Breast Cancer Risk Assessments Comparing Gail and CARE Models in African-American Women

Abstract:  The Gail model has been used to predict invasive breast cancer risk in women using risk factors of age, age at menarche, age at first live birth, number of first-degree relatives with breast cancer, and number of previous benign breast biopsies. However, this model underestimates breast cancer risk in African-American women. The Contraceptive and Reproductive Experience (CARE) model has been developed to replace the Gail model in predicting breast cancer risk in African-American women. In a sample of 883 women who participated in the breast cancer screening program at Howard University Cancer Center, we compared the breast cancer risk estimates from the Gail model and the CARE model. The mean 5-year breast cancer risk was 0.88% (Range: 0.18–6.60%) for the Gail model and 1.29% (Range: 0.20–4.50%) for the CARE model. Using the usual cutoff-point of 1.67% or above for elevated risk, there is a significant difference in the proportion of women with elevated breast cancer risk between the Gail and the CARE models (McNemar's test, p < 0.0001). For both models, there was a significant mean risk difference between those with and without a family history of breast cancer (Wilcoxon rank-sum test, p < 0.0001). Our results confirm the need for validation of the Gail model in African-Americans and diversity in research. Although these findings are not perfect and perhaps not definitive, they are additive in the discussions during counseling and risk assessment in African-Americans. Furthermore, these findings will be complemented by new technologies such as genomics in refining our ability to assess risk.     

A Comparison of Sexual Outcomes in Primiparous Women Experiencing Vaginal and Caesarean Births

Background and Objective:

We conducted this study to evaluate and compare postpartum sexual functioning after vaginal and caesarean births.

Materials and Methods:

This was a cross-sectional study that was carried out in postnatal health care in a hospital. A total of 50 primiprous women who had given birth 6-12 months ago and came to the hospital for postnatal care were asked to join the study. Forty of the women completed the entire questionnaire. Among these women, 20 delivered spontaneously with mediolateral episiotomy and 20 had elective caesarean section. Sexual function was evaluated by a validated, self-created questionnaire. A statistical evaluation was carried out by SPSS v.11. A two-part self-created validated questionnaire for data collection was administered regarding sexual function prior to pregnancy and 6-12 months postpartum.

Results:

The median time to restart intercourse in the normal vaginal delivery with episiotomy (NVD/epi) group was 40 days and in the caesarean section (C/S) group was 10 days postpartum. The most common problems in the NVD/epi group was decreased libido (80%), sexual dissatisfaction (65%), and vaginal looseness (55%). In the C/S group, the most common problems were vaginal dryness (85%), sexual dissatisfaction (60%), and decreased libido (35%). There were clinically significant differences between the two groups regarding sexual outcomes, but these differences were not statically significant.

Conclusion:

Postnatal sexual problems were very common after both NVD/epi and C/S. Because sexual problems are so prevalent during the postpartum period, clinicians should draw more attention to the women''s sexual life and try to improve their quality of life after delivery.     

IMPROVED BLOOD PRESSURE CONTROL BY MONITORING COMPLIANCE WITH ANTIHYPERTENSIVE THERAPY

Compliance with antihypertensive therapy was monitored for three months using an electronic medication dispenser in 35 patients remaining hypertensive despite the once-daily administration of a blood pressure lowering drug (either as monotherapy or as fixed-dose combination therapy). During the monitoring of compliance, the treatment was unchanged but blood pressure decreased significantly (p<0.001) from 167.9/100.4 ± 16.3/7.2 mmHg (mean ± SD) to 152.5/90.9 ± 20.9/11.5 mmHg. The percentage of days with one opening per day was 80.8 ± 20.5. Thus, discussing with the patient about compliance with the prescribed drug regimen and monitoring compliance for a few months allows better control of blood pressure. This most likely reflects increased compliance with antihypertensive drug therapy.     

Screening for ‘window‐period’ acute HIV infection among pregnant women in rural South Africa

Objectives

The aim of this study was to evaluate the HIV‐1 RNA pooled nucleic acid amplification testing (NAAT) strategy to screen pregnant women in the ‘window period’ of acute HIV infection (AHI) in rural South Africa.

Methods

In 2007 and 2008, 750 consecutive pregnant women on their first antenatal care visit to a primary health care clinic were tested anonymously for HIV infection. HIV‐1 RNA pooled NAAT was performed on HIV antibody‐negative samples. All positive pools were tested individually and positive samples were classified as incident cases to calculate HIV incidence.

Results

The overall HIV prevalence was 37.3% [95% confidence interval (CI) 34.3–41.3]. Of the 467 HIV antibody‐negative samples, four (0.9%) were HIV‐1 RNA‐positive. The mean viral load in the four samples was 386 260 HIV‐1 RNA copies/mL (range 64 200–1 228 130). The HIV incidence was 11.2% per year (95% CI 0.3–22.1) and all women with AHI were ≤21 years of age.

Conclusions

Identifying AHI in pregnancy is important for health interventions to reduce perinatal and heterosexual transmission of HIV, and to estimate HIV incidence for epidemiological surveillance.     

Orexin a suppresses gonadotropin-releasing hormone (GnRH) neuron activity in the mouse

GnRH neurons are critical for the central regulation of fertility, integrating steroidal, metabolic and other cues. GnRH neurons appear to lack receptors for many of these cues, suggesting involvement of afferent systems to convey information. Orexin A (orexin) is of interest in this regard as a neuromodulator that up-regulates metabolic activity, increases wakefulness, and affects GnRH/LH release. We examined the electrophysiological response of GnRH neurons to orexin application and how this response changes with estradiol and time of day in a defined animal model. Mice were either ovariectomized (OVX) or OVX and implanted with estradiol capsules (OVX+E). GnRH neurons from OVX+E mice exhibit low firing rates in the morning, due to estradiol-negative feedback, and high firing rates in the evening, due to positive feedback. Orexin inhibited activity of GnRH neurons from OVX mice independent of time of day. In GnRH neurons from OVX+E mice, orexin was inhibitory during the evening, suggesting orexin inhibition is not altered by estradiol. No effect of orexin was observed in OVX+E morning recordings, due to low basal GnRH activity. Inhibitory effects of orexin were mediated by the type 1 orexin receptor, but antagonism of this receptor did not increase GnRH neuron activity during estradiol-negative feedback. Spike pattern analysis revealed orexin increases interevent interval by reducing the number of single spikes and bursts. Orexin reduced spikes/burst and burst duration but did not affect intraburst interval. This suggests orexin may reduce overall firing rate by suppressing spike initiation and burst maintenance in GnRH neurons.     

Infection of Nippostrongylus brasiliensis induces development of mucosal-type but not connective tissue-type mast cells in genetically mast cell-deficient Ws/Ws rats

Ws/Ws rats have a small deletion at the tyrosine kinase domain of the c- kit gene and are deficient in both mucosal mast cells (MMC) and connective tissue-type mast cells (CTMC). The role of the c-kit receptor in the development of MMC and CTMC was investigated by infecting Ws/Ws and control +/+ rats with Nippostrongylus brasiliensis (NB), which induces T-cell-dependent mast cell proliferation. Although mast cells did not develop in the skin of Ws/Ws rats, a significant number of mast cells developed in the jejunum after NB infection. These mast cells had the MMC protease phenotype (rat mast cell protease [RMCP] I-/II+) and lacked heparin because they were not stained with berberine sulfate. Globule leukocytes were also detected in the mucosal epithelium of these rats. However, the number of MMC and the serum concentration of RMCP II in NB-infected Ws/Ws rats were only 13% and 7% of those of NB-infected +/+ rats, respectively. A small number of mast cells also developed in the lung, liver, and mesenteric lymph nodes of Ws/Ws rats after NB infection. Although mast cells in these tissues had the MMC phenotype throughout the observation period, the increased mast cells in the lung and liver of +/+ rats acquired a CTMC-like phenotype and were RMCP I+/II+, berberine sulfate+, and formalin resistant. These results indicate that the need for the stimulus through the c-kit receptor appears to be greater in the development of CTMC in the skin as well as for CTMC-like mast cells in the lung and liver than for the development of MMC.     

Magnetic resonance angiography

Pulse sequences that permit selective detection of moving spins in a magnetic resonance image have been developed. Experiments were performed by the authors to produce projected angiographic data without the use of contrast agents, with the intensity of each image pixel determined by the macroscopic velocity of the detected spins. With this method, suppression of nonmoving spins is essentially complete, yielding a high dynamic range in signal intensity for detected vessels. Selective detection of moving spins is not dependent on pulsatile flow. Consequently, not only arterial structures, but also venous structures can easily be visualized. High-resolution angiographic images can be obtained by combining the flow experiment with surface coil techniques.     

Effect of priming polymorphonuclear leukocytes with cytokines (granulocyte-macrophage colony-stimulating factor [GM-CSF] and G-CSF) on the host resistance to Streptococcus pneumoniae in chinchillas infected with influenza A virus

Patients infected with influenza A virus (IAV) are at increased risk for bacterial superinfections, and this occurs in association with depressed polymorphonuclear leukocyte (PMNL) function. Recently, we reported that in vitro exposure of human PMNL to granulocyte-macrophage colony-stimulating factor (GM-CSF) reverses IAV-induced cell dysfunction. The present study used an established animal model of IAV infection to examine whether G-CSF and/or GM-CSF can overcome IAV- induced PMNL dysfunction and thereby prevent secondary infections. Preliminary studies determined a dosing schedule of these cytokines that caused significant priming of chinchilla PMNL. In subsequent studies, animals were inoculated intranasally with IAV (day 1) followed 3 days later by Streptococcus pneumoniae, and administered daily intraperitoneal injections with a cytokine or placebo on days 3 through 9. Animals had blood obtained on multiple occasions for PMNL studies, and were followed-up for evidence of pneumococcal disease. Both cytokines caused significant priming of the PMNL chemiluminescence response and this was associated with reversal of the IAV-induced PMNL dysfunction. However, neither cytokine decreased the incidence of pneumococcal disease.