor infiltration (p = 0.0002) and extensive tumor fibrosis (p = 0.003). Univariate survival analysis revealed that, although diploid tumors tended to have a better prognosis than nondiploid tumors (p = 0.06), no flow cytometric variable was significantly related to survival. Flow cytometry similarly was not of prognostic value in instances without lymph node metastases or without distant metastases. Multivariate regression analysis of flow cytometric and clinicopathologic variables identified Dukes' stage, patient age and tumor differentiation as the combination of variables most closely related to survival. No flow cytometric variable could significantly improve on the prognostic model containing these three variables. It is concluded that conventional histologic variables remain the best predictors of prognosis in carcinoma of the colon and rectum.

Adenocarcinoma↗
PubMed1990

Rates of drug detection in urine samples from various populations.

About 14% of all substance abuse urine tests are positive for 1.2 substances. Cannabinoid and cocaine metabolites are most frequently the cause of positivity. Individuals in probation or parole programs have the highest numbers of positive urine substance abuse tests. Our data suggest that a consistency of positivity exists for substance abuse urine tests and that this positivity, once developed by testing laboratories, can be used for purposes of contractual relations and cost predictions. Valuable educational information that may assist the population serviced by the laboratory in regard to substance abuse can also be obtained.

Humans↗
PubMedDate not supplied

A functional hypothesis for LGN-V1-TRN connectivities suggested by computer simulation.

We employ computer simulation to investigate the function of neural circuitries between thalamic sensory relay nuclei, primary sensory cortices, and the thalamic reticular nucleus (TRN). Computational similarities exist between these circuits and the architecture of a simple artificial neural network. We impose processing parameters on this network architecture in keeping with anatomical and physiological details of the mammalian geniculo-cortical visual pathway, and then run the simulation on a task involving multiple simultaneous inputs from the simulated visual field. After two to three loops through the simulation, activity in cortical and thalamic units whose receptive fields include the stronger stimulus remains constant, while activity in other cortical and thalamic units activated by weaker stimuli declines toward resting values. These results suggest that the modeled neural circuitry functions to "prime" selective attentional mechanisms further up the visual streams toward specific portions of the total visual stimulus. Besides extending existing models and evidence about the function of these neural circuits, our results also provide physiologists with predicted activity profiles of thalamic and cortical elements of the modeled neural system for a task not yet studied experimentally.

Animals↗
PubMedDate not supplied

Intermediate filament expression of ductal carcinoma cells in fine needle aspirates of the breast.

OBJECTIVE: To assess the frequency of occurrence of vimentin expression in fine needle aspirates of ductal carcinoma of the breast and the association of vimentin expression with established prognostic indicators. STUDY DESIGN: Cytocentrifuge preparations made from fine needle aspirates of 51 cases of ductal carcinoma were studied. RESULTS: Vimentin expression, detected in 61% of cases, was positively associated with tumor size, lymph node status, tumor grade, growth fraction and negative estrogen receptor status, but only in the case of lymph node status did the association reach the level of statistical significance. CONCLUSION: Vimentin expression can be detected in breast cancer using fine needle aspiration. Further study is necessary to determine whether it provides independent prognostic information.

Biopsy, Needle↗