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Biomedical subjects

D L Morton

Publications and source records attributed to D L Morton.

At least 199 records · Page 11Linked to original sources
PubMed1988

Thermal dose-response of magnetic-induction thermoradiotherapy.

Sixty-three patients with advanced cancer underwent greater than or equal to 5,000 cGy combined with Concentric Coil magnetic-induction localized hyperthermia. Tumor regression (CR + PR) was compared to thermal dose received, incorporating the premise that hyperthermia response is a function of time as well as temperature. A computer program was developed (after Sapareto and Dewey [2]) which stored minimum tumor temperatures recorded spatially and temporally during treatment and correlated response with T43 (equivalent minutes at 43 degrees C during the first treatment) and CT43 (cumulative T43, computed by multiplying T43 by the actual number of identical subsequent treatments received during the course of therapy). Those who responded--N = 46 (73%)--had significantly higher median thermal doses than those who did not respond. Comparison of T43 and CT43 thermal dose values between responders and nonresponders was significantly different at p values of 0.05 and 0.04, respectively. The data indicate that magnetic-induction hyperthermia and high-dose XRT was an effective treatment combination in advanced disease and that tumor response improved as thermal dose increased.

Combined Modality Therapy↗
PubMed1988

Recovery of a cell surface fetal antigen from circulating immune complexes of melanoma patients.

A well-characterized 69.5 x 10(3) dalton glycoprotein fetal antigen (FA), isolated from the spent culture medium of a melanoma cell line, UCLA-SO-14 (M14), was utilized to characterize the antigen component of circulating immune complexes (CIC) from melanoma patients. Ten serum samples from five patients with stage II melanoma at 1 and 4 months prior to the clinical detection of recurrent disease were selected for study. The CIC were dissociated with low pH and ultrafiltered through a 100 x 10(3) dalton exclusion limit membrane. The low pH treatment resulted in an increase in antibody titer in eight of ten serum samples. The antibody activity in membrane immunofluorescence was quantitatively inhibited by the filtered antigen fraction and purified FA, suggesting the presence of anti-FA antibodies in the treated serum, which possibly were complexed with FA in the untreated sample. As determined by competitive inhibition in an enzyme-linked immunosorbent assay, the filtrate (antigen fraction) contained an antigen that was immunologically similar to FA. These results clearly demonstrate that FA, expressed on the cell surface of melanoma cells, is present in CIC of selected melanoma patients.

Antigen-Antibody Complex↗
PubMed1988

Prognostic significance of melanoma arising in the scalp.

Thirty-five patients with stage I melanoma of the scalp were retrospectively reviewed and compared with similar patients with melanoma of the extremity and trunk. Patients with melanoma of the scalp were predominantly male. The 5-year survival rate was 89 percent. This compared favorably with similar patients with melanoma arising either in the trunk or the extremity. The prognosis of patients with stage I melanoma of the scalp is no worse than that of patients with melanoma arising in the trunk or extremity; therefore, they should be treated in a comparable manner.

Abdomen↗
PubMed1988

A comparison of solutions for lung preservation using pulmonary alveolar type II cell viability.

Many special solutions have been developed to protect the ischemic lung in preparation for transplantation. To determine an effective solution, we isolated pulmonary alveolar type II cells from rat lungs. These cells play an important role in sodium transport and the production of surfactant; thus, they are crucial to the respiratory physiology of the lung. In this study, we examined in vitro the effect of various solutions such as Collins' solution, Collins-Sacks solution, and glucose-insulin-potassium solution on alveolar type II cell viability. The cell viability was examined with a trypan blue dye exclusion test and [3H]thymidine uptake proliferation assay after 24 and 72 hours of incubation. The alveolar type II cells in the glucose-insulin-potassium solution had greater viability compared with cells cultured in either Collins' or Collins-Sacks solution. This study demonstrates that glucose-insulin-potassium solution has the least toxic effect on isolated alveolar type II cells compared with other preserving solutions.

Animals↗
PubMed1988

A randomized prospective trial using postoperative adjuvant chemotherapy (adriamycin) in high-grade extremity soft-tissue sarcoma.

From March 1981 to December 1984 119 patients with primary grade III extremity soft-tissue sarcoma were randomized postoperatively to single agent Adriamycin (57) or to control, no adjuvant chemotherapy (62). Adjuvant therapy was begun within 6 weeks of surgery, and consisted of Adriamycin 90 mg/m2 given over 2 days, once a month for 5 months. All patients had received preoperative intraarterial Adriamycin, radiation therapy (1,750 cGy) and subsequent surgical excision. At a median follow-up of 28 months there was no difference between the two groups in overall survival (Adriamycin = 84%, control = 80%), local tumor recurrence, or in the disease-free survival (Adriamycin = 58%, control = 54%). This study indicates that the use of single-agent Adriamycin as postoperative adjuvant chemotherapy has no significant clinical benefit in patients with high-grade extremity soft-tissue sarcoma treated with preoperative Adriamycin, radiation, and surgical excision. Although the Adriamycin postoperative adjuvant chemotherapy did not significantly benefit the experimental group relative to the control group, both groups of patients had an improved disease-free and overall survival rate compared to historical controls.

Adolescent↗
PubMed1988

Occult tumor cells in the lymph nodes of patients with pathological stage I malignant melanoma. An immunohistological study.

We examined 2,227 lymph nodes from 100 patients with clinical Stage I cutaneous melanoma for the presence of microscopic deposits of tumor. On examination of hematoxylin-and-eosin-stained sections, none had melanoma. Sixteen nodes from 14 patients had melanoma detectable by an antiserum to S-100 protein in a peroxidase-antiperoxidase (PAP) assay. The melanomatous nature of these cells was confirmed by their reaction with the melanoma-directed monoclonal antibody NKl/C3. The incidence of occult nodal metastases was highest in patients with deeply invasive and micrometrically thick primary tumors. The incidence of occult melanoma was not increased where additional serial sections were cut and semiserial sections examined. Pitfalls in the identification of occult melanoma cells (OMC) include S-100 protein-positive interdigitating dendritic cells, capsular nevus cells, a minority of sinus "macrophages," and the Schwann cells of node-associated nerves. Thus, we conclude that the incidence of early melanoma metastases in the regional lymph nodes of patients with clinical Stage I melanoma is greater than has previously been appreciated on the basis of assessment of routine hematoxylin-and-eosin-stained sections. Six of the 14 patients with OMC died of melanoma (41%), as compared to only 18 of 86 patients without OMC (21%; 0.10 greater than P greater than 0.05).

Adult↗
PubMed1988

Detection of malignant melanoma with monoclonal antibodies.

Eleven murine monoclonal antibodies (MoAbs) were isolated that defined unique membrane antigens expressed on human melanoma cells but not detectable on human lymphoid cells by radioimmunometric assays. Five of these MoAbs each identified a separate melanoma cell surface antigen as shown by distinctly different in vitro MoAb binding patterns to a diverse panel of tumor cell lines. One of these 5 monoclonals, MoAb 34.1, reacted specifically with 9/11 melanoma lines and 0/28 other human tumor or lymphoid cell lines. The other 4 MoAbs reacted strongly with melanomas, but also bound to 1 or more non-melanoma lines. The remaining 6 MoAbs defined three distinct regions of a single melanoma cell membrane protein with a molecular weight of 125 kiloDaltons (kD) as shown by antibody crossblocking and gel electrophoresis. A sensitive radioimmunoassay developed with MoAbs to 2 epitopes of this 125 kD protein detected up to 500-fold higher levels of this antigen in extracts of melanoma cells compared to autologous lymphoid cells. The 125 kD antigen also was detected by indirect immunoperoxidase assays with the MoAbs on biopsied tumors in histologic tissue sections of 5/11 metastatic melanomas and 1/11 carcinomas but was found on some normal endothelium and smooth muscle. Another monoclonal, MoAb 705, reacted more broadly with tumor cells in 10/14 biopsied melanomas and 10/11 carcinomas, but also was reactive with basal epidermis and normal fibroblasts. By contrast, MoAb 34.1 bound specifically to tumor cells of 7/11 biopsied metastatic melanomas, but bound 0/10 carcinomas and few normal tissues except for some macrophages. Thus, MoAb 34.1 was the most specific diagnostic reagent for immunohistologic detection of melanoma. The 250 kD antigen defined by MoAb 34.1 is similar to a high molecular weight proteoglycan reported to be an excellent tumor marker for human melanomas. The results of these studies show that murine monoclonal antibodies can be used as sensitive reagents for radioimmunoassays and immunohistology of malignant melanoma.

Animals↗
PubMed1988

The protection of ischemic lung with verapamil and hydralazine.

The optimum method for lung preservation in preparation for transplantation remains unresolved. In this study, we evaluated the effectiveness of two pharmacologic agents for prolonging the preservation time of the ischemic lung. We compared hydralazine, a vasodilator, and verapamil, which is both a vasodilator and a calcium channel blocker, in regard to their effectiveness in promoting functional recovery of the ischemic dog lung in a new experimental model. The model consists of exposing the left lung of each dog to normothermic ischemia after clamping the pulmonary artery, vein, and bronchus. After ischemic periods of 1 to 5 hours, pulmonary circulation was reestablished. The functional integrity of the left lung was then evaluated by ligating the right bronchus, so that the dog was completely dependent on the previously ischemic lung. The left lung of eight dogs was perfused with 200 ml of Collins-Sachs solution alone in group A, with Collins-Sachs solution containing 20 mg of hydralazine in group B (n = 8), and with Collins-Sachs solution containing 5 mg of verapamil in group C (n = 8). The mean ischemic time was 2.3 hours in group A, 3.0 hours in group B, and 3.1 hours in group C. One dog in group A survived after 1 hour of ischemia, two dogs in group B survived after 1 and 3 hours of ischemia, and six dogs in group C survived 2 to 4 hours of ischemia. Oxygen tension in room air after bronchial ligation was 39.9 +/- 10.2 mm Hg in group A, 59.4 +/- 35.3 in group B, and 76.1 +/- 32.9 in group C. Statistical significance existed between groups A and C (p less than 0.05). Pulmonary vascular resistance after bronchial ligation was 428.9 +/- 158.8 dynes.sec.cm-5 in group A, 219.9 +/- 51.9 in group B, and 208.3 +/- 84.5 in group C. Thus tissue damage caused by ischemia was significantly less with verapamil than with the vasodilating drug hydralazine.

Animals↗
PubMed1987

Isolation of lymphocytes from clotted blood.

A problem often faced in clinical cell-mediated immunology research is to obtain peripheral blood lymphocytes (PBLs) in sufficient numbers to carry out cellular immune assays. Obtaining sufficient amounts of blood for serum is usually more practical than for PBLs. Blood is usually drawn easily for serum, but obtaining PBLs from clotted blood has not been very practical. In this report we describe a procedure whereby PBLs can be recovered from clotted blood and used in functional immune assays. Using the enzyme streptokinase (SK) blood clots were dissolved and viable PBLs recovered up to 24 h post clotting. Concentrations of SK from 250 to 500 SK U/ml gave maximum recovery of PBLs.

Blood Coagulation↗
PubMed1987

Surgical treatment of lymph nodes with metastatic melanoma from unknown primary site.

To determine the prognosis of patients with lymph node metastases from an unknown primary melanoma, we retrospectively reviewed the clinicopathologic features of 188 such patients treated from 1971 through 1986 and compared their records with those of patients with clinical stage II melanoma with known primary lesions. Patients with lymph node metastases from an unknown primary melanoma represented 4.6% of all patients with melanoma treated during that period. The five- and ten-year survival rates were 42% and 40%, respectively (median, 37 months). When stratified by number of tumor-containing lymph nodes, there was no significant difference in survival between patients with an unknown primary melanoma and lymph node metastases and those with clinical stage II melanoma and known primary sites. The prognosis of the former patients is no worse than that of patients with lymph node metastases from a known primary site and should be treated in a comparable manner.

Combined Modality Therapy↗
PubMed1987

Cyclophosphamide-induced alterations in human monocyte functions.

This investigation was designed to study the effects of relatively low doses of cyclophosphamide (CY) on monocyte function in patients with surgically resected melanoma. Monocytes taken from patients 3 days after receiving 300 mg, 150 mg, or 75 mg CY/m2 had decreased interleukin-1 (IL-1) production. Production of tumor necrosis factor (TNF)-like molecules by the same monocytes appeared to be enhanced following 300 mg/m2 CY but not after 150 or 75 mg/m2 CY. In vitro studies of the direct effects of CY metabolites (mafosfamide and 4-hydroperoxycyclophosphamide) on human monocytes showed only concomitant decreases in production of IL-1 and TNF-like molecules. This occurred at concentrations that did not obviously affect viability, although monocyte spreading was inhibited. No evidence was obtained for in vitro enhancement of TNF-production. We conclude that CY can affect monocyte function. In vivo it may have both direct effects leading to decreased TNF and IL-1 production and indirect effects through lymphocytic or haematopoietic systems that activate monocytes to enhanced TNF production. The effects are dose-dependent. These CY-induced changes could be responsible in part for some of the alterations in host immunity and tumor resistance that follows administration of the drug.

Combined Modality Therapy↗
PubMed1987

Tumor stabilization after hyperthermia: an important criterion of response to thermal therapy.

Several investigators have indicated that changes in tumor size may not occur after hyperthermia therapy even with substantial tumor cell kill, because of early edema and subsequent fibrosis of background stroma, suggesting that "tumor stabilization" might be an important benefit of thermal therapy. Recently, 9 institutions completed a national cooperative study of localized hyperthermia for patients with advanced, recurrent, or metastatic solid cancer that evaluated the potential significance of this response variable in a standardized clinical trial. Of 960 evaluable patients who completed at least one course of hyperthermia, thermoradiotherapy, or thermochemotherapy, 85 (9%) had complete responses for 1-34 months, 173 (18%) had partial responses for 1-39 months, 95 (10%) had minimal responses for 1-15 months, and 313 (33%) had disease stabilization for 1-32 months. Of 313 patients who had no change (i.e., +/- 25%) in the size of their tumors after hyperthermia, the response lasted only 1-3 months in 170 (54%) patients, a finding of questionable clinical significance. However, disease stabilization was observed for more than 3 months in 143 (46%), for more than 6 months in 67 (21%), more than 9 months in 33 (10%), and more than 12 months in 16 (5%). Disease stabilization was also associated with improved activity for 1-22 months in 79 (25%) of these patients, and improved pain for 1-22 months in 100 (32%). Disease stabilization appeared to be independent of tumor histology, location, or depth within the body, size, or minimum treatment temperature, but was somewhat more frequent after hyperthermia combination therapy. There is sufficient accumulative data to suggest that tumor stabilization after hyperthermia should not be dismissed as a placebo effect. This response variable well may be a unique and potentially important criterion of response to localized hyperthermia therapy.

Adult↗
PubMed1987

Natural history of surgically treated mucosal melanoma.

Thirty-three patients with melanoma arising in a mucosal site were reviewed. Sixteen patients were treated either with abdominoperineal resection or radical vulvectomy and superficial inguinal lymphadenectomy. Three patients were treated palliatively. Fourteen patients were treated conservatively with local excision, wide local excision, and radiation therapy. One patient received systemic chemotherapy and radiation therapy. Local recurrence developed in seven patients. The overall survival rate was poor. Neither local control nor survival appeared to be influenced by the initial surgical approach.

Adult↗
PubMed1987

A radioimmunometric assay for the detection and characterization of lung cancer-associated antibodies in sera of lung cancer patients.

A radioimmunometric assay was developed from P3 lung carcinoma target cells to detect anti-lung cancer antibodies. Of 100 sera from lung cancer patients tested, 80 (80%) were positive. However, only 6/30 (20%) sera from cancer patients with other cancers, 1/25 (4%) of sera from patients with nonmalignant lung disease, and 0/20 sera from healthy donors were positive. Quantitative absorptions showed that sera from lung cancer patients cross-reacted with other lung cancers, gastrointestinal cancers, and/or fetal lung tissues, but not with breast carcinomas, melanomas, sarcomas, fetal skin, or normal lung tissues. Two lung cancer antigens were defined: LCA-1, which shared antigenic determinants with GI tumors and fetal lung tissues, and LCA-2, which showed cross-reactivity only with GI tumors.

Adult↗
PubMed1987

Gangliosides of human melanoma.

The ganglioside composition of human malignant melanoma was studied with the use of 80 melanoma specimens, including 52 surgical specimens and 28 cultured cell lines. A ganglioside fraction was isolated and purified from each of these tissues, and the amount of each component ganglioside was assessed by thin-layer chromatography (TLC) and a TLC scanner. Five gangliosides (GM3, GD3, GM2, GD2, and alkali-labile ganglioside) were most commonly expressed by these melanomas. However, the total ganglioside amount (ranging from 33 to 302 micrograms/g wet wt of tissue) as well as the distribution of each ganglioside were widely heterogeneous in both biopsied and cultured melanomas. When the ganglioside expressions of cultured and biopsied melanomas were compared, GM2 and GD2 were minor components of biopsied melanomas but often became major components of cultured melanoma cells. Conversely, alkali-labile ganglioside was expressed more strongly on biopsied melanomas. This heterogeneity suggests that it will be necessary to analyze the ganglioside composition of biopsied melanomas before using monoclonal antibodies to melanoma-associated gangliosides for melanoma diagnosis or therapy.

Biopsy↗
PubMed1987

Bronchial anastomosis with a tissue adhesive.

Air leakage and necrotic degeneration may occur after bronchial anastomosis and can lead to death from secondary pneumothorax and pneumonia. We studied the ability of a new tissue adhesive (N-butyl-cyanoacrylate monomer) to enforce the bronchial suture line. The left main bronchus in each of five pigs in Group A was completely transected and closed by four stitches and tissue adhesive. The transected left main bronchus in each of the other five pigs in Group B was connected with 11 to 14 interrupted polyglycolic acid 3-0 sutures. The time required for reconstruction was 10 +/- 3.6 minutes in Group A and 25.0 +/- 6.5 minutes in Group B. No symptoms of a constricted airway were apparent in Group A. All pigs were examined at an interval of from 5 to 8 weeks after operation. Evidence of infection at the bronchus appeared in three animals: two in Group A and one in Group B. One instance of air leakage at the anastomosis occurred in Group B. We measured the maximum tensile strength of the bronchial suture line by means of an electromechanical testing machine comparing the tensile strength of the treated left bronchus with that of the control right bronchus. The maximum tension of the treated bronchus in Group A was 10.3 +/- 1.52 (pounds) and that of control was 8.0 +/- 1.56 (pounds) (p less than 0.05). The maximum tension of Group B was 7.93 +/- 0.29 (pounds) on the treated side and 6.78 +/- 0.32 (pounds) on the control side (p less than 0.05). The suture line with tissue adhesive was enforced sufficiently to act as a stable connective tissue. Histologic studies in Group A revealed that the suture line was completely healed without tissue damage and was strengthened by the tissue adhesive.

Animals↗
PubMed1986

Effect of localized magnetic-induction hyperthermia on the brain. Temperature versus intracranial pressure.

Normal brain and brain tumor temperatures were studied for their effects on intracranial pressure (ICP) in 13 patients who received 37 localized thermochemotherapy treatments for recurrent primary or metastatic brain tumors. Two transient neurologic complications occurred in patients with an elevated initial ICP value; thus, the authors concluded that an initial ICP value of 30 cm H2O or greater may contraindicate brain hyperthermia. It appears that noninvasive brain hyperthermia by magnetic-loop induction can cause an initial rise in ICP value, although a protective mechanism(s) that tends to lower ICP occurs over time, and also at a normal brain temperature of approximately 42.0 degrees C. Possible mechanisms of ICP reduction include direct heating of the hypothalamus with a reduction in pCO2 and the development of tachypnea and hyperpnea with a reduction in pCO2. Hyperthermia applied to the brain should be undertaken only with adequate monitoring of ICP; in addition, extreme caution should be taken in patients with an elevated initial ICP value and in those patients in whom adaptation to elevated pressure does not occur.

Adult↗