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Biomedical subjects

D L Morton

Publications and source records attributed to D L Morton.

At least 361 records · Page 20Linked to original sources

Selective reduction of human tumor cell populations by human granulocytes in vitro.

Human peripheral blood granulocytes at a 10:1 effector cell:target cell ratio were shown by an in vitro semiquantitative staining procedure to reduce the number of human tumor cells, but not that of normal cells. Microscopic observations revealed that this selective reduction of tumor cells by granulocytes was a function of both detachment and cytolysis. The cytotoxic effect of granulocytes on the tumor cells was confirmed by a quantitative 5-[125I]iodo-2-deoxyuridine release assay. The data indicate that human granulocytes at a relatively low effector:target cell ratio (10:1) have the capacity to recognize and destroy human tumor cells in vitro.

Animals↗

The determination of lymph shed by colloidal gold scanning in patients with malignant melanoma: a preliminary study.

Colloidal gold radionucleotide 198Au scanning can demonstrate the direction of regional lymphatic drainage in patients with primary malignant melanoma. Each of 32 patients with primary melanoma of the trunk received an intradermal injection of 0.1 mCi of 198Au colloid around the primary melanoma site. Imaging was accomplished with a tomographic scanner 24 hours following the injection. Twenty-seven of these patients underwent 36 regional lymph node dissections; nine had nodal metastases histologically demonstrated in the area (s) of nucleotide uptake. In clinical evaluation of up to 55 weeks, no patients demonstrated regional lymph node metastases in node groups which did not show preoperative gold uptake. Early evidence shows excellent correlation between the route of regional lymph node metastases and the direction of lymphatic flow to regional node groups, as demonstrated by gold colloid scanning. This procedure may be useful for evaluating patients with histologically defined high risk melanomas situated on the trunk in areas which drain to one or more lymph node regions.

Gold Colloid, Radioactive↗

Disseminated melanoma presenting as a catastrophic event.

The possibility of a patient with malignant melanoma having a catastrophic event as the presenting sign of tumor dissemination cannot be dismissed. Should such an event occur, it would pose not only a risk to the patient, but also a potential risk to others. Since 1971, 712 patients with malignant melanoma have been evaluated. Twenty patients presented with brain metastases and an additional 12 patients developed brain metastases simultaneously with other organ involvement. Four patients (0.6%) had a catastrophic event, such as a stroke or seizure, with no antecedent symptoms. Microstaging of a primary melanoma by the methods of Clark and Breslow, in addition to the recognition of the presence or absence of regional lymph node metastases, provides reliable information for predicting the probability of tumor dissemination. Patients with deep primary melanomas or with lymph node metastases should be advised regarding their participation in potentially hazardous occupations or recreations.

Adult↗

In vitro assessment of immunocompetence in patients with malignant melanoma.

Ninety-four patients with malignant melanoma and 96 healthy controls were tested for lymphocyte proliferative capacity in a microblastogenesis assay. Each lymphocyte sample was assayed for incorporation of (3H)thymidine after stimulation with PHA, PWM, Con A (two doses), PPD, and allogeneic lymphocytes (MLC). MLC was the only assay that revealed a substantial and significant difference between the melanoma patients and controls. Almost all assays showed lower values in patients with more advanced disease. However, it was not possible to accurately predict clinical outcome from data obtained from in vitro immunocompetence tests. These results indicate the relatively limited clinical usefulness of assays of lymphocyte proliferative capacity in melanoma patients.

Adult↗

Comparison of the classification by microscopic level (stage) of malignant melanoma by three independent groups of pathologists.

The ability of groups of pathologists to classify and stage malignant melanoma varies with their familiarity with the new nomenclature proposed for that process. Primary lesions of malignant melanoma from 79 patients were independently examined and classified by community pathologists, university pathologists, and a referee pathologist all without access to each others diagnoses. The diagnoses of these groups were compared for agreement in variety of melanoma as well as depth of dermal penetration (stage or level). Greatest success (agreement with the referee) of both the community pathologists and the university pathologists was achieved when assessment of level of invasion (+/- 1) of the referee was compared (community pathologists = 94% +/- 12% agreement, university pathologists = 99% +/- 2% agreement). Our survey demonstrates that only a relatively small number of community pathologists (23%) employ the new nomenclature, but they do so with a facility equal to that of the university pathologists. Based upon this study and our continuing experiences, we recommend the review of all primary lesions of malignant melanoma by a pathologist or group experienced in the diagnosis and microscopic staging of the disease.

Diagnostic Errors↗

Sequential examination of lymphocyte proliferative capacity in patients with malignant melanoma receiving BCG immunotherapy.

A series of 42 patients with malignant melanoma treated with BCG adjuvant immunotherapy were studied for sequential changes in cellular immune reactivity to non-specific mitogens. Lymphocyte preparations were made monthly and stored in a viable condition in liquid nitrogen. After 6 months of treatment, all lymphocyte samples from an individual were recovered and tested for DNA synthesis after stimulation with PHA, PWM, Con A, PPD and MLC. The responses to the mitogens in the blastogenesis test were stable during the course of therapy. The MLC response did not increase significantly in patients treated with tumor-cell vaccines, and declined sharply in the six patients who subsequently relapsed and died. The in vitro PPD response increased 1 to 3 months after initiation of BCG in patients who were initially unresponsive to PPD in vitro. However, PPD-positive patients did not show any significant alteration of the PPD response. The PPD response did increase less sharply in patients whose disease eventually recurred than in those who remained without evidence of clinical disease. BCG therapy does not appear to correct lymphocyte proliferative defects in melanoma patients. Of the assays employed, the MLC and PPD tests appear to be the most useful as monitors of clinical status and response to therapy.

BCG Vaccine↗

Failure of adjuvant immunotherapy to prevent central nervous system metastases in malignant melanoma patients.

A review of our experience using BCG immunotherapy as a postsurgical adjunct in the treatment of melanoma shows that the incidence of systemic metastases appears to have been reduced. However, central nervous system (CNS) metastases continue to develop in these patients and represent the single most frequent cause of death. Serial studies of immune competence in these patients reveal that those with CNS metastases usually retain normal immune responses, whereas those with metastases at other sites exhibit progressive immunosuppression with advancing disease.

Adjuvants, Immunologic↗

Primary melanoma of skin of the breast region.

Primary melanoma of skin of the breast region accounted for less than 5% of all malignant melanomas. During a two-year period, 12 patients were seen with these unique lesions. It appears that wide excision and prophylactic lymphadenectomy, including radical mastectomy, gave the best long-term local and regional control. Dissection of the internal mammary nodes did not seem to be beneficial. Pertinent literatures emphasizing several important pathological factors which correlate with higher incidence of metastases to the regional lymph nodes are reviewed. A rational therapeutic approach, synthesizing above information and incorporating postoperative adjuvant immunotherapy, is suggested.

Adult↗

A rational approach to the surgical management of melanoma.

Our experience with 294 regional lymph node dissections in 250 patients are reviewed. The relationship between the Clark's level of invasion and the thickness of the primary is related to regional lymph node metastases. Patients with Clark's Level III melanoma had a 29% incidence of regional lymph node metastases, Clark's Level IV had a 42% incidence of regional lymph node metastases and Clark's Level V a 58% incidence of regional lymph node metastases. Primary melanomas greater than 1.5 mm in thickness had a 38% incidence of positive regional lymph nodes. We therefore recommend a regional lymphadenectomy in patients with Clark's Levels III, IV and V and all melanomas that are greater than 1.5 mm in thickness. A new technique is described which is helpful in localizing the direction of ambiguous lymphatic drainage in patients with truncal melanoma. The use of radioactive colloidal gold scanning has been useful in predicting lymphatic shed in these ambiguous truncal melanomas. Certain technical aspects of inguinal lymph node dissection are emphasized in an attempt to reduce the morbidity of these dissections. It is emphasized that iliac-obturator lymph node dissections are not performed unless the inguinal lymph nodes are found to be involved by frozen section examination at the time of surgery.

Female↗

A new in vivo assay of human lymphocyte-mediated immunity to melanoma.

Lymphocytes from melanoma patients more frequently inhibited the growth of human melanoma cells in the hamster cheek pouch than did lymphocytes from normal donors. Growth inhibition was accomplished with a much lower ratio of target cells to lymphocytes than in in vitro assays. The hamster cheek pouch assay can be used to study the relationship of blocking factors and humoral antibodies to cell-mediated immunity against human cancers.

Animals↗

Immunotherapy of cancer.

Clinical studies have indicated a close relationship between immunological competency and the growth of human cancer. Studies in animal systems have indicated that immunological mechanisms are important in host-tumor existence. A number of agents are in the process of being evaluated for their immunotherapeutic potential in patients with cancer. These include levamisole, bacille Calmette Guérin (BCG) and Corynebacterium parvum. While the precise role of these agents in the treatment of human malignancy remains to be clearly defined, they do appear to be useful as adjuncts to other forms of cancer therapy such as radiation therapy, chemotherapy and surgical operation.

BCG Vaccine↗

Monitoring immunotherapy with Bacillus Calmette-Guérin by antibody titer.

Antibody titer to Bacillus Calmette-Guérin (BCG) was determined by complement fixation in 111 normal volunteers and 83 melanoma patients. In 43 of these melanoma patients, sequential determination of antibody titer was made and correlated with clinical course. Low titers of antibody to BCG were found frequently in normal volunteers and in melanoma patients prior to BCG immunotherapy. The typical response to BCG immunotherapy was a rapid rise of antibody titer to high levels. Six of 19 patients with recurrence had disappearance of antibody preceding clinical recurrence by up to 5 months. In 13 of 40 patients receiving BCG, serum antibody was a better indicator of the patient's response than measurement of delayed cutaneous hypersensitivity to purified protein derivative. These results suggest that measurement of the antibody response to BCG may be useful in developing an optimum mode of BCG immunotherapy as well as predicting clinical recurrence in patients with melanoma.

Antibodies, Bacterial↗