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Biomedical subjects

L Löfgren

Publications and source records attributed to L Löfgren.

At least 19 recordsLinked to original sources

Are estrogen receptor content in breast cancer and effects of tamoxifen on sex hormone-binding globulin markers for individual estrogen sensitivity?

Individual women differ with respect to their sensitivity to estrogen and serum levels of sex hormone-binding globulin (SHBG) may reflect the individual response. We found a significant correlation between estrogen receptor (ER) concentrations in breast cancer tissue and SHBG levels during tamoxifen treatment. Estrogen sensitivity may be a general characteristic common to various organs and different between individual women.

Biomarkers, Tumor↗

Expression of sex steroid receptor subtypes in normal and malignant breast tissue - a pilot study in postmenopausal women.

Female sex steroids are implied in breast cancer development. The estrogen (ER) and progesterone (PR) receptor subtypes may have different roles to modulate the cellular response. Paired samples of cancer and adjacent normal tissue were collected from postmenopausal women at surgery for ductal breast cancer. The expression of ERa, ERss, PRA and PRB was quantified by immunostaining and digitized image analysis. We found ERss to be significantly reduced in breast cancer tissue (35% vs 50%; p?=?0.001) and there was also a decrease of the ERss/ERa ratio. Among women using hormones at the time of diagnosis tumor tissue showed higher values for both PRB and PRA, as compared to women without such treatment. The results extend previous animal data to be valid also in women. There is evidence that loss of ERss expression may relate to estrogen dependent tumor progression. Increased PR expression could possibly relate to breast cancer risk during combined estrogen/progestogen treatment.

Aged↗

Tamoxifen and megestrol acetate for postmenopausal breast cancer: diverging effects on liver proteins, androgens, and glucocorticoids.

AIM: To compare the effects of tamoxifen and megestrol acetate on liver proteins, androgens, and glucocorticoids during adjuvant treatment for postmenopausal breast cancer. METHODS: A subgroup of women within a large prospective multicenter trial were followed with blood sampling every 3 mo during 2 yr. Women were randomized to receive either continuous tamoxifen 40 mg/d or repeated sequential treatment with tamoxifen and megestrol acetate (MA) 160 mg/d. RESULTS: We found profound and distinct differences between the two regimens. Tamoxifen increased steroid-binding proteins (SHBG and CBG) and suppressed circulating androgens and IGF-I. In contrast, the metabolic effects of tamoxifen were clearly antagonized by MA. There was a rise in IGF-I and marked suppression of steroid-binding proteins. Levels of free testosterone were reduced by 70%. MA also caused apparent adrenal suppression. CONCLUSION: The different effects on anabolic/catabolic balance and adrenal function may relate to certain clinical effects during treatment.

Aged↗

Hormone receptor status in breast cancer--a comparison between surgical specimens and fine needle aspiration biopsies.

The present study was performed to evaluate the immunocytochemical analysis (ICA) of oestrogen (ER) and progesterone receptor (PR) in fine needle aspiration (FNA) biopsies from primary breast cancers as compared with the established enzyme immunoassays (ER-EIA and PR-EIA) based on cytosol homogenates from the corresponding resected tumour specimens. A total of 967 primary breast cancers were assessed for ER and PR content by both methods. Correlations between EIA and ICA expressed as percentage of tumour cells with a positive staining were highly significant (P < 0.001) for ER and PR. Staining intensity yielded only limited additional information. The concordance between the two techniques was about 80%. Evaluation of biological parameters by FNA may be useful to decide the optimal treatment for breast cancer patients.

Adult↗

Ontogenetic development and spatial distribution of the ileal apical sodium-dependent bile acid transporter and the ileal lipid-binding protein in apoE knockout and C57BL/6 mice.

BACKGROUND: Although apoE-/- mice are characterized by hypercholesterolemia, the bile acid enterohepatic circulation, which plays a crucial role in cholesterol homeostasis, has not been examined in these mice. The differences between apoE-/- and C57BL/6 mice in expression of the ileal ASBT and ILBP and in intestinal bile acid absorption were studied. METHODS: The intestinal tissues of the fetal, neonatal and post-weaning mice were processed for immunohistochemistry. Body retention and fecal excretion of 75SeHCAT were measured. The bile acid pool size and its composition were analysed by HPLC. RESULTS: In apoE-/- and C57BL/6 mice, the bile acid pool size was 75 +/- 13 and 78 +/- 13 micromol/ 100 g body weight, respectively, while the ratio of cholic acid/beta-muricholic acid was 1.8 +/- 0.3 and 1.4 +/- 0.3 (P < 0.05), respectively. The daily body retention of 75SeHCAT was 48% = 1.8% in C57 black mice and 58.4% +/- 2.7% in apoE-/- mice (P < 0.05). In both mouse strains, ASBT expression in the small intestine was found in the near-term fetal and post-weaning mice, while ILBP expression was found in all postnatal mice. In the post-weaning mice, ILBP expression was limited to the distal 25%-30% of the small intestine, while ASBT expression was limited to the distal 18%. CONCLUSIONS: The bile acid enterohepatic circulation in apoE-/- mice probably does not differ greatly from that in C57BL/6 mice.

Animals↗

The influence of UV exposure on 5-aminolevulinic acid-induced protoporphyrin IX production in skin.

The skin of nude mice was exposed to erythemogenic doses of UV radiation, which resulted in erythema with edema. An ointment containing 5-aminolevulinic acid (ALA) was topically applied on mouse and human skin. Differences in the kinetics of protoporphyrin accumulation were investigated in normal and UV-exposed skin. At 24 and 48 h after UV exposure, skin produced significantly less protoporphyrin IX (PpIX) than skin unexposed to UV. Human skin on body sites frequently exposed to solar radiation (the lower arm) also produced less PpIX than skin exposed more rarely to the sun (the upper arm). It is concluded that UV radiation introduces persisting changes in the skin, relevant to its capability of producing PpIX from ALA. The observed differences in ALA-induced PpIX fluorescence may be the result of altered penetration of ALA through the stratum corneum or altered metabolizing ability of normal and UV-exposed skin (or both).

Aminolevulinic Acid↗

Uptake and distribution of intravenously or intravesically administered photosensitizers in the rat.

Photodynamic therapy using i.v. injected porphyrin photosensitizers have been used to treat selected cases of superficial bladder cancer. Since cutaneous photosensitivity, lasting 6-8 weeks, is a well known undesirable side effect of this therapy, we instilled the photosensitizers intravesically in rats and compared the uptake of photosensitizers in different tissues by this route of administration with the uptake after intravenous injection. The intravesical mode of delivery enhanced photosensitizer uptake in the bladder wall, while giving low concentrations in extravesical organs. Intravesical instillation of the photosensitizers may therefore increase their efficacy and reduce phototoxicity as compared with intravenous injection. Comparing the results obtained by two assays, one based on porphyrin fluorescence and the other based on the application of radioactively labelled photosensitizers, it was concluded that the i.v. administration route may result in tissue uptake of significant amounts of aggregated non-fluorescent, supposedly inactive drug, while the intravesical administration led to less uptake of aggregates relative to active drug monomers.

Animals↗

Butenes and butadiene in urban air.

Samples of urban air hydrocarbons were taken on specifically made adsorbent cartridges and analysed by gas chromatography after thermal desorption. The four isomeric butenes and 1,3-butadiene were favourably resolved and separated from the abundant alkanes on an aluminium oxide PLOT column. The concentrations of butadiene, reflecting outdoor urban exposure, were in the range of 0.5-5 micrograms/m3. An approximate 1:4 ratio was observed between butadiene and propene which both originate predominantly from vehicle exhaust. The four butenes made up approximately 50% of the propene concentration in exhaust-polluted air, with methylpropene greater than 1-butene greater than trans-2-butene greater than cis-2-butene. Petrol vapour contributed less than exhaust but about five times more to the 2-butenes than to methylpropene and 1-butene. The highest exposure levels of butadiene and butenes were consistently observed in the vicinity of exhaust pipes and petrol-fuelled vehicles.

Air Pollutants↗

Photoionization assessment of C3-C5 alkadienes and alkenes in urban air.

Hydrocarbons from samples of traffic-polluted urban air were separated by gas chromatography on an aluminium oxide column and assessed simultaneously by photoionization detection (PID) and flame ionization detection (FID) after effluent splitting. The 10.2 eV photoionization detector selectively detects alkadienes and alkenes but not alkanes and alkynes in the C3-C5 region. The maximum PID/FID response ratio for alkadienes and alkenes is also obtained in this region. The analytical system as a whole is particularly favourable for the C3-C5 alkenes. Analytical data are given for propadiene, 1,3-butadiene, propene, butenes and pentenes.

Air Pollutants↗

Exposure of commuters to volatile aromatic hydrocarbons from petrol exhaust.

Twenty-two volatile aromatic hydrocarbons were determined in the air of an automobile during commuting. Sampling was made on Tenax cartridges and laboratory determinations were carried out using thermal desorption combined with temperature-programmed capillary gas chromatography. Selected hydrocarbons representative of petrol exhaust were determined in the automobile and in an electric commuter train during eight parallel commuter trips. In the automobile, the concentrations of benzene were 35-70 micrograms/m3 and those of total aromatic hydrocarbons 200-400 micrograms/m3. The petrol exhaust levels were 5-10 times higher in the automobile than in the compartment of the commuter train.

Air Pollution↗

Olfactory function in painters exposed to organic solvents.

The olfactory receptor cells are in direct contact with the exterior environment, and some chemical agents can impair olfactory function. The olfactory function of 54 painters exposed to organic solvents was compared with that of 42 unexposed referents. A new clinical test validated for the sense of smell was used, the University of Pennsylvania Smell Identification Test. Age, smoking habits, exposure to organic solvents, and medical disorders of importance for the sense of smell were recorded. The painters had a somewhat lower test score than the referents. However, the influence of the exposure variable was not statistically significant in a multiple regression analysis including age and smoking habits. The exposure to organic solvents was low, and therefore an effect of high exposure on olfactory function cannot be ruled out. Since some of the painters had earlier been highly exposed, the effects of high exposure are likely to be reversible.

Adult↗

Airway repair with pedicled composite grafts--clinical experience.

In particular surgical situations, part of the airway wall may have to be excised for different reasons, perhaps because of a large tumor or extensive scar tissue. The repair of large laryngotracheal defects, impossible to reconstruct with segmental resection and end-to-end anastomosis or to repair with existing adjacent tissue, is a challenge. A prerequisite for reconstruction of such defects is a graft composed of well-vascularized mucosal lining and a supportive framework to keep the airway patent. A three-stage procedure, based on the creation of an autogenous mucosal cyst, has been developed and used clinically in a series of patients. The three most recent patients who have undergone reconstruction with pedicled muscle Proplast mucosa grafts are presented. In two of the patients, large unilateral laryngeal tumors were removed and the third had a large patent tracheostoma.

Adult↗

Airflows after inhalation of terbutaline sulphate aerosol from a 750-ml spacer for four weeks.

Terbutaline sulphate was administered to 40 adult asthmatic patients via an ordinary metered-dose inhaler (MDI) or one connected to a 750-ml spacer in an open, randomized, crossover study. Spirometry was obtained before the start of the study and again after four weeks of treatment with each inhaler. The patients recorded on a diary card the severity of their asthma symptoms and the peak expiratory flow rate (PEFR) in the morning before and after drug administration and in the evening. Preinhalation spirometric values were higher after four weeks with the 750-ml spacer than at the start of the study (P less than or equal to 0.05). Daily morning and evening PEFR values were higher after use of the 750-ml spacer than after use of the ordinary MDI (P less than 0.05). Daily symptom scores were generally low. A significantly better effect (P less than or equal to 0.05) with the 750-ml spacer was achieved only in daytime dyspnea. The investigators conclude that the attachment of a 750-ml spacer to an ordinary metered-dose inhaler can improve the efficacy of terbutaline sulphate in the long-term treatment of asthma.

Adult↗