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Biomedical subjects

B Fisher

Publications and source records attributed to B Fisher.

At least 163 records · Page 9Linked to original sources
PubMed1991

Significance of ipsilateral breast tumour recurrence after lumpectomy.

Breast cancer treatment trials from the US National Surgical Adjuvant Breast and Bowel Project have established breast-conserving operations as a replacement for radical mastectomy (NSABP B-04), and have shown that in terms of survival free from distant disease there was no significant difference between lumpectomy, lumpectomy plus breast irradiation, and total mastectomy (NSABP B-06). 9-year follow-up data from B-06 are used here to address the issue of ipsilateral breast tumour recurrence (IBTR) and the development of distant disease, a question with important clinical and biological implications. A Cox regression model on fixed co-variates (ie, features such as tumour type or size present at surgery and not subsequently alterable) and on IBTR, which is time dependent and not fixed, revealed that the risk of distant disease was 3.41 times greater after adjustment for co-variates in patients in whom an IBTR developed. IBTR proved to be a powerful independent predictor of distant disease. However, it is a marker of risk for, not a cause of, distant metastasis. While mastectomy or breast irradiation following lumpectomy prevent expression of the marker they do not lower the risk of distant disease. These findings further justify the use of lumpectomy.

Breast Neoplasms↗
PubMed1991

Antinociceptive properties of intrathecal dexmedetomidine in rats.

Dexmedetomidine is a highly selective alpha 2-adrenoceptor agonist. In this study, the intrathecal administration of dexmedetomidine into the rat lumbar subarachnoid space produced dose-dependent, prolonged antinociception as measured by hot plate and tail flick testing. Intrathecal administration of 3 or 10 micrograms of dexmedetomidine increased hot plate and tail flick latencies to cutoff values within 15 min of injection. Animals receiving 1 microgram of intrathecal dexmedetomidine did not show any significant antinociception when compared to saline controls. The intrathecal administration of the alpha 2-adrenoceptor antagonist, idazoxan, ablated all measurable antinociception produced by the prior injection of 10 micrograms of dexmedetomidine.

Adrenergic alpha-Agonists↗
PubMed1991

Conservative management of intraductal carcinoma (DCIS) of the breast. Collaborating NSABP investigators.

Seventy-six patients with intraductal carcinoma (DCIS) of the breast have been observed for 83 months (range 50-141) following treatment by lumpectomy (L) only (21), L and breast irradiation (XRT) (27), or mastectomy (28). All represented examples of DCIS retrieved after pathologic examination of a much larger cohort of patients with stage I and II invasive breast cancer enrolled in NSABP protocol 6. Local breast recurrences were similar for women with DCIS and those from this cohort at a similar period of follow-up with invasive cancer treated by L only (43% vs. 39%) and L + XRT (7% vs. 10%). The presence of moderate/marked comedonecrosis was suggestively related to local breast recurrence (P = .07). This latter was significantly reduced for patients receiving post L XRT (P = .01). All local breast recurrences in this study and 29 of 31 recorded by others occurred at or close to the site of extirpation of the index cancer minimizing multicentricity as a contraindication for the conservative surgical treatment of DCIS. Survival rates which were similar for patients with DCIS regardless of form of local treatment were better than that observed for negative node patients with invasive cancer enrolled in protocol 6. Thus, DCIS is a less, not more, ominous disease than invasive cancer. This and other features of its natural history indicate that it would be a contradiction to treat invasive cancer but not DCIS conservatively.

Adult↗
PubMed1991

The effect of lonidamine (LND) on radiation and thermal responses of human and rodent cell lines.

Rodent and human cells were tested for response to Lonidamine (LND) (1-(2,4 dichlorobenzyl) 1-indazol-3-carboxylic acid) combined with radiation or hyperthermia. Lonidamine exposure before, during, and after irradiation caused varying degrees of inhibition of potentially lethal damage (PLD) repair which was cell line dependent. In human glioma, melanoma, squamous cell carcinoma, and fibroblasts, LND exposure did not inhibit or only partially inhibited repair of potentially lethal damage. LND up to 100 micrograms/ml produced only a low level of toxicity in these cells and only slightly inhibited glucose consumption at the maximum concentration. In human glioma cells, LND treatment alone did not inhibit PLD repair, but when combined with hyperthermia treatment at moderate levels easily achievable in the clinic, there was complete inhibition of potentially lethal damage repair. These data suggest that LND effectiveness is cell type dependent. Combinations of LND, hyperthermia, and radiation may be effective in cancer therapy especially in tumors such as glioma in which repair of potentially lethal damage may be extensive.

Animals↗
PubMed1991

A standardized technique for lower limb radiography. Practice, applications, and error analysis.

The normal standing radiograph, which provides a view of the knee only, is prone to errors of parallax and poor control of patient positioning. A standardized radiographic procedure was developed to control these sources of error. Anteroposterior and lateral views of the lower limb (hip and knee) are obtained without moving the patient from a standardized position; this includes control of ankle position and limb rotation. To correct for parallax error, radiopaque markers are positioned between the patient and the x-ray source. The locations of bone landmarks and reference markers on the radiographs are digitized, and a software package provides a display of key parameters. Error analysis of the method confirmed that most angles were sensitive to contrived positional variations, especially limb rotation and knee flexion. Load distribution between limbs was not critical. The greatest error was random. Most angles were reproducible within +/- 1.3 degrees or less at 95% confidence.

Aged↗
PubMed1991

A quantitative approach to radiography of the lower limb. Principles and applications.

A method is described which provides standardised reproducible radiographic images of the lower limb. Anteroposterior and lateral radiographs are digitised and processed by computer to provide graphic/numeric displays of angles and linear measurements, relating the centre points of the hip, knee, and ankle. Two cases illustrate how surgical planning is facilitated when standardised data are available. These data confirm the close relationship between postoperative limb alignment and positioning of prosthetic elements.

Aged↗
PubMed1991

Panel sees high demand for diverse CFO skills.

A more sophisticated healthcare industry, challenged by competition and payer demands, also looks for sophistication when filling its senior financial positions. Individuals with experience in managed care contract negotiations, knowledge of hospital-physician ventures, and superior planning and treasury management skills are increasingly sought by hospitals. Some organizations also may single out chief financial officers able to assume broader administrative duties, including chief executive officer positions. These are among the observations of a panel convened by HFMA to discuss recent trends in healthcare executive recruiting. Highlights of the session, moderated by HFMA President Richard L. Clarke, FHFMA, follow.

Employment↗
PubMed1990

Effect of tamoxifen on serum insulinlike growth factor I levels in stage I breast cancer patients.

Insulinlike growth factor I (IGF-I) has been shown to be a potent mitogen for breast cancer cells in vitro, and IGF-I receptors have been demonstrated on human primary breast neoplasms. In a randomized, placebo-controlled study, we document that administration of the antiestrogen tamoxifen to patients with breast cancer was associated with a statistically significant (P = .002) reduction in the serum level of IGF-I. The mean IGF-I level was 1.4 U/mL in the placebo-treated group and 0.9 U/mL in the tamoxifen-treated group. Because serum IGF-I level is growth hormone (GH) dependent and because data suggest that the pubertal surge in GH and IGF-I levels is sex steroid dependent, we speculate that the mechanism underlying our observation may involve blockade by tamoxifen of estrogen action in the hypothalamic-pituitary axis. We conclude that tamoxifen treatment reduces IGF-I levels and that this reduction may contribute to the therapeutic effect of the drug.

Aged↗
PubMed1990

Evaluation of the worth of corynebacterium parvum in conjunction with chemotherapy as adjuvant treatment for primary breast cancer. Eight-year results from the National Surgical Adjuvant Breast and Bowel Project B-10.

During the 1970s, information obtained from animal tumor models and from patients with a spectrum of solid tumors indicated the worth of a variety of immunostimulating agents. These findings provided a biological and clinical rationale for conducting randomized trials to evaluate the worth of those agents. Consequently, in May 1977 the National Surgical Adjuvant Breast and Bowel Project (NSABP) implemented a randomized trial to determine whether Corynebacterium parvum (C. parvum, CP) plus chemotherapy would be more effective than chemotherapy alone in prolonging the disease-free survival (DFS) and survival (S) of patients with primary operable breast cancer and positive axillary nodes. The results of that trial through 8 years of follow-up fail to indicate that treatment with CP used in conjunction with l-phenylalanine mustard (L-PAM) plus 5-fluorouracil (PF) results in a better DFS and S than that observed after chemotherapy alone. Use of the immunomodulator has instead resulted in a poorer, but not statistically significant, outcome. Despite adjustments made to account for any imbalance in distribution of prognostic factors between the two treatment groups and despite considering treatment compliance as a factor, the unfavorable outcome persisted. A high incidence of fever and chills was associated with the administration of CP. The administration of hydrocortisone before each CP treatment reduced the frequency of those and other systemic effects. The failure to demonstrate a benefit from CP is in keeping with the failure of other nonspecific stimulating agents to contribute to the creation of a new paradigm for the treatment of breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Pathologic findings from the National Surgical Adjuvant Breast and Bowel Projects (NSABP). Prognostic discriminants for 8-year survival for node-negative invasive breast cancer patients.

Twenty-two pathologic features (including estrogen and progesterone receptors) and four clinical features observed in 950 women with node-negative Stage I invasive breast cancer who enrolled in the National Surgical Adjuvant Breast and Bowel Projects (NSABP) protocol B-06 were evaluated for their possible prognostic significance. Preliminary univariate analysis revealed ten characteristics that were significant in this regard at the 1% level. Their assessment in a Cox regression model demonstrated only three to be prognostically important; notable among these were nuclear grade, histologic tumor type, and race. Life-table plots revealed that 86% of patients whose cancers exhibited good nuclear grade survived for 8 years as opposed to 64% in whom the nuclear grade was scored as poor. Analyses demonstrated three prognostic categories for histologic tumor type. Patients with either mucinous, tubular, or papillary cancers fared significantly better than those having not otherwise specific (NOS) or atypical medullary tumors. Survival for those with typical medullary, NOS combinations, or lobular invasive cancers was intermediate. Blacks fared worse than whites. Survival was correspondingly better or worse when two favorable or unfavorable characteristics were detected. The number of black women in this cohort was considered too small for further subset analysis although generally the pattern of findings suggested that survival was worse for blacks than for whites in all subsets. A review, as well as our own experience, suggested that nuclear grade is as good if not better as a predictor of survival in node negative patients as information derived from DNA analyses, immunohistochemical demonstration of erb-B2 overexpression, and, possibly, the tumor labeling index at predicting survival in node-negative patients.

Breast Neoplasms↗
PubMed1990

Medullary cancer of the breast revisited.

Common as well as unusual, heretofore unmentioned histopathologic features observed in 336 typical and 273 atypical medullary breast cancers from 6404 patients enrolled in various stage I and II protocols of the National Surgical Adjuvant Breast and Bowel Projects (NSABP) are presented. Both medullary types exhibited comparable pathologic findings, except for the infiltrative border and/or slight or absent tumor lymphoid infiltrate which by definition characterize the atypical form. Both also demonstrated a similar, high proclivity to be aneuploid, and to lack estrogen and progesterone receptors and nodal metastases. After appropriate statistical adjustments, survival (analyzed for 198 patients with typical and 149 with atypical medullary cancers) was found to be better for untreated, node-negative and node-positive patients treated with L-PAM + 5Fu who had typical medullary cancers than those with the NOS histologic type. The magnitude of this difference was 6% at 5 and 17% at 10 years post-operatively (cumulative odds = 1.81 with a 95% confidence interval of 1.08 - 3.3) for the former group, and 4% at 5 and 16% at 10 years (cumulative odds = 1.56 with a 95% confidence interval of 1.08 - 2.23) for the latter. Survival was comparable for patients with atypical medullary and NOS types in both situations. No clear difference in survival was found in untreated, positive node patients with the 3 histologic types examined, although the sample sizes in this subset were relatively small. This information as well as other pertinent considerations indicate that the prognosis of typical medullary cancer is not as 'good' as previously perceived. It is also concluded that there is insufficient evidence at present to exclude the atypical medullary variant as a histologic type of breast cancer.

Biomarkers, Tumor↗
PubMed1990

Evaluation of the carcinogenic potential of pesticides. 2. Methidathion.

The carcinogen potential of methidathion, a dimethoxyorganic phosphorus pesticide and cholinesterase inhibitor, was evaluated by the Health Effects Division of the Office of Pesticide Programs using a consensus peer review process and the EPA's guidelines for risk assessment. Methidathion was categorized as a Group C (possible human) carcinogen based upon evidence of an increased incidence of benign and malignant hepatocellular tumors, alone and in combination, in a single study involving male Chr-CD-1 mice. The compound was not carcinogenic in female Chr-CD-1 mice in the same study or in Sprague-Dawley rats of either sex in a second study. Methidathion was not genotoxic in a variety of in vitro or in vivo tests designed to detect DNA damage, chromosome aberrations, gene mutations, and sister chromatid exchange. Although methidathion was identified as being structurally similar to two other organophosphate insecticides, prothidathion and lythidathion, no toxicological data were available on either of these agents for comparative purposes. The biological information on methidathion was reviewed by the agency's FIFRA Scientific Advisory Panel who agreed with the category C designation for methidathion. The data were not found to be sufficient to quantify human risk to methidathion.

Adenoma↗
PubMed1990

Saccadic suppression of displacement is strongest in central vision.

Perception of target displacement is severely degraded if the displacement occurs during a saccadic eye movement, but the variation of this effect across the visual field is unknown. A small target was displaced from a starting point at the midline, or 10 deg to the right or left, while the eye made a saccade from the 10 deg right position to the 10 deg left position. Saccades were detected and the target displaced on line. Assessed with a signal detection measure, suppression was stronger in central vision than in more peripheral locations for all three subjects. Leftward and rightward displacements yielded equal thresholds. The results complement the findings of others to reveal a picture of perceptual events during saccades, with both deeper saccadic suppression and faster correction of spatial values (the correspondences between retinal position and perceived egocentric direction), favouring more accurate spatial processing in central vision than in the periphery.

Adult↗
PubMed1990

Abnormal beta and gamma sialoglycoprotein associated with the low-frequency antigen Lsa.

This paper describes the association of the low-frequency antigen Lsa with high-molecular-weight variants of beta- and gamma-sialoglycoproteins (beta-SGP, gamma-SGP). The variant beta-SGP, designated beta Lsa, carries the Ge3 epitope and the epitopes recognised by 3 murine monoclonal anti-beta-SGP antibodies. The variant gamma-SGP, designated gamma Lsa, carries the Ge2 and Ge3 epitopes. Both beta Lsa and gamma Lsa showed enhanced reactions in immunoblotting with anti-Ge3 sera--which may indicate the presence of 2 Ge3 epitopes on beta Lsa and gamma Lsa. These findings would be consistent with the proposed structure of the Lsa glycophorin C gene.

Epitopes↗
PubMed1990

Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein overexpression in primary breast cancer.

In order to investigate the prognostic significance of erbB-2 overexpression, immunohistochemical staining for the erbB-2 protein was performed on sections from paraffin blocks of 292 primary invasive breast cancers obtained from women enrolled in the National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-06. Positive reaction indicative of erbB-2 overexpression was observed on tumor cells in 62 (21%) samples. Women whose cancers were judged to have erbB-2 overexpression had a significantly worse overall survival (P = .0012) with twice the mortality rate of women without detectable erbB-2 expression. No statistically significant effect was evident for disease-free survival (P = .22). In multivariate analysis, detection of erbB-2 overexpression was the second most predictive independent variable for survival after nodal status. Overexpression of erbB-2 was more common among tumors of poor nuclear grade (29%) than those of good nuclear grade (12%). The association of erbB-2 overexpression with decreased survival was evident only among women with tumors of good nuclear grade. In this subgroup, erbB-2 overexpression was associated with an approximately fivefold increase in mortality rate (P = .00001). The combined predictive value of erbB-2 overexpression and nuclear grade was evident regardless of their lymph node status. These results provide evidence that detection of erbB-2 overexpression may be an independent prognostic variable for patient survival. Moreover, when combined with evaluation of nuclear grade, it may be possible to use immunostaining for erbB-2 protein to identify patients at increased risk from within a relatively low-risk group.

Antibodies, Monoclonal↗
PubMed1990

A prospective randomized trial evaluating prophylactic antibiotics to prevent triple-lumen catheter-related sepsis in patients treated with immunotherapy.

During a 15-month period, 92 patients undergoing 129 treatment episodes of immunotherapy with interleukin-2 (IL-2) alone or with immune cells underwent insertion of central venous catheters (CVCs) in the Surgery Branch, National Cancer Institute. Before each catheter insertion patients were prospectively randomized into one of three treatment groups; therapy with intravenous (IV) placebo using D5W, IV oxacillin, or change of the catheter to a new site every 72 hours. The mean duration of catheterization was 3.8 +/- 1.1 days. No patient in the oxacillin arm developed catheter-related sepsis, while eight patients in the control arms (five, line change, three, placebo) developed catheter-related sepsis (P2 = .050). Seven episodes of catheter-related sepsis were due to Staphylococcus aureus and one was due to Staphylococcus epidermidis. Catheter colonization was reduced significantly in the oxacillin arm versus control arms (P = .0001). Staphylococcus aureus, Staphylococcus epidermidis, and other coagulase-negative Staphylococci were sensitive to oxacillin in 89%, 60%, and 50% of cultures, respectively. No evidence of bacterial overgrowth, candida colonization, or candidemia was observed in these patients. Thus this trial demonstrates that treatment with prophylactic oxacillin can decrease the incidence of catheter-related sepsis in patients undergoing immunotherapy with interleukin-2 (IL-2). To our knowledge this is the first prospective randomized trial to evaluate the prophylactic use of systemic antibiotics in the prophylaxis of CVC sepsis.

Catheterization, Central Venous↗