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Biomedical subjects

R M Simon

Publications and source records attributed to R M Simon.

68 records · Page 4Linked to original sources
PubMed1977

Biological markers in breast carcinoma. II. Clinical correlations with human chorionic gonadotrophin.

Serum hCG levels were measured in female patients with breast carcinoma and examined with respect to the clinical stage of disease, the clinical tumor burden, prognosis, and the organ sites of involvement. Elevated levels were observed in 65/134 (48.5%) patients with metastatic disease, 5/14 (35.7%) patients preoperatively, and in 9/33 (27.2%) N+ patients from one-six months postoperatively. The greatest proportion of elevated values (60.5%) was in patients with one metastatic site of involvement. Although no correlations were demonstrated between the preoperative or postoperative samples and subsequent disease recurrence, it was observed that 4/10 patients who did have a recurrence had preceding hCG elevations. In metastatic disease the level in 13 patients starting with values greater than 5.8 mIU/ml fell with the attainment of a response or rose with therapeutic failure. The hCG level rose from normal to greater than 6.1 mIU/ml in six additional patients that developed progressive disease. A normal hCG level was associated with a 94.5% response rate to combination chemotherapy whereas the response rate with levels greater than 5 mIU/ml was 71.4%. Only hepatic involvement was associated with a disproportionate incidence of elevations, being 63% compared to 42-47% for other sites. Monitoring hCG levels may be of prognostic use in patients being treated with selected chemotherapy programs for metastatic disease. It appears that further studies are warranted to ascertain if these results will extend to additional treatment approaches.

Breast Neoplasms↗
PubMed1977

Biological markers in breast carcinoma. III. Clinical correlations with carcinoembryonic antigen.

Plasma CEA levels were evaluated by radioimmunoassay in patients with breast carcinoma in relation to clinical-pathologic staging, clinical tumor burden, prognosis and organ sites of involvement. Elevated levels were observed in 83/117 (70.9%) patients with metastatic disease, 2/14 preoperative patients and in 3/39 one-six month postoperative patients. Preoperative levels were elevated in two patients; the levels fell to normal after operation. Changes of elevated CEA levels followed the clinical response to therapy in 22/22 metastatic disease patient-trials. The levels decreased with a response in 15 trials and rose with progressive disease or relapse in seven trials. The incidence of CEA elevations and quantitative CEA levels both rose with increasing clinical tumor burden from the postoperative state through the preoperative state to two or more organ sites of metastatic involvement. No relationship was demonstrable among limited samples between preoperative or postoperative CEA levels and prognosis; however, in metastatic disease, pretherapy CEA levels greater than 5 ng/ml were associated with low response rates and early therapeutic failure to chemotherapy. The highest frequency of elevated CEA levels was observed in patients with osseous involvement (79%) and the lowest frequency with skin (52%) and breast (50%) metastases. Liver and osseous disease were also associated with higher mean CEA levels than were other sites of metastatic involvement. CEA levels appear to be elevated in the majority of patients with metastatic disease and be of prognostic importance in metastatic disease. The level in patients with metastatic disease appears to reflect the therapy-associated tumor burden of the host, especially in patients with elevated levels.

Breast Neoplasms↗
PubMed1977

Prognostic factors in patients undergoing lymphadenectomy for malignant melanoma.

Review of a 19 year experience in melanoma patients undergoinglymphadenectomy at the National Cancer Institute revealedthat the preoperative assessment of the status of theregional lymph nodes was accurate 91% of the time when thesurgeon felt the nodes were clinically positive, and accurate79% of the time when the nodes were judged clinically negative. The 10-year survival in patients with one to three histologicallypositive nodes or no positive nodes was 50-55%, compared to a25% 8-year survival in patients with four or more histologicallypositive nodes. Stepwise multivariate evaluation of prognosticfactors indicated that the most important factor for predictingprognosis is the number of nodes histologically involved. Nodepalpability was the second most important factor because of itshigh correlation with number of nodes histologically involved. Site of melanoma was the third most important factor, aspatients with extremity (upper or lower) melanoma had a bettersurvival (P = 0.002) than patients with axial melanoma (trunkor head and neck). Five years following lymphadenectomythere appeared to be substantial differences in survivalaccording to differences in the level of invasion of the primarylesion, however, these differences were not nearly aspronounced 10 years following node dissection.B The division of melanoma thicknesses into <1.50 mm and>1.50 mm provided some prognostic discrimination at fiveyears but again the differences were not pronounced 10 yearsfollowing node dissection. The thickness measurements wereeasier to determine than the level of invasion, and more reproduceableon resubmission to the same pathologist. Fourpatients with melanoma less than 0.76 mm had subsequentmetastases, but these may represent inadequate sampling of theprimary melanoma both in our series and in the four similarpatients previously reported with such thin metastasizingmelanomas.

Female↗
PubMed1976

Immunosuppression in Burkitt's lymphoma. II. Peripheral blood lymphocyte populations related to clinical status.

We have studied peripheral blood lymphocyte populations, defined in terms of their E and EAC' rosette-forming capacity in patients with Burkitt's lymphoma and controls. Total lymphocyte counts were reduced in patients compared to controls (p less than 0.005), and correlated with clinical stage and disease status. Presenting patients with Stage D tumours had the lowest levels, while patients in remission for at least 18 months had total lymphocyte counts similar to those of controls. Absolute numbers of both E and EAC' rosette-forming cells (RFC) were reduced, compared to controls, in tumour-bearing patients (p less than 0.0005 for both E and EAC' RFC) and also, to a lesser extent, in patients in remission (p less than 0.025 and less than 0.05 for E and EAC' RFC respectively). In the case of E RFC a significant reduction was present even when patients in remission for over 18 months were considered alone (p less than 0.05). Non-RFC were present in similar numbers in patients and controls, so that the reduction in total lymphocyte count can be accounted for entirely by the reduced numbers of RFC. As anticipated by this, percentages of RFC were also reduced in patients compared to controls, EAC' RFC to a lesser extent than E RFC. Non-RFC percentages were correspondingly increased. Tumour-bearing patients had significantly impaired PHA responses and cutaneous reactivity, which correlated significantly with very low levels of RFC. One possible explanation for these results is that immunoreactive lymphocytes are sequestered within the tumour. This is consistent with the immunosuppression observed in tumour-bearing patients, and would also result in difficulty in detecting even a powerful tumour-specific immune reaction by means of an assay dependent upon the participation of peripheral blood lymphocytes.

Adolescent↗
PubMed1976

Randomized clinical trials. Perspectives on some recent ideas.

In spite of the controversy over the role of randomized clinical trials in medical research, the rationale underlying such trials remains persuasive as compared to recent suggestions for alternative non-randomized studies such as those relying on the use of historical controls and adjustment technics. Others have suggested that recent statistical innovations for improving clinical trials, including adaptive allocation of treatment to patients and sequential stopping procedures, are underutilized. These innovations, though theoretically interesting, are not easily adapted to large-scale, complex medical trials in which there may be multiple end points and delayed response times. Ethical considerations suggest that randomized trials are more suitable than uncontrolled experimentation in protecting the interests of patients. Randomized clinical trials remain the most reliable method for evaluating the efficacy of therapies.

Biometry↗
PubMed1976

Evaluation of tamoxifen dose in advanced breast cancer: a progress report.

The results of an ongoing trial randomizing patients with progressive, metastatic breast carcinoma between tamoxifen (Tam, NSC-180973) and Tam plus fluoxymesterone (Flu) (7 mg/m2 bid) are reported. Each patient received a single dose level of Tam in the range of 2-100 mg/m2 bid. The combination had a higher response rate overall (45% vs 28%) and when only the patients' soft tissue sites were analyzed (54% vs 9%, P=0.04). The time to treatment failure was longer for the combination among those patients with a response or disease stabilization (P=0.08). Response rates with Tam doses less than 12 mg/m2 bid were also higher than with doses greater than or equal to 12 mg/m2 for all patients in the study (62% vs 30%, P=0.025) and for those where only soft tissue sites were evaluable (43% vs 29%, P=0.07). Side effects were mild and consisted primarily of transient hematologic suppression, nausea, masculinization, hepatic enzyme elevations, and edema. The latter three were observed only with the Flu regimen. Leukopenia and thrombocytopenia were more frequent at Tam doses less than 12 mg/m2 bid whereas nausea was more common at higher doses. Tam doses as high as 100 mg/m2 bid were well tolerated. Tam amy be more effective at low doses, has only mild side effects, and is well tolerated at doses up to 100 mg/m2 bid. Combining Tam with Flu appears to enhance the therapeutic effectiveness.

Adult↗
PubMed1975

Effects of 5-fluorouracil on the cell kinetic and growth parameters of hepatoma 3924A.

The effect of 5-fluorouracil (5-FU) on the growth and cellular proliferation of hepatoma 3924A was studied using the following parameters as indices of tumour response: (1) volume measurements, (2) cell kinetic analysis including estimates of both growth and cell loss fractions, (3) changes in tumour histology and (4) tumour DNA content and DNA synthesis. Of a series of single intraperitoneally injected doses (25-300 mg/kg body weight), 150 mg/kg interrupted tumour growth most effectively with minimal toxicity within 168 h, and after 10 days treated tumour volumes were only 42% of untreated tumour size. Doses of 25 mg/kg failed to change the rate of growth while 300 mg/kg exceeded the LD50. Alterations of both tumour cell proliferation and histology developed well in advance of changes observed in growth. A dose of 150 mg/kg body weight blocked the transition of cells from G1 through S for a 24 h interval when cell kinetics were measured by 3H-TdR autoradiography. However, 3H-UdR incorporation into DNA following 5-FU suggested that cellular recovery from the drug was delayed for an additional 24 h. Concurrently, significant losses of tumour tissue and tumour DNA occurred during the first 48 h with an expected increase in both necrotic and connective tissue. During the subsequent 120 h both tumour and necrotic tissue had returned to non-treated levels, while kinetic analysis revealed (a) a slight reduction in the cell cycle time and growth fraction and (b) an increased cell loss factor. The observations from this tumour model system suggest that before using tumour volume or weight as an index of therapeutic response, the relationship between the kinetics of tumour cellularity and tumour volume must be defined.

Animals↗
PubMed1975

Art - a strategic and empirical therapy?

Art therapy in Britain has progressed on two main lines, the empirical (aesthetic) and the strategic (psychological). In the writer's experience neither approach is adequate to deal with one particular style of creative expression, referred to as the basic archaic, linear style, and indicative of severe autistic regression when it becomes stereotyped. Attention is drawn to the importance of the appearance of fragments of other (transitional) styles that may appear and offer the key to therapeutic progress.

Art Therapy↗
PubMed1974

On eclecticism.

Explore the source record for details and available documents.

Attitude of Health Personnel↗
PubMedDate not supplied

Discrimination techniques applied to the NCI in vitro anti-tumour drug screen: predicting biochemical mechanism of action.

The National Cancer Institute currently tests approximately 400 compounds per week against a panel of human tumour cell lines in order to identify potential anti-cancer drugs. We describe several approaches, based on these in vitro data, to the problem of identifying the primary biochemical mechanism of action of a compound. Using linear and non-parametric discriminant procedures and cross-validation, we find that accurate identification of the mechanism of action is achieved for approximately 90 per cent of a diverse collection of 141 known compounds, representing six different mechanistic categories. We demonstrate that two-dimensional graphical displays of the compounds in terms of the initial three principal components (of the original data) result in suggestive visual clustering according to mechanism of action. Finally, we compare the classification accuracy of the statistical discrimination procedures with the accuracy obtained from a neural network approach and, for our example, we find that the results obtained from the various approaches are similar.

Antineoplastic Agents↗