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H Bharucha

Publications and source records attributed to H Bharucha.

At least 19 recordsLinked to original sources
PubMed2004

Inter-observer variation between pathologists in diffuse parenchymal lung disease.

BACKGROUND: There have been few inter-observer studies of diffuse parenchymal lung disease (DPLD), but the recent ATS/ERS consensus classification provides a basis for such a study. METHODS: A method for categorising numerically the percentage likelihood of these differential diagnoses was developed, and the diagnostic confidence of pathologists using this classification and the reproducibility of their diagnoses were assessed. RESULTS: The overall kappa coefficient of agreement for the first choice diagnosis was 0.38 (n = 133 biopsies), increasing to 0.43 for patients (n = 83) with multiple biopsies. Weighted kappa coefficients of agreement, quantifying the level of probability of individual diagnoses, were moderate to good (mean 0.58, range 0.40-0.75). However, in 18% of biopsy specimens the diagnosis was given with low confidence. Over 50% of inter-observer variation related to the diagnosis of non-specific interstitial pneumonia and, in particular, its distinction from usual interstitial pneumonia. CONCLUSION: These results show that the ATS/ERS classification can be applied reproducibly by pathologists who evaluate DPLD routinely, and support the practice of taking multiple biopsy specimens.

Biopsy↗
PubMed2003

Computerized diagnostic decision support system for the classification of preinvasive cervical squamous lesions.

Previous studies have revealed considerable interobserver and intraobserver variation in the histological classification of preinvasive cervical squamous lesions. The aim of the present study was to develop a decision support system (DSS) for the histological interpretation of these lesions. Knowledge and uncertainty were represented in the form of a Bayesian belief network that permitted the storage of diagnostic knowledge and, for a given case, the collection of evidence in a cumulative manner that provided a final probability for the possible diagnostic outcomes. The network comprised 8 diagnostic histological features (evidence nodes) that were each independently linked to the diagnosis (decision node) by a conditional probability matrix. Diagnostic outcomes comprised normal; koilocytosis; and cervical intraepithelial neoplasia (CIN) I, CIN II, and CIN III. For each evidence feature, a set of images was recorded that represented the full spectrum of change for that feature. The system was designed to be interactive in that the histopathologist was prompted to enter evidence into the network via a specifically designed graphical user interface (i-Path Diagnostics, Belfast, Northern Ireland). Membership functions were used to derive the relative likelihoods for the alternative feature outcomes, the likelihood vector was entered into the network, and the updated diagnostic belief was computed for the diagnostic outcomes and displayed. A cumulative probability graph was generated throughout the diagnostic process and presented on screen. The network was tested on 50 cervical colposcopic biopsy specimens, comprising 10 cases each of normal, koilocytosis, CIN I, CIN II, and CIN III. These had been preselected by a consultant gynecological pathologist. Using conventional morphological assessment, the cases were classified on 2 separate occasions by 2 consultant and 2 junior pathologists. The cases were also then classified using the DSS on 2 occasions by the 4 pathologists and by 2 medical students with no experience in cervical histology. Interobserver and intraobserver agreement using morphology and using the DSS was calculated with kappa statistics. Intraobserver reproducibility using conventional unaided diagnosis was reasonably good (kappa range, 0.688 to 0.861), but interobserver agreement was poor (kappa range, 0.347 to 0.747). Using the DSS improved overall reproducibility between individuals. Using the DSS, however, did not enhance the diagnostic performance of junior pathologists when comparing their DSS-based diagnosis against an experienced consultant. However, the generation of a cumulative probability graph also allowed a comparison of individual performance, how individual features were assessed in the same case, and how this contributed to diagnostic disagreement between individuals. Diagnostic features such as nuclear pleomorphism were shown to be particularly problematic and poorly reproducible. DSSs such as this therefore not only have a role to play in enhancing decision making but also in the study of diagnostic protocol, education, self-assessment, and quality control.

Bayes Theorem↗
PubMed2002

Increased nm23 immunoreactivity is associated with selective inhibition of systemic tumour cell dissemination.

AIMS: In vitro transfection experiments show that the nm23 gene suppresses metastasis, although the evidence from clinical studies is contradictory. The purpose of this study was to investigate whether nm23 selectively influences systemic, pleural, and lymphatic metastasis in non-small cell lung cancer (NSCLC). METHODS: Forty two patients undergoing resection of NSCLC and lymph node sampling were enrolled prospectively. In each case, a bone marrow aspirate, pleural lavage, and lymph nodes were assessed using immunohistochemistry for epithelial antigens and morphology. The intensity of nm23-H1 immunoreactivity of the primary tumour was compared with the internal control of normal bronchial epithelium in 32 cases where available. The microvessel count (MVC) of each tumour was determined using immunohistochemistry for the endothelial cell marker CD34. RESULTS: Tumour cell dissemination was detected in the bone marrow in 18 patients, in the pleura in seven, and in the lymph nodes in 21. Increased immunoreactivity for nm23 was found in the primary tumour in six patients, with none having tumour cells in the bone marrow, compared with 12 of 26 patients who showed nm23 immunoreactivity equal to or less than the control (Fisher's exact test: p = 0.043). This effect was confirmed to be independent of the MVC on multivariate analysis. There was no significant difference in the incidence of pleural or lymphatic tumour cell dissemination between the two groups. CONCLUSION: nm23 appears to be a suppressor of systemic, but not lymphatic, metastasis in primary NSCLC.

Aged↗
PubMed2000

An automated machine vision system for the histological grading of cervical intraepithelial neoplasia (CIN).

The histological grading of cervical intraepithelial neoplasia (CIN) remains subjective, resulting in inter- and intra-observer variation and poor reproducibility in the grading of cervical lesions. This study has attempted to develop an objective grading system using automated machine vision. The architectural features of cervical squamous epithelium are quantitatively analysed using a combination of computerized digital image processing and Delaunay triangulation analysis; 230 images digitally captured from cases previously classified by a gynaecological pathologist included normal cervical squamous epithelium (n=30), koilocytosis (n=46), CIN 1 (n=52), CIN 2 (n=56), and CIN 3 (n=46). Intra- and inter-observer variation had kappa values of 0.502 and 0.415, respectively. A machine vision system was developed in KS400 macro programming language to segment and mark the centres of all nuclei within the epithelium. By object-oriented analysis of image components, the positional information of nuclei was used to construct a Delaunay triangulation mesh. Each mesh was analysed to compute triangle dimensions including the mean triangle area, the mean triangle edge length, and the number of triangles per unit area, giving an individual quantitative profile of measurements for each case. Discriminant analysis of the geometric data revealed the significant discriminatory variables from which a classification score was derived. The scoring system distinguished between normal and CIN 3 in 98.7% of cases and between koilocytosis and CIN 1 in 76.5% of cases, but only 62.3% of the CIN cases were classified into the correct group, with the CIN 2 group showing the highest rate of misclassification. Graphical plots of triangulation data demonstrated the continuum of morphological change from normal squamous epithelium to the highest grade of CIN, with overlapping of the groups originally defined by the pathologists. This study shows that automated location of nuclei in cervical biopsies using computerized image analysis is possible. Analysis of positional information enables quantitative evaluation of architectural features in CIN using Delaunay triangulation meshes, which is effective in the objective classification of CIN. This demonstrates the future potential of automated machine vision systems in diagnostic histopathology.

Female↗
PubMed1998

Anaplastic large cell malignant lymphoma with extensive eosinophilic or neutrophilic infiltration.

AIMS: We describe the clinicopathological features of eight cases of Ki-1 positive anaplastic large cell malignant lymphoma (Ki-1 ALCL) in which there was extensive infiltration by eosinophils and/or neutrophils in the absence of necrosis. METHODS AND RESULTS: The patients comprised four males and four females with an age range of 24-74 years. Five cases had originally been diagnosed as Hodgkin's disease and one as true histiocytic lymphoma. In all cases, there was massive infiltration by eosinophils and/or neutrophils sometimes to such an extent that malignant cells were obscured. Immunohistochemical staining was performed using the monoclonal antibodies CD30, CD15, CD45, CD20, CD3, CD45RO, epithelial membrane antigen (EMA), CAM5.2, vimentin and CD68. In all cases, tumour cells were strongly positive for CD30 but negative for CD15. One case was positive for CD45 but none expressed B or T-cell markers. Five cases were positive for vimentin and two for EMA. Three of seven patients in whom adequate clinical details were available had stage III or IV disease at presentation and four exhibited B symptoms. Four patients had a peripheral neutrophilia and one a peripheral eosinophilia. CONCLUSIONS: The study shows that an eosinophil and/or neutrophil-rich variant of Ki-1 ALCD exists, expanding the morphological spectrum of this tumour.

Adult↗
PubMed1998

Immunohistochemical detection of metallothionein and MIB1 in uterine cervical squamous lesions.

Metallothioneins (MTs) are ubiquitous low molecular weight proteins with a high affinity for heavy metal ions such as zinc, copper, cadmium, and platinum. Immunohistochemically detectable MT overexpression has been demonstrated in a variety of cancers, especially breast carcinoma. In this study, the immunohistochemical expression of MT in normal cervical squamous epithelia, cervical intraepithelial neoplasms (CINs), and invasive cervical squamous carcinomas was investigated. Immunohistochemical staining for proliferating cells using the MIB1 antibody was also performed. In normal squamous epithelia (n = 31), positive staining with MT was confined to basal and parabasal cells. In cases of koilocytosis (n = 14) and CIN I (n = 10), staining was also largely confined to basal and parabasal cells, with only occasional cases of CIN I exhibiting positivity within higher cell layers. Cases of CIN II (n = 14) showed positive staining largely confined to basal and parabasal cells, with staining of higher cell layers in a few cases. In the majority of cases of CIN III (n = 29), there was diffuse positive staining throughout the full epithelial thickness and, in almost all cases, positive staining was present above the basal and parabasal layers. Positive staining was present in 19 of 21 invasive squamous carcinomas. With MIB 1, positivity was confined to the parabasal layer in normal squamous epithelia. In cases of CIN, positive cells were present in progressively higher cell layers, in accordance with the grade of CIN. There was widespread positive staining in all cases of invasive squamous carcinoma. Overexpression of MT, demonstrated immunohistochemically, is associated with CIN III and invasive cervical squamous carcinoma, lesions which exhibit the highest proliferative activity, as shown by MIB1 immunostaining. MT overexpression in cervical squamous lesions appears to occur at some point along the spectrum of high grade CIN and may be related to cell proliferation.

Antigens, Nuclear↗
PubMed1998

Inter- and intra-observer variation in the histopathological reporting of cervical squamous intraepithelial lesions using a modified Bethesda grading system.

OBJECTIVE: 1. To assess inter- and intra-observer variation in the histopathological reporting of cervical colposcopic biopsies using a histologic modification of the cytological Bethesda grading system; 2. to determine the histologic profile of those cases which resulted in diagnostic disagreement. METHODS: Consecutive cervical colposcopic biopsies (n = 125) were assessed independently by six experienced histopathologists. Cases were classified as normal, low grade squamous intraepithelial lesion or high grade squamous intraepithelial lesion. Six months later the process was repeated. The degree of inter and intra-observer variation was assessed by kappa statistics. All cases in which there was less than perfect inter and intra-observer agreement were reviewed by the coordinator of the study. RESULTS: In the first round of the study inter-observer agreement was generally poor, with unweighted and weighted kappa values ranging from 0.15 to 0.58 (average 0.30) and from 0.21 to 0.61 (average 0.36) respectively. In the second round inter-observer agreement was better, with unweighted and weighted kappa values ranging from 0.08 to 0.55 (average 0.33) and from 0.22 to 0.59 (average 0.42). Ten of the 15 pairs of observers achieved fair inter-observer agreement using weighted kappa analysis. The degree of intra-observer agreement was better, unweighted and weighted kappa values ranging from 0.26 to 0.61 (average 0.47) and from 0.34 to 0.62 (average 0.51) respectively. Two of the six participants achieved fair intra-observer agreement and two achieved good intra-observer agreement using weighted kappa analysis. There were marked difficulties in the separation of normal squamous epithelium from low grade squamous intraepithelial lesion and in the separation of low grade from high grade squamous intraepithelial lesions. Histopathological review revealed that many of the difficulties in the separation of normal and low grade squamous intraepithelial lesion were in the distinction between superficial vacuolated cells and true koilocytes. Difficulties also resulted in the separation of basal cell hyperplasia, inflammatory associated changes and immature squamous metaplasia from low grade squamous intraepithelial lesion. Conditions which resulted in difficulty in the separation of low grade and high grade squamous intraepithelial lesions included florid koilocytotic change and immature metaplastic squamous epithelium with atypia. In some cases, there was a full spectrum of diagnoses from normal to high grade squamous intraepithelial lesion. These were largely cases of immature metaplastic squamous epithelium with atypia and of thin or atrophic squamous epithelium with atypia. CONCLUSIONS: Most pairs of observers can achieve fair inter-observer agreement in the reporting of cervical colposcopic biopsies using a modified Bethesda system. Intra-observer agreement is also generally fair to good using this system. It may be that a two tier grading system is more appropriate for the histopathological reporting of these biopsies than the traditional three-tier intraepithelial neoplasia (CIN) system.

Biopsy↗
PubMed1998

Mediastinal granulocytic sarcoma: a report of two cases.

We describe the cases of two patients who presented with granulocytic sarcoma with mediastinal involvement 15 and 21 months before development of acute myeloid leukemia. In both cases several bone marrow aspirates and trephine biopsy specimens, obtained at presentation and subsequently, revealed no evidence of leukemic infiltration. One case was originally misdiagnosed as large-cell non-Hodgkin's lymphoma, which resulted in inappropriate therapy. In both cases immunohistochemical staining revealed that tumor cells were positive for leucocyte common antigen but not for conventional B- or T-lymphoid-cell markers. Retrospective analysis revealed that tumor cells in both cases were positive for myeloid markers. Histopathologists should be aware that granulocytic sarcoma may occur in unusual extramedullary sites without evidence of bone marrow involvement. If inappropriate treatment is to be avoided, a diagnosis of granulocytic sarcoma should be considered when hemopoietic tumor cells do not stain with conventional antibodies against B- and T-lymphoid cells. Both histochemical and immunohistochemical staining should be performed in such cases to determine whether the cells are of myeloid lineage. A diagnosis of granulocytic sarcoma is not ruled out when bone marrow biopsy specimens show no evidence of leukemic infiltration.

Adult↗
PubMed1998

Automated histometry in quantitative prostate pathology.

OBJECTIVE: To review progress on the development of machine vision and image understanding in prostate tissue histology and to discuss the problems and opportunities afforded to pathology through the use of these techniques. STUDY DESIGN: A variety of concepts in machine vision are explored, and methodologies are described that have been developed to deal with the complexities of histologic imagery. The theory of human vision and its impact on machine vision are discussed. Software has been specifically developed for the analysis of prostate histology, allowing accurate gland segmentation, basal cell identification and measurement of vascularization within lesions. RESULTS: Image interpretation can be achieved using knowledge-based image analysis and the application of local object-oriented processing. This successfully allows an automated quantitative analysis of histologic morphology in the diagnosis of prostate intraepithelial neoplasia and invasive prostatic cancer. The use of low-power image scanning, based on textural or n-gram mapping, permits the development of fully automated devices for the rapid detection of tissue abnormalities. High-power, knowledge-guided scene segmentation can be carried out for the quantitative analysis of cellular features and the objective grading of the lesion. CONCLUSION: Automated tissue section scanning and image interpretation is now possible and holds much promise in prostate pathology and other diagnostically demanding areas. Issues of standardization still need to be addressed, but the development of such systems will undoubtedly enhance our diagnostic capabilities through the automation of time-consuming procedures and the quantitative evaluation of disease processes.

Humans↗
PubMed1997

Immunohistochemical detection of p53 and bcl-2 proteins in neoplastic and non-neoplastic endocervical glandular lesions.

The study examines p53 and bcl-2 protein expression in a variety of neoplastic and non-neoplastic endocervical glandular lesions. Immunohistochemical staining, using monoclonal antibodies against p53 (DO-7) and bcl-2, was performed on archival paraffin-embedded tissue following microwave antigen retrieval. With DO-7 there was positive nuclear staining in 23/33 cases of adenocarcinoma, 2/10 adenocarcinoma in situ, 2/10 tubo-endometrial metaplasia, 1/10 microglandular hyperplasia, and 1/17 normal endocervix. With adenocarcinoma in situ and non-neoplastic lesions, positive staining was confined to scattered cells. Nine of 23 positive cases of adenocarcinoma showed widespread staining. With anti-bcl-2 antibody, there was positive cytoplasmic staining in 9/33 cases of adenocarcinoma, 0/10 adenocarcinoma in situ, 7/10 tubo-endometrial metaplasia, 1/10 microglandular hyperplasia, and 0/17 normal endocervix. Five of nine positive adenocarcinomas showed widespread staining. There was widespread positive staining for bcl-2 in six of seven positive cases of tubo-endometrial metaplasia. The results indicate that p53 protein expression is frequent in endocervical adenocarcinoma and suggest that mutation of the p53 gene may be important in the evolution of some cases of endocervical adenocarcinoma. Scattered p53-positive cells may be seen in endocervical adenocarcinoma in situ and in non-neoplastic endocervical glandular lesions, the significance of which is uncertain. Bcl-2 protein expression is seen in a proportion of endocervical adenocarcinomas and may play a role in the evolution of these tumors through inhibition of apoptosis. Widespread positivity for bcl-2 protein is seen in most cases of tubo-endometrial metaplasia, suggesting that this type of metaplastic epithelium may represent an unusually stable population of cells.

Adenocarcinoma↗
PubMed1997

A comparison of three standard methods of identifying mast cells in endobronchial biopsies in normal and asthmatic subjects.

Reported mast-cell counts in endobronchial biopsies from asthmatic subjects are conflicting, with different methodologies often being used. This study compared three standard methods of counting mast cells in endobronchial biopsies from asthmatic and normal subjects. Endobronchial biopsies were obtained from atopic asthmatic subjects (n = 17), atopic nonasthmatic subjects (n = 6), and nonatopic nonasthmatic control subjects (n = 5). After overnight fixation in Carnoy's fixative, mast cells were stained by the short and long toluidine blue methods and antitryptase immunohistochemistry and were counted by light microscopy. Method comparison was made according to Bland & Altman. The limits of agreement were unacceptable for each of the comparisons, suggesting that the methods are not interchangeable. Coefficients of repeatability were excellent, and not different for the individual techniques. These results suggest that some of the reported differences in mast-cell numbers in endobronchial biopsies in asthma may be due to the staining method used, making direct comparisons between studies invalid. Agreement on a standard method is required for counting mast cells in bronchial biopsies, and we recommend the immunohistochemical method, since fixation is less critical and the resultant tissue sections facilitate clear, accurate, and rapid counts.

Adolescent↗
PubMed1997

Nosological Inaccuracies in death certification in Northern Ireland. A comparative study between hospital doctors and general practitioners.

We aimed to audit nosological inaccuracies in death certification in Northern Ireland and to compare performance of hospital doctors and general practitioners. Nosology is the branch of medicine which treats of the classification of disease. 1138 deaths were registered in Northern Ireland in a 4-week period commencing 3/10/94. 195 of these were either registered by HM Coroners (HMC) or required further investigation by their staff; these cases were excluded from the study. The remaining 943 were analysed for wording and formulation inaccuracies according to the revised notes (1974), Northern Ireland Medical Certificate of Cause of Death. These are issued in book form by the Registrar of Births and Deaths. The commonest inaccuracies in death certification occur in the areas of poor terminology, sequence errors and unqualified mode. One or more inaccuracies were found in 317 (33.6%) of cases. In 13 of these (4%) cases, the inaccuracies were serious enough to warrant referral by the Registrar of Deaths to HM Coroner. The numbers of general practitioners and hospital doctors were recorded, with general practitioners being responsible for 122 (38%) and hospital doctors being responsible for 195 (62%) of inaccuracies.

Cause of Death↗
PubMed1996

Importance of human immunodeficiency virus-associated lymphadenopathy and tuberculous lymphadenitis in patients undergoing lymph node biopsy in Zambia.

The relative importance of human immunodeficiency virus (HIV)-associated lymphadenopathy amongst patients presenting for lymph node biopsy in Central Africa is unknown. HIV-1 serology and histology of patients undergoing superficial lymph node biopsy during 1989-1990 in Lusaka, Zambia, were examined in a prospective cohort study of HIV serology and by retrospective review of laboratory records. Of 727 lymph nodes biopsied in Lusaka in 1989-1990, 380 (52 per cent) showed tuberculous lymphadenitis, 160 (22 per cent) histology suggestive of primary HIV lymphadenopathy and 66 (9 per cent) nodal Kaposi's disease. HIV serology was tested in 280 adults and was positive in 91 per cent (255 patients), including 89 per cent (153 of 171) of those with tuberculous lymphadenitis, 98 per cent (63 of 64) of those with histology suspicious of primary HIV lymphadenopathy and all (24 of 24) with nodal Kaposi's disease. Other HIV-associated lymphadenopathy included nodal lymphomas and lymphoepithelial cysts. HIV serology was tested in 22 children and was positive in eight, including four of 14 with tuberculous lymphadenitis. It is concluded that HIV-associated lymphadenopathy, especially tuberculous lymphadenitis, is very common amongst patients presenting for lymph node biopsy in Central Africa.

AIDS-Related Complex↗
PubMed1996

Florid reactive periostitis of the thumb.

A case of florid reactive periostitis of the thumb is presented. This is a rare pseudosarcomatous lesion which generally has a benign radiographic appearance, but on histology it may be mistaken for a malignant process. The clinical behaviour may simulate a malignant tumour but after local excision there is very little propensity for recurrence. Local resection is the recommended treatment. Surgeons and pathologists should consider the possibility of florid reactive periostitis before making a diagnosis of sarcoma in the hand.

Humans↗
PubMed1996

Monoclonal antibody MIB1 in the assessment of cervical squamous intraepithelial lesions.

The aims of the study were to assess patterns of cell proliferation, using the monoclonal antibody MIB1, in a variety of non-neoplastic and neoplastic cervical squamous intraepithelial lesions. We also wished to determine whether this antibody is of value in the discrimination of different grades of cervical intraepithelial neoplasia (CIN) and in the distinction of CIN from non-neoplastic lesions that may histologically mimic CIN. Tissue sections of formalin-fixed, paraffin-embedded cervical colposcopic biopsies were stained immunohistochemically with MIB1 after microwave heating. Normal ectocervix and cervical specimens exhibiting immature squamous metaplasia, koilocytosis, CIN grades I, II, and III, and atrophic squamous epithelium were studied. In normal ectocervix, MIB1-positive cells were confined almost exclusively to the parabasal cell layer. Increased expression was seen in cases of koilocytosis and CIN, positive staining being present in progressively higher layers of epithelium in accordance with the degree of CIN. In immature squamous metaplasia, positive staining was generally confined to the parabasal layer with occasional scattered positive cells in higher layers of epithelium. There was little or no staining of atrophic squamous epithelium. The study confirms that proliferating cells, as demonstrated by MIB1 immunostaining, are found at progressively higher levels in cervical squamous epithelia from normal to koilocytosis to CIN grades I, II and III. Immunostaining with MIB1, which can be easily performed on routinely processed tissues, is of potential value as an adjunct to histology in the grading of CIN and the distinction of CIN from non-neoplastic lesions that may mimic CIN.

Antibodies, Monoclonal↗
PubMed1996

Endometrial stromal sarcoma with sex cord-like areas and focal rhabdoid differentiation.

An unusual uterine lesion is described in a patient with postmenopausal bleeding. Grossly, a yellow, polypoid mass projected into the uterine cavity. Histological examination showed a distinct biphasic pattern with areas of typical low-grade endometrial stromal sarcoma and areas where tumour cells were arranged in cords and trabeculae, resulting in a sex cord-like pattern. In these areas the cells assumed a rhabdoid morphology with eccentric vesicular nuclei, prominent nucleoli and eosinophilic hyaline cytoplasmic inclusions. Immunohistochemistry showed positive cytoplasmic staining of both components for vimentin, desmin and the cytokeratin marker CAM 5.2, but no staining for CEA and EMA. Electronmicroscopy revealed prominent paranuclear arrays of intermediate filaments. This is the second reported case of endometrial stromal sarcoma with rhabdoid differentiation and the first documented example of rhabdoid cells in sex cord-like areas. The report adds to the list of diverse neoplasms which may display a characteristic rhabdoid morphology and supports the hypothesis that extrarenal rhabdoid tumours are not a distinct clinicopathological entity. A diagnosis of malignant rhabdoid tumour of the uterus should be considered only when extensive sampling fails to disclose areas with an appearance typical of an endometrial stromal lesion.

Biomarkers↗