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Biomedical subjects

B Fisher

Publications and source records attributed to B Fisher.

At least 199 records · Page 11Linked to original sources
PubMed1989

Evaluation of the carcinogenic potential of pesticides. 1. Acifluorfen.

The Health Effects Division of the Office of Pesticide Programs evaluates the carcinogenic properties of pesticides by a consensus peer review process in which all available biological information on a compound is evaluated according to EPA's guidelines for cancer risk assessment. In many cases, pesticides are also evaluated by an external group of accomplished scientists who comprise the Agency's Scientific Advisory Panel. The herbicide acifluorfen was evaluated by these processes and was classified as a Category B2 (probable human) carcinogen based upon evidence of an increased incidence of malignant, or combined benign and malignant, tumors in multiple experiments involving two different strains of mice. The compound produced benign and malignant liver tumors in male and female B6C3F1 mice and in female CD1 mice. Stomach papillomas were also observed in male and female B6C3F1 mice. Acifluorfen was mutagenic in bacteria and yeast, but not in mammalian cell systems. In addition, acifluorfen is structurally related to eight other diphenyl ether pesticides, all of which evoke liver tumours in mice or rats. The data were found to be sufficient to quantify human risk to acifluorfen.

Animals↗
PubMed1989

A comparison of two and three years of adjuvant tamoxifen.

The aim of the present investigation was to determine whether the administration of a third year of tamoxifen, following 2 years of L-phenylalanine mustard, 5-fluorouracil and tamoxifen, would benefit women with primary breast cancer. The data at 5 years indicate that in patients receiving a third year of tamoxifen treatment, a significant prolongation in disease-free survival occurs, when compared to patients who receive only 2 years of tamoxifen. This benefit is limited to patients older than 49 years of age, and is not apparent in women younger than 50. It is concluded that an additional year of tamoxifen therapy, following the completion of chemotherapy prolongs both disease-free survival and actual survival in node-positive, 'tamoxifen-responsive' patients.

Adult↗
PubMed1989

Interleukin-2 induces profound reversible cholestasis: a detailed analysis in treated cancer patients.

Interleukin-2 (IL-2)-based immunotherapy is associated with profound reversible cholestasis and hyperbilirubinemia. We performed a nonrandomized retrospective and prospective analysis to determine the incidence, characteristics, clinical course, and nature of the IL-2-induced liver dysfunction in patients with cancer. Patients received IL-2 at a dose of 20,000 to 100,000 units (U)/kg thrice daily for up to 5 days. Fifty-one patients on adjuvant treatment protocols received a mean of 10.18 +/- 2.38 IL-2 doses and 11.67 +/- 4.16 doses were delivered to 210 patients with advanced disease during this period. Retrospective analysis of all patients receiving this therapy revealed increases in the following liver function tests expressed as median, 25th percentile, and 75th percentile (range): bilirubin (mg/dL) 4.5, 2.6, 6.5 (.4 to 38.5); alkaline phosphatase (U/L) 256, 179, 378 (56-1680); SGOT (U/L) 80, 52, 117 (18 to 483); SGPT (U/L) 91, 64, 132 (20-540); prothrombin time 13.4, 12.8, 14.5 (10.8 to 35.4); and albumin (g/dL) values decreased (trough) slightly 3.0, 2.8, 3.2 (2.3 to 3.8). Multiple regression analysis revealed several factors that were significantly associated with the increase in bilirubin when jointly considered (model P2 less than or equal to .001) including total IL-2 dosage, increase in creatinine, alkaline phosphatase, weight, and SGOT. Similar increases were noted in a prospectively evaluated group of 10 patients. A return to normal levels of bilirubin was noted within 5.6 days of stopping IL-2. Fasting serum cholylglycine increased from a mean of 32.3 +/- 1.6 to a peak of 1556.0 +/- 625.0 mg/mL. Although conventional ultrasound examinations were unrevealing, tissue ultrasound examinations revealed a mean scatterer spacing (MSS) increase compared to baseline of .10 +/- .04 (P less than .02) suggesting hepatic edema or an infiltrative process. Further, computerized hepatobiliary nuclear medicine scans revealed a delay in uptake (2.2 +/- 0.5 fold greater) and excretion (8.0 +/- 5.9 fold greater) of technetium-99m labeled disofenin. These findings support the development of profound reversible cholestasis as the primary basis for the elevated bilirubin in patients undergoing IL-2 treatment and may have implications for understanding the jaundice observed in some patients postoperatively as well as that associated with sepsis and other inflammatory disorders. Specifically, the release of IL-2 or the induction of other factors similarly induced by IL-2 may be responsible for these findings. Tissue ultrasound and computerized hepatobiliary scans provide additional noninvasive assessments of liver function and physiology.

Bilirubin↗
PubMed1989

Tumor localization of adoptively transferred indium-111 labeled tumor infiltrating lymphocytes in patients with metastatic melanoma.

Lymphoid cells infiltrating into human tumors can be expanded in vitro in medium containing interleukin-2 (IL-2). Adoptive transfer of these tumor-infiltrating lymphocytes (TIL) mediates potent antitumor effects in murine tumor models. Clinical trials to evaluate the efficacy of these cells in patients with advanced cancer are underway. We have investigated whether infused TIL labeled with indium 111 (111In) oxine can traffic and localize to metastatic deposits of tumor. Six patients with metastatic malignant melanoma who had multiple sites of subcutaneous, nodal, and/or visceral disease were the subjects of the study. The patients received cyclophosphamide 36 hours before receiving the intravenous (IV) infusion of TIL followed by IL-2 IV every eight hours. The distribution and localization of the TIL were evaluated using serial whole body gamma camera imaging, serial blood and urine samplings, and serial biopsies of tumor and normal tissue. 111In-labeled TIL localized to lung, liver, and spleen within two hours after the infusion of activity. Activity in the lung diminished within 24 hours. As early as 24 hours after injection of 111In-labeled TIL, localization of TIL to sites of metastatic deposits was demonstrated in all six patients using either imaging studies or biopsy specimens or both. 111In activity in tumor tissue biopsies ranged from three to 40 times greater than activity in normal tissue. A progressive increase in the radioactive counts at sites of tumor deposit was seen. This study shows that labeled TIL can localize preferentially to tumor, and provides information concerning the possible mechanism of the therapeutic effects of TIL.

Adult↗
PubMed1989

Doxorubicin-containing regimens for the treatment of stage II breast cancer: The National Surgical Adjuvant Breast and Bowel Project experience.

Despite numerous reports of findings obtained following the use of doxorubicin (Adriamycin [A]; Adria Laboratories, Columbus, OH) for the postoperative treatment of patients with primary breast cancer and positive axillary nodes, no clear consensus exists regarding its worth when used in that setting. In June 1981, the National Surgical Adjuvant Breast and Bowel Project (NSABP) implemented two randomized clinical trials aimed at evaluating the worth of doxorubicin when administered in conjunction with melphalan (L-PAM) and fluorouracil (5-FU) (PF). A prior NSABP study identified cohorts of patients who did or did not benefit from tamoxifen (TAM, T) when used with chemotherapy. That information was employed in the design of the present studies. Women considered responsive to TAM (1,106) were randomized between PFT and PAFT, and those nonresponsive to TAM (707) were randomized between PF and PAF. Findings through 6 years of follow-up (mean duration of potential time on study, 64 months and 63 months, respectively) indicate that non-TAM-responsive patients who received PAF had a significantly better disease-free survival (DFS) (P = .003) and survival (P = .05) than did those receiving PF. By contrast, there was no significant difference in DFS (P = .6) or survival (P = .7) between PFT- and PAFT-treated patients. No disparity in the amount of drug received, whether related to the median amount or to dose-intensity, is present to account for the difference in findings between the studies. Aside from alopecia and emesis, the toxicity from the doxorubicin-containing regimens was similar to those in which doxorubicin was omitted. Cardiomyopathy was not a significant finding; there were no deaths from cardiac toxicity. The incidence of arterial and venous complications in patients receiving TAM was less than reported by others.

Aged↗
PubMed1989

Value of assessment of ploidy in rectal cancers.

Flow cytometry was performed on available archival material from 232 patients with rectal cancer enrolled in the National Surgical Adjuvant Breast and Bowel Project protocol R-01. Tumor ploidy was not found to be significantly related to such pathologic and clinical parameters as Dukes' stage; nodal status; nuclear or histologic grades; patient's age, sex, or overall survival rate with an average study time of 79 months. A trend was evident that patients with poor histologic grade, or those with Dukes' B and C tumors that were aneuploid fared worse than those with diploid cancers. However, measurements of survival were found to be more strongly and consistently related to such conventional prognostic parameters as tumor differentiation, Dukes' stage, and nodal status. Further, numbers of nodes with metastases (ie, 1 to 4 or 5+) more significantly discriminated Dukes' C cases than estimation of tumor ploidy. Although tumor ploidy may reflect some features of rectal cancers, their natural history and prognosis are explained better by assessment of conventional parameters used for these purposes.

Age Factors↗
PubMed1988

Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01.

Information is presented from 555 patients with Dukes B and C rectal cancers treated by curative resection who were entered into the National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol R-01 between November 1977 and October 1986. Their average time on study was 64.1 months. The patients were randomized to receive no further treatment (184 patients), postoperative adjuvant chemotherapy with 5-fluorouracil, semustine, and vincristine (MOF) (187 patients), or postoperative radiation therapy (184 patients). The chemotherapy group, when compared with the group treated by surgery alone, demonstrated an overall improvement in disease-free survival (P = .006) and in survival (P = .05). Employing the proportional hazards model, a global test was used to determine the presence of treatment interactions. Investigation of stratification variables employed in this study indicated that sex, and to a lesser extent age and Dukes stage, made individual contributions to the disease-free survival and the survival benefit from chemotherapy. When evaluated according to sex, the benefit for chemotherapy at 5 years, both in disease-free survival (29% vs. 47%; P less than .001; relative odds, 2.00) and in survival (37% vs. 60%; P = .001; relative odds, 1.93), was restricted to males. When males were tested for age trend with the use of a logistic regression analysis, chemotherapy was found to be more advantageous in younger patients. When the group receiving post-operative radiation (4,600-4,700 rad in 26-27 fractions; 5,100-5,300 rad maximum at the perineum) was compared to the group treated only by surgery, there was an overall reduction in local-regional recurrence from 25% to 16% (P = .06). No significant benefit in overall disease-free survival (P = .4) or survival (P = .7) from the use of radiation has been demonstrated. The global test for interaction to identify heterogeneity of response to radiation within subsets of patients was not significant. In conclusion, this investigation has demonstrated a benefit from adjuvant chemotherapy (MOF) for the management of rectal cancer. The observed advantage was restricted to males. Postoperative radiation therapy reduced the incidence of local-regional recurrence, but it failed to affect overall disease-free survival and survival.

Aged↗
PubMed1988

Postoperative adjuvant chemotherapy or BCG for colon cancer: results from NSABP protocol C-01.

Data are presented from 1,166 patients with Dukes B and C carcinoma of the colon who were entered into the National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol C-01 between November 1977 and February 1983. Patients were randomized to one of three therapeutic categories: 1) no further treatment following curative resection (394 patients); 2) postoperative chemotherapy consisting of 5-fluorouracil, semustine, and vincristine (379 patients); or 3) postoperative BCG (393 patients). The average time on study was 77.3 months. A comparison between patients receiving postoperative adjuvant chemotherapy and those treated with surgery alone indicated that there was an overall improvement in disease-free survival (P = .02) and survival (P = .05) in favor of the chemotherapy-treated group. At 5 years of follow-up, patients treated with surgery alone were at 1.29 times the risk of developing a treatment failure and at 1.31 times the likelihood of dying as were similar patients treated with combination adjuvant chemotherapy. Comparison of the BCG-treated group with the group treated with surgery alone indicated that there was no statistically significant difference in disease-free survival (P = .09). There was, however, a survival advantage in favor of the BCG-treated group (P = .03). At 5 years of follow-up, patients randomized to the surgery-alone arm were at 1.28 times the risk of dying as were similar patients treated with BCG. Further investigation disclosed that this survival advantage in favor of BCG was a result of a diminution in deaths that were non-cancer related. When analyses were conducted on which events not related to cancer recurrence were eliminated, the survival difference between the BCG and control groups became nonsignificant (P = .40); the cumulative odds at 5 years decreased from 1.28 to 1.10. The findings from this study are the first from a randomized prospective clinical trial to demonstrate that a significant disease-free survival and survival benefit can be achieved with postoperative adjuvant chemotherapy in patients with Dukes B and C carcinoma of the colon who have undergone curative resection.

Aged↗
PubMed1988

Surgical treatment of primary breast cancer.

The background to the Halstedian era of breast cancer treatment is sketched, and the development of the changes in surgical treatment are outlined, with a review of the most important findings from the several clinical trials conducted to evaluate the alternative operative procedures. Included is a short description of operative techniques; also pathological examination of the operation specimen, and the use of radiation therapy when performing a segmental mastectomy are briefly described. This review is based almost entirely on observations from clinical trials conducted by the National Surgical Adjuvant Breast and Bowel Project.

Axilla↗
PubMed1988

Mandibular fractures in association with chin trauma in pediatric patients.

The combination of chin trauma and bleeding from the ear should alert the physician to the possibility of a mandibular fracture. Not all hemotympanums represent basilar skull fractures, especially when they occur in association with chin trauma. Diagnosis of mandibular condylar fractures or temporomandibular joint disruptions can be very difficult. A high index of suspicion and a proper choice of imaging modalities are necessary to ensure a timely diagnosis.

Accidental Falls↗
PubMed1988

Relative worth of estrogen or progesterone receptor and pathologic characteristics of differentiation as indicators of prognosis in node negative breast cancer patients: findings from National Surgical Adjuvant Breast and Bowel Project Protocol B-06.

This study correlates the disease-free survival (DFS), distant disease-free survival (DDFS), and survival (S) of 1,157 histologically node negative breast cancer patients with the estrogen and/or progesterone receptor (ER, PR) and with the nuclear or histologic grade (NG, HG) of their tumors. All were treated by operation without systemic adjuvant therapy. The DFS, DDFS, and S were significantly greater (P = .005, .004, less than .001) in patients with ER positive than ER negative tumors but the magnitude of the differences after 5 years of follow-up was slight (8% in both DFS and DDFS and 10% in S). Differences of that magnitude are insufficient to discriminate clearly between patients who should or should not receive systemic therapy. As with ER, there were outcome differences in favor of PR positive tumors but only in S was the difference significant (8% at 5 years; P = .002). When combined with ER, PR made no independent contribution in the outcome prediction. Regression analysis indicated that NG was the most important single marker of outcome. The prognosis of women with unknown ER or PR was equivalent to or better than that in those with ER or PR positive tumors. This finding seems to be related to tumor size in that a higher proportion of tumors with unknown receptors were less than 1.0 cm, thus having insufficient tissue for analysis. Our findings disclose that in node negative breast cancer patients, NG is a better marker of prognosis than is tumor ER, and that PR is of little or no value. Tumor NG may also be useful for selecting the type of systemic therapy to be used in these patients.

Biomarkers, Tumor↗
PubMed1987

Pathologic findings from the national surgical adjuvant breast project. Correlations with concordant and discordant estrogen and progesterone receptors.

Pathologic materials were available for review from 1597 women with Stage II (positive regional node metastases) invasive breast cancer in whom estrogen receptor (ER) and progesterone receptor (PR) assays of the primary tumor were performed. These women were enrolled in a clinical trial comparing the effect of postmastectomy adjuvant L-phenylalanine mustard (L-PAM) and 5-fluorouracil (5-FU) with and without tamoxifen (NSABP Protocol No. 9). Significant pathologic and clinical associations with receptor status were similar for both ER and PR except that the latter, unlike ER, was not related to patient age. Regression analyses revealed that the most significant pathologic features related to a concordant positive ERPR receptor status was low (well differentiated) nuclear and histologic grades, slight or absent tumor lymphoid infiltrate, slight or absent necrosis and moderate or marked elastica in decreasing order of importance. All of the factors enumerated are directly or indirectly related to tumor differentiation. Recognition of four or five conforming pathologic features allows for the prediction of either ER or PR status in 70% to 80% of instances respectively, and the presence of three features in 69%. This latter figure is similar to that of estimation of nuclear grade alone. Thirty percent of ERPR estimates were discordant i.e., either ER-PR+ or ER+PR-. Pathologic features associated with discordant assays were not similar to those found when the ERPR estimates were concordant. Life table analyses revealed patients with discordant receptors to exhibit disease-free survival intermediate to that of those with ER+PR+ and ER-PR- values. This information suggests that a discordant receptor status is more reflective of an aberration of ER metabolism than a methodologic error. Histograms correlating frequency of nuclear grades with levels of ER and PR were comparable and revealed patterns indicating the propriety of relating values less than 10 fm/mg as being receptor negative. The frequency of well-differentiated nuclei increased with ascending levels of ER and PR.

Breast Neoplasms↗
PubMed1987

Prevalence of antibody to hepatitis B virus in foreign-born hospital employees.

Hepatitis B surface and core antibodies were measured in 512 community hospital employees at increased risk for developing infection with hepatitis B virus. Antibody was detected in 140 (27 percent) participants. Multivariate logistic regression analysis indicated that seropositivity was strongly associated with the prevalence of hepatitis B in an employee's country of birth and with age. These results suggest that reported differences among hospitals in hepatitis B seropositivity may in part be a reflection of the national origin of its employees. These data also indicate that each hospital should assess its own risk for hepatitis B infection and that prevaccination serologic testing is particularly worthwhile in hospitals having large numbers of foreign-born employees.

Carrier State↗
PubMed1987

Use of doxapram to increase respirations without a concomitant increase in intracranial pressure.

We treated a brain-damaged 8-month-old male with iv doxapram in order to discontinue mechanical ventilation. We were able to monitor intracranial pressure (ICP) throughout the course of doxapram via an ICP monitor. Despite normal and then excessive PaCO2, the patient's spontaneous respiratory rate remained nil before doxapram treatment. However, after an iv bolus dose followed by a maintenance drip, the patient's spontaneous respiratory rate increased while his ICP remained at baseline or slightly less than baseline, thereby allowing mechanical ventilation to be discontinued.

Brain Damage, Chronic↗