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Biomedical subjects

A Mattsson

Publications and source records attributed to A Mattsson.

At least 55 records · Page 3Linked to original sources
PubMed1994

Pregnancy in B-cell-deficient mice: postpartum transfer of immunoglobulins prevents neonatal runting and death.

Mice lacking functional B cells because of a genetic deletion of the mu chain (IgM) gene were used to investigate the role of perinatal and postnatal transfer of maternal IgG in neonatal growth. Our results confirmed that immunoglobulin (Ig)-deficient mice successfully complete pregnancy and deliver healthy offspring. However, neonates nursed by Ig-deficient mothers showed growth retardation (runting) and high mortality during their first 10 days of life. This fatal course was seen whether or not the neonates were Ig-deficient. Cross-switching litters from phenotypically normal mothers to Ig-deficient mothers immediately after birth showed that perinatal Ig transfer normalized neonatal development for 10 days, but was not sufficient to sustain survival during the later part of the neonatal period. On the other hand, all Ig-deficient litters nursed by normal foster mothers showed normal development and 0% neonatal mortality. Administration of mouse IgG to an Ig-deficient mother or a neonate during the first critical week prevented runting. We assume that the growth- and health-promoting effects of IgG during early neonatal life are attributable mainly to the transfer of passive immunity to environmental pathogens. However, the finding that monoclonal IgG antibodies also enhanced neonatal growth and survival suggests that IgG-dependent growth-promoting mechanisms could be involved as well.

Animals↗
PubMed1994

Phenotypic and functional activation of alveolar macrophages, T lymphocytes and NK cells in patients with systemic sclerosis and primary Sjögren's syndrome.

OBJECTIVES: Attempts to differentiate between the pathogenesis of the severe pulmonary manifestations observed in systemic sclerosis (SSc) and the mild form in primary Sjögren's syndrome (pSS) were performed by studying cell populations recovered during bronchoalveolar lavage (BAL). METHODS AND RESULTS: Two-colour flow cytometric analysis of BAL fluid lymphocytes showed a similar degree of phenotypic activation (DR+) of CD4+ and CD8+ T lymphocyte subsets and CD16+ NK cells in patients with SSc (n = 13) and pSS (n = 11) groups and healthy controls (n = 11). Alveolar macrophages expressed the CD14 antigen at significantly increased densities in patients with SSc. Alveolar macrophage activation in SSc was also suggested by increased IL-6 concentrations in neat BAL fluid and increases in macrophage production of TNF alpha and EGF in vitro. SSc patients also had increased proportions of neutrophils and eosinophils in BAL fluid. No correlations were found between any cellular subsets or cytokine levels in BAL fluid and lung status at the time of lavage in SSc or pSS patients or the subsequent course of the pulmonary function in SSc patients. CONCLUSION: It is concluded that the phenotypical activation of alveolar helper/inducer (DR+CD4+) and suppressor/cytotoxic (DR+CD8+) T lymphocytes and NK (DR+CD16+) cells is not a prerequisite for the development of lung fibrosis in SSc or bronchial hyper-responsiveness in pSS. Alveolar macrophage activation may contribute to the development of lung fibrosis in SSc.

Adult↗
PubMed1993

Radiation-induced breast cancer: long-term follow-up of radiation therapy for benign breast disease.

BACKGROUND: From the 1920s through the 1950s, radiation therapy was used in Sweden as a treatment for benign breast diseases. It is now known that exposure of the breast to ionizing radiation increases the relative risk of subsequent breast cancer, especially for younger women. However, the degree to which the patient's age contributes to the elevation of risk for subsequent development of breast cancer is not yet completely understood. PURPOSE: The purpose was to study the risk of breast cancer after irradiation of the female breast and, in particular, to analyze the duration of the effect and the risk for women older than 40 years at first exposure. METHODS: In this cohort study, data were obtained through population-based registers. The exposed group consisted of 1216 women (median age, 40 years) who, during the period spanning 1925 through 1954, received radiation therapy for benign breast disease. The reference group consisted of 1874 women (median age, 36 years) who had the same diagnosis during that time period but did not receive radiation therapy. The radiation doses were determined from the original medical records (mean dose, 5.8 Gy; range, 0.003-50.1 Gy). The follow-up lasted up to 60 years after first exposure. The incidence rate ratio was analyzed with Poisson regression models. RESULTS: The total number of breast cancers in the exposed cohort was 198 versus 101 in the unexposed cohort. Overall, the radiation-associated incidence rate ratio was 3.58 (95% confidence interval = 2.77-4.63). The dose-response gradient was statistically significant (P < .001) but leveled off at higher doses. The incidence rate ratios decreased starting about 25 years after first exposure but were at increased levels throughout the entire follow-up period. The incidence rate ratio decreased with age at first exposure but was significantly increased (P < .001) even when the age at time of first exposure was greater than 40 years. CONCLUSIONS: Total dose, age at first exposure, and time since first exposure were all determinants of the incidence rate ratio of breast cancer after exposure of the breast to ionizing radiation. A statistically significant increase in the incidence of breast cancer following radiation treatment of various benign breast diseases was observed even among women older than 40 years at the time of first treatment. IMPLICATIONS: These findings need to be considered when weighing the relative benefits versus risks of generalized screening of younger women for breast cancer by mammography.

Adult↗
PubMed1993

Cardiac and thromboembolic morbidity among postmenopausal women with early-stage breast cancer in a randomized trial of adjuvant tamoxifen. The Stockholm Breast Cancer Study Group.

BACKGROUND: Tamoxifen, which binds to estrogen receptors, is widely used as adjuvant therapy after surgery for early-stage breast cancer. Our previous randomized trial of adjuvant tamoxifen therapy for breast cancer showed a significant decrease of new, contralateral breast cancers in patients who received tamoxifen. Tamoxifen may also influence risk factors for cardiac and thromboembolic disease (e.g., serum cholesterol and antithrombin III). PURPOSE: The purpose of this study was to assess morbidity from cardiac and thromboembolic disease among 2365 postmenopausal patients with early-stage breast cancer in the Stockholm randomized trial of adjuvant tamoxifen (40 mg daily for 2 or 5 years) versus no adjuvant endocrine therapy. Patients were entered in the study from November 1976 through December 1988. METHODS: In our retrospective study, the analysis of morbidity was based on data from a computerized, population-based register of hospital admissions and discharge diagnoses. Mortality data were obtained from the Swedish National Central Bureau of Statistics. In the Stockholm study, treatment with tamoxifen was initiated within 4-6 weeks of modified radical mastectomy or breast-conserving surgery including axillary lymph node dissection and postoperative radiation therapy to the breast. In that randomized trial, 755 patients at low risk of death from breast cancer received adjuvant tamoxifen only; 760 received no treatment. In addition, 628 high-risk patients were randomly assigned to receive adjuvant chemotherapy plus tamoxifen (173 patients) or postoperative radiotherapy plus tamoxifen (151) or, as a control, to receive chemotherapy (171) or postoperative radiation therapy (133), both without tamoxifen or other endocrine therapy. Median follow-up was 6 years. RESULTS: Tamoxifen therapy resulted in a statistically significant reduced incidence of hospital admissions due to cardiac disease. The relative hazard (tamoxifen for 2 or 5 years versus control) was 0.68 (95% confidence interval [CI] = 0.48-0.97; P = .03). In the randomized comparison of 5 versus 2 years of tamoxifen, there was a statistically significant difference favoring the longer treatment (relative hazard = 0.37; 95% CI = 0.15-0.92; P = .03). There was little difference between the tamoxifen and control groups in terms of admissions due to thromboembolic disease. CONCLUSIONS: These findings suggest that long-term adjuvant treatment with tamoxifen may result in substantial reduction of cardiac morbidity in patients with low risk of death from breast cancer as well as in women in chemopreventive studies who have high risk of developing breast cancer. IMPLICATIONS: Our results support continuation of ongoing trials of tamoxifen therapy in these two groups of subjects.

Aged↗
PubMed1993

Morphometric, DNA and PCNA in thin malignant melanomas.

Morphometric assessment of nuclear area, shape and density, nucleolar area, analysis of DNA content and expression of proliferating cell nuclear antigen (PCNA) was performed in a case control study of 72 malignant melanomas, thickness < or = 0.8 mm and Clark level II-III. Twenty-four thin metastasizing melanomas (TMM) were individually compared to two thin non-metastasizing melanomas (TNM) after individual matching for site of primary tumor, tumor thickness, level of invasion, tumor regression and duration of follow-up. Conditional logistic regression analysis with maximum likelihood estimates showed significant differences between TMM and TNM with regard to the nuclear correlation coefficient (p = 0.005), standard deviation of nuclear shape NCI (p = 0.017), and nuclear density (p = 0.030), indicating that thin melanomas with pleomorphic and possibly densely packed nuclei are associated with recurrence. No significant differences were found regarding nuclear or nucleolar area, mean nuclear shape NCI, nuclear DNA content or expression of PCNA.

Antigens, Neoplasm↗
PubMed1993

Expression of tenascin in developing and adult mouse lymphoid organs.

The extracellular matrix (ECM) is essential in regulating many cell functions in non-lymphoid cells, and the ECM may also play a role in the function of the immune system. Tenascin is a hexameric glycoprotein of the ECM. In mouse, two major polypeptides of MW 210 KD and 260 KD are formed by differential splicing. Northern blot screening of various mouse tissues showed that the short 6 KB tenascin message was strongly expressed in the adult thymus, whereas very little or no tenascin mRNA could be detected in spleen. In addition, immunoblotting and histological analysis with monoclonal anti-tenascin antibodies revealed the presence of tenascin in lymph nodes and spleen. In thymus, only a short-splice variant of tenascin was detected by immunoblotting, which supported the Northern blot results. Immunohistology showed that the epithelial reticular stroma in both embryonic and adult mouse thymus expressed tenascin, as did the postnatal mesenchymal reticular stroma in lymph nodes and spleen. The distribution of tenascin in the thymus was more restricted than that of fibronectin and laminin.

Animals↗
PubMed1992

Leukaemia incidence after iodine-131 exposure.

Leukaemia is one of the most prominent late effects of exposure to ionising radiation. We have studied the incidence of leukaemia among 46,988 Swedish patients exposed to iodine-131 (131I) for diagnostic reasons or to treat hyperthyroidism or thyroid cancer. The observed number of leukaemias was compared with that expected based on incidence data from the general population. The mean absorbed dose to the bone marrow was estimated as 14 mGy (range 0.01-2.226). 195 leukaemias occurred more than 2 years after exposure, and the standardised incidence ratio (SIR) was 1.09 (95% confidence interval 0.94-1.25). Similar, but again not significantly, increased risks were seen for chronic lymphocytic leukaemia (CLL) (SIR = 1.08), a malignant condition not found to be increased after irradiation, and for non-CLL (SIR = 1.09). The risk of leukaemia did not vary by sex, age, time, or radiation dose from 131I. One reason for the absence of a radiation effect, other than chance, includes the possible lowering of risk when exposure is protracted over time as occurs with 131I. Excess leukaemia risks of more than 25% could thus be excluded with high assurance in this population of mainly adults. These results should be reassuring to patients exposed to 131I in medical practice and to most individuals exposed to the fall-out from the Chernobyl accident.

Adolescent↗
PubMed1992

In vivo treatment with interferon-gamma during early pregnancy in mice induces strong expression of major histocompatibility complex class I and II molecules in uterus and decidua but not in extra-embryonic tissues.

Allopregnant (NFR/N [Swiss-derived] H-2q females x 57/Bl H-2b males) and syngeneically pregnant (NFR/N x NFR/N) mice were subjected to daily injections (10(5) U/mouse/day, from Day 5.5 of gestation) of recombinant rat or mouse interferon-gamma (IFNg) in order to investigate its ability to induce extra-embryonic major histocompatibility complex (MHC) expression and antipaternal immune reactions if administered during the first part of the gestation period. In addition, a limited number of IFNg-treated embryo-transferred NFR/N mice carrying C57/B1 embryos (representing a complete allogenic pregnancy) were investigated. Mouse and rat IFNg caused the same type of histological and physiological changes, and most of the experiments were performed by using rat IFNg. Several IFNg-treated mice (irrespective of type of mating) showed a drop in weight and a high rate of resorptions at Day 12.5 of gestation. This interference with pregnancy appeared not to be caused by immunological reactions against the feto-placental unit (no leukocyte infiltration and no significant effect on serum levels of antipaternal antibodies in preimmunized allopregnant IFNg-treated mice). Immunohistochemical stainings of cryosectioned tissues at Day 9.5 of pregnancy revealed that IFNg treatment caused a strong induction of MHC class I and class II expression on most cells in the uterus and on several cells in the maternal decidua, while there was a complete absence of detectable MHC class I and class II expression in the extra-embryonic tissues. Characteristic for a Day 12.5 placenta of an IFNg-treated mouse (including embryo-transferred mice) was a strongly MHC class II-induced maternal decidua and a completely MHC class II-negative fetal placenta. The pattern of IFN-induced MHC class I expression was similar to that of class II, with the exception of class I expression on scattered cells within the basal zone. Thus, the present study provides immunohistological evidence that IFNg administered in vivo during the first part of gestation is not capable of inducing MHC expression on murine extra-embryonic cells despite an extremely high expression of MHC molecules on decidual cells in intimate contact with extra-embryonic tissues. It is likely that the resistance to IFNg-mediated induction of MHC expression on extra-embryonic cells is of basic importance for the protection of mammalian semi-allogeneic fetuses.

Animals↗
PubMed1992

Prognostic significance of axillary nodal status in primary breast cancer in relation to the number of resected nodes. Stockholm Breast Cancer Study Group.

The prognostic significance of the number of metastatic axillary lymph nodes in relation to the number of identified nodes among 1,622 patients with operable breast cancer was assessed. We present a Cox's analysis of the prognostic significance of nodal status in relation to loco-regional recurrence, axillary recurrence, distant metastasis and death due to breast cancer respectively. As expected, the relative risks were generally higher for patients with nodal involvement, particularly those with 4 or more positive nodes or with few examined nodes. However, among those with more than 4 positive nodes the risk of distant metastases and death due to breast cancer was about the same irrespective of the number of nodes examined.

Antineoplastic Agents↗
PubMed1992

Increased levels of prolactin during, but not after, the immunisation with rat collagen II enhances the course of arthritis in DBA/1 mice.

In addition to its well known effects on reproductive organs and lactation the pituitary hormone prolactin (PRL) also influences immune functions. The present investigation was performed in order to clarify the regulatory role of prolactin in autoimmune disease by using the collagen II arthritis model. Groups of virgin female DBA/1 mice were subjected to different short-term treatment protocols (5-10 days) with rat PRL and the drugs bromocriptine (inhibits prolactin secretion) and haloperidol (enhances prolactin secretion). Treatments were performed at different stages of disease development, and effects on clinical scores, anti-collagen II antibody titres as well as agalactosyl IgG levels were recorded. The effects of the treatment protocols on serum PRL levels were assessed by using a radioimmunoassay (RIA) system. Although the accumulated results of the present study indicate that PRL does not fulfil a major role in the regulation of collagen II arthritis, some interesting observations were made. High levels of PRL (PRL injections) made the arthritis worse only if treatment was performed during the induction stage of the disease. Bromocriptine treatment during the immunisation period did not significantly affect the course of arthritis, but treatment at later stages tended to cause exacerbation (significant at the onset period only). These results indicate that PRL has different effects during early and late stages of the development of collagen II-induced arthritis.

Animals↗
PubMed1991

Contralateral primary tumors in breast cancer patients in a randomized trial of adjuvant tamoxifen therapy.

Prophylactic treatment with the anti-estrogen tamoxifen may reduce the risk of breast cancer because estrogens are thought to act as promoters in the pathogenesis of the disease. This article presents results on the incidence of contralateral new primary tumors among 1846 postmenopausal breast cancer patients included in a randomized trial of adjuvant tamoxifen therapy for 2 or 5 years after surgery versus no adjuvant endocrine therapy. The median follow-up was 7 years (range, 3-13 years). There was a significant reduction of contralateral breast cancer in the 931 patients in the tamoxifen group versus that in the 915 control patients (29 versus 47 cases, respectively; P = .03). The cumulative incidence at 10 years in the tamoxifen group and the control group was 5% and 8%, respectively. Analysis of the relative hazard of contralateral tumor over time showed that the benefit with tamoxifen therapy was greatest during the first 1-2 years, but there was a continued risk reduction during the entire follow-up period, i.e., more than 10 years after cessation of treatment. There was no significant difference in the number of contralateral cancers in the patients randomly assigned to 2 or 5 years of treatment, but the 95% confidence interval of the relative hazard was wide. The proportion of estrogen receptor-negative contralateral breast cancers was higher in the tamoxifen group than in the control group. There was no difference, however, between the two groups in recurrence-free survival time from the diagnosis of the contralateral cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Placental MHC class I antigen expression is induced in mice following in vivo treatment with recombinant interferon-gamma.

Allogeneically pregnant mice (NFR/N (Swiss-derived) H2q x 57/B1 H2b) were injected daily from day 11 to 18 of gestation with recombinant rat interferon-gamma (IFN-gamma) and the effects on placental MHC antigen expression were evaluated by immunohistochemistry. The results demonstrated that a daily dose of 200,000 U/mouse induces a significant increase in placental MHC class I expression in the decidua and the basal zone spongiotrophoblast as well as the fetal mesenchyme, while the labyrinthine trophoblast was almost completely MHC negative. No significant induction of MHC class II antigen expression was observed in the placental tissue, with the exception of a few scattered cells. The MHC class II-inducing efficiency of the treatment protocol used was ascertained by staining maternal skin (ear), which proved to contain considerably elevated numbers of MHC class II-positive cells (mainly keratinocytes). The IFN-gamma treated group showed a higher incidence of fetal resorptions than the corresponding controls, but this was probably due to a non-specific toxic effect of the treatment as none of the sera analysed contained detectable amounts of anti-paternal antibodies, no infiltrating lymphocytes were detectable on histological examination of placental sections, and most of the IFN-gamma treated animals successfully completed their pregnancy.

Animals↗
PubMed1991

Maintained pregnancy levels of oestrogen afford complete protection from post-partum exacerbation of collagen-induced arthritis.

Pregnancy is known to influence the course of rheumatoid arthritis (RA) in women, as well as type II collagen-induced arthritis (CIA) in DBA/1 mice. A characteristic feature is the remission during gestation and the exacerbation of the diseases during the post-partum period. In the case of CIA in DBA 1 mice, two hormonal changes have been assumed to be critical for the induction of the post-partum flare: (i) the fall in steroid hormone levels from those present during pregnancy; and (ii) surges of prolactin (PRL) release at and after delivery. Our results show that treatment with oestradiol during a short period immediately after parturition protects the mouse from a post-partum flare of the disease, and that treatment with bromocriptine, a drug known to inhibit the endogenous PRL release, has a significant though less marked effect. Studies of lactating (i.e. animals with physiological stimulation of endogenous PRL release) and non-lactating arthritic mice revealed no clear-cut differences, indicating that PRL is of minor importance for the induction of the post-partum flare. Some steroids other than oestradiol, which may be implicated in the exacerbation of arthritis, namely progesterone and hydrocortisone, had no clinical effect. Analyses of agalactosyl IgG levels in mice with CIA, and anti-collagen II antibodies in sera collected at the end of the experiments revealed no significant differences between the oestradiol and the control groups. The successful oestradiol treatment of the mice indicates that the drop in endogenous oestradiol levels prior to delivery ends the oestrogen-mediated protection against arthritis during pregnancy.

Animals↗
PubMed1991

Adjuvant tamoxifen in early-stage breast cancer: effects on intercurrent morbidity and mortality.

Intercurrent mortality and the pattern of inpatient hospital care was studied among 1,846 postmenopausal patients included in the Stockholm randomized trial of adjuvant tamoxifen (40 mg daily for 2 years) versus no adjuvant endocrine therapy. The median follow-up time was 54 months (range, 2 to 123 months). The patients were matched to the Swedish National Registry of Causes of Death and a computerized register covering about 95% of all hospital admissions in Stockholm County. There was no significant difference in the pattern of intercurrent mortality among the tamoxifen and control patients. The total number of hospital admissions was similar in both groups, but the tamoxifen patients were admitted significantly less frequently because of immunologic diseases (relative risk [RR] = 0.4; 95% confidence interval [CI], 0.2 to 0.9). Admissions because of thrombotic diseases were slightly, but not significantly, more frequent among the tamoxifen patients (RR = 1.2; 95% [CI], 0.6 to 2.3). The risk of hospital stay for benign gynecologic diseases other than prolapse or uterine bleeding was increased in the tamoxifen group (RR = 3.2; 95% CI, 1.2 to 8.6). No significant differences were found for diseases related to arteriosclerosis or osteoporosis. The study confirms and extends previous reports, which have shown that tamoxifen has few and usually mild side effects. However, the current results should be judged cautiously because of the relatively short median follow-up time (4.5 years) and the limitation of data in detecting morbidity that does not necessarily result in hospitalization.

Aged↗
PubMed1990

Estrogen induced suppression of collagen arthritis. V: Physiological level of estrogen in DBA/1 mice is therapeutic on established arthritis, suppresses anti-type II collagen T-cell dependent immunity and stimulates polyclonal B-cell activity.

Immunization of castrated female DBA/1 mice with rat type II collagen (CII) induces severe polyarthritis with an onset 3-5 weeks after immunization and with 80-100% incidence. Estrogen treatment, inducing physiological 17 beta-estradiol (E2) levels, during a limited period before and after the immunization, or during another period before the expected onset of arthritis, delayed the arthritic onset by approximately 10 days but did not affect the incidence of severity of arthritis. Treatment with physiological doses of E2 after onset of arthritis decreased severity and duration of disease. The T-cell dependent anti-CII autoantibody response was suppressed if the E2 treatment was given immediately before and after CII immunization and was not significantly affected if E2 treatment was given after CII immunization. Neither the total anti-CII Ig levels nor the anti-CII IgG2a levels correlated with development of arthritis. We also titrated the serum levels of estrogen and recorded the vaginal smear response after injections of various doses of E2. This enabled us to work in a physiological range of estrogen levels, spanning the levels found at the end of pregnancy and those found during the normal estrous cycle. These levels were found to suppress antigen-specific T-cell functions but enhance certain B-cell activities since the delayed type hypersensitivity (DTH) reaction against CII was suppressed while the total number of splenic Ig-secreting cells increased. These findings suggest that estrogen in physiological doses is therapeutic for the development of collagen-induced arthritis and that estrogen exerts dualistic effects on the immune system by suppressing T-cell functions and stimulating certain B-cell activities. The suppressive effect on arthritis could not be explained by suppression of anti-CII autoantibody response and must therefore depend on other T-cell-mediated functions.

Analysis of Variance↗
PubMed1990

The incidence of cancer among blood donors.

This study presents data on cancer incidence among 37,795 blood donors in an attempt to test the hypothesis that blood donation might be associated with cancer development. At a median follow-up time of nine years (range 5-13 years) a total of 1152 cancer cases have been diagnosed. The expected number of cancer cases derived from an age-matched population was 1459 giving a relative risk ratio (RR) of 0.79 (p less than 0.001). Calculations were made with and without latency periods between first blood donation and the diagnosis of cancer (0, 5, 10, 15 years). Overall, significantly decreased cancer incidence was observed (p less than 0.001) though the number of observed cases of haematological malignancies was not significantly different from that expected. For polycythaemia vera, however, the O/E ratio was 1.81 possibly indicating an association with blood donation. A more likely explanation is that this reflects increased diagnosis of polycythaemia vera in the blood donor population.

Blood Donors↗
PubMed1990

Long-term adjuvant tamoxifen in early breast cancer: effect on bone mineral density in postmenopausal women.

The decrease in sex steroid hormone levels after the onset of menopause is associated with bone loss and subsequent osteoporosis. Tamoxifen has antiestrogenic properties and may thus theoretically decrease bone mineral density, particularly after long-term treatment. Bone mineral density (BMD) was assessed in 75 recurrence-free postmenopausal breast cancer patients included in a randomized trial of adjuvant tamoxifen (40 mg daily) for 2 or 5 years versus no adjuvant endocrine therapy. The measurements were done about 7 years after the initial randomization. BMD was measured with single-photon absorptiometry (SPA) at two levels of the distal forearm representing cortical and trabecular bone. The BMD was found to be similar among tamoxifen patients compared with the controls. For cortical bone, the BMD was 1.03 g/cm2 (95% confidence interval [Cl], 0.97 to 1.09) among tamoxifen patients and 1.03 g/cm2 (95% Cl, 0.96 to 1.11) in controls. For trabecular bone, the values were 0.74 g/cm2 (95% Cl, 0.70 to 0.79) and 0.73 g/cm2 (95% Cl, 0.68 to 0.79), respectively. The results thus did not indicate an accelerated postmenopausal bone loss with long-term adjuvant tamoxifen.

Aged↗