Biomedical subjects
P P Sordillo
Publications and source records attributed to P P Sordillo.
Ethical and social issues in organ procurement for transplantation.
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Fetal tissue research and transplantation.
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Ethical considerations concerning the HIV-positive physician.
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HIV-associated Hodgkin disease: a clinical study of 18 cases and review of the literature.
Intermediate- and high-grade B-cell non-Hodgkin lymphoma (NHL) occurring in a human immunodeficiency virus (HIV)-infected patient is considered diagnostic of the acquired immunodeficiency syndrome (AIDS). Other neoplasms (both hematopoietic and nonhematopoietic) have also been reported in patients with HIV infection, although none except Kaposi sarcoma carries the same diagnosis of AIDS as B-cell NHL in an HIV-infected host. There have been previous reports in the literature of Hodgkin disease (HD) in HIV-infected patients. We describe our clinical and pathological experience with HD from 1984-1989, in 18 patients with documented HIV infection and also review the literature on HD in HIV-infected patients. Almost all patients described herein presented with advanced disease and mixed cellularity histology and did very poorly despite some good initial responses to therapy. By statistical analysis, we found that the patients with HIV-associated HD had a strong tendency to be outside the age range seen in non-HIV-associated HD (P less than 0.005). We also discuss the possible relationship between HIV and HD and consider whether HIV-associated HD, like B-cell NHL, is a manifestation of AIDS.
The allocation of scarce medical resources.
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Leiomyosarcomas of the extremities.
Leiomyosarcomas are uncommon malignant neoplasms that rarely arise in the extremities. We report on the clinical characteristics of 17 cases seen at the Memorial Sloan-Kettering Cancer Center over a 32 year period. Most neoplasms occurred in the lower extremities, and most of the tumors recurred after surgery alone, with several late recurrences. The overall prognosis was grim, with a median survival of 24 months. More aggressive multidisciplinary approaches to this disease are warranted.
Etoposide (VP-16) in the treatment of advanced adenocarcinoma of the pancreas.
Twenty-six patients with advanced adenocarcinoma of the pancreas were treated with etoposide (VP-16), 100-180 mg/m2 i.v., days 1, 2, and 3, monthly. Twenty-five had bidimensionally measurable disease and one had evaluable disease only. This regimen and dosage schedule were well tolerated, with minimal toxicity including myelosuppression; a median WBC count nadir of 3,600 cells/mm3 (range 200-2,400); and a median platelet nadir of 215,000 cells/mm3 (range 15,000-405,000). However, no patients responded and only two had stable disease for 3.5 and 4 months, respectively. At this dosage and schedule, there is no role for VP-16 in the treatment of advanced pancreatic adenocarcinoma.
Cisplatin. A phase II evaluation in previously untreated patients with soft tissue sarcomas.
A Phase II trial of moderately high-dose cisplatin (120 mg/m2 with mannitol diuresis) was conducted in 26 previously untreated patients with soft tissue sarcomas. One partial response (major response rate, 4%) and two minor responses were seen. Severe nausea and vomiting and transient increases in the serum creatinine level were the most common side effects of treatment. Cisplatin has minimal activity as a single agent in patients with soft tissue sarcoma.
Evaluation of new anticancer agents against human pancreatic carcinomas in nude mice.
Heterotransplantation of human cancers in nude mice has provided an in vivo model for studying the biologic characteristics of human tumors, particularly their response to chemotherapy. In an effort to identify cytotoxic agents effective against pancreatic carcinoma, this model was used to evaluate the efficacy of three new anticancer agents--menogarol, 4'-epirubicin, and taxol--against two human transplanted pancreatic tumors. Relative area (tumor length X width) differed significantly between menogarol-treated and control groups (p = 0.034). A marked response was also observed in the tumors to 4'-epirubicin (p = 0.01). Taxol was ineffective in controlling tumor growth; by the fourth week, the size of treated tumors was similar to that of the control group (p = 0.55). No toxicity was observed in either the menogarol- or taxol-treated animals. Animals bearing the P2 tumor, and treated with 4' epirubicin displayed severe toxicity by day 18 with death by day 21 in most animals. For the second tumor, Capan-1, relative area differed significantly between the menogarol-treated and the control group (p = 0.003). In animals given 4'-epirubicin, a smaller difference was observed when comparing the relative areas (p = 0.09). Animals treated with taxol again showed no difference in the tumors when compared with controls (p = 1.0). The use of the nude mouse system has evolved so that tumor-oriented trials are now feasible with the hope of clinical applicability. This study illustrates that at least two agents--menogarol and 4'-epirubicin--may have some antitumor activity against pancreatic carcinoma in this system.
Ethical considerations of reproductive technologies.
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Tumor imaging with carbon-11 labeled alpha-aminoisobutyric acid (AIB) in a patient with advanced malignant melanoma.
A 29 year-old-man presenting with advanced metastatic malignant melanoma was successfully imaged using carbon-11 (11C) labeled alpha-aminoisobutyric acid (AIB), a synthetic, non-metabolized amino acid transported into viable cells by the A-type, or alanine-preferring, amino acid transport system. Tumor located in the hilum of the lung was well visualized with 11C-AIB prior to chemotherapy. A gallium image with liver subtraction using 99mTc-sulfur colloid demonstrated regions of increased activity in liver which correlated with regions of increased activity on the 11C-AIB liver image.
Tumor localization of the metabolically trapped radiolabeled substrates 2-deoxy-D-glucose and aminocyclopentanecarboxylic acid in human melanoma heterotransplants.
Analysis of the accumulation of metabolically trapped radiolabeled substrates in normal and malignant tissues may be useful for studying biochemical processes in vivo with positron emission tomography (PET). If labeled with the short-lived, positron-emitting radionuclide carbon-11 (T1/2 = 20.4 min), the glucose analog, 2-deoxy-D-glucose (2-DG), and the synthetic amino acid, aminocyclopentanecarboxylic acid (ACPC), may be useful for studying glucose utilization and amino acid transport in vivo. This study evaluated the biodistribution of the C-14 labeled analogues of these compounds in nude mice bearing human malignant melanoma heterotransplants. The data suggest that both 2-DG and ACPC accumulate in tumor tissue within 45 min.
Further characterization of a transplantable murine osteogenic sarcoma.
A transplantable murine osteogenic sarcoma was characterized to determine its suitability as a model for human cancer and to evaluate specific end points to study therapeutic intervention. Palpable tumors developed at implantation sites following latent periods of 8 to 21 days and grew to 3 g masses within 60 days. The tumor model was predictable in its manner of tumor growth, tumor production of alkaline phosphatase, formation of pulmonary metastases, and the survival of the host. It was found to be sensitive to treatment with cyclophosphamide and vincristine and to a lesser extent to adriamycin and 4'-epi-adriamycin. It did not show a response to treatment with cis-platinum, actinomycin D, or m-AMSA. Survival of the host is limited by the progression of metastatic disease and local control does not appreciably extend the median survival time. Thus, population survival should be used as a measure of the effectiveness of treatment of pulmonary metastases. Circulating alkaline phosphatase levels may best be used in assessing the response to treatment of the primary osteogenic sarcoma.
Imaging of human tumors and organs with N-13-labeled L-methionine.
The work described herein is the first reported use of nitrogen-13-labeled L-methionine in human subjects. Three volunteers and 14 patients with a variety of solid tumors were scanned after intravenous administration of L-(N-13) methionine. In both volunteers and cancer patients, uptake of label was seen in the liver and pancreas, with smaller amounts of label detected in the heart, urinary bladder, and salivary glands. Concentration of N-13 in tumor was seen in 12 of the 14 cancer patients. Five had repeat studies after chemotherapy; in each case, the change in tumor uptake of N-13 after N-13 methionine injection paralleled the clinical response to chemotherapy. Three patients had L-(N-13) glutamate scans the same day that they were studied with N-13 methionine. Concentration of the radiolabel in the tumor was very similar for the two compounds in each case. The systemic distribution of N-13 from methionine is similar to that from glutamate, except for a much smaller myocardial uptake and a prominent accumulation in the intestinal region. It is concluded that L-(N-13) methionine is potentially useful as a biologically significant agent for tumor visualization and assessment of therapeutic response.
Tumor localization of alpha-aminoisobutyric acid (AIB) in human melanoma heterotransplants.
The nude mouse bearing a human tumor heterotransplant is a useful model for studying the tumor localization of radiolabeled compounds. The biological tissue distribution of carbon 14-labeled alpha-aminoisobutyric acid (AIB), a synthetic, nonmetabolized amino acid, was determined in nude mice bearing human malignant melanoma heterotransplants in order to investigate the feasibility of using carbon 11 (t 1/2, 20.4 min)-labeled AIB for the visualization of human melanoma in vivo with positron emission tomography (PET). Our laboratory has previously demonstrated the use of 11C-labeled AIB as a tumor-imaging agent in a number of animal tumor models. The mean relative concentration of 14C-labeled AIB in tumor tissue at 45 min was 1.95 in this melanoma model. Tumor/blood and tumor/muscle ratios at 45 min postinjection were 5.42 and 12.2, respectively. These values suggest that 11C-labeled AIB may be useful for the in vivo study of malignant melanoma in humans. Alpha-aminoisobutyric acid (AIB), a synthetic, nonmetabolized amino acid, is thought to be actively accumulated into viable cells primarily by the A-type, or "alanine-prefering", amino acid transport system. AIB has been labeled with the short-lived, positron-emitting radionuclide, carbon 11 (t 1/2, 20.4 min), using a modified Bucherer-Strecker synthesis for amino acids. 11C-labeled AIB has been used to visualize tumors in dogs bearing spontaneous cancers, such as adenocarcinoma, lymphosarcoma, and osteogenic sarcoma, by utilizing positron-emission tomography (PET) and high-energy gamma (HEG) scintigraphy at the Sloan-Kettering Institute.(ABSTRACT TRUNCATED AT 250 WORDS)
Phase II trial of methylglyoxal-bis-guanylhydrazone (methyl-GAG) in patients with soft-tissue sarcomas.
A phase II study of Methylglyoxal-bis-guanylhydrazone (Methyl-GAG) was conducted on 20 previously treated patients with soft-tissue sarcomas. No major responses were seen among 18 adequately treated patients. Toxicity including severe fatigue, muscle pains, and pharyngitis was noted in most patients. Methyl-GAG does not have significant antitumor activity in previously treated patients with soft-tissue sarcomas.
Cytokinetics of a human neuroblastoma cell line following treatment with dianhydrogalactitol.
Studies were carried out on the effect of dianhydrogalactitol on a human neuroblastoma cell line in culture. The drug was cytotoxic at concentrations of 5 micrograms/ml and 10 micrograms/ml for 1 hour, but not at 1 microgram/ml. Flow cytometry of DNA showed that cell kill was preceded by a transient accumulation of cells in early S at 10 hours, and in late S at 36 hours. Smaller increases in the percent of cells in S phase were seen after treatment with 1 microgram/ml, without cell kill. It may be concluded that dianhydrogalactitol causes an S-phase block, followed by death of cells in late S at concentrations above 5 micrograms/ml.