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Biomedical subjects

William D Dupont

Publications and source records attributed to William D Dupont.

16 recordsLinked to original sources
PubMed2006

Excellent survival, cancer type, and Nottingham grade after atypical lobular hyperplasia on initial breast biopsy.

BACKGROUND: Atypical lobular hyperplasia (ALH) is associated with a 10% to 20% risk of subsequent invasive carcinoma, primarily in the ipsilateral breast. Nottingham grading, special tumor types, and survival after invasive cancer diagnosis were analyzed consistently for the first time. METHODS: A longitudinal follow-up study of 252 women who underwent 261 benign surgical biopsies between 1950 and 1985 with a diagnosis of ALH was undertaken. Subsequent invasive breast cancers were graded and subtyped based on histologic features and the cohort assessed for cancer survival. RESULTS: Forty-eight (19%) women developed invasive breast cancer at an average of 15.1 years. Twenty (42%) of the tumors were special subtype tumors with good prognosis. By an average of 13 years after invasive cancer diagnosis, 2 (10%) of 20 women with special type and variant tumors had died of breast cancer, compared with 9 (32%) of 28 women with tumors of no special type (24 tumors) or an unknown type (4 tumors). Only 1 patient with a tumor of low Nottingham grade died of breast cancer. CONCLUSIONS: ALH is a nonobligate cancer precursor associated with a moderate risk of breast cancer and predicts that later cancers are associated with overall excellent survival. Nearly half of the subsequent cancers show classic or variant patterns of special types with a good prognosis and the majority are of low or intermediate combined histologic grade. Treatment of women with ALH should be influenced by their modest elevation in breast cancer risk and the good prognosis and low mortality of many of these cancers.

Biopsy↗
PubMed2006

Interdependence of radial scar and proliferative disease with respect to invasive breast carcinoma risk in patients with benign breast biopsies.

BACKGROUND: Radial scars (RS) are benign breast lesions that have been implicated as independent risk factors for invasive breast carcinoma (IBC). METHODS: A retrospective cohort study of 9556 women who underwent biopsy between 1950-1986 and enrolled in the Nashville Breast Cohort was performed to investigate the association between RS in a benign breast biopsy and the risk of IBC. The risk associated with RS and coexistent proliferative disease (PD) was assessed adjusting for age at biopsy using a Cox hazards regression analysis with time-dependent covariates. RESULTS: RS were identified in 880 women (9.2%). The average follow-up time was 20.4 years. Sixty-two women (7.0%) with RS developed IBC compared with 5.5% of controls. The relative risk of IBC associated with RS was 1.82 (95% confidence interval [95% CI], 1.2-2.7) at 10 years. Restricting the analysis to women age > 49 years increased the risk to 2.14 (95% CI, 0.6-2.8). These risks decreased with increasing years of follow-up. Approximately 92% of women with RS also had PD, but RS were present in only 1.3% of biopsies without PD. Analyses stratifying relative risk with regard to PD found RS to minimally elevate the relative risk of subsequent IBC. CONCLUSIONS: RS in the absence of PD is uncommon. Although the presence of RS in a benign breast biopsy mildly elevates the risk of IBC risk, the current analysis indicated that this risk can be largely attributed to the category of coexistent PD. In women with both RS and atypical hyperplasia, recommendations for interventions beyond biopsy should be based on the extent of atypical hyperplasia.

Adult↗
PubMed2006

Relationship between plasma S-adenosylhomocysteine concentration and glomerular filtration rate in children.

S-Adenosylhomocysteine (SAH) is the metabolic precursor of all the homocysteine (Hcy) produced in the body. It is formed by the enzyme SAH hydrolase in a reversible reaction. In a previous study we have shown that plasma SAH is a more sensitive indicator of the risk for cardiovascular disease, and in a second study involving patients with renal disease, we also showed that it is a more sensitive indicator of renal insufficiency than plasma Hcy. However, in the latter study, the patients with renal disease were older and had a variety of other diseases such as diabetes and primary hypertension, which are associated with vascular disease and which could reduce renal function by involvement of the kidneys. Our objective was to rule out these complicating factors as the cause of the elevated SAH in renal disease and determine whether renal insufficiency alone was the cause of the elevated SAH. We therefore measured SAH, Hcy, folate, and vitamin B12 in 23 patients between the ages of 1 and 18 years with a wide range of renal function, but who had none of these complicating factors. Glomerular filtration rate (GFR) was calculated using serum creatinine according to the Schwartz formula. None of the children were deficient in folate or vitamin B12. After adjusting for age, folate, and vitamin B12, there was a modest and insignificant decrease of 0.033 micromol/L of Hcy associated with an increase of 1 mL/min of GFR (95% confidence interval, -0.066 to 0.0002). However, there was a strong and statistically significant association between log(SAH) and log(GFR): P < .0005, R2 = 0.76. This result suggests that plasma SAH rather than Hcy is the metabolite primarily affected in renal disease. We suggest that plasma Hcy elevations that have been linked to vascular disease may be due to elevated SAH resulting from renal insufficiency.

Adolescent↗
PubMed2006

Quality-of-life impact of non-neoplastic voice disorders: a meta-analysis.

OBJECTIVES: We undertook to explore the relationship between non-neoplastic voice disorders and patients' quality of life. METHODS: A PubMed search (1966 to 2003) for the terms Voice Handicap Index (VHI), Short Form-36 (SF-36), voice disorders, voice quality, treatment outcome, voice outcome, quality of life, and questionnaires was performed. Raw data were obtained whenever possible. Studies were analyzed by meta-analysis techniques. RESULTS: Of 54 VHI studies identified, 11 were excluded, and of 21 SF-36 studies, 7 were excluded for incomplete data, non-English language, measuring malignant disease, or duplicate publication. Patients with neurologic and inflammatory or traumatic laryngeal disease had worse VHI scores than controls, and those with neurologic laryngeal disease had the most severe impairment (p < .001, Kruskal-Wallis analysis of variance; p < .05, Dunn's method of multiple comparisons). Those with neurologic laryngeal disease had worse SF-36 subdomain scores than did controls in 6 of 8 subdomains (p < .03, Kruskal-Wallis analysis of variance; p < .05, Dunn's method of multiple comparisons). Both patients with neurologic disease and patients with inflammatory or traumatic laryngeal disorders had changes in SF-36 subdomains similar to those of patients with other chronic disease states. CONCLUSIONS: Non-neoplastic voice disorders adversely impact patients' voice-related and general quality of life, and neurologic voice disorders have the greatest impact.

Analysis of Variance↗
PubMed2006

Voice-related quality of life in T1 glottic cancer: irradiation versus endoscopic excision.

OBJECTIVES: Several studies have explored posttreatment voice outcomes for early glottic cancer with varying results. To further clarify the voice-related quality of life (QOL) of T1 glottic cancer patients treated by external beam radiotherapy (EBRT) compared to endoscopic carbon dioxide laser excision (CLE), we performed a meta-analysis. METHODS: We performed a meta-analysis review for the years 1966 to 2005 for the Voice Handicap Index (VHI), laryngeal cancer, voice outcome, voice quality, and quality of life. Studies in which the VHI was assessed at least 3 months after treatment for T1 glottic cancer were identified and analyzed by meta-analysis techniques. RESULTS: Six studies with 208 patients (6 T1b and 202 T1a) treated with CLE and 91 patients (6 T1b and 85 T1a) treated with EBRT were identified. The posttreatment VHI scores were similar for the EBRT- and CLE-treated patients (p = .1, Wilcoxon rank sum test). CONCLUSIONS: We conclude that CLE and EBRT provide comparable levels of voice handicap for patients with T1 glottic cancer.

Endoscopy↗
PubMed2006

Estimating influenza hospitalizations among children.

Although influenza causes more hospitalizations and deaths among American children than any other vaccine-preventable disease, deriving accurate population-based estimates of disease impact is challenging. Using 2 independent surveillance systems, we performed a capture-recapture analysis to estimate influenza-associated hospitalizations in children in Davidson County, Tennessee, during the 2003-2004 influenza season. The New Vaccine Surveillance Network (NVSN) enrolled children hospitalized with respiratory symptoms or fever and tested them for influenza. The Tennessee Emerging Infections Program (EIP) identified inpatients with positive influenza diagnostic test results through review of laboratory and infection control logs. The hospitalization rate estimated from the capture-recapture analysis in children <5 years of age was 2.4 per 1,000 (95% confidence interval 1.8-3.8). When NVSN estimates were compared with capture-recapture estimates, NVSN found 84% of community-acquired cases, EIP found 64% of cases in which an influenza rapid test was performed, and the overall sensitivity of NVSN and EIP for influenza hospitalizations was 73% and 38%, respectively.

Child, Preschool↗
PubMed2005

The natural history of low-grade ductal carcinoma in situ of the breast in women treated by biopsy only revealed over 30 years of long-term follow-up.

BACKGROUND: Opportunities to study the natural history of ductal carcinoma in situ (DCIS) are rare. A few studies of incompletely excised lesions in the premammographic era now recognized as DCIS have provided critical insights into its proclivity for local recurrence in the original site. At the time the biopsies in the current study were originally examined, small DCIS was not diagnosed and, by default, these women were treated by biopsy only. METHODS: The authors report the latest results from a follow-up study, which was published originally in 1982, of 28 women with low-grade DCIS who were treated by biopsy only. These women were from a large, prospectively identified, completely characterized cohort. RESULTS: Eleven of 28 women developed invasive breast carcinoma (IBC), all in the same breast and quadrant from which their low-grade DCIS biopsy was taken. Seven IBCs were diagnosed within 10 years of the DCIS biopsy, 1 was diagnosed within 12 years of the DCIS biopsy, and the remaining 3 IBCs were diagnosed over 23-42 years. Five of these women, including 1 woman who developed IBC 29 years after her DCIS biopsy, developed distant metastasis, which resulted in death 1-7 years after the diagnosis of IBC. CONCLUSIONS: The natural history of low-grade DCIS can extend greater than 4 decades, with IBC developing at the same site as the previous DCIS in the majority of women. This natural history differs markedly from that of patients with high-grade DCIS and from the outcome of patients with any completely delimited DCIS excised to negative margins.

Adult↗
PubMed2005

Effect of CPOE user interface design on user-initiated access to educational and patient information during clinical care.

OBJECTIVE: Authors evaluated whether displaying context sensitive links to infrequently accessed educational materials and patient information via the user interface of an inpatient computerized care provider order entry (CPOE) system would affect access rates to the materials. DESIGN: The CPOE of Vanderbilt University Hospital (VUH) included "baseline" clinical decision support advice for safety and quality. Authors augmented this with seven new primarily educational decision support features. A prospective, randomized, controlled trial compared clinicians' utilization rates for the new materials via two interfaces. Control subjects could access study-related decision support from a menu in the standard CPOE interface. Intervention subjects received active notification when study-related decision support was available through context sensitive, visibly highlighted, selectable hyperlinks. MEASUREMENTS: Rates of opportunities to access and utilization of study-related decision support materials from April 1999 through March 2000 on seven VUH Internal Medicine wards. RESULTS: During 4,466 intervention subject-days, there were 240,504 (53.9/subject-day) opportunities for study-related decision support, while during 3,397 control subject-days, there were 178,235 (52.5/subject-day) opportunities for such decision support, respectively (p = 0.11). Individual intervention subjects accessed the decision support features at least once on 3.8% of subject-days logged on (278 responses); controls accessed it at least once on 0.6% of subject-days (18 responses), with a response rate ratio adjusted for decision support frequency of 9.17 (95% confidence interval 4.6-18, p < 0.0005). On average, intervention subjects accessed study-related decision support materials once every 16 days individually and once every 1.26 days in aggregate. CONCLUSION: Highlighting availability of context-sensitive educational materials and patient information through visible hyperlinks significantly increased utilization rates for study-related decision support when compared to "standard" VUH CPOE methods, although absolute response rates were low.

Decision Making, Computer-Assisted↗
PubMed2005

Breast cancer risk associated with estrogen receptor expression in epithelial hyperplasia lacking atypia and adjacent lobular units.

Estrogen is associated with many epidemiologic risk factors for invasive breast cancer. Cells that express estrogen receptors (ERs) in epithelial hyperplasia lacking atypia (EHLA) may influence breast cancer progression. We conducted a nested case-control study of 268 women with biopsy-confirmed EHLA to determine whether immunohistochemical expression of ERalpha in EHLA affects subsequent breast cancer risk. Study subjects could not have a prior or current history of breast cancer or atypical hyperplasia. Immunohistochemical stains in individual lesions and adjacent normal lobules were considered positive if >or= 10% of epithelial cells stained for ERalpha. The risk of invasive breast cancer in EHLA patients with ERalpha-positive normal lobules was twice that of other EHLA patients (95% CI = 1.0-3.8). This risk was not affected by the ERalpha status of EHLA lesions. ERalpha expression in adjacent normal lobules increases the moderate breast cancer risk previously associated with EHLA.

Breast Neoplasms↗
PubMed2005

Immunohistochemical expression of estrogen receptor in enlarged lobular units with columnar alteration in benign breast biopsies: a nested case-control study.

The prognostic and therapeutic implications of estrogen receptor (ER) status in breast cancer are well known. Whether ER status plays a role in benign breast lesions and the progression to malignancy has not been proven. Enlarged lobular units with columnar alteration (ELUCA), also known as unfolded lobular units, have been associated with mild elevations in subsequent breast cancer risk. We examined the association of ERalpha expression in ELUCA with invasive breast cancer risk. A nested case-control study was performed of women with ELUCA who had undergone benign breast surgery. Eighty-two women who developed invasive breast cancer on follow-up were matched by age and year of biopsy with 166 women who did not develop invasive breast cancer. Entry biopsies were stained for ERalpha (clone 6F11) without knowledge of subsequent cancer outcome. ELUCA lesions were scored as positive if greater than 10% of epithelial nuclei stained with ERalpha and at least one ELUCA contained >50% of cells staining for ERalpha. Relative risks of breast cancer were estimated by odds ratios derived from conditional logistic regression analyses. Thirty-nine percent of cases and 56% of controls had positive ERalpha staining in ELUCA. The relative risk of invasive breast cancer in women with ERalpha-negative ELUCA was 1.85 times that of women with ERalpha-positive lesions (95% confidence interval, 1.0-3.4, P=0.04). The presence of ERalpha staining in women with ELUCA is associated with a lower risk of developing subsequent invasive carcinoma. These findings have implications for risk assessment in benign breast biopsies and are of particular interest given the controversy currently surrounding hormone replacement therapy.

Adenocarcinoma↗
PubMed2005

Adenomyoepithelioma: clinical, histologic, and immunohistologic evaluation of a series of related lesions.

Adenomyoepithelioma, strictly defined, is a proliferation of both epithelial and myoepithelial elements. The broad range of lesions that may fall under this umbrella, however, may be quite diverse. The diagnostic confusion surrounding this entity and its prognostic implications have led to a diagnosis by default as malignant and to overtreatment of some patients. We evaluated available material from a series of 35 women whose slides were seen in consultation and who were diagnosed with adenomyoepithelioma or a closely related lesion. This comprehensive review of the varied histology of adenomyoepithelioma and similar lesions and their immunohistochemical properties will assist general pathologists in evaluating these sometimes difficult lesions. Follow-up and treatment information demonstrates their benignity. Architecture and histologic features should be combined with immunohistochemistry when determining categorization.

Adenomyoma↗
PubMed2004

The impact of peer management on test-ordering behavior.

BACKGROUND: Laboratory testing of hospitalized patients, although essential, can be expensive and sometimes excessive. Attempts to reduce unnecessary testing have often been difficult to implement or sustain. OBJECTIVE: Use of peer management through a resource utilization committee (RUC) to favorably modify test-ordering behavior in a large academic medical center. DESIGN: Interrupted time-series study. SETTING: Medical center with inpatient care provider order entry (CPOE) system and database of ordered tests. PARTICIPANTS: Predominantly housestaff physicians but all clinical staff (attending physicians, housestaff, medical students, nurses, advance practice nurses, and other clinical staff) at Vanderbilt University Hospital who used CPOE systems. INTERVENTION: The RUC analyzed the ordering habits of providers during previous years and made 2 interventions by modifying software for the CPOE system. The committee first initiated a daily prompt in the system that asked providers whether they wanted to discontinue tests scheduled beyond 72 hours. After evaluating this first intervention, the committee further constrained testing options by unbundling serum metabolic panel tests (sodium, potassium, chloride, bicarbonate, glucose, blood urea nitrogen, and creatinine tests) into single components and by reducing the ease of repeating targeted tests (including electrolyte, blood urea nitrogen, creatinine, and glucose tests; electrocardiography; and portable chest radiography). MEASUREMENTS: Pre- and postintervention volumes of tests; proportion of patients with abnormal targeted chemistry levels after 48 hours; rates of repeated admission, transfer to intensive care units, and mortality; adjusted coefficient of variation for test ordering; and length of stay. RESULTS: Voluntary reduction of testing beyond 72 hours (first intervention) decreased orders for metabolic panel component tests by 24% (P = 0.02) and electrocardiograms by 57% (P = 0.006) but not orders for portable chest radiographs. Prospective constraints on recurrent test ordering with panel unbundling (second intervention) produced an additional decrease of 51% for metabolic panel component tests (P < 0.001) and 16% for portable chest radiographs (P = 0.03). Incidence of patients with abnormal targeted blood chemistry levels after 48 hours decreased after the intervention (P = 0.02). Postintervention-adjusted coefficients of variation decreased for metabolic panel component tests (P = 0.03) and electrocardiography (P = 0.04). Rates of (adjusted) monthly readmission, transfers to intensive care units, hospital length of stay, and mortality were unchanged. LIMITATIONS: Other activities occurring during the time period of the interventions might have influenced some test-ordering behaviors, and we assessed effects on only a limited number of commonly ordered tests. CONCLUSIONS: Peer management reduced provider variability by addressing the imperfect ability of clinicians to rescind testing in a timely manner. Hospitals with growing health care costs can improve their resource utilization through peer management of testing behaviors by using CPOE systems.

Clinical Laboratory Techniques↗
PubMed2004

Association of homozygous wild-type glutathione S-transferase M1 genotype with increased breast cancer risk.

More than 500 studies have examined the association of the glutathione S-transferase M1 (GSTM1) genotype with various malignancies yielding inconsistent results. The genotyping was based on a PCR assay that identified the GSTM1 null (-/-) genotype but did not distinguish homozygous wild-type (+/+) and heterozygous (+/-) individuals. We developed an assay that allowed the definition of +/+, +/-, and -/- genotypes by separate identification of wild-type and null alleles, which were found with frequencies of 0.225 and 0.775, respectively, in Caucasian women. We applied the new assay to a breast cancer case-control study and identified the +/+ genotype in 14 (6.9%) of 202 control subjects compared with 37 (18.2%) of 203 patients. Compared with women with the -/- genotype, the relative risk of breast cancer for the +/+ genotype was 2.83 (95% confidence interval, 1.45-5.59; P = 0.002), suggesting a protective effect of the GSTM1 deletion.

Breast Neoplasms↗
PubMed2003

Atypical lobular hyperplasia as a unilateral predictor of breast cancer risk: a retrospective cohort study.

BACKGROUND: Clinical decisions about atypical lobular hyperplasia are based on the belief that later invasive breast-cancer risk is equal in both breasts. We aimed to show laterality and subsequent risk implications of invasive breast cancer in women with atypical lobular hyperplasia. METHODS: We did a retrospective cohort study of 252 women who had undergone 261 benign surgical biopsies that showed atypical lobular hyperplasia from 1950 to 1985, as part of the Nashville Breast Studies. Primary outcomes were development of invasive breast cancer and laterality of cancer compared with side of the biopsied breast. FINDINGS: 50 (20%) of 252 women treated by biopsy only developed invasive breast cancer. Relative risk of breast cancer in women with atypical lobular hyperplasia was 3.1 (95% CI 2.3-4.3, p<0.0001). Of these 50 women, the breast with invasive cancer was the same breast diagnosed with atypical lobular hyperplasia (ipsilateral) in 34 (68%) and the contralateral breast in 12 (24%). The ratio of ipsilateral/ contralateral cancers for atypical lobular hyperplasia without other atypical lesions was 17/5. For six women with atypical lobular hyperplasia plus atypical ductal hyperplasia, the ratio was 1/1. INTERPRETATION: Invasive carcinoma after atypical lobular hyperplasia is about three times more likely to arise in the breast diagnosed with atypical lobular hyperplasia than in the opposite breast without these initial findings. Our findings suggest a model of premalignancy for atypical lobular hyperplasia intermediate between a local precursor and a generalised risk for both breasts. See Commentary page 96

Aged↗
PubMed2002

Albumin and furosemide therapy in hypoproteinemic patients with acute lung injury.

OBJECTIVE: Hypoproteinemia, fluid retention, and weight gain are associated with development of acute lung injury and mortality in critically ill patients, without proof of cause and effect. We designed a clinical trial to determine whether diuresis and colloid replacement in hypoproteinemic patients with acute lung injury would improve pulmonary physiology. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: All adult intensive care units from two university hospitals. PATIENTS: Thirty-seven mechanically-ventilated patients with acute lung injury and serum total protein </=5.0 g/dL. INTERVENTIONS: Five-day protocolized regimen of 25 g of human serum albumin every 8 hrs with continuous infusion furosemide, or dual placebo, targeted to diuresis, weight loss, and serum total protein. MEASUREMENTS AND MAIN RESULTS: Measured outcomes included change in weight, serum total protein, fluid balance, hemodynamics, respiratory system compliance, and oxygenation. Baseline characteristics were similar between groups (treatment, n = 19; control, n = 18), with trauma being the major cause of acute lung injury. Diuresis and weight loss over 5 days (5.3 kg more in the treatment group, p =.04) was accompanied by improvements in the Pao2/Fio2 ratio in the treatment group within 24 hrs (from 171 to 236, p =.02). Respiratory mechanics were unchanged. Mean arterial pressure increased from 80 to 88 mm Hg (p =.10), and heart rate decreased from 110 to 95 beats/min (p =.008) over time in the treatment group. No difference in mortality was observed, with favorable trends in measures of intensive care. CONCLUSIONS: Albumin and furosemide therapy improves fluid balance, oxygenation, and hemodynamics in hypoproteinemic patients with acute lung injury. Determining the effect of this simple therapy on cost, outcomes, and other patient populations requires further study.

Adult↗