Biomedical subjects
Publications and source records attributed to D Rosner.
Explore the source record for details and available documents.
Since the 1930s threshold limit values have been presented as an objectively established measure of US industrial safety. However, there have been important questions raised regarding the adequacy of these thresholds for protecting workers from silicosis. This paper explores the historical debates over silica threshold limit values and the intense political negotiation that accompanied their establishment. In the 1930s and early 1940s, a coalition of business, public health, insurance, and political interests formed in response to a widely perceived "silicosis crisis." Part of the resulting program aimed at containing the crisis was the establishment of threshold limit values. Yet silicosis cases continued to be documented. By the 1960s these cases had become the basis for a number of revisions to the thresholds. In the 1970s, following a National Institute for Occupational Safety and Health recommendation to lower the threshold limit value for silica and to eliminate sand as an abrasive in blasting, industry fought attempts to make the existing values more stringent. This paper traces the process by which threshold limit values became part of a compromise between the health of workers and the economic interests of industry.
The current study attempted to assess the potential proficiency of radioimmunodetection (RAID) of primary, residual, multicentric, and recurrent breast carcinoma using two radiolabeled murine monoclonal antibodies (MoAbs), anti-human milk fat globulin (HMFG1) labeled with iodine (123I) and anti-carcinoembryonic antigen (CEA) labeled with technetium (99Tc). Thirteen patients with suspicious clinical and/or mammographic primary or recurrent breast carcinoma were studied in a phase I-II prospective, consecutive, nonrandomized, noncontrolled study. Five patients received intravenous infusion with 0.5-2.0 mg anti-CEA MoAb type CYT 380 labeled with 99Tc [13-22 millicurie (mCI)] and 8 patients received intravenous infusion with 0.25-1.0 mg anti-HMFG1 MoAb (Unipath, U.K.) labeled with 123I (4-17 mCI). Both MoAbs used in this study demonstrated ability to bind specifically to breast cancer lesions, resulting in successful RAID in 10 of 12 of studied patients (5 of 5 patients in the anti-CEA-99Tc and 5 of 7 in the anti-HMFG-123I group--accuracy 83.3%). One patient was excluded due to protocol violation. Seven patients had true-positive scans when correlated with surgery (sensitivity 87.5%). The MoAb scans accurately diagnosed lesions in 3 of the 4 primary invasive breast carcinomas confirmed histologically. Presence of residual carcinoma following wide excision was established in 1 of 2 patients and presence of soft tissue metastases in 3 patients. Three patients had true-negative scan (specificity 75%): 2 patients presented with suspicious mammographic recurrence postlumpectomy and 1 patient had questionable soft tissue recurrence. One patient with primary breast carcinoma had a false-negative scan and another had a false-positive scan in the presence of fibrosis following lumpectomy and radiation therapy. No adverse reactions were noted in the patients studied. RAID findings were confirmed by immunohistochemistry in 6 of 9 cases studied. Our data suggest that radiolabeled MoAbs used in this study are potentially useful diagnostic agents for evaluation of primary or recurrent breast carcinoma, particularly in the areas where conventional methodology is limited.
This essay focuses on the early history of industry and professional relationships around silicosis, the debilitating occupational lung disease, through a study of the role of the Industrial Health Foundation, an industry-sponsored group which has played a critical role in shaping the nation's agenda regarding industrial disease. From its start during the Depression, it has portrayed itself as an industry-sponsored agency that depended upon detached, disinterested professionals and experts to develop effective programs to address occupational disease. As an organization that brought together professional industrial hygienists, business groups, government officials, academics and researchers it serves as a means for understanding the intertwining of industrial and academic agendas. We explore some of the issues that arose regarding public policy and scientific investigations, asking: Under what conditions is it appropriate for professionals and scientists to work together with industrially sponsored organizations? What are the pressures that shape research questions, the range of possible solutions, and the control of scientific data? How can technically trained individuals avoid real or perceived conflicts of interest? At what point does the ostensibly disinterested goals of professionalism conflict with the self-interest of the sponsoring organizations?
As a society, we share assumptions that exhibit a profound historical ambivalence regarding young people at work. On the one hand, we all acknowledge that there is something socially and morally reprehensible about forcing children to toil. Many of us see child labor as a vestigial remnant of the harshest aspects of the Industrial Revolution. On the other hand, we also continue to see work as a sign of the moral and social health of a community and hence, we see employment among the young as a stabilizing and redemptive activity. Especially when addressing the nation's poor, urban and African-American populations, youth unemployment is almost universally understood as a root cause of social unrest and community breakdown. This paper outlines some of the historical arguments about children in the work force and raises the question about the national resolve to seriously address this issue.
This study attempted to identify the risk groups in axillary node negative breast cancer patients using validated first-generation prognostic clinical and pathologic factors. An updated 10-year follow-up in 407 such patients treated by surgery alone at Roswell Park between 1976-1987 showed a 10-year recurrence rate (RR) of 19% (95% confidence interval +/- 5%). Predictors of outcome were, in order of strength: (1) Tumor size (p = 0.0006); RR at 10 years was 2% +/- 4 for tumors < or = 0.5 cm, 6% +/- 7 for tumors 0.6-1.0 cm, 16% +/- 9 for 1.1-2 cm, 29% +/- 12 for 2.1-5 cm, and 40% +/- 31 over 5 cm; (2) Histologic differentiation (p = 0.017); poorly differentiated/anaplastic (P/A) tumors had a greater RR (24% +/- 8) than well or moderately differentiated (W/M) tumors (13% +/- 8); (3) Age (p = 0.046); patients < 35 showed a RR of 28% +/- 20, pts 35-50, 22% +/- 10, and pts > 50,17% +/- 7 (p = 0.046). Cox Model analysis showed tumor size (4 groups) significant at < 0.0001, histologic differentiation (2 groups) significant at < 0.0005 after allowing for size, and age (+/- 50) significant at < 0.05 after allowing for size and differentiation. Combining these variables into subgroups enables selecting groups at various risks of recurrence. Groups with low risk are: (1) patients with tumor < or = 1 cm, W/M (0% RR), (2) patients with ductal carcinoma in situ with microinvasion (0% RR), and (3) patients with tumors < or = 1 cm, P/A (8% RR). In a suggestive finding in this last group, those over age 50 achieved a RR of 3% +/- 6, while those age 50 or less had RR 14% +/- 15. With the exception of this last group, all should be considered highly curable using loco-regional therapy alone, and might be spared the risks and costs of routine systemic adjuvant therapy. Groups with high risk are: (1) patients with tumors > 2 cm (RR 32% +/- 12), and (2) patients with tumors 1.1-2 cm, P/A (RR 21% +/- 14). These should receive adjuvant therapy. Groups with intermediate risk are patients with tumor 1.1-2 cm, W/M (RR 12% +/- 12). In a suggestive finding, those in this group over age 50 had a RR of 11% +/- 12, while those up to 50 had a RR of 17% +/- 30. These patients should be considered to be prime candidates for clinical trials.(ABSTRACT TRUNCATED AT 400 WORDS)
Explore the source record for details and available documents.
This study, which used combined first-generation prognostic factors (tumor size, histologic differentiation, and age) on 408 patients with axillary node-negative (ANN) breast cancer treated by surgery alone without systemic adjuvant therapy between 1976 and 1987 at the Roswell Park Cancer Institute, discerned four subsets of low-risk patients with a 7-year relapse rate of 6% or better. The first subset consisted of 48 patients (12% of the population) with tumors 1 cm or less in diameter that were well or moderately differentiated. These patients had a disease-free rate (DFR) of 100% (95% confidence interval [CI], 94% to 100%). The second subset consisted of 35 patients (9% of the population) with tumors less than or equal to 1 cm that were poorly differentiated or anaplastic. These patients older than 50 years of age had a DFR of 97% (95% CI, 91% to 100%). The third subset consisted of 36 patients (9% of the population) with tumors 1.1 to 2 cm that were well or moderately differentiated. These patients were older than 50 years of age and had a DFR of 94% (95% CI, 85% to 100%). The fourth subset consisted of 36 patients with ductal carcinoma in situ with microscopic invasion. These patients had a DFR of 100% (95% CI, 87% to 100%). Twenty-two of these patients, not in the other subsets mentioned, comprised 5% of the total population. These patients at low risk of recurrence, who comprise one third of the entire node-negative population, are highly curable by local therapy alone and may be spared the risks and costs of routine adjuvant systemic therapy (AST). Patients with tumors larger than 2 cm (152 patients; 37% of the population) are at high risk of recurrence (26% with a DFR of 74% [95% CI, 64% to 84%]) and should routinely receive systemic adjuvant therapy. Patients with tumors up to 2 cm who are not in the low-risk groups fall in a gray area (recurrence, 15% to 21%; DFR, 79% to 85%). For these groups, combining second-generation prognostic factors such as DNA ploidy, S-phase fraction, or cathepsin D should give the physician additional information to aid in making decisions regarding adjuvant therapy.
Between 1980 and 1988, 122 women with operable invasive breast cancers underwent wide excision and axillary dissection without subsequent irradiation. During the follow-up period of 1 to 8 years (median, 4 years), recurrences were observed in 23 patients (19%), 22 occurring in the breast and one in the axilla. This is a significant rate of recurrence and supports the need for breast irradiation after conservative surgery. The incidence of recurrence in the breast did not appear to be related to the presence or absence of axillary nodal metastasis. No recurrences were noted in 20 patients whose primary tumors were smaller than 1 cm. The incidence of recurrence was directly correlated to the increasing size of the tumor, but it also appeared to decrease with advancing age. In 31 patients over 70 years of age, only one (3%) recurrence was observed. If these early findings are confirmed, it is likely that patients with tumors smaller than 1 cm or patients over 70 years of age may be spared breast irradiation after wide excision.
Of 408 negative axillary node (NAN) patients surgically treated at Roswell Park Cancer Institute (Buffalo, NY, 1976 through 1987), 36 (8.8%) presented with ductal carcinoma in situ with microinvasion (DCISM). In more than 50% of the patients (20/36) the disease was detected solely by mammography (microcalcifications and/or radiological density less than 1.5 cm). Thirty-three patients underwent modified radical mastectomy; three had wide excision +/- axillary dissection. Residual disease after excisional biopsy was found in 22 of 33 mastectomy specimens (67%): 11 (33%) pure ductal carcinoma in situ, five (15%) DCISM, and six (18%) frankly invasive. Of the 22 incidents of residual disease, 50% (11) were multicentric (one third of all specimens). These findings imply a high likelihood of residual cancer after excisional biopsy in these patients. All patients were free of disease for a mean follow-up of 57 months (range, 16 to 137). These findings indicate that DCISM is an entirely curable disease when treated by mastectomy alone, without the need for adjuvant therapy, regardless of the status of other prognostic factors such as tumor size, histologic differentiation, age, or steroid receptor status.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
In recent years, voluntary health insurance costs have become a major source of friction in labor-management negotiations. What was once a "fringe" has led to job actions, strikes, and intensive bargaining. We examine the history of labor's participation in New York Blue Cross from the 1930s to the recent past and show that labor's participation in the plan was crucial to Blue Cross's success in the plan's early decades. By the late 1950s, serious tensions developed over rate increases and the participation of labor in Blue Cross governance. Ultimately, the issue was one of the control over what was provided by the plans and who would pay for the costs of care. We posit that labor was never able to achieve an important role in the control of the third-party payer, and in the antilabor environment of the 1980s this proved detrimental to labor's interests.
Ninety-one patients with invasive breast carcinoma with a diameter of 1 cm or less and histologically negative axillary nodes were treated between 1976 and 1986 with radical surgery alone (67), or with conservative surgery (24). Cases were analyzed in relation to tumor size, steroid receptors, histologic and nuclear grade, age, and type of therapy, none of which showed a significant relationship to relapse or survival. There were 22% well-differentiated, 20% moderately differentiated, and 56% poorly differentiated or anaplastic tumors. Estimated disease-free survival (DFS) for this group was 91% at 7 years, and overall survival 96% for the same period. There were five relapses (all among poorly differentiated tumors) and three deaths unrelated to breast cancer. With the three deaths censored, 100% of the well-differentiated and moderately differentiated tumors were disease-free at 7 years versus 91% for poorly differentiated and anaplastic tumors (P = 0.076). These data suggest that node-negative patients with minimal invasive breast cancer are highly curable by primary surgical therapy alone, and the authors believe that these patients are not appropriate candidates for adjuvant therapy until such time as subgroups at high risk of recurrence can be identified.
The surgical treatment and outcome of 31 women with a pathologic diagnosis of cystosarcoma phyllodes at Roswell Park Memorial Institute were reviewed. Surgical excision was performed upon 20 patients with a mean tumor size of 4.5 centimeters (range of 1.0 to 9.0 centimeters). Mastectomy was performed initially upon 11 patients with a mean tumor size of 15 centimeters (range of 3 to 40 centimeters). Local recurrence was seen in five patients treated by excision and one patient treated by mastectomy. All patients retreated by repeat excisions were controlled; one patient retreated with mastectomy died with local recurrence and distant disease. Routine axillary dissections were not performed. Involvement of the axillary lymph nodes occurred in one patient and was associated with advanced systemic disease. Local recurrences did not imply associated systemic spread and were controlled in five of six patients by repeat excision or mastectomy. Although the benign behavior of this tumor is commonly emphasized, four of the patients we studied died of malignant spread of cystosarcoma phyllodes.
One hundred five patients undergoing therapeutic oophorectomy for metastatic breast cancer (n = 105) from 1975 to 1985 were reviewed. There were 54 responders (51%) to oophorectomy, with a median duration of response of 16 months (range, 3 to 129 months). Thirty of 42 (71%) estrogen receptor (ER)-positive patients responded to oophorectomy versus five of 24 (21%) ER-negative patients (P less than 0.001). Of the 39 patients with unknown ER status, 19 (49%) responded to oophorectomy. Osseous, soft tissue, and pulmonary metastases responded at similar rates. Of the 16 patients who had received adjuvant chemotherapy, there were five responders (31%) to oophorectomy. Second-line endocrine therapy was effective in 29 of 53 (55%) patients. Fifteen of 28 (54%) ER-positive patients responded to second-line endocrine therapy while two of six (33%) ER-negative patients responded. Twenty-three of 37 (62%) oophorectomy responders responded to second-line endocrine therapy versus six of 16 (38) nonresponders. Oophorectomy appears to be a valuable palliative treatment for metastatic breast cancer. ER-positive patients have the best chance of responding to this therapy. However, ER-negative patients have a reduced but definite chance of responding with a good duration of response. Response to further endocrine treatments is predicted by response to oophorectomy and to a lesser degree by ER status.
The predictive value of estrogen receptor (ER) level for response to chemotherapy was studied in 182 patients with metastatic breast cancer in a prospective study. Patients were stratified according to ER status and dominant site of disease and randomized to one of three regimens: cyclophosphamide, 5-Fluorouracil, and prednisone (CFP) versus CFP, methotrexate, and vincristine (CFPMV) versus doxorubicin and cyclophosphamide (AC). There was no significant differences in all response categories (P = 0.21), was taken as a predictor for response to chemotherapy, there was no significant difference in overall response (P = 0.61) between ER+ (62/108, 57%) and ER- patients (31/49, 63%). However, there was a significant trend toward a higher degree of response in ER- patients (more complete response [CR] nine of 49, 18%, and fewer failures six of 49, 12%) than in ER+ (less CR seven of 108, 7%, and more failures 37/108, 34%) (P = 0.006). Patients with higher measured levels of ER showed worse response (Kendall's tau C, P = 0.026). This trend for ER- patients to have better response than ER+ patients was generally consistent, regardless of the predominant site of metastases or chemotherapy regimen (P = 0.04 for CFP; P = 0.08 for CFPMV; and P = 0.20 for AC). The advantage of a better response for ER- patients was nullified by an earlier relapse which was reflected in longer duration of remission, time to treatment failure, and survival in favor of ER+ patients (12.3 months versus 7.3 months remission duration, 18.7 months versus 13.6 months survival in partial responders). These data suggest that ER- patients respond to a higher extent to chemotherapy but relapse sooner than ER+ patients, suggesting a more rapid growth for ER- tumors. In patients with ER- tumors and poorer prognosis on conventional chemotherapy, new trials of intensive consolidation after response should be considered.
Aminoglutethimide (AG) was administered as palliative therapy in 112 patients with metastatic breast cancer. In 36 patients, the dose level was 1000 mg/day; 76 patients received a dose level of 500 mg/day. Patients with brain or liver metastasis were excluded, as were patients with tumors determined to be negative for estrogen receptors. Objective regression was observed in 35 (31%) patients, with the duration of response ranging from 4 to 36 + months (mean, 12 months; median, 10 months). Response was observed in 11 of 31 (35%) patients with soft tissue metastasis; 16/59 (27%) patients with osseous metastasis; and 8 of 22 (36%) having visceral metastasis. In 93 patients with positive estrogen receptor (ER), 33 responded (35%), whereas in 19 patients with unknown ER status, two responded (11%). Response to previous treatment with tamoxifen (TAM) had occurred in 31 patients; of these, response to AG was noted in 11 (35%). Of 24 patients failing to respond to prior treatment with tamoxifen, four (17%) responded to subsequent therapy with AG. Thirteen patients had previously received combination chemotherapy, and response to AG was noted in two (15%). The side effects observed in this study included skin rash in ten patients, fever in eight, somnolence in three, weakness and dizziness in one, headache in one, insomnia in one, dyspnea in one, and ataxia in one. Treatment had to be discontinued in eight patients, due to the severity of the side effects. As expected, patients receiving AG at the lower dose level of 500 mg/day experienced fewer and less severe side effects than those treated with the higher dose. The response rate in the 1000 mg/day group was 10/36 (28%) and in the 500 mg/day group, it was 25/76 (33%). The lower dosage was better tolerated without apparent compromise in therapeutic efficacy.