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Biomedical subjects

J H Muchmore

Publications and source records attributed to J H Muchmore.

36 records · Page 2Linked to original sources

Chemotherapy by regional perfusion for limb melanoma.

The administration of chemotherapy by isolated regional perfusion was developed in 1957 at Tulane University and was found to be of greatest benefit for patient with melanoma of the limbs. From 1957 to 1984, 897 patients were treated by this method. The 10-year survival rate for 831 patients with primary melanoma was 77 per cent. Women survived longer than men, with 10-year rates of 81 per cent and 65 per cent, respectively. Prophylactic lymph node dissection was of benefit for males with poor prognosis distal lower limb lesions, but other groups did not benefit. Primary lesions on the arm and thigh did better than lesions of the hand or foot, with plantar and subungual lesions having the least favorable results. Thickness, level, and histologic type were also significant prognostic indicators. Thirty-three patients with locally recurrent melanoma (stage II) treated by perfusion and excision had a 10-year survival rate of 59 per cent. For 129 patients with metastases to the regional lymph nodes (IIIB), perfusion plus RLND produced a 10-year rate of 51 per cent; survival rates for those with a single positive node was 64 per cent. Seventy patients with satellitosis or intransit metastases (IIIA) had a 10-year survival rate of 23 per cent. Thirty-eight patients with metastases to limbs from unknown primaries had a 10-year survival rate of 52 per cent. The overall 10-year rate for all stage III patients was 41 per cent. Perfusion produced useful palliation in 144 patients with limb melanoma in the presence of systemic metastases.

Chemotherapy, Cancer, Regional Perfusion↗

Noninvasive evaluation of peripheral vasculature following regional hyperthermic chemotherapeutic perfusion (RHCP).

Regional hyperthermic chemotherapeutic perfusion (RHCP) has been used to treat over 1000 patients with advanced melanoma and soft tissue sarcoma. This study analyzes the impact of RHCP on the peripheral vasculature. Forty-one patients (23 women, 18 men) with an average age of 51.3 years were treated by RHCP of an upper or lower extremity using phenyalanine mustard for 60 minutes at a mean extremity temperature of 40 C. Patients were examined preoperatively and postoperatively at 36 hours, 7 days, 1 month, and 6 months by noninvasive arterial (Doppler-resting analog velocity waveform, response to stress) and venous (Doppler, impedance plethysmography [IPG], phleborrheography [PRG]) measurements. Upper-extremity evaluation of 14 patients (9 women, 5 men) indicated no abnormal studies. Response to stress showed an increase of the brachial:distal vessel ratio of 0.1 +/- 0.05; tendency of the analog velocity waveform toward triphasic; and response to stress augmented by 0.18 +/- .03 at 36 hours. Lower-extremity evaluation of 27 patients (15 women, 12 men) indicated two with thrombophlebitis. Response to stress showed an increase of the ankle: brachial ratio of .016 +/- 0.04; change in the analog velocity waveform toward triphasic; and response to stress augmented by 0.08 +/- 0.08 at 36 hours. All measurements returned to preoperative values at 7 days. Results of this study indicate RHCP has no long-term adverse effect on the vasculature of the extremity, as monitored by the noninvasive blood flow studies.

Adult↗

Isolated perfusion of extremities for metastatic melanoma from an unknown primary lesion.

Since 1957, 822 patients with invasive malignant melanoma of the limbs were treated by regional perfusion at the Tulane Medical Center. Between 1958 and 1982, there were 32 patients with regional metastatic melanoma from an unknown primary site involving either the upper limb and axillary lymph nodes or lower limb and femoral or inguinal lymph nodes. This group represents 3.5% of patients with regional melanomas treated during this period. There were 16 patients with upper limb regional metastases and 14 patients with lower limb metastases. Sixteen patients had stage IIIB disease (ie, regional lymph node metastases), ten had stage IIIA disease (ie, satellitosis), and four had stage IIIAB disease. Six patients had a history of a suggestive limb lesion that had completely regressed and showed no residual tumor on biopsy. All 30 patients were treated by regional isolated perfusion and regional lymph node dissection, with surgical excision of in-transit disease when possible. The cumulative five-year survival for all patients is 50%. Interestingly, the patients with a history of a lesion that regressed had 85% cumulative five-year survival, and the patients with stage IIIB disease did almost as well, with 62% surviving for five years.

Adult↗

Immunological heterogeneity in human melanoma: immunogenic alloantigen expression in autologous host.

A patient presented with a primary melanoma, Level IV, 2.5 mm thick; 30 excised lymph nodes were all negative for tumor. Four local recurrences followed in the ensuing 17 months. Tumor cells cultured at this time were epithelioid. Autoimmunization was followed by a disease-free interval of 15 months. Postimmunization, the patient's lymphocytes destroyed his melanoma cells in culture and were stimulated in mixed cell culture by his irradiated tumor cells. Cells grown from the relapsing tumor were spindle/dendritic with bizarre morphology and were not attacked by his lymphocytes in culture. Using a C' fixation technique, DR antigen profiles of the patient's B-cells and both tumor cell types showed that the immunizing tumor was positive for DR antigens 3, 5, and 8, none of which were present on his B-cells which had DR 2 and 4. Both B-cells and immunizing tumor cells were positive for DQ antigens. The relapsing tumor cells were positive for DR2 and negative for all other D region antigens tested. The evidence suggests that given a melanoma of heterogeneous cell population, autoimmunization against the predominant immunogenic cell inhibits tumor growth but allows the ascendance of a nonimmunogenic tumor cell type.

Antigens, Neoplasm↗

Response to aminoglutethimide after failure of tamoxifen therapy in breast cancer.

A 54-year-old woman had a primary breast cancer with an estrogen receptor of 11.9 fmoles/mg of protein. One year later bony metastases were treated with tamoxifen. The disease progressed rapidly, and therapy was changed to aminoglutethimide, which has resulted in an almost complete remission. This case shows that patients who fail to respond to tamoxifen therapy may have a good response to other endocrine manipulation--in this instance, aminoglutethimide.

Aminoglutethimide↗

Effect of impaired renal function on tamoxifen.

There is no information available in the literature on the blood levels of tamoxifen in patients with decreased renal function. As serious side effects of tamoxifen administered at high doses have been reported, a patient with decreased renal function and metastatic breast cancer was studied to determine the blood levels of tamoxifen while under therapy. Since no abnormally elevated levels of tamoxifen were found in this patient during the month of therapy, results of this study indicate that tamoxifen can be administered to patients with some degree of renal impairment without the risk of giving rise to abnormally elevated blood levels.

Breast Neoplasms↗

Lipid-F1 nucleohistone interactions.

High concentrations of phospholipids determine destabilization of F1 histone-DNA complex at the weight ratios, histone:DNA, 0.8:1 and 1:1, but low concentrations cause only negligible destabilization. Cholesterol at high weight ratios has little effect on nucleohistone stability. Only linolenic acid of the fatty acids used reproduces similar changes in the thermal stability of F1 histone-DNA complex as phospholipids. The type of interaction of phospholipids with the F1 histone-DNA complex is analyzed, and the involvement of phospholipids in DNA replication in vivo is discussed.

Binding Sites↗

Effect of phospholipids on the activity of DNA polymerase I from E. coli.

Sphingomyelin, phosphatidylethanolamine and lecithin at concentrations which destabilize the DNA helix enhance the DNA polymerase activity, but sphingosine and phosphatidylserine have only a moderate effect. MgCl2 was shown to modify the action of sphingomyelin on the DNA polymerase activity. The role of phospholipids in the DNA replicating process was analyzed.

DNA Nucleotidyltransferases↗

Regional chemotherapy with hemofiltration: a rationale for a different treatment approach to advanced pancreatic cancer.

BACKGROUND/AIMS: Since 1989, thirty-two patients with advanced, intra-abdominal pancreatic cancer were treated with regional chemotherapy in combination with extracorporeal hemofiltration. PATIENTS AND METHODS: Eleven patients had locally advanced, unresectable cancer, and ten had advanced disease with liver metastases. Three patients had developed liver metastases following a radical resection. One patient had an incomplete resection with local residual disease, and a second had developed a local recurrence after a radical resection. One patient had an unresectable cystadenocarcinoma. Five patients had failed prior systemic therapies for unresectable pancreatic cancer. The patients underwent 85 treatments with regional chemotherapy plus hemofiltration, an average of 2.7 treatments per patient. RESULTS: Of 21 patients treated primarily with regional chemotherapy plus hemofiltration, there were two complete responses (9%) and eight partial responses (38%), an overall total response rate of 47%. The average survival for patients with Stage II/III localized, unresectable disease is 13 months and that for Stage IV unresectable disease with liver metastases is 9 months. CONCLUSIONS: Patients with recurrent disease following a radical resection or having failed prior systemic therapies generally had no benefit from regional chemotherapy plus hemofiltration.

Adenocarcinoma↗