Chronic fetal distress with subsequent cerebral palsy.
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Biomedical subjects
Publications and source records attributed to T Hamilton.
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The therapeutic value of 131I-OC125, a radiolabeled monoclonal antibody directed against a human ovarian tumor associated antigen CA125, was examined in an ascites forming intraperitoneal human ovarian carcinoma nude mouse model. Nude mice were injected intraperitoneally with NIH:OVCAR3 cells. Twenty-one days after tumor transplantation, groups of animals were injected intraperitoneally as follows: Group 1 with 200 microCi of 131I-OC125 (n = 20), Group 2 with 200 microCi of 131I (n = 17), Group 3 with 200 microCi of 131I-IgG (n = 21), Group 4 with 60 micrograms of OC125 (n = 18), and Group 5 was left untreated (n = 21). Survival of the tumor-bearing animals was used as the endpoint of the experiment. Mean survivals were found to be 52 +/- 18 days for the 131I-OC125 group, 53 +/- 16 days for the 131I-IgG group, 49 +/- 13 days for the 131I group, 47 +/- 24 days for the OC125 group, and 47 +/- 15 days for the untreated control. These results would indicate no therapeutic advantage of 131I-OC125 over controls in this animal model. However, other approaches using single as well as multiple radiolabeled monoclonal antibodies need to be tested in this model in order to definitely establish the efficacy of this treatment modality.
Systemic intradermal and topical inhibitors of eicosanoid synthesis have been shown to decrease the intensity delay the onset of erythema produced with a single exposure to ultraviolet (UV) light. We studied the effect of single and multiple doses of meclofenomate on erythema induced by single and multiple doses of UV light. Thirty Caucasian subjects took either meclofenomate 100 mg t.i.d. or matching placebo for 5 days, crossing over to the alternative for 5 more days after a 2-day washout period. A statistical analysis was made of erythema response immediately prior to the study and then on 8 successive days during the study. Analysis of single and multiple exposure data revealed a statistically significant inhibition of erythema from meclofenomate therapy as compared with placebo.
The antiproliferative effect of alpha-difluoromethylornithine (DFMO) was investigated in a human ovarian cancer cell line (NIH:OVCAR3) both in vitro and in vivo. DFMO at 5 X 10(-5) M, 5 X 10(-4) M and 1 X 10(-3) M concentrations showed growth inhibition of NIH:OVCAR3 cells in culture. Parallel determination of CA 125 in the culture media of these cells show significant decrease in the presence of DFMO compared to controls. Oral administration of DFMO (2% aqueous solution) to nude mice bearing intraperitoneal tumors resulted in a mean survival of 45 days (38-60) versus 25 days (20-35) for control. Both in vitro and in vivo results suggest that DFMO has potential value in the treatment of ovarian carcinoma and should be considered for clinical trials in appropriate cancer patients.
Human ovarian carcinomas in nude mice were radioimaged using a well-characterized antibody against a tumor-associated antigen (CA 125) and three transplantable human ovarian carcinoma tumor lines: NIH:OVCAR 3, NIH:OVCAR 5, and NIH:OVCAR 9. Radioiodinated monoclonal antibody OC125 was used in these studies. In order to establish the optimal conditions for imaging, tumor/blood ratios were determined. Gamma scintigraphy of nude mice bearing subcutaneous transplants of human ovarian carcinomas 3-4 days after 131I-OC125 administration demonstrated selective localization of the radiolabeled monoclonal antibody by these tumors without need for any background subtraction techniques.
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Inflammation and the release of potentially damaging substances, such as reactive oxygen intermediates (ROI) and lipid oxidation products from inflammatory cells, have been linked to the potentiation of carcinogenesis. Murine macrophages when stimulated with phorbol esters induce 5,6 ring saturated thymine residues (T'), a lesion of known oxidative origin, in co-cultivated mammalian cells. Induction of this damage was inhibited by catalase and induced in target cells by reagent H2O2 alone. In the present studies, we used defined populations of macrophages with high, low and intermediate capacities for the release of H2O2 or metabolites of arachidonic acid (AA) to assess the relative contribution of these classes of compounds to the induction of saturated thymines. Macrophages activated with Bacillus Calmette-Guerin (BCG), which have the highest capacity for the release of H2O2 and the lowest for the release of metabolites of AA, induced the lowest levels of saturated thymines. Resident macrophages from the unmanipulated peritoneum, which have the lowest capacity for the production of H2O2 and the highest capacity for release of AA metabolites, induced more saturated thymines than did the BCG macrophages. Inflammatory macrophages elicited by casein, which have an intermediate capacity for release of H2O2 and AA metabolites, induced the highest level of saturated thymines. Zymosan, which induced more release of AA metabolites than release of H2O2, was a better stimulant for the induction of T' than TPA, which is a better stimulant for secretion of H2O2. Nordihydroguaiaretic acid (NDGA), an inhibitor of the lipoxygenase and cyclooxygenase pathways for metabolism of AA, inhibited the induction of T' by resident macrophages. Indomethacin, an inhibitor of the cyclo-oxygenase path, enhanced induction of T'. Taken together, the data suggest that while H2O2 has the capacity to induce T' in 3T3 cells, it may not be the only mediator of DNA damage and that lipoxygenase generated metabolites of AA may (alone or in concert with ROI) play an important role in the induction of oxidative DNA damage by macrophages.
The HLA type of patients with various kinds of immune reactions to bovine collagen implants were evaluated to determine a possible genetic basis for such responses. All patients suffering adverse clinical reactions to bovine collagen implants were lacking the HLA-DR4 antigen. All patients who received multiple bovine collagen injections without having adverse clinical reactions were lacking HLA-B5 and HLA-DR5 and had a significantly increased incidence of HLA-DR4. Combinations of histocompatibility antigens may influence immune response to bovine collagen implants.
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The results of a randomized controlled clinical trial in the management of operable breast cancer are given. Between 1964 and 1971 498 women, aged 35-69 years, were treated within the trial protocol. Those under 60 years of age on entry underwent ovarian ablation, usually by surgery, and were allocated randomly to treatment by either radical mastectomy (RM) or simple mastectomy and postoperative radiotherapy (SM). Follow-up data for the first 12 years are presented and show that survival in the radical mastectomy group is significantly better (P less than 0.05), particularly in clinical stage 1 disease. The pattern of survival once recurrence was detected also showed interesting differences between the two treatment groups. Overall there was a significantly prolonged survival after detection of recurrence in the RM group (P less than 0.05) which was most marked when local recurrence and distant metastases coincided (P less than 0.01). The duration of survival once recurrence had taken place was independent of tumour size, clinical stage of the disease or menstrual status at the time of presentation, but was directly proportional to the duration of the disease-free inerval (P less than 0.01).
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Sixty patients with advanced metastatic adenocarcinoma of the liver from a colorectal primary were treated by prolonged and continuous intra-arterial hepatic arterial infusion chemotherapy over a period of time from December 1969 through July 1976. A 10-day course of 5-FU was administered in the hospital, and patients were discharged receiving 5-FUDR by continuous arterial infusion through a chronometric infusion pump. Objective responses of 100% were obtained in 15% of patients, 50% response in 39% of patients, and 25% response in 21% of patients. The median survival from onset of treatment was 8.5 months, 6.9 months, and 7 months, respectively, for 100%, 50%, and 25% responders versus 3.6 months for nonresponders. Survivals from onset of treatment were generally less in those with no disease-free interval. No relationship of response to sex and age was found. Patients previously treated with 5-FU intravenously responded to intra-arterial chemotherapy; 13% had a 100% response, and 54% had a 50% response. No relationship of drug dose to response was observed. Drug toxicity was frequently systemic and mild to moderate. Numerous complications occurred due to the catheter, complete or partial thrombosis occurring in 18.6% and 20.8%, respectively, and 30% of patients had displacement of the catheter. The role of partial arterial occlusion in terms of response and survival may be significant. Future studies should involve comparison of direct surgical placement versus percutaneous placement of catheters.
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Etiocholanolone levels have been measured in both premastectomy and postoperative urines from 86 women with early breast cancer. Levels did not differ between patients subsequently surviving five years following mastectomy and those dying from recurrent disease within this period.
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The incidence and prevalence of disorders of the breast have been assessed in 13,456 women examined annually at a family planning clinic over 5 years. Screening for disorders of the breast was by clinical examination alone and abnormalities were detected in 1 of every 58 women attending the clinic and these were referred for hospital opinion: biopsy was required in 1 in 114. Only 12 cancers of the breast were detected and all of these in women over 35 years. It is suggested that the usual policy of examining the breasts of women taking oral contraceptive preparations should be restricted to those over 40 years.
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