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Biomedical subjects

N Kirkham

Publications and source records attributed to N Kirkham.

At least 19 recordsLinked to original sources
PubMed1992

A computer-based decision support system for diagnostic histopathology of the breast.

Accurate histological diagnosis of breast lesions is essential for the appropriate management of the patient. However, the technique of histological typing is problematic due to the large number of histological patterns, often of a complex and variable nature, which occur in breast disease. The introduction of the Breast Screening Programme has increased the burden on pathologists, and emphasised the need for training. Problems arise because mammographic screening detects a greater proportion of special histological types, with their attendant difficulties of identification, when compared to clinically palpable lesions. A computer-based decision support tool has been developed to assist pathologists in the histological diagnosis of breast disease. Unlike conventional expert systems, which seek to recreate the problem-solving processes of an expert, this system has been designed to act as an intelligent assistant to the pathologist. The system represents knowledge in the form of 'disease profiles', and utilises a novel inference model based upon the mathematical technique of hypergraphs. Initial trials with this system have demonstrated that a high level of diagnostic accuracy can be achieved.

Breast Diseases↗
PubMed1992

Malignant parotid salivary gland peripheral nerve sheath tumour in a twelve-year-old girl.

A case of a malignant parotid salivary gland nerve sheath tumour is reported in a 12-year-old girl who developed a right parotid mass. Initial incisional biopsy showed a tumour with a mesenchymal spindle cell appearance. Immunohistochemical studies showed positive staining of tumour cells for vimentin and focally for S-100 protein. These features together with ultrastructural evidence of basal lamina material suggested that the tumour was of nerve sheath origin. After subtotal parotidectomy the tumour metastasised to cervical lymph node and lung. There was evidence of a partial response to chemotherapy. A detailed illustrated histopathological description of the tumour is given.

Child↗
PubMed1992

Splenic marginal zone cell lymphoma.

We describe four female patients with primary splenic low-grade non-Hodgkin's B-cell lymphomas with the morphology and immunophenotype of splenic marginal zone lymphocytes. The patients presented with splenomegaly, anemia, and weight loss. The bone marrow was involved in all four cases. Liver involvement was found in one patient; and in another, a CT scan revealed lymphadenopathy in the chest and abdomen. The histology of the spleen was characterized by broad concentric strands of monomorphic medium-sized lymphocytes around lymphoid follicles in one case and infiltrating follicles in two cases. Selective replacement of follicles was seen in one case. Tumor in splenic hilar lymph nodes (four cases) and liver (one case) was similar. Three patients remain well 4, 9, and 12 months, respectively, after splenectomy without further treatment. One patient who received chemotherapy died 1 year after splenectomy.

Adult↗
PubMed1992

Cutaneous malignant melanoma and human immunodeficiency virus (HIV) infection: a report of three cases.

Cutaneous malignant melanoma was diagnosed in three patients suffering from human immunodeficiency virus (HIV) infection. Staging at presentation inversely correlated with absolute CD4 count. In addition, a notably sparse lymphocytic inflammatory response to the melanoma was observed in two cases. Established data on melanoma in non-HIV immunosuppressed patients suggests a poor prognosis for melanoma in HIV disease.

Adult↗
PubMed1991

Decision support system for the differential diagnosis of breast disease.

The histopathological diagnosis of breast disease is representative of many problems of differential diagnosis encountered in the medical domain. It requires highly trained and experienced experts and is characterized by a large number of features whose presence or absence involves much uncertainty. Computer-based decision support systems intended to function in a consultative capacity during differential diagnosis have had limited success for two fundamental reasons. Firstly, they take an autonomous role and assume that the user has no contribution to make to the problem-solving process. Secondly, the established techniques for representing and reasoning with medical knowledge are of limited suitability in this domain. Such systems are unable to reach a correct diagnosis quickly and often subject the user to a cumbersome dialogue. These are not tolerated by pathologists working under severe time constraints. We first look at the problem-solving methods employed by pathologists in this domain and examine the functionality of traditional expert system methodologies. We then present a cooperative design which allows the pathologists to express his or her ideas within a decision support system whilst gaining assistance in required areas. A novel inference technique based upon the set partitioning technique in hypergraphs is also described. This mathematical method has the ability to cope with the incomplete or inadequate knowledge which is a characteristic of breast disease, whilst directing data gathering in a meaningful manner. In particular this approach can significantly reduce the amount of irrelevant data which the pathologist must enter before a conclusion is reached. Thus it can potentially improve the efficiency and user acceptability of medical expert systems.

Algorithms↗
PubMed1991

Object-oriented design and programming in medical decision support.

The concept of object-oriented design and programming has recently received a great deal of attention from the software engineering community. This paper highlights the realisable benefits of using the object-oriented approach in the design and development of clinical decision support systems. These systems seek to build a computational model of some problem domain and therefore tend to be exploratory in nature. Conventional procedural design techniques do not support either the process of model building or rapid prototyping. The central concepts of the object-oriented paradigm are introduced, namely encapsulation, inheritance and polymorphism, and their use illustrated in a case study, taken from the domain of breast histopathology. In particular, the dual roles of inheritance in object-oriented programming are examined, i.e., inheritance as a conceptual modelling tool and inheritance as a code reuse mechanism. It is argued that the use of the former is not entirely intuitive and may be difficult to incorporate into the design process. However, inheritance as a means of optimising code reuse offers substantial technical benefits.

Adult↗
PubMed1991

Symptoms of notalgia paresthetica may be explained by increased dermal innervation.

Notalgia paresthetica is a sensory neuropathy characterized by infrascapular pruritus, burning pain, hyperalgesia, or tenderness. To assess whether the symptoms may be caused by alterations in the cutaneous innervation, skin from the affected area of patients (n = 5) was compared with controls (n = 10) comprising the contralateral unaffected area from the same patients and site-matched biopsies of normals, using immunohistochemistry. Frozen sections were immunostained with antisera to the neuropeptides substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide, and neuropeptide with tyrosine, and to the general neural marker PGP 9.5 and the glial marker S-100 to show the overall innervation and glial cells, respectively. No discernible change in the distribution of neuropeptide-immunoreactive axons was found, but all of the specimens from the affected areas had a significant increase in the number of intradermal PGP 9.5-immunoreactive nerve fibers compared with unaffected areas from the same patients and normal controls. Epidermal dendritic cells immunoreactive for S-100, possibly Langerhans cells, were substantially increased. It is concluded that there is an increase in the sensory epidermal innervation in the affected skin areas in notalgia paresthetica, which could contribute to the symptoms, and that neural immunohistochemistry of skin biopsies could be helpful in the diagnosis of the disease.

Aged↗
PubMed1991

Knowledge-based computer system to aid in the histopathological diagnosis of breast disease.

A knowledge-based computer system, designed to assist pathologists in the histological diagnosis of breast disease, is described. This system represents knowledge in the form of "disease profiles" and uses a novel inference model based on the mathematical technique of hypergraphs. Its design overcomes many of the limitations of existing expert system technologies when applied to breast disease. In particular, the system can quickly focus on a differential problem and thus reduce the amount of data necessary to reach a conclusion. The system was tested on two sets of samples, consisting of 14 retrospective cases and five hypothetical cases of breast disease. Its recommendations were judged "correct" by the evaluating pathologist in 15 cases. This study shows the feasibility of providing "decision support" in histopathology.

Breast↗
PubMed1991

Breslow thickness of cutaneous malignant melanoma in paraffin wax and frozen sections.

Breslow tumour thickness was measured in frozen and paraffin wax sections from 21 excision biopsies of cutaneous malignant melanomas by two observers. There was no consistent variation between frozen and paraffin wax sections, with recorded differences ranging from +0.3 mm to -0.2 mm. Interobserver differences ranged from +0.4 mm to -0.2 mm. The interobserver variations exceeded the intraobserver variations, but neither were significant. These findings show conclusively that, when using high quality frozen sections, there is no significant difference between Breslow thickness measured in frozen or paraffin wax sections and therefore that frozen sections can be used to microstage melanoma. Interobserver variations seem to be a more likely source of erroneous measurements of tumour thickness.

Biopsy↗
PubMed1990

Monoclonal antibody MAC 387 recognizes a myelomonocytic antigen shared by epithelial cells in inflammatory skin diseases.

The monoclonal antibody MAC 387 recognizes an antigen expressed by human macrophages and granulocytes. Normal epidermis does not react with the antibody, but the inflamed epidermis may react. In this immunocytochemical study we have investigated the intracytoplasmic expression of the MAC 387 antigen in biopsies of a variety of skin disorders. In lichen planus the basal cells were usually negative, whilst suprabasal cells were positive. In the majority of other inflammatory dermatoses studied, there was positive staining of basal and suprabasal cells. A parallel frozen- and paraffin-section study of biopsies of cutaneous T-cell lymphomas and inflammatory conditions failed to demonstrate HLA Class II expression in the cytoplasm of keratinocytes. Expression of the MAC 387 antigen in the epidermis is directly associated with cell-mediated activity in the papillary dermis, but is not related to HLA Class II expression.

Antibodies, Monoclonal↗
PubMed1990

Computer assisted diagnosis of fine needle aspirate of the breast.

The development of the National Breast Screening Programme has created a demand for the widespread availability of fine needle aspiration cytology services. To meet this demand there must be a rapid increase in the number of pathologists and laboratories able to offer this service. In turn there is a need for improved training methods. The technique of fine needle aspiration cytology is not inherently complicated. The number of possible conclusions is essentially limited to four: unsatisfactory, benign, suspicious and malignant. A computer based expert system, designed to assist pathologists in the diagnosis of fine needle aspirates of the breast, has been developed. The system prompts pathologists to categorize a number of variables in the aspirate including nuclear and cytoplasmic features, and the degree of cellular cohesion, and uses these data to reason about possible conclusions. The final diagnosis is displayed with a detailed explanation listing the factors supporting it. Initial trials with this system have been encouraging and it is envisaged that this system will be of value both in training and as an aid to routine diagnosis.

Biopsy, Needle↗
PubMed1990

Elevated human chorionic gonadotrophin levels in a patient with pancreatic carcinoma presenting with a testicular metastasis.

Elevated levels of human chorionic gonadotrophin are associated with primary testicular tumours and usually indicate the presence of trophoblastic elements. Human chorionic gonadotrophin can also be secreted by extragonadal tumours which may metastasize to the testes. A patient is described presenting with a testicular tumour secreting human chorionic gonadotrophin which later proved to be a metastasis from a pancreatic adenocarcinoma. Up to 70% of malignant pancreatic tumours can secrete human chorionic gonadotrophin.

Adenocarcinoma↗
PubMed1989

Type VII collagen antibody LH 7.2 identifies basement membrane characteristics of thin malignant melanomas.

A monoclonal antibody (LH 7.2) to the carboxy terminal of type VII collagen has been used in an indirect immunoperoxidase method on frozen sections of biopsies of benign compound and intradermal cellular naevi, dysplastic naevi, and malignant melanomas, to label the epidermal basement membrane. Benign intradermal naevi had an intact membrane with the dermal naevus cell component lying beneath it. Compound naevi showed proliferating junctional nests of naevus cells pushing through the membrane towards the dermis beneath. In contrast, dysplastic naevi and melanomas showed a progressive displacement of the membrane downwards. Thin lesions were confined above the membrane. With increasing tumour thickness, discontinuities in the membrane were seen and foci of invasive growth through the line of the membrane were identified. These studies suggest that the good prognosis of thin melanomas is associated with confinement of the tumour within an expanded epidermis above the basement membrane.

Antibodies, Monoclonal↗
PubMed1989

A comparison of antibodies to type VII and type IV collagen laminin and amnion as epidermal basement membrane markers.

We have compared four monoclonal antibodies which label basement membrane components using an indirect immunoperoxidase method in frozen sections of skin biopsies. The antibodies LH 7.2 and GB3 showed expression limited to epidermal and adnexal basement membrane. Antibodies to laminin and type IV collagen also decorated dermal blood vessels and stromal components. The antibodies LH 7.2 and GB3 are more suitable for labelling epidermal basement membrane in the study of cutaneous lesions.

Antibodies, Monoclonal↗
PubMed1989

Synchronous extra-parotid Warthin's tumour.

Warthin's tumour (also known as adenolymphoma or papillary cystadenoma lymphomatosum) is benign and accounts for 12 per cent of all neoplasms of the parotid gland. A case of extra-parotid Warthin's tumour occurring synchronously in a peri-parotid lymph node is described. This is not a metastatic phenomenon and occurs as a result of salivary gland inclusions of local lymph nodes during the embryological development of the parotid. Extra-parotid Warthin's tumour should be regarded as a benign incidental finding and the prognosis is excellent.

Adenolymphoma↗
PubMed1989

c-erbB-2/c-erbA co-amplification indicative of lymph node metastasis, and c-myc amplification of high tumour grade, in human breast carcinoma.

A panel of 73 samples, including 52 primary breast carcinomas, 10 normal breast tissues and 11 axillary lymph nodes, has been analysed for the presence of amplifications and gross structural alterations, in the oncogenes c-erbB-2, c-erbA, c-myc, N-myc, c-mos and c-Ha-ras. The tumours were also classified, graded and staged histopathologically and their DNA ploidy (42 samples) was determined by flow cytometry. Three breast cancer cell lines (MCF7, ZR-75-1 and T47D) were also included in the study. Amplification of c-erbB-2 was detected in 28% of the tumours, of which 91% had an increased steady-state level of c-erbB-2 mRNA. Amplification of c-erbA was found in 23% of tumours and was always associated with the amplification of c-erbB-2. Ten out of 12 (83%) tumours which had c-erbB-2 and c-erbA co-amplification had metastasised to axillary lymph nodes (P less than 0.006). However, the human thymidine kinase gene, which is present at the same chromosomal location as these two oncogenes (17q21-22), was amplified in only tw tumours. Amplification of c-myc was detected in 21% of the tumours studied, of which 82% (P less than 0.005) were of histopathological grade 3 and none were of grade 1. Flow cytometry showed that 90% (P less than 0.01) of the analysed tumours with c-erbB-2 and c-erbA co-amplification, and 70% (P less than 0.1) of those with c-myc amplification were DNA aneuploid. This study demonstrates the potential value of c-myc amplification in the assessment of the tumour grade, rather than metastatic potential; and of the co-amplification of c-erbB-2 and c-erbA as a strong indicator of metastatic potential, rather than tumour grade.

Breast Neoplasms↗