Evaluation of Quantra Hologic Volumetric Computerized Breast Density Software in Comparison With Manual Interpretation in a Diverse Population.

OBJECTIVE: Increased mammographic breast density is a well-established risk factor for breast cancer development, regardless of age or ethnic background. The current gold standard for categorizing breast density consists of a radiologist estimation of percent density according to the American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) criteria. This study compares paired qualitative interpretations of breast density on digital mammograms with quantitative measurement of density using Hologic's Food and Drug Administration-approved R2 Quantra volumetric breast density assessment tool. Our goal was to find the best cutoff value of Quantra-calculated breast density for stratifying patients accurately into high-risk and low-risk breast density categories. METHODS: Screening digital mammograms from 385 subjects, aged 18 to 64 years, were evaluated. These mammograms were interpreted by a radiologist using the ACR's BI-RADS density method, and had quantitative density measured using the R2 Quantra breast density assessment tool. The appropriate cutoff for breast density-based risk stratification using Quantra software was calculated using manually determined BI-RADS scores as a gold standard, in which scores of D3/D4 denoted high-risk densities and D1/D2 denoted low-risk densities. RESULTS: The best cutoff value for risk stratification using Quantra-calculated breast density was found to be 14.0%, yielding a sensitivity of 65%, specificity of 77%, and positive and negative predictive values of 75% and 69%, respectively. Under bootstrap analysis, the best cutoff value had a mean ± SD of 13.70% ± 0.89%. CONCLUSIONS: Our study is the first to publish on a North American population that assesses the accuracy of the R2 Quantra system at breast density stratification. Quantitative breast density measures will improve accuracy and reliability of density determination, assisting future researchers to accurately calculate breast cancer risks associated with density increase.

Factors Affecting Gynecologic and Sexual Assessment in Older Women: A Lesson for Primary Care Providers.

Guidelines for screening of cervical cancer and pelvic exams for older women have recently changed. These changes may have unexpected sequelae in women over 65 years of age. This manuscript provides a review of gynecologic screening recommendations for older women in the U.S. and potential ramifications of these recent changes. Peer reviewed guidelines from the American College of Obstetrics and Gynecology, U.S. Preventative Task Force Services, the American Cancer Society, The Centers for Disease Control, and multiple original research articles and reviews were reviewed for this manuscript. Women over 65 are at greatest risk to develop late stage diagnoses of cancers, pelvic organ disease, incontinence, and infections. Clinicians will need to acutely consider this fact when communicating and screening this population. We conclude that practitioners should be aware of the new guidelines and should consider including gynecologic health history and symptom analysis as part of annual exams in women of all ages.

Protective cardiovascular and renal actions of vitamin D and estrogen.

Both basic science and clinical studies support the concept that vitamin D deficiency is involved in the pathogenesis of cardiovascular and renal diseases through its association with diabetes, obesity, and hypertension. Understanding the underlying mechanisms may provide a rationale for advocating adequate intake of vitamin D and calcium in all populations, thereby preventing many chronic diseases. This review explores the effect of vitamin D deficiency in the development of cardiovascular and renal diseases, and the role of vitamin D supplementation on cardiovascular outcomes. In addition, it highlights the importance of vitamin D intake for the prevention of adverse long-term health consequences, and in ways to facilitate the management of cardiovascular disease. This is particularly true for African American and postmenopausal women, who are at added risk for cardiovascular disease. We suggest that the negative cardiovascular effects of low vitamin D in postmenopausal women could be improved by a combined treatment of vitamin D and sex steroids acting through endothelium-dependent and/or -independent mechanisms, resulting in the generation of nitric oxide and calcitonin gene-related peptide (CGRP).

Green tea extract inhibits proliferation of uterine leiomyoma cells in vitro and in nude mice.

OBJECTIVE: The purpose of this study was to investigate the effect of epigallocatechin gallate (EGCG) on rat leiomyoma (ELT3) cells in vitro and in a nude mice model. STUDY DESIGN: ELT3 cells were treated with various concentrations of EGCG. Cell proliferation, proliferation cell nuclear antigen (PCNA), and cyclin-dependent kinase 4 (Cdk4) protein levels were evaluated. ELT3 cells were inoculated subcutaneously in female athymic nude mice. Animals were fed 1.25 mg EGCG (in drinking water)/mouse/day. Tumors were collected and evaluated at 4 and 8 weeks after the treatment. RESULTS: Inhibitory effect of EGCG (200 micromol/L) on ELT3 cells was observed after 24 hours of treatment (P < .05). At > or = 50 micromol/L, EGCG significantly decreased PCNA and Cdk4 protein levels (P < .05). In vivo, EGCG treatment dramatically reduced the volume and weight of tumors at 4 and 8 weeks after the treatment (P < .05). The PCNA and Cdk4 protein levels were significantly reduced in the EGCG-treated group (P < .05). CONCLUSION: EGCG effectively inhibits proliferation and induces apoptosis in rat ELT3 uterine leiomyoma cells in vitro and in vivo.

Antiproliferative and proapoptotic effects of epigallocatechin gallate on human leiomyoma cells.

OBJECTIVE: To investigate the effects of epigallocatechin gallate (EGCG), an extract of green tea on cultured human leiomyoma cells (HuLM). DESIGN: Laboratory study. SETTING: University hospitals. PATIENT(S): Not applicable. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): The HuLM cells were treated with various EGCG concentrations. Cell proliferation was assayed using Hoechst 33258 dye, and apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Total RNA was isolated, and gene expression profiling was performed on 84 key genes related to 18 different signal transduction pathways. The protein levels of PCNA, CDK4, BCL2, and BAX were examined by Western blot analysis. RESULT(S): The HuLM cells treated with EGCG showed a dose-dependent and time-dependent inhibition of cell proliferation. The TUNEL staining indicated a significant increase in apoptosis in HuLM cells treated with 100 µM of EGCG compared with untreated control. Gene expression profiling indicated that EGCG treatment up-regulated representative genes from the transforming growth factor ß (TGF-ß) and stress pathways, while inhibiting the survival pathway and NFκB-dependent inflammatory pathway. Western blot analysis confirmed that EGCG at ≥50 µM significantly decreased the expression of PCNA, CDK4, and BCL2 as well as increased the expression of the proapoptotic BAX in a dose-dependent manner. CONCLUSION(S): Epigallocatechin gallate inhibits the proliferation of HuLM cells and induces apoptosis. These results suggest that EGCG may be a potential anti-uterine fibroid agent acting through multiple signal transduction pathways.

Goserelin acetate 10.8 mg plus iron versus iron monotherapy prior to surgery in premenopausal women with iron-deficiency anemia due to uterine leiomyomas: results from a Phase III, randomized, multicenter, double-blind, controlled trial.

BACKGROUND: Women with symptomatic uterine leiomyomas (fibroids) may have iron-deficiency anemia (IDA); therefore, surgery places them at risk of blood-borne morbidity from perioperative transfusions. Such women might benefit from a preoperative treatment that restores hematologic normality and alleviates fibroid symptoms. OBJECTIVE: The purpose of this study was to examine the effects of a single preoperative depot injection of goserelin acetate plus iron treatment compared with iron monotherapy, in premenopausal women with IDA due to uterine leiomyomas. METHODS: This Phase III, randomized, multicenter, double-blind, controlled trial (12 weeks of treatment plus a 24-week follow-up period) was conducted from October 1997 to August 1999. Patients received an injection of goserelin acetate 10.8 mg (3-month formulation) or a sham, with both groups receiving PO iron (ferrous sulfate) 325-mg tablets TID during the 12-week treatment period. Surgery (hysterectomy or myomectomy) was planned for week 12. Hemoglobin (Hb) level, symptoms of uterine leiomyomas, requirement for blood transfusion throughout, ability to donate blood for autologous transfusion, and leiomyoma and uterine volume were assessed for efficacy. The tolerability assessment included bone mineral density measurements and subjective symptomatology (ie, menstrual bleeding [uterine hemorrhage], fatigue, pelvic pain, and pelvic pressure). RESULTS: A total of 110 women received treatment (n = 54, goserelin acetate 10.8 mg; n = 56, sham). The majority of patients (69.1%) were black and the mean age at study entry was 39.9 years, with a mean weight of 80.1 kg. At approximately 12 weeks, Hb levels were significantly higher in the goserelin group compared with the sham group (difference of least squares mean, 1.17 g/dL; 95% CI, 0.68-1.66; P < 0.001), and significantly more patients in the goserelin group had an increase in Hb concentration of >or=2 g/dL (odds ratio 6.36; 95% CI, 2.00-20.18; P < 0.001). A nonsignificant decrease in both uterine and leiomyoma volume was experienced by patients who administered goserelin compared with increases in the sham group. Uterine hemorrhage was also experienced numerically less often by goserelin-treated patients compared with those given the sham injection (9.3% vs 28.6%, respectively). One or more adverse events (AEs) were reported by 89% of patients in each treatment group. Goserelin acetate 10.8 mg was generally well tolerated by patients, with no serious drug-related AEs reported during this 36-week trial. CONCLUSION: A single, preoperative injection of goserelin acetate 10.8 mg in addition to PO iron 325 mg TID was associated with improved Hb levels in these premenopausal women with IDA due to uterine leiomyomas.

Concerns of patients with allergic rhinitis: the Allergic Rhinitis Care Programme in South Africa.

BACKGROUND: The major reason for treating chronic rhinitis is to improve quality of life. Although primary symptoms cause morbidity in their own right, these symptoms are significantly aggravated by the impact of cognitive dysfunction and quality of life. OBJECTIVE: The Allergic Rhinitis Care Programme was initiated by the South African Allergic Rhinitis Working Group. An important task of this programme was to document health-related quality of life impairment amongst allergic rhinitis patients in South Africa. METHODS: A questionnaire, appropriate to South Africa, was distributed to patients. The questionnaire inquired about symptoms, quality of life, complications, trigger factors, associated allergic conditions, medication preference, medication adherence and concerns about the condition. RESULTS: 1181 people completed the questionnaire and returned the survey. Nasal congestion was identified as a common and frequent problem, while seasonality of symptoms was uncommon. Symptoms affected sleep in 76.6% of sufferers, and in at least a third this was every night. Over 1000 respondents felt miserable due to allergic rhinitis (85.2%). 63.1% indicated that they always followed instructions for taking rhinitis medication. A variety of perceived concerns around having and being treated for allergic rhinitis were identified, suggesting multiple reasons for non-adherence. CONCLUSIONS: We report symptom frequency and quality of life impairment for respondents who identify themselves as having allergic rhinitis. Since allergic rhinitis is, in the main, a doctor-diagnosed condition, this would suggest a significant problem with inappropriate, insufficient or incorrect therapy.

DNA hypomethylation and imbalanced expression of DNA methyltransferases (DNMT1, 3A, and 3B) in human uterine leiomyoma.

OBJECTIVE: Despite the high prevalence of uterine leiomyoma in women, little is known about the pathophysiology of this tumor. This study intends to define the epigenetic modulation of this tumor. METHODS: Twenty-three pairs of leiomyomas and their adjacent myometria were collected. Status of DNA global methylation was determined by using DNA methyl acceptance assay and immunohistochemistry staining with 5-methylcytidine antibody. MRNA level of DNA methyltransferases (DNMT1, 3A, and 3B) was assessed by quantitative real time PCR. RESULTS: DNA global hypomethylation was detected in the leiomyoma tissues as compared with the adjacent myometria. DNMT1 expression was increased in 47.5% and was equal in 47.5% in leiomyomas compared to the adjacent myometria. On the other hand, over 74% of cases showed decreased expression of DNMT3A and 3B in leiomyomas compared to the adjacent myometria. CONCLUSION: Global hypomethylation and imbalanced expression of DNMTs in uterine leiomyoma suggested a potential mechanism of epigenetic modulation in the development of this tumor.