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Biomedical subjects

R Moore

Publications and source records attributed to R Moore.

At least 127 records · Page 7Linked to original sources

Multicenter evaluation of the Bayer Immuno I CA 15-3 assay.

We conducted a multicenter evaluation of the analytical and clinical features of the automated Bayer Immuno 1 CA 15-3 assay and compared assay performance to two manual tests. Results of the 10-day imprecision study of the Bayer Immuno 1 assay pooled across four evaluation sites and three lots of reagent produced total CV < or = 4%. Lot-to-lot reproducibility for 26 different lots of reagents and calibrators manufactured over a 2-year period was demonstrated (CV, 1.1%). Results for the Bayer Immuno 1 assay correlated well with the Biomira TRUQUANT BR 27.29 and Centocor CA 15-3 RIAs (r > or = 0.94). The upper limit of the reference interval for the Bayer Immuno 1 assay was 35.9 kilounits/L (35.9 units/mL); values were similar for all methods. Longitudinal monitoring of healthy women yielded assay values with an average CV of 11% and 21% for the Bayer Immuno 1 and Biomira assays, respectively. The Bayer Immuno 1 assay demonstrated the analytical features, intermethod correlation, and long-term performance characteristics that are essential for longitudinal monitoring of breast cancer patients.

Adolescent↗

Characterization of cardiac troponin subunit release into serum after acute myocardial infarction and comparison of assays for troponin T and I. American Association for Clinical Chemistry Subcommittee on cTnI Standardization.

We examined the release of cardiac troponin T (cTnT) and I (cTnI) into the blood of patients after acute myocardial infarction (AMI). Three postAMI serum samples were applied in separate analytical runs onto a calibrated gel filtration column (Sephacryl S-200), and the proteins were separated by molecular weight. Using commercial cTnT and cTnI assays measured on collected fractions, we found that troponin was released into blood as a ternary complex of cTnT-I-C, a binary complex of cTnI-C, and free cTnT, with no free cTnI within the limits of the analytical methodologies. The serum samples were also examined after incubation with EDTA and heparin. EDTA broke up troponin complexes into individual subunits, whereas heparin had no effect on the assays tested. We added free cTnC subunits to 24 AMI serum samples and found no marked increase in the total cTnI concentrations, using an immunoassay that gave higher values for the cTnI-C complex than free cTnI. To characterize the cross-reactivity of cTnT and cTnI assays, purified troponin standards in nine different forms were prepared, added to serum and plasma pools, and tested in nine quantitative commercial and pre-market assays for cTnI and one approved assay for cTnT. All nine cTnI assays recognized each of the troponin I forms (complexed and free). In five of these assays, the relative responses for cTnI were nearly equimolar. For the remainder, the response was substantially greater for complexed cTnI than for free cTnI. Moreover, there was a substantial difference in the absolute concentration of results between cTnI assays. The commercial cTnT assay recognized binary and ternary complexes of troponin on a near equimolar basis. We conclude that all assays are useful for detection of cardiac injury. However, there are differences in absolute cTnI results due to a lack of mass standardization and heterogeneity in the cross-reactivities of antibodies to various troponin I forms.

Biomarkers↗

Perceived need for local anesthesia in tooth drilling among Anglo-Americans, Chinese, and Scandinavians.

This study explored ethnic differences in perceptions of pain and the need for local anesthesia for tooth drilling among age- and gender-matched Anglo-American, Mandarin Chinese, and Scandinavian dentists (n = 129) and adult patients (n = 396) using a systematic qualitative research strategy. Semistructured qualitative interviews determined: (a) the relative frequency of use or nonuse of anesthetic for similarly specified tooth drilling, (b) the reasons for nonuse of anesthetic as reported by dentists about their patients, and (c) the distribution of reasons for not using anesthetic. American dentists (n = 51) reported that about 1% of their adult patients did not use anesthetic compared with 90% among Chinese (n = 31) and 37.5% among Scandinavian dentists (n = 40). Of patients, Americans (n = 112) reported 6% nonuse of anesthetic for tooth drilling compared with 90% of 159 Chinese and 54% of 125 Scandinavians. Reasons among Anglo-Americans and Scandinavians were similar (ranked): the sensation was tolerable, to avoid numb feelings afterwards, and fear of injections. Danish patients were an exception; the fact that they had paid extra and out-of-pocket for anesthetic ranked second. In contrast, Chinese dentists made their decisions not to use anesthetics because they explained drilling as only a suan or "sourish" sensation, whereas injections were described as "painful." It was concluded that ethnic pain beliefs and differences in health-care systems are powerful psychosocial variables that affect pain perception and the perceived need for anesthetic.

Adult↗

Acute pain and use of local anesthesia: tooth drilling and childbirth labor pain beliefs among Anglo-Americans, Chinese, and Scandinavians.

Differences in ethnic beliefs about the perceived need for local anesthesia for tooth drilling and childbirth labor were surveyed among Anglo-Americans, Mandarin Chinese, and Scandinavians (89 dentists and 251 patients) matched for age, gender, and occupation. Subjects matched survey questionnaire items selected from previously reported interview results to estimate (a) their beliefs about the possible use of anesthetic for tooth drilling and labor pain compared with other possible remedies and (b) the choice of pain descriptors associated with the use of nonuse of anesthetic, including descriptions of injection pain. Multidimensional scaling, Gamma, and Chi-square statistics as well as odds ratios and Spearman's correlations were employed in the analysis. Seventy-seven percent of American informants reported the use of anesthetics as possible remedies for drilling and 51% reported the use of anesthetics for labor pain compared with 34% that reported the use of anesthetics among Chinese for drilling and 5% for labor pain and 70% among Scandinavians for drilling and 35% for labor pain. Most Americans and Swedes described tooth-drilling sensations as sharp, most Chinese used descriptors such as sharp and "sourish" (suan), and most Danes used words like shooting (jagende). By rank, Americans described labor pain as cramping, sharp, and excruciating, Chinese used words like sharp, intermittent, and horrible, Danes used words like shooting, tiring, and sharp, and Swedes used words like tiring, "good," yet horrible. Preferred pain descriptors for drilling, birth, and injection pains varied significantly by ethnicity. Results corroborated conclusions of a qualitative study about pain beliefs in relation to perceived needs for anesthetic in tooth drilling. Samples used to obtain the results were estimated to approach qualitative representativity for these urban ethnic groups.

Adult↗

Randomised trial of basiliximab versus placebo for control of acute cellular rejection in renal allograft recipients. CHIB 201 International Study Group.

BACKGROUND: Currently available immunosuppressive regimens for cadaver-kidney recipients are far from ideal because acute-rejection episodes occur in about 30% to 50% of these patients. In the phase III study described here we assessed the ability of basiliximab, a chimeric interleukin (IL)-2 receptor monoclonal antibody, to prevent acute-rejection episodes in renal allograft recipients. METHODS: 380 adult recipients of a primary cadaveric kidney transplant were randomly allocated, in this double-blind trial, to receive a 20 mg infusion of basiliximab on day 0 (day of surgery) and on day 4, to provide IL-2-receptor suppression for 4-6 weeks (n=193), or to receive placebo (n=187). Both groups received baseline dual immunosuppressive therapy with cyclosporin and steroids throughout the study. The primary outcome measure was incidence of acute-rejection episodes during the 6 months after transplantation. Safety and tolerability were monitored over the 12 months of the study. FINDINGS: 376 patients were eligible for intention-to-treat analysis (basiliximab, n=190; placebo, n=186). No significant differences in patient characteristics were apparent. The incidence of biopsy-confirmed acute rejection 6 months after transplantation was 51 (29.8%) of 171 in the basiliximab group compared with 73 (44.0%) of 166 in the placebo group (32% reduction; 14.2% difference [95% Kaplan-Meier CIs 3% to 24%], p=0.012). The incidence of steroid-resistant first rejection episodes that required antibody therapy was significantly lower in the basiliximab group (10% vs 23.1%, 13.1% difference [5.4% to 20.8%], p<0.001). At weeks 2 and 4 post-transplantation, the mean daily dose of steroids was significantly higher in the placebo group (p<0.001 with one-way analysis of variance). The incidence of graft loss at 12 months post-transplantation was 23 (12.1%) of 190 in the basiliximab group and 25 (13.4%) of 186 in the placebo group (1.3% difference [-5% to 9%], p=0.591). The incidence of infection and other adverse events was similar in the two treatment groups. The acute tolerability of basiliximab was excellent, with no evidence of cytokine-release syndrome. 14 deaths (basiliximab n=9; placebo n=5; -2.0% difference [-6% to 2%], p=0.293) occurred during the 12-month study and a further three deaths (basiliximab n=1; placebo n=2) occurred within the 380-day cut-off period. One post-transplantation lymphoproliferative disorder was recorded in each group. INTERPRETATION: Prophylaxis with 40 mg basiliximab reduces the incidence of acute rejection episodes significantly, with no clinically relevant safety or tolerability concerns.

Acute Disease↗

Developmental exposure to diethylstilbestrol elicits demethylation of estrogen-responsive lactoferrin gene in mouse uterus.

Alteration of DNA demethylation in five CpG sites (-547, -533, -475, -464, and -454) immediately upstream from the estrogen response element of lactoferrin promoter was determined in the uteri of immature (17-day-old) and mature (21- and 30-day-old) mice treated neonatally with DES. Only the CpG/-464 was found to be abnormally demethylated by diethylstilbestrol (DES) treatment in the mature uteri. This abnormal demethylation occurred in specific response to DES in neonatal mice, because DES injected into the 30-day-old mature mice did not demethylate CpG/-464. This site, however, remained methylated in the neonatally DES-treated/ovariectomized mice, indicating that this DES-elicited demethylation is under hormonal control. Thus, neonatal DES treatment appeared to imprint an abnormal, site-specific demethylation of CpG/-464, which requires ovarian hormones to occur in adult mice. Moreover, the demethylation was maintained in uterine tumors of the neonatally DES-treated mice. This mode of demethylation is reminiscent of uterine tumor formation, which also depends on both neonatal DES exposure and ovarian hormone stimulation in adulthood. Thus, neonatal DES treatment may induce tumor formation as well as demethylation through a common cellular process.

Age Factors↗

Comparison of clinical characteristics and frequency of implantable defibrillator use between randomized patients in the Antiarrhythmics Vs Implantable Defibrillators (AVID) trial and nonrandomized registry patients.

In the Antiarrhythmics Vs Implantable Defibrillators (AVID) trial, all patients who meet the study entry criteria are followed in a registry. During the period between June 1993 and June 1995, of 1,117 patients who were enrolled in the registry and met the study entry criteria, 476 were randomized to receive either implantable cardioverter-defibrillators (ICDs) or drug therapy (amiodarone or sotalol), and 641 patients were not randomized for a variety of reasons including: patient refusal (42%); physician refusal (43%); concerns about ability to maintain follow-up over several years (10%), and others (6%). There were no significant differences between the 476 randomized and 641 nonrandomized patients with regard to clinical characteristics, left ventricular function, history of congestive heart failure, medical history, and previous cardiac procedures performed before the index event, except that randomized patients were slightly older (65 vs 62 years) and had a slightly higher prevalence of coronary artery disease and previous myocardial infarction. The index event and location of the index event were not significantly different between the 2 groups. Although 14% of registry patients received neither ICD nor antiarrhythmic drug therapy, ICDs were no more frequently used in the registry patient than antiarrhythmic drugs (45% for ICD vs 42% for drugs). Thus, randomized AVID patients have very similar clinical characteristics, cardiac history, and presenting arrhythmias as to nonrandomized eligible patients. Therefore, the results of the AVID trial may be generalized for all patients with AVID-eligible arrhythmias.

Adolescent↗

Epidemiology of sepsis syndrome in 8 academic medical centers.

CONTEXT: Sepsis syndrome is a leading cause of mortality in hospitalized patients. However, few studies have described the epidemiology of sepsis syndrome in a hospitalwide population. OBJECTIVE: To describe the epidemiology of sepsis syndrome in the tertiary care hospital setting. DESIGN: Prospective, multi-institutional, observational study including 5-month follow-up. SETTING: Eight academic tertiary care centers. METHODS: Each center monitored a weighted random sample of intensive care unit (ICU) patients, non-ICU patients who had blood cultures drawn, and all patients who received a novel therapeutic agent or who died in an emergency department or ICU. Sepsis syndrome was defined as the presence of either a positive blood culture or the combination of fever, tachypnea, tachycardia, clinically suspected infection, and any 1 of 7 confirmatory criteria. Estimates of total cases expected annually were extrapolated from the number of cases, the period of observation, and the sampling fraction. RESULTS: From January 4, 1993, to April 2, 1994, 12759 patients were monitored and 1342 episodes of sepsis syndrome were documented. The extrapolated, weighted estimate of hospitalwide incidence (mean+/-95% confidence limit) of sepsis syndrome was 2.0+/-0.16 cases per 100 admissions, or 2.8+/-0.17 per 1000 patient-days. The unadjusted attack rate for sepsis syndrome between individual centers differed by as much as 3-fold, but after adjustment for institutional differences in organ transplant populations, variation from the expected number of cases was reduced to 2-fold and was not statistically significant overall. Patients in ICUs accounted for 59% of total extrapolated cases, non-ICU patients with positive blood cultures for 11%, and non-ICU patients with negative blood cultures for 30%. Septic shock was present at onset of sepsis syndrome in 25% of patients. Bloodstream infection was documented in 28%, with gram-positive organisms being the most frequent isolates. Mortality was 34% at 28 days and 45% at 5 months. CONCLUSIONS: Sepsis syndrome is common in academic hospitals, although the overall rates vary considerably with the patient population. A substantial fraction of cases occur outside ICUs. An understanding of the hospitalwide epidemiology of sepsis syndrome is vital for rational planning and treatment of hospitalized patients with sepsis syndrome, especially as new and expensive therapeutic agents become available.

Adult↗

A comparison of the inflammatory potential of particulates derived from two composite materials.

In order to develop total joint prostheses with moduli of elasticity close to bone while retaining excellent strength characteristics, composite materials are being developed. Composites consist of graphite fibers embedded in a polymer matrix. We studied the inflammatory potential of particulates derived from two composites with different matrix components, polysulfone (PFS) and polyetherketoneketone (PEKK), in the rat subcutaneous air pouch model. Neat components of the composites were studied separately in the air pouch. Particulates also were studied in culture using the macrophage cell line RAW 264.7, adherent synovial cells (ASC), and human polymorphonuclear neutrophils (PMNs). Particles derived from the PEKK-containing composite material consistently were less inflammatory than the PFS composite-derived particles, as measured by PMN infiltration, neutral metalloprotease activity, tumor necrosis factor (TNF) activity, and prostaglandin E2 (PGE2) accumulation. Results from the neat materials confirmed the findings in the composite-derived material. PEKK composite-derived material produced less TNF from macrophage cultures, but there were no significant differences noted in PGE2 production from ASC or in superoxide anion generation from PMNs. Particles from both PSF and PEKK produced minimal inflammatory responses in the rat subcutaneous air pouch. PEKK elicited a response virtually the same as the saline control and significantly less than that produced by particles of PSF.

Animals↗

Elevated synthesis of biglycan and decorin in an ovine annular lesion model of experimental disc degeneration.

The aim of this study was to extend our earlier observations on the changes that occur in the proteoglycans (PGs) of discs subjected to experimental injury to the annulus fibrosus (AF). We employed the alginate bead culture method to examine the metabolism of the dermatan sulphate (DS) containing PGs by cells derived from different regions of ovine discs that had been subjected to experimental annular injury. This was compared with the metabolism of the DS-PGs by cells isolated from equivalent regions of normal sham-operated discs. Six months after induction of the annular lesion, AF cells isolated from the lesion produced significantly higher levels of decorin and biglycan in alginate bead culture than did cells from equivalent zones of the controls. Decorin and biglycan were identified in culture media samples by immunoblotting, using specific antibodies (6-B-6, LF-96), and also by positive identification of their de-glycosylated core proteins. The core protein of the DS-PGs has been shown to inhibit type I/II collagen fibrillogenesis, to negatively regulate the action of transforming growth factor-beta (TGF-beta) and to diminish cellular proliferation in vitro; events which may be detrimental to tissue repair. The findings are therefore consistent with our previous observation the annular lesions in the avascular inner annulus have no capacity to heal.

Animals↗

Consensus analysis: reliability, validity, and informant accuracy in use of American and Mandarin Chinese pain descriptors.

A quantitative method for validating qualitative interview results and checking sample parameters is described and illustrated using common pain descriptions among a sample of Anglo-American and mandarin Chinese patients and dentists matched by age and gender. Assumptions were that subjects were members of a sociocultural group (e.g. ethnic or professional/lay) and answered questions independently about a monotonic domain (e.g. pain). Subjects answered 18 true/false items derived from and selected to reflect pain perceptions consistent with published and unpublished interview data. Estimates of consistency in use of descriptors within groups, validity of description, accuracy of individuals compared with others in their group, and minimum required sample size were calculated using Cronbach's alpha, factor analysis, and Bayesian probability. Ethnic and professional differences within and across groups were also tested using multidimensional scaling (MDS) and hypothesis testing. Consensus (consistency of subject response by group) was .99 among Anglo-Americans and .97 among Chinese. Mean subject accuracy was .81 for Americans and .57 for Chinese, indicating the need for larger numbers of Chinese to supplement each others' statements. However, larger numbers of subjects were recruited than actually required for each ethnic group at .95 confidence limits. MDS showed similarities in use of descriptors within ethnic groups, while there were differences (p < .001) between Chinese and American groups. Use of covalidating questionnaires that reflect results of qualitative interviews are recommended in order to estimate sample parameters such as intersubject agreement, individual subject accuracy, and minimum required sample sizes.

Adult↗

Conversion from cyclosporin to tacrolimus in a patient with prolonged acute tubular necrosis.

Acute tubular necrosis (ATN) is a common condition of following cadaveric renal transplantation with an incidence in many series of nearly 50%. The aetiology is uncertain; however, it would appear to be related to damage to the transplant kidney either prior to retrieval, During cold preservation or during re-warming of the kidney at the time of anastamotic construction. There is no specific therapy for ATN and treatment is comprised of an expectant policy with supportive dialysis and fluid restriction. Renal function improves in the majority of cases, though there may be delayed function for several weeks. We report a case of dialysis-dependent ATN that had persisted for 5 months following transplantation. Following conversion to tacrolimus there was immediate improvement in renal function, and after a month of tacrolimus therapy the patient was dialysis-independent.

Adult↗

Perirenal MR high signal--a new and sensitive indicator of acute ureteric obstruction.

PURPOSE: This study was carried out to determine the incidence of perirenal magnetic resonance (MR) high signal in acute ureteric obstruction as demonstrated by half-Fourier acquisition single shot turbo spin-echo (HASTE) MR. In addition, we evaluated the sensitivity of this perirenal MR high signal as a predictor of acute ureteric obstruction. MATERIALS AND METHODS: A prospective evaluation of 55 consecutive patients with suspected ureteric obstruction was carried out using the HASTE MR sequence. Images were compared to concurrent IV urography (IVU) or to computed tomography (CT) where these were available. Acute and chronic ureteric obstruction were differentiated by clinical evaluation. RESULTS: Forty-one patients had obstructed kidneys. HASTE MR accurately predicted the presence of acute ureteric obstruction in 20/23 (87%) based on presence of perirenal MR high signal. None of these showed evidence of contrast medium extravasation on the concurrent i.v. urogram. 15/18 (83%) chronically obstructed kidneys demonstrated no perirenal high signal on HASTE MR, and the remaining three showed only a trace of perirenal high signal. CT showed perirenal stranding in only 2/8 patients with acutely obstructed kidneys. CONCLUSION: In acute ureteric obstruction, HASTE MR shows perirenal high signal intensity much more commonly than IVU shows extravasation or CT showing perirenal stranding. The origin of this MR signal is uncertain but may represent oedema, lymphatic distension or free fluid from forniceal rupture. HASTE MR can accurately distinguish between acute and chronic ureteric obstruction based on the degree of perirenal high signal.

Acute Disease↗

Treatment of human prostate tumors PC-3 and TSU-PR1 with standard and investigational agents in SCID mice.

Both the PC-3 and the TSU-PR1 prostate tumor models were found to be satisfactory for chemotherapeutic investigations in ICR-SCID mice. The 30 to 60 mg fragments implanted took in all mice (as judged by 100% takes in the controls of all experiments as well as the passage mice). The tumor volume doubling time was 4.0 days for PC-3 and 2.5 days for TSU-PR1. Nine agents were evaluated IV against early stage subcutaneous PC-3 tumors, with Nano-piposulfan being the only agent highly active (4.9 log kill). Three other agents were moderately active: Taxol (1.5 log kill), Cryptophycin-8 (1.6 log kill), Vinblastine (1.0 log kill). Five agents were inactive: VP-16, Adriamycin, CisDDPt, 5-FUra, and Cyclophosphamide. Ten agents were evaluated IV against early stage subcutaneous TSU-PR1 tumors. Three agents were highly active, producing > 6 log kill and cures: Taxol (5/5 cures), Cryptophycin-8 (5/5 cures), Vinblastine (2/4 cures). Two other agents were moderately active: Nano-piposulfan (1.2 log kill), and Cyclophosphamide (1.1 log kill). Five agents were inactive: VP-16, Adriamycin, CisDDPt, 5-FUra, and BCNU. In part, activity was determined by the ability of the SCID mice to tolerate meaningful dosages of the agents. Agents producing granulocyte toxicity (e.g., Adriamycin) were poorly tolerated and appeared less active than expected. Vinblastine, producing little or no granulocyte toxicity was very well tolerated and appeared to be more active than expected.

Aged↗

Discovery of cryptophycin-1 and BCN-183577: examples of strategies and problems in the detection of antitumor activity in mice.

Historically, many new anticancer agents were first detected in a prescreen; usually consisting of a molecular/biochemical target or a cellular cytotoxicity assay. The agent then progressed to in vivo evaluation against transplanted human or mouse tumors. If the investigator had a large drug supply and ample resources, multiple tests were possible, with variations in tumor models, tumor and drug routes, dose-decrements, dose-schedules, number of groups, etc. However, in most large programs involving several hundred in vivo tests yearly, resource limitations and drug supply limitations have usually dictated a single trial. Under such restrictive conditions, we have implemented a flexible in vivo testing protocol. With this strategy, the tumor model is dictated by in vitro cellular sensitivity; drug route by water solubility (with water soluble agents injected intravenously); dosage decrement by drug supply, dose-schedule by toxicities encountered, etc. In this flexible design, many treatment parameters can be changed during the course of treatment (e.g., dose and schedule). The discovery of two active agents are presented (Cryptophycin-1, and Thioxanthone BCN 183577). Both were discovered by the intravenous route of administration. Both would have been missed if they were tested intraperitoneally, the usual drug route used in discovery protocols. It is also likely that they would have been missed with an easy to execute fixed protocol design, even if injected i.v.

Animals↗

Predicting bacteremia in patients with sepsis syndrome. Academic Medical Center Consortium Sepsis Project Working Group.

The goal of this study was to develop and validate clinical prediction rules for bacteremia and subtypes of bacteremia in patients with sepsis syndrome. Thus, a prospective cohort study, including a stratified random sample of 1342 episodes of sepsis syndrome, was done in eight academic tertiary care hospitals. The derivation set included 881 episodes, and the validation set included 461. Main outcome measures were bacteremia caused by any organism, gram-negative rods, gram-positive cocci, and fungal bloodstream infection. The spread in probability between low- and high-risk groups in the derivation sets was from 14.5% to 60.6% for bacteremia of any type, from 9.8% to 32.8% for gram-positive bacteremia, from 5.3% to 41.9% for gram-negative bacteremia, and from 0.6% to 26.1% for fungemia. Because the model for gram-positive bacteremia performed poorly, a model predicting Staphylococcus aureus bacteremia was developed; it performed better, with a low- to high-risk spread of from 2.6% to 21.0%. The prediction models allow stratification of patients according to risk of bloodstream infections; their clinical utility remains to be demonstrated.

Adult↗

Digital tomosynthesis in breast imaging.

PURPOSE: To describe and evaluate a method of tomosynthesis breast imaging with a full-field digital mammographic system. MATERIALS AND METHODS: In this tomosynthesis method, low-radiation-dose images were acquired as the x-ray source was moved in an arc above the stationary breast and digital detector. A step-and-expose method of imaging was used. Breast tomosynthesis and conventional images of two imaging phantoms and four mastectomy specimens were obtained. Three experienced readers scored the relative lesion visibility, lesion margin visibility, and confidence in the classification of six lesions. RESULTS: Tomosynthesis image-reconstruction algorithms allow tomographic imaging of the entire breast from a single arc of the x-ray source and at a radiation dose comparable with that in single-view mammography. Except for images of a large mass in a fatty breast, the tomosynthesis images were superior to the conventional images. CONCLUSION: Digital mammographic systems make breast tomosynthesis possible. Tomosynthesis may improve the specificity of mammography with improved lesion margin visibility and may improve early breast cancer detection, especially in women with radiographically dense breasts.

Female↗