Biomedical subjects
Publications and source records attributed to A Worth.
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.
A patient with recurrent glioma treated with BCNU developed pneumothorax and interstitial pulmonary fibrosis. She died from "BCNU lung" and its complications, although she was free of her initial disease.
A patient with retroperitoneal diffuse histiocytic lymphoma treated with combination chemotherapy developed breathlessness and fever after receiving 30 units of bleomycin. At this stage pulmonary function tests were impaired and gallium scanning showed diffuse uptake in both lungs although a chest X-ray film was normal. Bleomycin treatment was stopped but interstitial infiltrates appeared on subsequent chest X-ray films. Open lung biopsy showed histologic changes of bleomycin toxicity. After treatment with prednisone, the patient felt well and was shown to have a normal gallium scan ad normal respiratory function studies.
A 62-year-old woman had multiple plasmacytomas of the skin with no roentgenographic or bone marrow evidence of multiple myeloma. Serum IgA-lambda level was increased to 1,000 mg/dL (normal range, 90 to 450 mg/dL). The skin lesions regressed completely when the patient was treated with melphalan. She had recurrence of a skin plasmacytoma and lytic bone lesions ten months later and died of bronchopneumonia 11 months after the was first seen. Solitary skin plasmacytomas are rare, and multiple skin plasmacytomas are even rarer. Occasionally, these lesions may precede roentgenographic and bone marrow evidence of multiple myeloma.
Questionnaires were sent to patients who had tracheal intubation for periods longer than three days in a large multidisciplinary Intensive Care Unit. The information sought was of complaints related to talking, breathing, coughing, swallowing and chest infection. Of patients who had been intubated for seven days or less, 63 per cent of the 52 patients responding had no complications while only one of the remainder had a major complication requiring surgical removal of a granuloma. Forty-eight per cent of patients intubated for more than seven days had no complaints and the rest of the patients had minor complaints which did not persist. Most complained of hoarseness. Of patients who had a tracheostomy following prolonged intubation, only 23 per cent were free of complications. From this it is concluded that tracheal tubes can be left in place for seven days and at this time direct laryngoscopy should be done. If no significant laryngeal pathology is seen at this examination, tracheal intubation may be continued.
Four tumors in the extremities were initially diagnosed as extraskeletal osteogenic sarcoma. Recent review of these tumors had led to their reclassification. Three of these are now recognized as malignant giant cell tumors of soft tissue and one as a malignant fibrous histiocytoma. All four patients have been cured. Some special features of malignant giant cell tumors of soft parts are described. The importance of treatment planning is stressed.
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As an example of advanced testing in the field of metabolism in an industrial environment, the introduction of some novel approaches, including the use of genetically engineered cell lines for assessing CYP 2D6-related polymorphic effects is illustrated. In this paper, it is demonstrated that novel in vitro test systems can be developed by using these genetically engineered cell lines for evaluating the potential risks associated with proprietary drugs (especially if their metabolism depends to a high extent on CYP 2D6). Moreover, it is demonstrated that, by the use of these in vitro methods, issues such as polymorphism, for which no animal models are available, can be assessed in such a way that predictions can be made on adverse effects which, up to now, could only be detected during clinical trials. Through the use of these new biotechnological in vitro metabolism models, clinically relevant data can be obtained for a scientifically-based human risk assessment, and animal use can be reduced.