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Biomedical subjects

H F Seigler

Publications and source records attributed to H F Seigler.

At least 145 records · Page 8Linked to original sources

Malignant melanoma in black American and white American populations. A comparative review.

Malignant melanoma, a type of cancer that accounts for 1% to 3% of all malignant neoplasms in 20 times more frequent in the American white than black population. During a computer-aided retrospective chart review of more than 2,500 patients with melanoma being followed up at the Duke University Comprehensive Cancer Center, 31 blacks have been identified. Primary lesions of the foot were predominant in blacks with melanoma, and a high percentage of these were classified pathologically as acral lentiginous primary lesions. Black patients had a more advanced stage of disease at first presentation and a more deeply invasive primary lesion than their white counterparts. Five-year survival for the total black population was 23%. Blacks had a significantly worse prognosis than the white population when a comparison with the total group was made that was controlled for sex, age, site of primary lesion, stage of disease at presentation, and Clark level of primary melanoma lesion. This emphasizes the aggressive nature of this disease in the American black.

Adolescent↗

Multiple assay characterization of murine monoclonal antimelanoma antibodies.

Selected murine monoclonal antimelanoma antibodies have been extensively evaluated using multiple radioimmunoassay methods, immunoprecipitation and immunohistochemistry. Use of this approach has permitted more complete definition of the specificity of these reagents and provided information regarding the nature and distribution of the respective tumor associated antigens (TAA). Several patterns of reactivity were identified. Some of the reagents were highly reactive with melanomas but also with a variety of tissues of nonmelanoma origin. Others were less highly reactive but of greater specificity for melanoma. Finally, certain of the reagents were poorly reactive in the assays utilized or demonstrated assay-dependent reactivity. None of the included monoclonal antibodies appeared to detect TAA restricted in distribution solely to melanoma.

Animals↗

Rationale for immediate reconstruction of the breast following modified radical mastectomy.

In 62 patients in whom modified radical mastectomy was accompanied by immediate breast reconstruction, the operative and pathologic findings are compared to the clinical results. Immediate reconstruction following modified radical mastectomy appears to offer several advantages over delayed reconstruction. The data indicate that immediate reconstruction provides excellent technical results, is associated with less expense and morbidity as compared to delayed reconstruction, and does not adversely affect the natural course of the disease within the follow-up period studied. No adverse effect of adjuvant chemotherapy on the reconstructive effect was noted in this series of 62 patients when the initiation of adjuvant chemotherapy was timed so as to avoid difficulties with hemostasis. The technical aspects of the immediate reconstruction are described.

Adult↗

Immunoglobulin localization in the normal human mammary gland: variation with the menstrual cycle.

Differences in immunoglobulin localization (IgG, IgM, IgA) in benign versus malignant lesions of the human mammary gland have been previously demonstrated. The present investigation was undertaken to evaluate the influence of menstrual cycling on these immunoglobulins in the breast. Tissues were studied from 53 normal breasts. The patients were 16 to 51 years old, with a mean age of 35 +/- 9 years, and were documented as having regular menstrual cycling, lack of debilitating disease, and abstinence from use of hormones or from medications that might influence the pituitary-ovarian axis. Immunoglobulin localization in the tissue section was determined by direct immunofluorescence with antibodies specific for IgG, IgA, IgM, and IgA secretory component. The breast tissues were categorized into 5 histologically distinct menstrual cycle phases. No significant IgG localization was noted. IgA concentration was noted principally in the preovulatory phase of the cycle (P less than 0.03). IgM showed a similar variance, and IgA secretory component paralleled IgA localization. No correlation between IgA and IgM localization and plasma cells infiltration nor between plasma cell infiltration and menstrual cycle phase could be documented. These data suggest that menstrual cycling influences the human breast as part of the secretory immune system.

Adolescent↗

[Basis for a specific-active immunotherapy in malignant melanoma].

Since Morton demonstrated in 1968 that malignant melanoma is antigenic, many immunologists have taken an interest in this disease. A basis for specific active immunotherapy has been worked out at Duke University Medical Center, Durham, N.C. (USA). A female chimpanzee was hyperimmunized with melanoma cells grown in tissue culture. After appropriate absorptions the xeno-antiserum was tested by indirect immunofluorescence. Apart from unspecific activities in the serum detectable against normal human fetal and adult fibroblasts as well as other non-melanotic human tumors, following further absorptions with these cells a melanoma-specific antigen could be demonstrated on the surfaces of melanoma cells. The melanoma-specific tumor-associated antigens were further evaluated by direct and indirect immunoautoradiography. These studies suggest that there are indeed cross-reacting specific tumor-associated antigens on the cell surface of melanoma cells. At DUMC melanoma patients have therefore been hyperimmunized with melanoma cells + BCG. Clinical experience is discussed.

Adolescent↗

Immunoglobulin localization in benign and malignant lesions of the human mammary gland.

Using direct imunofluorescence, lesions from 266 human breast specimens were studied for the presence of IgA, IgM, or IgG localization. The lesions included benign elements from 66 subcutaneous mastectomy specimens in which the absence of simultaneous breast malignancy was documented, primary breast carcinomas from 153 mastectomy specimens, and 47 biopsies containing metastatic breast cancer. A statistically significant association of IgA and IgM with benign lesions was contrasted to the association of IgG with malignant lesions. In both primary and metastatic lesions, IgG localization was associated with estrogen-receptor-poor primary cancers as compared with estrogen-receptor-rich primary cancers. Among primary breast cancer patients, IgG localization in the tumor correlated with relative lymphopenia. A shorter disease-free interval was noted in association with IgG localization among the metastatic breast lesions. No statistically significant association between stage of disease and immunoglobulin presence was demonstrable. Moderate-to-severe intraductal epithelial hyperplasias were more often associated with immunoglobulin G localization that were other benign lesions.

Adult↗

In vivo evaluation of cell mediated immunity against human melanoma.

Evaluation of cell mediated immunity against human melanoma target cells was performed in an in vivo model using human tumor xenografts growing in Balb/c athymic mice. Intraperitoneal inoculation of 1 x 10(7) human melanoma cells produced carcinomatosis which lead to death of the animals at 23.8 +/- 2.6 days (N = 12). Peripheral blood lymphocytes (PBL) from normal donors were administered to tumor bearing mice, and survival times of 22.0 +/- 2.3 days were observed (N = 8). Peripheral blood lymphocytes from the four of five normal donors which had been presensitized on monolayers of melanoma tissue culture cells in vitro failed to prolong host survival times. In contrast, PBL obtained from 15 or 20 melanoma patients were found to prolong survival of the tumor bearing nude mice. Of these 15 patients, 8 were undergoing specific active immunotherapy, while 7 had not been sensitized except by the disease process. The ability of PBL obtained from patients to prolong survival of tumor bearing animals did not appear to correlate with either the stage of the disease or the patient's clinical course. The possible mechanisms for the prolonged survival and usefulness of this model are discussed.

Animals↗

Human melanoma growth in the peritoneal cavity of the athymic mouse--a model for in vivo study of cell-mediated immunity.

Intraperitoneal injections of 2 X 10(7) SH-Me cells (human metastatic melanoma cells)( to 20 Balb/c nu/nu mice (Group A) and 1 X 10(7) cells to 20 mice (Group B) were performed. All animals were studied clinicopathologically. Five animals in Group A were sacrificed serially, revealing marked tumor growth of the melanoma within the peritoneal cavity. These tumors grew in multiple nodular configurations and tumor ascites was present by the third week. The remaining 15 animals in Group A were allowed to progress and seven subsequently died with mouse viral hepatitis (MVH). These animals had suppressed tumor growth. The remaining eight animals died of peritoneal carcinomatosis with survival time of 24.1 +/- 5.0 days. Eight of the animals in Group B died of mouse viral hepatitis while the remainder died of peritoneal tumor without distant metastasis. Survival time in these animals was 23.8 +/- 2.6 days. Both 2 X 10(7) and 1 X 10(7) tumor cells injected intraperitoneally will constantly produce tumor nodules in non-MHV-infected nude mice with similar survival. This experimental model has proven useful for in vivo study to assess the immunoreactivity of melanoma patient cells reactive against target tumor cells.

Animals↗

Influence of mouse hepatitis virus on the growth of human melanoma in the peritoneal cavity of the athymic mouse.

Mouse hepatitis virus (MHV) infection was found in 15 of 40 athymic mice (Balb/c nu/nu) used in an experimental model designed to study the effect of cell mediated immunity on target human melanoma cells growing in the peritoneal cavity. Most non-MHV-infected mice died of peritoneal tumor within predictable periods following injection of the melanoma cells. Twelve of 15 MHV-infected mice which showed either poor or no tumor growth died of MHV infection, whereas only 3 showed good tumor growth. Peritoneal macrophages in the ascites from the MHV-infected mice were greatly reduced in number compared to those in the ascites from the non-MHV-infected mice. Although the fibrohistiocytic reaction was more prominent in the MHV-infected mice, other aspects of spleen and lymph node lymphocytic reactions exhibited no remarkable differences between the two groups. The possible mechanisms whereby MHV infection influences tumor growth in nude mice are discussed.

Animals↗

Renal artery stenosis in children.

Because high blood pressure in children is rare and most of these patients are asymptomatic, many are overlooked until they present with a hypertensive crisis or irreparable damage. Most children with renal artery stenosis are asymptomatic and the hypertension is detected only by blood pressure recording during physical examination. Angiography is the most helpful diagnostic study. It is generally agreed that renal artery lesions in children should be considered for surgical correction. An illustrated case is described.

Child↗

Modified radical mastectomy with immediate reconstruction for carcinoma of the breast.

Fifty patients undergoing immediate reconstruction of the breast following modified radical mastectomy for carcinoma were characterized by their clinical findings and the pathologic features of their tumors. Evidence of nipple--areolar involvement by tumor was noted in five patients. This high incidence mitigates against nipple--areolar transplantation. In ten patients the breast contained multifocal tumor or intraductal carcinoma away from the primary tumor, thus emphasizing the importance of careful evaluation of the total tissue specimens. Four patients have had recurrence of tumor. The detection of the recurrence was not hindered by the presence of the prosthesis. In these four patients immediate reconstruction of the breast did not appear to adversely affect the natural history of the breast cancer. We suggest that when appropriate and thorough surgical extirpation followed by reconstruction is undertaken as a team effort among the general and plastic surgeons, pathologist and clinical psychologist, the optimal clinical and cosmetic results may be achieved. However, conclusive statements regarding the long-term implications of immediate reconstruction awaits additional follow-up.

Adult↗

In vivo tumor localization using tumor-specific monkey xenoantibody, alloantibody, and murine monoclonal xenoantibody.

Specific in vivo localization of antibodies reactive with human melanoma cell membrane tumor associated antigens (TAA) has been attempted using congenitally athymic nude mice bearing subcutaneous human melanoma tumor xenografts as the experimental model. IgG fractions were prepared from each of several immune and control sera. Antimelanoma antibody sources included human alloantibody obtained from melanoma patients immunized against allogeneic melanoma cells, a monkey antiserum raised by immunization against a single human melanoma cell line, and a murine monoclonal antimelanoma antibody-secreting hybridoma cell line. Localization of these radiolabeled antibodies and of control IgG preparations to tumor tissue was determined by whole body scintigraphy and by differential tissue counting. Compared with the different control IgG preparations, each of the antimelanoma IgG preparations exhibited significant specific accumulation within the melanoma tissue. However, variation existed in the ability of each antimelanoma IgG to tumor preparation to localize despite attempts to control model parameters such as tumor source, in vivo passage number and mass. This variation appears to reflect basic biologic differences between tumors in different animals and possibly differences in the antigen-binding capacities of each IgG preparation following radioiodination. This technique for tumor localization is very promising and has obvious potential for clinical application.

Animals↗

Central nervous system metastases in malignant melanoma.

In a series of 1341 patients with histologically proven malignant melanoma seen at Duke University Medical Center from 1968 to 1978, 107 patients developed central nervous system (CNS) metastases. These patients were evaluated on the basis of which factors were associated with the development of CNS metastases. Male patients, patients with invasive primary lesions as measured by Clark's system, and patients with primary lesions of the head/neck or oral mucosa had higher incidences of CNS metastasis. Age and race were not significant factors. Clinically, single CNS metastases were seen in 48.8% of the patients; multiple cerebral lesions were seen in 37.2% of the patients. In 22% of the patients there was CNS metastasis alone, in 41% a second organ was involved, and in 20% three organs were involved.

Adolescent↗

Metastatic melanoma in the thorax: report of 130 patients.

Early detection of metastatic melanoma has become more important as newer and more effective therapeutic regimens are used. Between 1970 and 1980, 1,600 patients were treated at one institution for malignant melanoma. Of these, 260 (16.3%) developed thoracic metastasis. Satisfactory chest radiographs were available for analysis in 130 of 260 patients. The patterns of the intrathoracic metastasis include multiple pulmonary nodules (52 patients), solitary nodule (26), miliary pattern (two), mediastinal and/or hilar adenopathy (nine), pleural effusion (three), lytic bony lesions (one), extra-pleural mass (one), and combined lesions (36). Both the staging of melanoma and the radiographic pattern of thoracic metastasis seemed to prognosticate the survival rate of these patients. Miliary metastasis and bone destruction implied a grave prognosis. Patients with a solitary lung nodule had the best survival experience. Immunotherapy, chemotherapy, and surgery of selected distal metastases significantly improved the survival of most of these patients.

Adolescent↗

Lymphoscintigraphy in malignant melanoma: 99mTc antimony sulfur colloid.

Lymphoscintigrams were performed using technetium-99m antimony sulfur colloid in 21 patients with cutaneous malignant melanoma. Scintigraphic results were concordant with clinical prediction of lymph drainage in six of 11 patients with trunk melanoma, in five of seven patients with extremity lesions, and in none of three patients with scalp melanoma. Thirteen patients showed activity in more than one regional node group. Eleven patients had focal activity in areas other than regional node groups (i.e., in-transit or central lymph nodes). Lymphadenectomy was performed in 19 patients. In each case, the regional lymph node area chosen for resection was positive scintigraphically. The presence of 99mTc activity in excised lymph nodes was documented by scintillation counting and autoradiography. Metastatic disease was found in the resected nodes of 12 patients. Lymphoscintigraphy may be useful in planning lymphadenectomy in some patients with cutaneous melanoma.

Adult↗