Effects of tamoxifen on normal breast tissue histological composition: Results from a randomised six-arm placebo-controlled trial in healthy women

Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.     

Job hazards and respiratory symptoms in Hispanic female domestic cleaners

Abstract

The occupational hazards and respiratory symptoms of domestic cleaners in USA are largely unknown. We conducted a cross-sectional study among 56 Hispanic female domestic cleaner on their health status and frequency of cleaning products used and tasks performed. While women used multi-use products (60.0%) and toilet bowl cleaners (51.8%) most days of the week, many (39.3%) reported not using personal protective equipment while cleaning. Itchy/watery eyes (61.8%) and itchy nose (56.4%) were the most frequently reported symptoms. A history of physician-diagnosed asthma was reported by 14.3% while 33.9% had symptoms of bronchial hyperresponsiveness (BHR). In conclusion, this vulnerable population has high prevalence of physician-diagnosis asthma and BHR symptoms and is potentially exposed to myriad occupational hazards. Further research exploring associations between products use, cleaning tasks and respiratory symptoms is warranted.     

Uptake of Adriamycin in tumour and surrounding brain tissue in patients with malignant gliomas

Summary Eight patients with malignant gliomas verified on CT scan, received an intravenous injection of 50 mg of Adriamycin R, 24 hours prior to surgical removal of the tumour. Peroperatively, both tumour and surrounding tissue specimens were obtained for determination of the tissue concentrations of Adriamycin and its reduced metabolite Adriamycinol. It was found that Adriamycin could be detected in tumour tissue from all patients. The concentration varied between 0,9 and 4,6 nmol/g tissue. In contrast, Adriamycin could only be detected in surrounding brain tissue from one patient.In anin vitro study a human malignant glioma cell line (U-251 MG) was exposed to various concentrations of Adriamycin for 24 hours. It was found that an intracellular drug concentration above 30 nmol/g cells caused a concentration dependent inhibition of cell growth. Thus, it is likely that the poor effect of Adriamycin on patients with malignant gliomas is due to an ineffective drug accumulation in the tumour tissue.     

Preliminary Findings from a Brief,Peer-Led Safer Sex Intervention for College Students Living in Residence Halls

The purpose of this study was to evaluate a single-session peer-led safer sex intervention, based on the Information-Motivation-Behavioral Skills theoretical model, for college students residing in campus residence halls. Participants (N = 108) were assigned to either an hour long control or 5-module intervention session. Compared to the control condition, the intervention increased participants’ information and women’s subjective norms about preventative behavior. Both the control and intervention sessions increased intentions to perform preventative behaviors (e.g., keep condoms available). These preliminary results suggest that this intervention is promising for increasing constructs associated with safer sexual behavior and could easily be implemented by residence hall staff.     

Comparison of the effects of three different combinations of general anesthetics on the electroretinogram of dogs

The objective of this study is to compare the effects of three different anesthetic combinations on the electroretinogram in the same animals under similar laboratory conditions. Thiopental–isoflurane (TI), medetomidine–ketamine (MK), and xylazine–ketamine (XK) were used on each of 12 healthy miniature schnauzer dogs (MS) with a period of at least 3 weeks in between subsequent anesthesia protocols, using the Dog Standard Protocol. The scotopic ERGs consisted of scotopic low stimulus strength (S) responses designated S1, S2, S3, S4, and S5, at 1, 5, 10, 15, and 20 min after dark adaptation, respectively, and scotopic standard stimulus strength (S-ST) responses. The photopic ERGs consisted of a photopic single flash (P) response and 31 Hz flicker (P-FL) responses. For S-ST (2.5 cd s/m²), the amplitude of the a-wave using TI was significantly lower than that using MK (adjusted P = 0.05) and XK (adjusted P = 0.03), and the implicit time of the a-wave was significantly shorter than that using MK (adjusted P = 0.04). For P (2.5 cd s/m²), the amplitude of the b-wave using XK was significantly higher than that using MK (adjusted P = 0.01). The implicit times of the b-wave using TI was significantly longer and shorter than that of MK for S1, S2 and P-FL and for S4 and S-ST, respectively, and than that of XK for S2 and P-FL and for S5 and S-ST, respectively. The results of the present study showed that TI affected both the amplitude and the implicit time of the a-wave for S-ST and the implicit time of the b-wave relatively more so than was the case when using XK or MK. Therefore, it appears that either XK or MK could be advantageous to use rather than TI for clinical studies.     

Intrapersonal, Interpersonal, and Contextual Factors in Engaging in and Responding to Extramarital Involvement

Extramarital involvement (EMI) occurs with high prevalence among couples in clinical and community settings, frequently resulting in considerable distress both to participants and their spouses. The field lacks a synthesized review of this literature. Without such a synthesis, it has been difficult for researchers and clinicians to have an understanding of what is and is not known about EMI. This article reviews the large and scattered EMI literature using a framework that encompasses multiple source domains across the temporal process of engaging in and responding to EMI. In addition, this review delineates conceptual and methodological limitations to previous work in this area and articulates directions for further research.     

Ileal release of glucagon-like peptide-1 (GLP-1)

There is evidence that the distal intestine participates in the regulation of gastric motor and secretory function. It was the aim of this study to examine in greater detail the effects of ileal nutrient exposure on human gastric acid secretion and to investigate potential intermediary mechanisms. Twelve normal subjects were intubated with an oroileal multilumen tube assembly for gastric, duodenal, and ileal perfusion of marker and test solutions, aspiration, and intestinal manometry. We studied ileal effects on gastric acid output in the unstimulated, interdigestive state (during early phase II,N=6), and during endogenous stimulation by intraduodenal essential amino acid perfusion,N=6) and on release of candidate humoral mediators, peptide YY (PYY) and glucagonlike peptide-1 (GLP-1), both known inhibitors of human gastric acid secretion. Compared with ileal saline perfusion, ileal carbohydrate (total caloric load: 60 kcal) decreased interdigestive gastric acid output by 64% (P<0.01), and endogenously stimulated output by 68%, respectively (P<0.005). Under all experimental conditions, ileal carbohydrate increased plasma GLP-1 by 80–100% (allP<0.005). Ileal lipid perfusion had similar inhibitory effects on gastric acid output and stimulatory effects on GLP-1 release as had ileal carbohydrate. By contrast, ileal perfusion with peptone had no or only weak effects on either acid output or plasma GLP-1. Plasma PYY concentrations and suppression of gastric secretion in response to ileal perfusions were not correlated. In humans, both interdigestive and endogenously stimulated gastric acid output are inhibited in response to intraileal carbohydrate or lipids, but not protein, Decreased acid output is associated with release of GLP-1, but not PYY. These findings support the hypothesis that the distal small intestine may participate in the late postprandial inhibitory regulation of gastric secretory function in humans and that GLP-1 may be an intermediary factor.     

Increased CSF neopterin levels in subarachnoid hemorrhage

Neopterin concentrations, reflecting T-cell macrophage activation, were analyzed in serum and cerebrospinal fluid (CSF) obtained from 14 patients with subarachnoid hemorrhage (SAH). Neopterin concentrations were elevated in both the serum and CSF. The increase in neopterin concentrations was most marked in the CSF, rising from Days 1 to 3 through Days 6 to 9; levels were highest in patient suffering from delayed cerebral ischemia. The present data were interpreted as signs of an ongoing T cell activation both systemically and in the CSF compartment following SAH.