Biomedical subjects
Publications and source records attributed to E Robinson.
Perfusion blood pool mismatch using Tc-99m labeled red blood cells (RBCs) in a hemangioma of the tongue is described. The method is useful in the evaluation of size of the residual blood pool after irradiation of the tumor.
The survival, and the patterns and mechanisms of failure of 41 patients with pure testicular seminoma treated at the Northern Israel Oncology Center from 1968 to 1983 were analyzed. The actuarial 5-year survival of all patients was 85.4% and of stage I patients, 92.2%. Treatment failures were analyzed. The following conclusions were reached: in order to increase the cure rate, the use of combination chemotherapy as the initial treatment modality in advanced seminoma is recommended. In cases of transscrotal approach, the scrotum should be irradiated. Adjuvant mediastinal irradiation is not needed.
The Chemical Manufacturers' Association voluntary test program on phthalate esters is described, and the results of certain key aspects of the program are presented. Representative phthalate esters were chosen for genotoxicity testing and peroxisome proliferation screening, and di-2-ethylhexyl phthalate (DEHP) and its initial metabolic products were tested in the genotoxicity battery. A comparative metabolism study was performed with DEHP in the mouse, rat, and cynomologus monkey, together with a study of the metabolism of DEHP in the rodent at several dose levels, and after prolonged feeding. A standard test for peroxisome proliferation in the rat, employing 21 days of feeding and several end points is described, based on DEHP as a reference compound. DEHP is shown to be nongenotoxic in the test battery, and its initial major metabolites are also nongenotoxic. A nonlinear dose response with respect to the beta-oxidation of DEHP in the rodent is demonstrated. Quantitative differences exist between the mouse and rat, and the cynomologus monkey with respect to the beta-oxidation of DEHP, beta-oxidation being a much less used pathway in the monkey. The significance of these results in interpreting the hepatocellular carcinogenesis of DEHP in the Fischer 344 rat is discussed.
VIF3 is a hybridoma-derived mouse IgG monoclonal antibody (MoAb) generated in a fusion with the use of a malignant fibrous histiocytoma as the immunizing agent and shown to recognize a 70-kilodalton antigen expressed within connective tissues. Of 55 human tissue culture cell lines tested by indirect immunofluorescence, VIF3 was shown to bind to 20 of 35 (57%) sarcomas, 4 of 9 (44%) normal fibroblasts, and none of 11 carcinomas and other neoplasm-derived cell lines. A panel of over 259 human frozen tissue sections obtained from surgical pathology specimens, postmortem studies, and elective abortions was used to further determine the histopathologic specificity of VIF3. MoAb VIF3 was found to bind to 15 of 19 (79%) human sarcoma tissue sections tested. It was also shown to recognize an antigen expressed on a subset of fibroblasts dispersed within the stroma of carcinomas obtained from all 46 patients tested, as well as a subset of cells within 3 of 10 benign hyperplastic tissues (30%). VIF3-positive cells were detected in all 60 fetal tissues tested including amniotic membranes, placentas, and umbilical cords. In contrast, fibroblasts of normal adult tissues tested stained infrequently (22/97 or 23%) with this reagent. The results confirm that this MoAb is directed against a human connective tissue-specific marker. VIF3 detects a marker appearing on fetal fibroblasts that is typically not present in normal adult tissues, but reappears in association with neoplastic diseases. MoAb VIF3 therefore defines a fibroblast-oncofetal antigen and as such may serve as a probe for immunopathologic studies.
Thirty-seven patients with disseminated breast cancer refractory to previous therapy were treated with a combination of mitomycin, doxorubicin, and vinblastine (MAV). One complete and eight partial responses were achieved, with an overall response rate of 24.3%. The median duration of response was 5+ months. The MAV regimen had generally moderate but acceptable toxicity. This study indicates that the MAV combination is no better than doxorubicin given as a single agent.
In a study of 523 patients with breast cancer, delay in diagnosis was examined in relation to stage of disease, age and ethnic origin. Localized disease was found in 44% of the patients, regional disease in 40%, and metastatic disease in 9%. Stage was unknown in 7%. The incidence of breast cancer was significantly higher in Occidental Jews (of European origin) than in Oriental Jews (of Asian or North African origin) or in Arabs. The median and mean age were significantly higher in the Occidental Jewish group. Older patients (greater than 70) had more advanced disease and longer delay. Diagnosis was delayed (greater than 6 weeks) in 43% of the patients. Diagnosis was attributable to the patient in 69% of cases and to the physician in 30%. There was no delay in diagnosis for most of the patients with localized disease, whereas there was for most of those at an advanced stage. When there was a delay, it was longer in those with advanced disease. Delay due to physician responsibility was longer than the delay due to patient responsibility. Although the percentage of patients with delayed diagnosis was similar in the three ethnic groups studied, the stage of disease was significantly more advanced in Oriental Jews and Arabs than in Occidental Jews. The possible explanations for these findings are discussed. The importance of patient education aimed at breast self-examination and the role of the physician in preventing delay in diagnosis are stressed.
Four monoclonal antibodies (McAbs) previously generated against human soft tissue sarcomas and reacting with connective tissue differentiation antigens were evaluated for their interaction with tissues obtained from patients with classic Kaposi's sarcoma. Biopsy was performed on active neoplastic lesions from the skin of 26 patients, frozen sections were prepared, and the binding of the McAbs was tested using the indirect immunofluorescence assay. Clinically uninvolved skin from the same patients as well as skin and muscle from eight non-cancer patients were treated similarly and served as controls. McAbs IXG11, 23H7, IIIE5, and 15G5 interacted strongly with the Kaposi's sarcoma lesions and weakly with the uninvolved skin in 22 of 26 (84%), 23 of 26 (88%), 12 of 14 (85%), and 1 of 6 (16%) of the patients, respectively. IXG11, 23H7, and IIIE5 interacted weakly with the skin of seven of eight non-cancer patients. McAb 15G5 was found to bind strongly to tumor lesions, to the respective uninvolved skin in four of five Kaposi's sarcoma patients, and also to skin and connective tissues of muscle from non-cancer patients. The mode of interaction was morphologically different for each McAb. It is suggested that McAbs IXG11, 23H7 and IIIE5 identify markers whose expression is markedly increased in Kaposi's sarcoma lesions as compared with uninvolved skin of the same patients. These markers may serve as immunologic probes for the investigation of this neoplastic process.
Forty-five patients with advanced ovarian carcinoma without prior chemotherapy were treated with cisplatin-Adriamycin (doxorubicin) combination, 50 mg/m2 intravenously, for 11 cycles. Second-look operation (SLO) was performed in patients without evidence of disease at the end of chemotherapy. Abdominopelvic irradiation was administered to those found to have microscopic or minimal disease (tumor less than 2 cm) at SLO. Forty patients were evaluable. Chemotherapy induced complete response in 56.7% and partial response in 16.7%. In 25% of the reoperated patients, no tumor was found; 30% had microscopic disease; 25% had minimal disease; and 20% had larger tumors. Two-year survival rate was 45%. The residual tumor left at initial operation, the histologic grade, and the response to chemotherapy influenced survival. Toxicity was moderate. There were three treatment-related deaths (one due to sepsis, one due to cardiotoxicity, and one at SLO, respectively). Radiotherapy was poorly tolerated after chemotherapy. The median duration of follow-up was 21.5 months. Further follow-up is needed to study the long-term benefits of this multimodal approach.
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Seven cases of soft tissue sarcoma developing after primary or postoperative radiotherapy for breast carcinoma are reported. The sarcomas occurred within the irradiated volume, after a latent period of 4-26 years. These cases conform well to established criteria for the diagnosis of radiation-induced sarcoma. Chemotherapy, consisting of the four-drug combination CYVADIC (cyclophosphamide, vincristine, adriamycin, DTIC) was employed in six of the seven patients. Only two of them achieved partial remission, lasting only 2 and 3 months, respectively. The effectiveness of adriamycin-containing chemotherapy regimens in soft tissue sarcomas as well as the remote hazard of radiation-related sarcoma in primary or postoperative breast irradiation are discussed.
Ethanol and tryptophan have been demonstrated earlier to induce a rapid stimulation of hepatic ornithine decarboxylase (ODC) activity in overnight-fasted rats. In this study the effect of the administration of retinyl acetate prior to administering ethanol or tryptophan was investigated. The levels of ODC activity in the livers of control and experimental rats were assayed in vitro by measuring the release of 14CO2 from DL-[1-14C]ornithine. Intraperitoneal administration of retinyl acetate (1 microgram/100 g body wt) 1 hr before tube feeding ethanol (0.75 g as a 50% solution/100 g body wt) or L-tryptophan (30 mg in 3 ml water/100 g body wt) and 3 hr before killing caused an enhanced stimulation of hepatic ODC activity compared to that when each agent was administered alone. In vitro [14C]leucine incorporation into protein using hepatic microsomes of tryptophan-treated rats with or without retinyl acetate was increased in comparison with that of controls while decreases were observed when using microsomes of ethanol-treated rats with or without retinyl acetate. Although retinyl acetate has been reported earlier to inhibit the stimulation of hepatic ODC activity due to a variety of agents, including some agents known as carcinogens or promoters, it did not act in this manner against the acute administration of ethanol or tryptophan.
Somatosensory evoked potentials (SEPs) were recorded in a group of 18 patients with dystrophia myotonica and in 28 control subjects after stimulating the right and left posterior tibial (SEP-PT) and sural (SEP-S) nerves at the ankles. Recording electrodes were placed in the popliteal fossae, overlying the L3 spinal vertebrae, and at the appropriate scalp sites. In all control subjects and dystrophia myotonica subjects SEP-PT latencies were shorter than equivalent SEP-S latencies, probably reflecting conduction along group I muscle afferents and along slower conducting cutaneous afferents, respectively. Intergroup comparisons revealed prolonged absolute and interpeak latencies in the dystrophia myotonica group, showing both peripheral and central somatosensory pathway involvement. Individual abnormal latencies which exceeded the control group mean plus 3 standard deviations were found in 66% of the dystrophia myotonica group, mainly due to prolonged peripheral conduction times. Results pointed to the concomitant involvement of both the posterior tibial and sural nerve somatosensory pathways in dystrophia myotonica.
A case of a female with advanced squamous carcinoma of the vagina is presented. Complete disappearance of the primary tumor and involved inguinal lymph nodes was achieved with three courses of the cis-platinum-containing chemotherapy regimen BMP administered prior to radiotherapy. The encouraging result obtained warrants the use of this combined treatment modality in other patients.
The Northern Israel Cancer Center serves 1 million inhabitants. Between 1968 and 1982, 33 patients with a diagnosis of nonseminomatous tumors of the testis were referred to this center. Of these patients inguinal lymph node metastasis developed in 4, each of whom had had risk factors for such metastasis. Two patients had undergone previous orchiopexy, and 2 had extension of the tumor to the epididymis and the tunica vaginalis testis. The inguinal region should be examined and watched carefully in patients with testicular tumor, especially those at high risk for inguinal metastases. Today, disease in patients with inguinal metastasis is curable by lymph node dissection and/or combination chemotherapy.
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Patients with inoperable non-small cell carcinoma of the bronchus were treated by iv methanol extraction residue of bacillus Calmette-Guérin (MER) followed by combination chemotherapy with methotrexate, doxorubicin, cyclophosphamide, and lomustine (MACC). Radiotherapy was added in patients with localized disease. MER was given iv in four weekly courses. The dose ranged between 0.1 and 0.8 mg/m2/course and was determined according to the skin reactivity to MER. None of the 19 patients treated with iv MER had an objective tumor response during immunotherapy. Five of 16 evaluable patients receiving MACC (31%) achieved partial response. The overall median survival for all 17 patients treated was 11 months according to the protocol. During immunotherapy the following side effects were observed: all patients had fever and chills and most had malaise, nausea and/or vomiting, and headache. Transient abnormalities of liver function tests were found in six patients, and in one patient roentgenographic changes suggestive of lung granulomas were seen. The side effects were more severe during the first course than in the further treatments. Side effects of the MACC combination were comparable to those observed in previously reported studies. Immunological monitoring performed during immunotherapy revealed that iv MER had an unfavorable effect on the immune system. Following four courses there was a decrease in the in vivo skin reactivity to MER and to five recall antigens. Twenty-four hours after the initiation of iv MER there was a tendency for decrease in the lymphoproliferation to phytohemagglutinin, an increase in the indices of the adherent cell suppressor system and the prostaglandin-related suppressor system, and an increase in the percentage of adherent mononuclear cells. No consistent changes in serum lysozyme were found. A transient increase in the total number of peripheral blood leukocytes and a decrease in the number of lymphocytes were noticed 24 hours after iv MER. Taking into account the results of the immunological studies and the overall therapeutic results, we do not feel justified in continuing to use this combined modality treatment.
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