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Biomedical subjects

L Pierce

Publications and source records attributed to L Pierce.

At least 19 recordsLinked to original sources
PubMed2004

Workshop on partial breast irradiation: state of the art and the science, Bethesda, MD, December 8-10, 2002.

Breast conserving surgery followed by radiation therapy has been accepted as an alternative to mastectomy in the management of patients with early-stage breast cancer. Over the past decade there has been increasing interest in a variety of radiation techniques designed to treat only the portion of the breast deemed to be at high risk for local recurrence (partial-breast irradiation [PBI]) and to shorten the duration of treatment (accelerated partial-breast irradiation [APBI]). To consider issues regarding the equivalency of the various radiation therapy approaches and to address future needs for research, quality assurance, and training, the National Cancer Institute, Division of Cancer Treatment and Diagnosis, Radiation Research Program, hosted a Workshop on PBI in December 2002. Although 5- to 7-year outcome data on patients treated with PBI and APBI are now becoming available, many issues remain unresolved, including clinical and pathologic selection criteria, radiation dose and fractionation and how they relate to the standard fractionation for whole breast irradiation, appropriate target volume, local control within the untreated ipsilateral breast tissue, and overall survival. This Workshop report defines the issues in relation to PBI and APBI, recommends parameters for consideration in clinical trials and for reporting of results, serves to enhance dialogue among the advocates of the various radiation techniques, and emphasizes the importance of education and training in regard to results of PBI and APBI as they become emerging clinical treatments.

Breast Neoplasms↗
PubMed1998

Associations of CYP1A1, GSTM1, and CYP2E1 polymorphisms with lung cancer suggest cell type specificities to tobacco carcinogens.

The dramatic shift in the pathological presentation of lung cancer [the proportional decrease in squamous cell carcinoma (SCC) and increase in adenocarcinoma (AC)] observed in the United States after the 1950s may have taken place as the result of the reduction in polycyclic aromatic hydrocarbons (PAHs) and the increase in N-nitrosamines in inhaled smoke from filtered low-yield cigarettes. The predominant mutation patterns of these tumors also suggest differences in their etiology. We tested the hypothesis that genetic susceptibility to PAHs, as determined by polymorphisms in CYP1A1 and GSTM1, predominantly causes lung SCCs, and susceptibility to nitrosamines, as determined by polymorphisms in CYP2E1, predominantly causes lung ACs. CYP1A1 and GSTM1 play a major role in the metabolic activation and detoxification of PAHs, respectively, and CYP2E1 plays a major role in the metabolic activation of nitrosamines. We conducted a population-based case-control study among 341 incident lung cancer cases and 456 controls of Caucasian, Japanese, or Hawaiian origin. In-person interviews collected detailed information on lifestyle risk factors, and DNA extracted from peripheral leukocytes was used in PCR-based genotyping assays. Logistic regression analyses were used to compute odds ratios and 95% confidence intervals (CIs) for each cell type, adjusting for smoking and dietary variables. The presence of at least one copy of the CYP1A1 MspI variant allele was found to be associated with a 2.4-fold (95% CI, 1.2-4.7) increase in the risk of SCC when this gene was considered singly and a 3.1-fold (95% CI, 1.2-7.9) increase in the risk of SCC when combined with a GSTM1 deletion. No significant association was found between MspI and all lung cancers or other cell types or with the CYP1A1 exon 7 polymorphism. In contrast, the CYP2E1 RsaI and DraI polymorphisms were not clearly related to SCC risk, but these homozygous variant genotypes were associated with a 10-fold (95% CI, 0.0-0.5) decrease in the risk of overall lung cancer (RsaI variant) and AC (DraI variant) compared to the homozygous wild-type genotypes. Inverse associations with these two closely linked CYP2E1 polymorphisms were also suggested for small cell carcinoma. In agreement with past experimental and epidemiological data, the associations found in this study between CYP1A1 and lung SCC and between CYP2E1 and lung AC suggest a certain specificity of tobacco smoke PAHs for lung SCC and tobacco-specific nitrosamines for lung ACs.

Adult↗
PubMed1998

Protection of mice against challenge with homologous and heterologous serovars of Actinobacillus pleuropneumoniae after live vaccination.

Protective immune responses and the virulence of Actinobacillus pleuropneumoniae (APP) have been attributed, in part, to toxins (Apx) produced by the bacterium. A mutant of the serovar 7 strain HS93 (HS93Tox-), lacking the genes encoding the structural toxin ApxA and the post-translational activating protein ApxC, but retaining the genes required for secretion ApxB and ApxD, was isolated and shown to be attenuated in a mouse model. A plasmid vector system was developed and used to express the ApxA gene from within the HS93Tox- strain. The resulting strain, HS93Tox-/pIG-T1K, expresses the Apx structural protein in a non-activated form. HS93Tox-/pIG-T1K was shown to be attenuated in a mouse model and to be capable of inducing Apx-specific antibodies, which were boosted on re-inoculation. Live vaccination of mice with HS93Tox-/pIG-T1K offered protection against homologous wild-type serovar 7 challenge, and also heterologous challenge with a serovar 1 strain. This is in contrast to vaccination with the HS93Tox- strain, which failed to protect mice against a heterologous challenge.

Actinobacillus Infections↗
PubMed1996

The use of mammography in breast preservation in locally advanced breast cancer.

PURPOSE: As the feasibility of breast preservation in locally advanced breast cancer is currently under evaluation, little information is available correlating mammographic changes to chemotherapy with local outcome. To evaluate the role of mammography in selecting candidates with locally advanced breast cancer for conservative local therapy, we analyzed mammographic changes in the breast to induction chemotherapy and correlated the radiologic appearance with pathologic outcome. METHODS AND MATERIALS: From 1985 through 1993, 91 patients with Stage III breast cancer were enrolled on a multimodality clinical trial using chemohormonal therapy followed by local treatment and maintenance therapy. Induction therapy consisted of cyclophosphamide, doxorubicin, methotrexate,and 5-fluorouracil with hormonal synchronization using tamoxifen and conjugated estrogens. After nine cycles, surgical biopsies of the breast were performed. Through 1988, clinical examination alone directed the site for postinduction biopsy; for patients treated after 1988, mammography, in addition to physical examination, determined the biopsy location. Local treatment was determined by biopsy result. Patients with a pathologic complete response received radiation only to the breast adn regional nodes, while those with pathologically proven residual disease underwent mastectomy and postoperative radiotherapy. Nine additional cycles of maintenance chemotherapy were administered. RESULTS: Fifty-five of 91 patients (58%) obtained a clinical complete response (CR) to induction chemotherapy. Twenty-eight of the 53 women with a clinical CR had both pre- and postinduction mammograms. Of these 28 women, 9 obtained a pathologic CR and 19 obtained a pathologic partial response (PR). Fifty-five percent of the pathologic complete responders had resolution of mammographic abnormalities on the postinduction mammograms. Sixty-eight percent (13) of the pathologic partial responders had abnormal mammographic findings. The positive predictive value for residual cancer using physical examination was 92%, while the negative predictive value was only 36%. Among patients with a clinical complete response, the positive and negative predictive values for residual cancer using postinduction mammography were 79% and 56%, respectively. Limitations of mammography included uncertain significance of residual microcalcifications and residual masses on postinduction chemotherapy mammograms. CONCLUSIONS: Although mammography improved the accuracy of noninvasive evaluations in patients with a clinical complete response, pathologic assessment was still required to determine appropriate local therapy. More sensitive imaging modalities or modifications of film-screen mammography may improve noninvasive detection of residual disease following induction chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Ten-year results of a comparison of conservation with mastectomy in the treatment of stage I and II breast cancer.

BACKGROUND: Breast-conservation therapy for early-stage breast cancer is now an accepted treatment, but there is still controversy about its comparability with mastectomy. Between 1979 and 1987, the National Cancer Institute conducted a randomized, single-institution trial comparing lumpectomy, axillary dissection, and radiation with mastectomy and axillary dissection for stage I and II breast cancer. We update the results of that trial after a median potential follow-up of 10.1 years. METHODS: Two hundred forty-seven patients with clinical stage I and II breast cancer were randomly assigned to undergo either modified radical mastectomy or lumpectomy, axillary dissection, and radiation therapy. The 237 patients who actually underwent randomization have been followed for a median of 10.1 years. The primary end points were overall survival and disease-free survival. RESULTS: At 10 years overall survival was 75 percent for the patients assigned to mastectomy and 77 percent for those assigned to lumpectomy plus radiation (P = 0.89). Disease-free survival at 10 years was 69 percent for the patients assigned to mastectomy and 72 percent for those assigned to lumpectomy plus radiation (P = 0.93). The rate of local regional recurrence at 10 years was 10 percent after mastectomy and 5 percent after lumpectomy plus radiation (P = 0.17) after recurrences successfully treated by mastectomy were censored from the analysis. CONCLUSIONS: In the management of stage I and II breast cancer, breast conservation with lumpectomy and radiation offers results at 10 years that are equivalent to those with mastectomy.

Breast Neoplasms↗
PubMed1993

A pilot study of pi-class glutathione S-transferase expression in breast cancer: correlation with estrogen receptor expression and prognosis in node-negative breast cancer.

PURPOSE AND METHODS: Previous studies have indicated that RNA levels for pi-class glutathione S-transferase (GST pi), a phase II, drug-metabolizing enzyme, were inversely related to estrogen receptor (ER) and progesterone receptor (PR) levels in human breast tumors. Because GST pi also is expressed in normal breast epithelium, an immunohistochemical assay that uses affinity-purified polyclonal antibodies to GST pi was developed to examine the possible relationship between GST pi expression in breast cancer cells and hormone receptor expression, as well as prognosis, in patients with primary breast cancer. RESULTS: A strong inverse correlation between GST pi expression and ER (two-sided P [P2] = .002) and PR status (P2 = .023) was found in our study of 189 patients with primary breast cancer. GST pi expression was not related to tumor size, nodal metastasis, nuclear grade, histology, or age of the patient. In node-negative breast cancer (n = 72), increased GST pi expression was associated with decreased disease-free survival (DFS) and overall survival (OS). When GST pi expression was divided into categories of negative (no GST pi-positive tumor cells), intermediate (1% to 70% GST pi-positive tumor cells), and high (> 70% GST pi-positive tumor cells), the relative risk of tumor recurrence in patients with node-negative breast cancer was increased 3.39-fold for each successive category of expression (P2 = .0045; 95% confidence interval, 1.46 to 7.87) and the relative risk of death was increased 4.49-fold for each successive category (P2 = .0003; 95% confidence interval, 2.02 to 10.42). The actuarial 5-year OS was 100%, 79%, and 51%, and the DFS was 94%, 77%, and 44%, for the negative, intermediate, and high tumor groups, respectively. Among the factors studied in multivariate analysis (ER status, PR status, nuclear grade, and tumor size), GST pi expression was the factor that most accurately predicted shorter DFS and OS in node-negative patients. CONCLUSION: GST pi expression is inversely related to hormone receptor status in breast cancer. This pilot study also suggests that increased GST pi expression may be an important predictor of early recurrence and death in node-negative breast cancer patients that merits additional investigation.

Breast Neoplasms↗
PubMed1992

Conservative surgery and radiation therapy in black women with early stage breast cancer. Patterns of failure and analysis of outcome.

Between 1977 and 1986, 75 black and 615 white women with American Joint Committee (AJC) Stages I and II breast cancer were treated with excisional biopsy, axillary dissection, and radiation therapy for breast conservation. Cyclophosphamide, methotrexate, and 5-fluorouracil, with and without prednisone and tamoxifen, was given to 92% of premenopausal, 83% of perimenopausal, and 63% of postmenopausal node-positive women; 20 of 106 (19%) postmenopausal node-positive women received tamoxifen only. The clinical characteristics of the similarly treated patients were compared. The 5-year actuarial local only first failure rate was 5% for black women and 6% for white women (P = 0.53). Regional only failure as the first site of failure was 9% for blacks versus 1% for whites (P = 0.002), with regional recurrence as any component of first failure being 16% for blacks and 4% for whites (P = 0.001). The supraclavicular fossa was identified as the primary site of regional recurrence in black patients with either pathologically positive or negative axillae. Distant metastases as the only site of first failure were significantly greater in the black population with a 20% 5-year actuarial failure rate versus 11% in white patients (P = 0.01). The 5-year actuarial overall survival for the black patients was 82% versus 91% for the white patients (P = 0.01), with no-evidence-of-disease (NED) survival being 64% and 83% (P = 0.0002) and relapse-free survival (RFS) being 61% and 77% (P = 0.01), respectively. Black patients younger than 40 years of age or with pathologically positive axillary nodes had significantly worse NED, RFS, and overall survival compared with similarly staged white patients. Cosmetic results were analyzed at 3 and 5 years after completion of therapy. Although significantly fewer black patients had an excellent-to-good cosmetic result at 3 years compared with white patients, the results were not significantly different at 5 years. These results show that appropriately selected black patients with early stage breast cancer have excellent local control after conservative surgery and radiation therapy and should continue to be offered breast preservation as an alternative to mastectomy. Patterns of failure, however, demonstrated higher regional and distant recurrence rates and lower NED, RFS, and overall survival rates in most subsets of black patients reviewed.

Age Factors↗
PubMed1991

Recurrent otitis media: a cost-utility analysis of simulated treatment using tympanostomy tubes vs antibiotic prophylaxis.

Using a cost-utility analysis, the effectiveness of tympanostomy tubes was compared to that of antibiotic chemoprophylaxis in young patients with recurrent otitis media. The tympanostomy approach (T-tubes) consisted of placement of a polyethylene grommet in the tympanic membrane, with systemic and local antibiotics administered for one week. The chemoprophylaxis approach consisted of antibiotics in full doses for seven to ten days, followed by continuous antibiotic chemoprophylaxis for six months. Because the T-tube strategy under the model assumptions was more expensive ($396.44 vs $281.30) and yielded slightly less benefit (net utility of .9325 vs. .9476 for initial antibiotic therapy), the chemoprophylaxis option was preferred. We conclude that the initial treatment for recurrent otitis media should consist of acute antibiotics followed by chemoprophylaxis, with T-tubes reserved for treatment failure. Extreme changes in the baseline probabilities of cure or recurrence with antibiotic therapy or in the cost of antibiotic therapy or tympanostomy surgery were required to alter this conclusion. Varying therapy preference (utility) values did not materially alter the conclusions.

Anti-Bacterial Agents↗
PubMed1990

Synthesis of insulin-like growth factor I using N-methyl pyrrolidinone as the coupling solvent and trifluoromethane sulphonic acid cleavage from the resin.

Insulin-like growth factor I (IGF-I), a protein of 70 amino acid residues and 3 cystine bridges, has been synthesized by two solid phase Boc methods. The first method used N-methylpyrrolidinone as the solvent with single coupling cycles while the second synthesis used dimethylformamide and dichloromethane as the solvents with a double-coupling protocol. In both cases, trifluoroacetic acid/trifluoromethanesulphonic acid cleavage of the peptide from the resin was employed. Purification of the cleavage products followed by removal of the S-acetamidomethyl protecting groups gave reduced peptides which were then oxidized under conditions favouring the formation of the correct disulphide bonds. The purified synthetic IGF-I peptides were full agonists of natural IGF-I in a radioimmunoassay, in an IGF-I radioreceptor assay, in a bioassay which measures the stimulation of protein synthesis in rat L6 myoblasts and in an IGF-binding protein competitive binding assay. Moreover, in each of these assays, the synthetic IGF peptides were found to be at least 70% as potent as natural IGF-I.

Animals↗
PubMed1988

Plasma and platelet von Willebrand factor defects in uremia.

PURPOSE: Several mechanisms have been proposed to explain the prolonged bleeding times and clinical bleeding in chronic renal failure. Recent evidence has implicated an abnormality in the structure or function of the von Willebrand factor or in its interaction with uremic platelets. We investigated this factor in 11 patients with chronic renal failure. PATIENTS AND METHODS: Blood samples for cell counts, chemistries, and coagulation studies were obtained from 11 patients with chronic renal failure and prolonged bleeding times. Concentrations of von Willebrand factor antigen and ristocetin cofactor activity were determined in plasma and platelets. Multimeric analysis of von Willebrand factor in plasma and platelets was conducted. In eight cases, the platelets of uremic patients were purified, and the thrombin- and ristocetin-induced binding of normal von Willebrand factor to these platelets was examined. RESULTS: The mean plasma von Willebrand factor antigen and activity (ristocetin cofactor assay) were elevated 2.77 mu/ml and 1.88 mu/ml, respectively (normal, 1.01 mu/ml and 1.07 mu/ml, respectively). The ratio of activity to antigen in uremic plasma was 0.67 (normal, 1.05). The mean platelet von Willebrand factor antigen and activity in the uremic patients was decreased (0.26 and 0.50 mu/10(9) platelets, respectively) compared with normal patients (0.46 and 0.93 mu/10(9) platelets, respectively). The oligomeric structure of the uremic plasma von Willebrand factor lacked the largest multimers. Collection of the blood for analysis in several protease inhibitors and/or EDTA did not change the multimeric structure. The von Willebrand factor multimeric structure of platelets from uremic patients was normal. The ristocetin-induced platelet aggregation of the uremic platelet-rich plasma was decreased compared with normal plasma samples. Thrombin and ristocetin-induced binding of normal von Willebrand factor to uremic patients' platelets was indistinguishable from the binding to normal platelets. CONCLUSION: These data suggest that the uremic platelet-binding sites for von Willebrand factor are intact and that the defect in ristocetin-induced platelet aggregation is most likely plasmatic in nature. At least one plasmatic defect was the observed reduction or absence of the largest plasma von Willebrand factor multimer in uremic patients. The platelet von Willebrand content was significantly decreased. These defects may play a role in the prolonged bleeding time and the clinical bleeding observed in patients with uremia.

Bleeding Time↗
PubMed1986

Necrotizing systemic vasculitis with features of both Wegener's granulomatosis and Churg-Strauss vasculitis.

We describe a patient who had nasal biopsy-demonstrated eosinophilic vasculitis and renal biopsy-demonstrated necrotizing glomerulonephritis with tissue eosinophilia. Despite corticosteroid therapy, the patient's renal function deteriorated, and nodular pulmonary infiltrates developed. Both conditions responded dramatically when cyclophosphamide was added to the treatment regimen. The renal disease activity was monitored with the aid of cytodiagnostic urinalysis, a technique of limited, albeit well-established, validity in monitoring renal allograft patients for signs of tissue rejection. This technique provided an improved, semi-quantitative method for examining urine sediment and, in this patient, was helpful as a measure of renal disease activity.

Adult↗