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.     

Focal spasticity therapy with botulinum toxin: effects on function, activities of daily living and pain in 100 adult patients.

OBJECTIVE: Analysis of the effects of a comprehensive focal spasticity program in adult patients. DESIGN: Retrospective study of an out-patient cohort. PATIENTS: One hundred patients were enrolled in the study (54 men and 46 women, mean age 41 years (SD 14). Cerebral palsy and stroke were equally common (80% in total). The remaining patients had miscellaneous diagnoses, including traumatic brain injury. METHODS: On average 230 units (SD 101) of botulinum toxin A Botox was given for 227 principal therapy targets chosen by the patient or the caregiver. One patient could have several targets for therapy. Administration of botulinum toxin was combined with 260 additional therapeutic interventions, most of which were forms of physical therapy. The effects were assessed after 6 weeks and compared with baseline functional abilities 1-2 weeks prior to therapy. RESULTS: Improvement was observed for 211 (93%) therapy targets, no change in 15 (7%), and impairment in 1, corresponding to an overall improvement in 90 patients (90%), 9 unchanged (9%) and worsening in 1. Spasticity assessment (Ashworth scale 0-4; 30 patients) showed a statistically significant improvement (median at baseline was 3 vs 2 after therapy, mean difference 1.2, p<0.001). CONCLUSION: Improvement was observed in >or=90% of patients and in their principal therapeutic targets in a cohort receiving their first focal spasticity treatment with botulinum toxin A and additional therapy. A strict strategy for patient selection and comprehensive management was followed.     

Relation between energy expenditure and body composition in man: specific energy expenditure in vivo of fat and fat-free tissue

The relationship between energy expenditure and body composition, in terms of fat and fat-free masses, has previously been described by a variety of predictive regression equations with parameters devoid of physiological content. We present here results obtained by calculating the specific energy expenditure, ie, the energy expenditure per unit of mass, of fat and fat-free tissue on the basis of measurements of the total energy expenditure (EE), the masses of fat (FM), and fat-free (FFM) tissue using the following simple model: EE = k1.FM + k2.FFM where k1 and k2 are the specific energy expenditures of fat and fat-free tissue, respectively. The results of observations on 104 women at rest yielded values for k1 and k2 of 0.31 and 1.35 watts/kg of fat and fat-free mass, respectively, with standard errors of estimate of 0.074 and 0.052 watts/kg, respectively. Analysis of several series of measurements, from other sources and on smaller samples of subjects, yielded similar values at rest but with larger standard errors of estimate. Data from subjects performing varying amounts of work in 24-h measurements showed, as expected, larger values for both tissues. The results explain to a very large extent the well-established relation between resting metabolic rate and body weight, ie, a linear relation with a non-zero intercept. The results also offer a clear-cut explanation for the well known difference in energy expenditure between men and women with the same body weight.     

Fixation of displaced femoral neck fractures: A comparison between sliding screw plate and four cancellous bone screws

In a prospective, randomized trial, 104 consecutive patients with displaced femoral neck fractures were allocated either to fixation with a sliding screw plate or 4 ASIF cancellous bone screws. The patients were reexamined at fixed intervals to determine the time of union. The 2-year-cumulated rate of union was 64 per cent in the plate group and 84 per cent in the screw group.