Biomedical subjects
Publications and source records attributed to A Worth.
To determine whether an appropriate level of nursing care is being provided in the community, this study aimed to explore whether patients' needs are being identified through the referral system and whether those needs are being met.
The use of group-based techniques to generate ideas and offer solutions to problems is commonplace in many disciplines and for many purposes. What were originally useful adjuncts to market research have become valuable and illuminating tools in education, policy and research. This paper will describe the use of one such technique, the Nominal Group Technique, and its practical application in bridging the gap between researchers and practitioners in one particular study of community nursing.
We have identified two epitopes for Epstein-Barr virus specific cytotoxic T lymphocytes (CTL) restricted by the common allele HLA-B7. They are EBNA 3C 881-9 (QPRAPIRPI) and EBNA 3A 379-387 (RPPIFIRRL). The epitopes conform well to the recently described motif for HLA-B7-binding peptides (Huckzo et al., J. Immunol. 1993. 151:2572). Titration of the peptides in CTL assays and detergent lysate binding assays revealed that extending the peptides at either the N or C terminus did not reduce their affinity for HLA-B7. This behavior contrasted with HLA-B51, which binds peptides with a similar motif to B7, and has identical amino acid residues at sites expected to form the "F" pocket of the peptide-binding groove. HLA-B51 also bound the peptide EBNA 3C 881-9, but was unable to bind peptides extended at the C terminus.
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The aim of this study was to demonstrate differences in nuclear morphology between ductal carcinoma in situ (DCIS) without an invasive component and DCIS associated with invasive carcinoma in adjacent breast tissue. DCIS specimens of 60 non-comedo and 21 comedo cases were obtained from two groups of patients with or without invasive carcinoma of the breast. The analysis of DCIS nuclei was performed on formalin fixed deparaffinized thin sections stained with a stoichiometric stain following the Feulgen procedure. Nuclear features, related to nuclear size, shape and DNA distribution, were quantitatively characterized by high resolution image cytometry. Features associated with the presence of invasive carcinoma in the surrounding breast tissue were identified in DCIS nuclei (independent of nuclear grade). Features selected by the stepwise procedure of the discriminant function analysis were typically texture features describing the DNA distribution in the nucleus. A classification function based on the selected nuclear features predicted accurately the presence of invasive carcinoma in all comedo DCIS and in 80% of non-comedo DCIS cases. Our results indicate that quantitative nuclear features of DCIS nuclei are predictive of the accompanying invasion and may be helpful as a new tool in evaluation of DCIS patients.
Malignancy-associated changes (MACs) have been described as subtle morphologic changes in normal-appearing tissues adjacent to or distant from malignant tumors. MACs might be applicable as a marker of occult malignancy, increased risk of subsequent carcinoma or recurrence of tumor after therapy. The aim of this study was to verify the existence of MACs in normal-appearing breast tissue adjacent to breast carcinoma. Image cytometry measurements were performed on 4-microns sections cut from formaldehyde-fixed tissue blocks and stained with thionin-SO2 following the Feulgen procedure. Morphologically normal appearing breast lobules were analyzed in patients with benign (20 cases) and malignant breast disease (23 invasive and 11 in situ tumors). The chromatin distribution features of the epithelial nuclei in normal-appearing breast lobules differed between patients with benign and malignant breast disease. Changes in nuclear features, detected in epithelial nuclei from normal-appearing lobules in breasts resected for carcinoma, were defined as MACs. The frequency of MAC nuclei was low in benign tissues, increased in tissues with ductal carcinoma in situ and highest in tissues with invasive carcinoma. Based on the measurements of nuclei in normal-appearing lobules, it was possible to discriminate between patients with benign breast disease and patients with invasive carcinoma in 86% of cases.
OBJECTIVE: To evaluate histometric measurement of nuclear texture in breast biopsy sections in order to detect malignancy-associated changes in apparently normal tissue in the vicinity of carcinoma in situ. STUDY DESIGN: We previously showed that image cytometry measurements of nuclear features--foremost, texture features, describing the organization of Feulgenstained DNA in the cell--can be used to distinguish normal-appearing, diploid epithelial cells from patients with invasive carcinoma of the breast from those with benign biopsies. In that study, referred to as the "single cell analysis," images of at least 200 epithelial cells were acquired for each slide, and substantial user interaction was required to segment cells from each field. Location of isolated cells and interactive segmentation are both time-consuming procedures, particularly in breast tissue, where nuclei can be tightly clustered within a duct. With histometric texture analysis on the same specimens, segmentation of individual cells was ignored, and texture measurements were performed over the entire cluster of relevant cells. With this approach, ploidy information is not available, and touching and overlapping nuclei are included in the measurements. Measurement of histometric texture properties requires substantially less time (at least an order of magnitude) than individual cell measurement and, if ploidy information is not significant, may therefore provide a more practical means of analysis for tissue sections. RESULTS: Seventeen cases of invasive carcinoma and 17 cases of nonproliferative breast disease were examined. Using stepwise discriminant function analysis, slides were classified into one of the two groups with an accuracy of 88.6% in the case of single cell analysis and with an accuracy of 88.2% using histometric analysis. CONCLUSION: The existence of malignancy-associated changes in the breast was confirmed by an independent analysis of the same specimens. Although the two methods are not directly comparable, we found that histometric texture analysis performs at least as well as single-cell analysis for the detection of malignancy-associated changes in breast carcinoma.
BACKGROUND AND METHODS: We examined the effect of adjuvant systemic therapy on survival after breast cancer among the residents of the Canadian province of British Columbia. Data on survival were collected for all women in whom breast cancer was diagnosed in British Columbia during each of three calendar years chosen to represent different province-wide treatment recommendations: 1974, when no adjuvant systemic therapy was recommended; 1980, when adjuvant chemotherapy was recommended only for premenopausal women with node-positive disease; and 1984, when adjuvant chemotherapy was also recommended for premenopausal women with node-negative disease and lymphatic, vascular, or neural invasion and tamoxifen was recommended for postmenopausal women with involved lymph nodes or lymphatic, vascular, or neural invasion unless their tumors were negative for estrogen receptors. RESULTS: For women less than 50 years of age, disease-specific survival at seven years (i.e., with censoring of data on women who died from causes other than breast cancer) improved from 65.2 to 76.3 percent between 1974 and 1984 (P = 0.008), and overall survival improved from 64.8 to 74.6 percent (P = 0.02). For women from 50 through 89 years of age, disease-specific survival at seven years improved from 62.5 to 70.4 percent between 1980 and 1984 (P = 0.001), and overall survival improved from 53.9 to 58.3 percent (P = 0.05). The timing of the improvements in survival correlated with the introduction of adjuvant systemic therapy in each group. CONCLUSIONS: Survival among women with breast cancer improved significantly in a geographically defined population during the period when adjuvant systemic therapy became widely used.
Telephone interviews were employed by nurse researchers as a means of collecting data from elderly people following their discharge from hospital. The paper reviews the literature concerning interviews with elderly patients by telephone and recounts first-hand experience of the method on the basis of over 500 telephone interviews. Although some difficulties were encountered in conducting interviews with the hearing-impaired and the unwell, the method was found to be a cost-effective and useful means of obtaining follow-up data for research purposes. The prime factor in ensuring successful use of the method was the recruitment of subjects via personal interview prior to telephone contact.
The first home visit is vital to the future relationship between health visitor and client, writes Allison Worth. Here she analyses the degree to which the client and the health visitor influence the agenda during an ante-natal visit to a 28 year old single woman six months pregnant with her first child.
The morphologic subgroups of intraductal carcinoma in situ (DCIS) of the breast may be biologically different. Thirty-eight patients with comedo-type DCIS treated with local resection with or without radiotherapy are presented. Thirteen of 35 patients had a family history of breast cancer, with 11 patients having an affected first-degree relative. This is significantly increased over other series of breast cancer patients. Recurrence was ipsilateral in all patients and occurred at the site of the original disease. Recurrence occurred in 4 of 30 patients treated with local resection only and 2 of 8 treated with local resection plus radiotherapy. The length of mean follow-up was 39 months. Because of the paucity of studies, these results cannot be compared with others, but there does appear to be a significant incidence of local recurrence after resection for comedo-type DCIS. Immunohistochemical and oncogene studies as they relate to comedo-type DCIS are discussed.
In a previous multivariate analysis of 151 malignant melanoma patients we identified measured depth of primary lesion (Breslow) and serum N-acetyl-neuraminic acid (NANA) concentration as significant independent predictors of recurrence. Our present study examines the contribution of flow cytometric DNA analysis to prediction of recurrence and survival. Fixed, paraffin-embedded specimens of primary lesions were evaluated from 63 of the previously studied patients. These were prepared for DNA analysis. Of the 28 primaries identified as aneuploid 17 later recurred, while this was true for only 9 of the 35 diploid tumors. On multivariate analysis measured depth was again the most significant predictor of recurrence (p less than 0.001). Additional independent predictors were DNA ploidy (p = 0.02) and NANA (p = 0.05). For survival the independent predictors were measured depth (p = 0.003) and NANA (p = 0.05). Measured depth, DNA ploidy and NANA can be used to construct a model predicting the recurrence risk for stage-I melanoma.
Between Jan. 1, 1985 and Aug. 31, 1987, 62 in-situ ductal carcinomas with a predominantly comedo pattern were identified in 61 patients in British Columbia from excisional biopsy of a palpable or mammographically demonstrable lesion of a breast. The biopsies were intended to remove the lesion completely. Fifty-seven (92%) of the 61 patients required wide re-excision or total mastectomy, usually within a month of the initial biopsy. Occult invasive disease was demonstrated in 14 of the re-excision specimens (24.5%) and residual in-situ carcinoma was present in a further 24 (42.1%), giving an overall rate of residual disease of 66.6%. Axillary lymph nodes were sampled in 54 cases. Metastases were found in two cases (3.7%) and each was associated with occult infiltrating ductal carcinoma in the breast. This suggests that in-situ ductal carcinoma having a predominant comedo pattern may be more widespread and associated with a higher incidence of invasive ductal carcinoma than is generally believed.
Fujinami sarcoma virus (FSV) encodes a protein-tyrosine kinase, p130gag-fps, whose enzymatic activity and ability to transform cultured cells to a neoplastic phenotype are reduced by substitution of the major autophosphorylation site tyrosine-1073 with other amino acids. We compared the histopathology of tumors formed in syngeneic immunocompetent rats by Rat-2 cells and by Rat-2 cells transformed in culture with (a) wild type (wt) FSV, (b) mutant FSV where the codon for tyrosine-1073 of p130gag-fps had been changed to codons for phenylalanine or serine, and (c) a revertant FSV, genotypically identical to wt FSV, in which the codon for tyrosine-1073 had been restored. Latency periods from cell inoculation to tumor formation were 12-29 weeks with Rat-2 cells, 6-8 weeks with mutant-transformed Rat-2 cells, and 2-4 weeks with wt FSV- and revertant FSV-transformed Rat-2 cells. Untransfected Rat-2 cells formed tumors that histologically resembled low grade fibrosarcomas or fibromas and were characterized by uniform fusiform cells in parallel arrays with a prominent collagenous stroma. The growth pattern of tumors produced by mutant FSV-transformed cells was generally similar, although cellular forms and intercellular organization were less uniform. In contrast, Rat-2 cells transformed with either wt FSV or revertant FSV produced tumors that resembled highly malignant sarcomas and were composed of diffuse sheets of pleomorphic, disorganized cells and stroma rich in hyaluronate but poor in fibrous components. Local invasion occurred in 25% of tumors produced by Rat-2 cells and in 53 and 36% of tumors formed by mutant FSV- and wt FSV-transformed cells, respectively. In culture, Rat-2 cells and mutant FSV-transformed cells produced fibrillar pericellular matrices of collagen I and fibronectin. From 5 to 15% of protein secreted by these cells was collagen. Cultures of wt FSV- and revertant FSV-transformed cells lacked collagen and fibronectin matrices and collagen secretion was reduced to 0-2%. These results show that clinically relevant histological characteristics of malignant tumors can correlate with single amino acid substitutions previously shown to affect the enzymatic activity and transforming ability of an oncogenic protein tyrosine kinase. The mechanisms underlying some of the histological differences in this system may be related to differences in the production of extracellular matrix components among the transformed cells.
The immunohistochemical localization of melanoma-associated antigen p94 kd200 was investigated in frozen sections of 3 congenital nevi, 4 benign intradermal nevi, 1 regressing nevus, 1 blue nevus, 1 dysplastic nevus, 1 lentigo maligna, 1 superficial spreading melanoma and 2 metastatic melanomas. The original avidin-biotin complex lectin method (Hsu SM, Raine L, Fanger H: Am. J. Clin. Pathol., 75: 734-738, 1981) was modified to detect the antigen. The sections were exposed to the monoclonal antibody to p94 kd200 (Hybritech Inc.), the linking biotin-labelled anti-mouse IgG, the avidin-biotin peroxidase complex and the 3-amino-9-ethylcarbazole solution in an incubator at 37 degrees C and 100% humidity. We found that the percentage of cells expressing p94 kd200 varied between 0 and 100% in congenital nevi, between 80 and 100% in benign intradermal nevi, between 0 and 20% in the regressing, blue and dysplastic nevi, and in the lentigo maligna, 80 to 100% in the superficial spreading melanoma, and between 0 and 40% in the metastatic melanomas. Positive cells were found to be hypomelanotic (did not have heavy melanin content). The intensity of labelling or the degree of antigen expression on benign and malignant hypomelanotic cells was also found to vary. These findings 1) reinforce the concept of quantitative rather than qualitative antigenic differences in benign and malignant cells 2) suggest that kd200 is lost with increasing pigment production 3) offer a potentially significant tool to investigate the antigenic changes during cell differentiation.
Lipoplastic lymphadenopathy is a pathological condition wherein accumulations of intranodal fat result in lymph node enlargement and may mimic abdominal, pelvic, and retroperitoneal neoplasms, particularly lymphomas. The pathology appears to be different from lipomatosis in that benign, mature adipocytes and lipids are located within lymph nodes, rather than deposited in body cavities. The case of a 49-year-old woman presenting as an ovarian neoplasm is presented as an example of the pathology and its ability to masquerade as other neoplasms. The etiology of lipoplastic lymphadenopathy is unclear although associated causes are suggested. The difficulties of radiological examination of this case and others makes open lymph node biopsy important for the final diagnosis.
We reviewed the records and biopsy specimens of 38 patients with clinically similar orbital lymphoproliferative and low-grade inflammatory lesions referred to one ophthalmologist at the University of British Columbia between 1977 and 1984. Twenty-six patients had lymphoproliferative lesions, the main feature being a densely cellular population of small lymphocytes. This group was further divided into reactive lymphoid hyperplasia, malignant lymphoma, Hodgkin's disease and atypical lymphoid hyperplasia. Symptoms and signs were similar within the subgroups. The mean length of follow-up was 3.7 years. Of the 26 patients 14 had extraorbital lymphoproliferative disease, 9 had orbital recurrences and 2 died of widespread disease. Twelve patients had inflammatory lesions with distinctly different histologic features from those of the lymphoproliferative group. Symptoms and signs were similar to those in the latter group. The mean length of follow-up was 2.1 years. Four of the 12 had orbital recurrences; none had extraorbital disease or died of their disease. We feel that orbital lymphoproliferative lesions can easily be separated from clinically similar low-grade inflammatory lesions histologically and that they should be staged and followed like small lymphocytic lymphomas. Guidelines are given for handling these specimens in the laboratory.
This is a case report of an aggressive multifocal non-Hodgkin's lymphoma in a cadaver kidney recipient arising in the early phase of her immunosuppressive maintenance therapy program with cyclosporin A and prednisone.