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Biomedical subjects

G Nagel

Publications and source records attributed to G Nagel.

At least 19 recordsLinked to original sources

Salmonella typhimurium meningitis in an adult patient with AIDS.

Salmonella meningitis is an unusual complication of Salmonella sepsis and occurs mainly in children. A rare case of Salmonella typhimurium meningitis occurring in an adult HIV positive man who presented with a history of fever and diarrhoea is reported. On examination he was dehydrated, and had oral thrush, weakness of lower limbs and neck stiffness. A septic diagnostic screen was performed and he was commenced on empiric intravenous cefotaxime therapy for meningitis. S typhimurium was cultured from cerebrospinal fluid and blood culture specimens. It was non-lactose fermenting, oxidase negative, H(2)S positive and motile. Cefotaxime was continued for 14 days and the patient responded without neurological sequelae.

AIDS-Related Opportunistic Infections↗

Diet, serum insulin-like growth factor-I and IGF-binding protein-3 in European women.

OBJECTIVE: The aim of this study was to examine the relationship of diet with serum insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in women. DESIGN: Cross-sectional study. SETTING AND SUBJECTS: The population are 2109 women who were control subjects in a case-control study of breast cancer nested in the European Prospective Investigation into Cancer and Nutrition. Control subjects were randomly chosen among risk sets consisting of female cohort members alive and free of cancer (except non-melanoma skin cancer) at the time of diagnosis of the index case. Matching criteria were age at enrolment, follow-up time, time of the day of blood collection and study centre. Diet was measured through validated questionnaires. Serum hormone concentrations were measured by enzyme-linked immunosorbent assays. The relationship between serum IGF-I, IGFBP-3, and intake of nutrients and foods was explored by linear regression in models adjusted for energy intake, age, body mass index, smoking, physical activity, centre and laboratory batch. RESULTS: Serum IGF-I levels were positively related to protein intake (P(trend)<0.001), but not related to energy, fat or carbohydrate intake. Positive relationships were observed with the intake of milk (P(trend)=0.007), calcium (P(trend)<0.001), magnesium (P(trend)=0.003), phosphorus (P(trend)<0.001), potassium (P(trend)=0.002), vitamin B6 (P(trend)=0.03), vitamin B2 (P(trend)=0.001) and inverse relationships with vegetables (P(trend)=0.02) and beta-carotene (P(trend)=0.02). IGFBP-3 was not related with most of the nutrients and foods in this study. CONCLUSIONS: In this population, circulating IGF-I is modestly related with the intake of protein and minerals, and with milk and cheese, while IGFBP-3 does not appear to be related with diet.

Adult↗

Biophysical characterisation of electrofused giant HEK293-cells as a novel electrophysiological expression system.

Giant HEK293 cells of 30-65 microm in diameter were produced by three-dimensional multi-cell electrofusion in 75 mOsm sorbitol media. These strong hypotonic conditions facilitated fusion because of the spherical shape and smooth membrane surface of the swollen cells. A regulatory volume decrease (RVD), as observed at higher osmolalities, did not occur at 75 mOsm. In contrast to field-treated, but unfused cells, the increase in volume induced by hypotonic shock was only partly reversible in the case of fused giant cells after their transfer into isotonic medium. The large size of the electrofused cells allowed the study of their electrophysiological properties by application of both whole-cell and giant excised patch-clamp techniques. Recordings on giant cells yielded a value of 1.1+/-0.1 microF/cm2 for the area-specific membrane capacitance. This value was consistent with that of the parental cells. The area-specific conductivity of giant cells (diameter > 50 microm) was found to be between 12.8 and 16.1 microS/cm2, which is in the range of that of the parental cells. Measurements with patch-pipettes containing fluorescein showed uniform dye uptake in the whole-cell configuration, but not in the cell-attached configuration. The diffusion-controlled uniform uptake of the dye into the cell interior excludes internal compartmentalisation. The finding of a homogeneous fusion was also supported by expression of the yellow fluorescent protein YFP (as part of the fusion-protein ChR2-YFP) in giant cells since no plasma-membrane bound YFP-mediated fluorescence was detected in the interior of the electrofused cells. Functional expression and the electrophysiological characterisation of the light-activated cation channel Channelrhodopsin 2 (ChR2) yielded similar results as for parental cells. Most importantly, the giant cells exhibited a comparable expression density of the channel protein in the plasma membrane as observed in parental cells. This demonstrates that electrofused cells can be used as a heterologous expression system.

Bacterial Proteins↗

Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition.

Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and alpha- and gamma-tocopherol, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and alpha-tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma beta-cryptoxanthin (odds ratio (OR) = 0.53, 95% confidence intervals (CI) = 0.30-0.94, P(trend) = 0.006), zeaxanthin (OR = 0.39, 95% CI = 0.22-0.69, P(trend) = 0.005), retinol (OR = 0.55, 95% CI = 0.33-0.93, P(trend) = 0.005) and lipid-unadjusted alpha-tocopherol (OR = 0.59, 95% CI = 0.37-0.94, P(trend) = 0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted alpha-tocopherol (OR = 0.26, 95% CI = 0.11-0.65, P(trend) = 0.003). These results show that higher plasma concentrations of some carotenoids, retinol and alpha-tocopherol are associated with reduced risk of GC.

Adenocarcinoma↗

Body mass index, waist circumference and waist-hip ratio and serum levels of IGF-I and IGFBP-3 in European women.

OBJECTIVE: To examine the relationship between body mass index (BMI) and waist-hip ratio (WHR) with serum levels of insulin-like growth factor-I (IGF-I), and its binding protein (IGFBP)-3. DESIGN: Cross-sectional study on 2139 women participating in a case-control study on breast cancer and endogenous hormones. Data on lifestyle and reproductive factors were collected by means of questionnaires. Body height, weight, waist and hip circumferences were measured. Serum levels of IGF-I and insulin-like binding protein (IGFBP)-3 were measured by enzyme-linked immunosorbent assays. Adjusted mean levels of IGF-I and IGFBP-3 across quintiles of BMI, waist circumference, and WHR were calculated by linear regression. Results were adjusted for potential confounders associated with IGF-I and IGFBP-3. RESULTS: Adjusted mean serum IGF-I values were lower in women with BMI<22.5 kg/m(2) or BMI>29.2 kg/m(2) compared to women with BMI within this range (P(heterogeneity)<0.0001, P(trend)=0.35). Insulin-like growth factor-I was not related to WHR after adjustment for BMI. IGF-binding protein-3 was linearly positively related to waist and WHR after mutual adjustment. The molar ratio IGF-I/IGFBP-3 had a non-linear relation with BMI and a linear inverse relationship with WHR (P (trend)=0.005). CONCLUSIONS: Our data confirm the nonlinear relationship of circulating IGF-I to total adiposity in women. Serum IGFBP-3 was positively related to central adiposity. These suggest that bioavailable IGF-I levels could be lower in obese compared to non-obese women and inversely related to central adiposity.

Adult↗

Relationship of alcohol intake and sex steroid concentrations in blood in pre- and post-menopausal women: the European Prospective Investigation into Cancer and Nutrition.

OBJECTIVE: Women with a moderate intake of alcohol have higher concentrations of sex steroids in serum, and higher risk of developing breast cancer, compared to non-drinkers. In the present study, we investigate the relationships between alcohol consumption and serum levels of sex steroids and sex-hormone binding globulin (SHBG) in 790 pre- and 1,291 post-menopausal women, who were part of the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Serum levels of testosterone (T), androstenedione (Delta4), dehydroepiandrosterone sulphate (DHEAS), estrone (E1), estradiol (E2) and SHBG were measured by direct immunoassays. Free T (fT) and free E2 (fE2) were calculated according to mass action laws. Current alcohol intake exposure to alcohol was assessed from dietary questionnaires. RESULTS: Pre-menopausal women who consumed more than 25 g/day of alcohol had about 30% higher DHEAS, T and fT, 20% higher Delta4 and about 40% higher E1, concentrations compared to women who were non-consumers. E2, fE2 and SHBG concentrations showed no association with current alcohol intake. In post-menopausal women, DHEAS, fT, T, Delta4, and E1 concentrations were between 10% and 20% higher in women who consumed more than 25 g/day of alcohol compared to non-consumers. E2 or fE2 were not associated with alcohol intake at all. SHBG levels were about 15% lower in alcohol consumers compared to non-consumers. CONCLUSION: This study supports the hypothesis of an influence of alcohol intake on sex hormone concentrations in blood.

Adult↗

[The expert patient: medical consequences].

The expression expert patient appeared about ten years ago. It defines the role of patients who are actively involved in their disease management. Most clinical oncologists are challenged by expert patients. Patient's expertise and complementary medicine are closely linked. Physicians respecting expert patients have to find a positive attitude towards patient self aide concepts. The medical skill to manage expert patients is increasingly important and new tools are being developed for support.

Decision Making↗

IGF-I, IGFBP-3 and breast cancer risk in women: The European Prospective Investigation into Cancer and Nutrition (EPIC).

Blood concentrations of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) have recently been associated with breast cancer risk, notably in women who developed breast cancer at a young age. Prospective studies published so far, however, were relatively small and odds ratio (OR) estimates imprecise. We present the results of a large prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition on total IGF-I, IGFBP-3 and breast cancer risk including 1081 incident cases of invasive breast cancer and 2098 matched control subjects. Increasing IGF-I and IGFBP-3 concentrations were associated with a significant increase in breast cancer risk in women who developed breast cancer after 50 years of age (highest vs lowest quintile OR 1.38 (95% confidence interval (CI) 1.02-1.86), P = 0.01, and 1.44 (95% CI 1.04-1.98), P = 0.01, respectively), but no relationship was observed in younger women (OR = 1.03 (95% CI 0.60-1.77), P = 0.81 for IGF-I, and OR = 0.92 (95% CI 0.50-1.70), P = 0.69 for IGFBP-3). There was, however, significant heterogeneity in the relationship of breast cancer with serum IGF-I and IGFBP-3 levels depending on the time interval between blood donation and tumor diagnosis. A reduction in breast cancer risk with increasing IGF-I concentrations was observed in cases with a diagnosis of cancer less than 2 years after blood donation, (OR = 0.76 (95% CI 0.57-1.03)), while an increase in risk was observed for women with a later diagnosis (above or equal to two years after blood collection, OR = 1.51 (95% CI 1.19-1.91)). A similar pattern was observed for IGFBP-3. This study confirms previous findings for an association of serum IGF-I and IGFBP-3 concentrations with breast cancer risk, particularly for women with a later diagnosis of cancer, but it does not support the hypothesis of an involvement of IGF-I in younger women.

Adult↗

CFTR fails to inhibit the epithelial sodium channel ENaC expressed in Xenopus laevis oocytes.

The cystic fibrosis transmembrane conductance regulator (CFTR) plays a crucial role in regulating fluid secretion by the airways, intestines, sweat glands and other epithelial tissues. It is well established that the CFTR is a cAMP-activated, nucleotide-dependent anion channel, but additional functions are often attributed to it, including regulation of the epithelial sodium channel (ENaC). The absence of CFTR-dependent ENaC inhibition and the resulting sodium hyperabsorption were postulated to be a major electrolyte transport abnormality in cystic fibrosis (CF)-affected epithelia. Several ex vivo studies, including those that used the Xenopus oocyte expression system, have reported ENaC inhibition by activated CFTR, but contradictory results have also been obtained. Because CFTR-ENaC interactions have important implications in the pathogenesis of CF, the present investigation was undertaken by our three independent laboratories to resolve whether CFTR regulates ENaC in oocytes and to clarify potential sources of previously reported dissimilar observations. Using different experimental protocols and a wide range of channel expression levels, we found no evidence that activated CFTR regulates ENaC when oocyte membrane potential was carefully clamped. We determined that an apparent CFTR-dependent ENaC inhibition could be observed when resistance in series with the oocyte membrane was not low enough or the feedback voltage gain was not high enough. We suggest that the inhibitory effect of CFTR on ENaC reported in some earlier oocyte studies could be attributed to problems arising from high levels of channel expression and suboptimal recording conditions, that is, large series resistance and/or insufficient feedback voltage gain.

Animals↗

Food and nutrient intake, anthropometric measurements and smoking according to alcohol consumption in the EPIC Heidelberg study.

AIMS: The study was carried out to determine associations of reported alcohol intake with dietary habits, body mass index, waist-to-hip ratio (WHR) and smoking. SUBJECTS AND METHODS: 24,894 subjects who participated in the baseline examination of the German part of the European Prospective Investigation into Cancer and Nutrition (EPIC) in Heidelberg and were between 35 and 65 years of age at baseline were included in the present cross-sectional analysis (11,617 men, 13,277 women). Diet and alcohol consumption were assessed with a semiquantitative food frequency questionnaire. Analysis of covariance with age as a covariate was used to analyse the association between alcohol intake and dietary consumption patterns, BMI, WHR and smoking. RESULTS: Alcohol did not replace other food items, but was an addition to the diet. Among alcohol consumers, fat and protein intake as a percentage of energy was slightly higher and carbohydrate intake was slightly lower than among abstainers. Alcohol consumers had a lower intake of fruits, dairy products, cereal products, and added vegetable fat and a higher intake of animal products such as meat, fish, eggs and added animal fat than abstainers. The prevalence of current smoking showed a U-shaped relation to alcohol intake in men and women. In men, a U-shaped association was also seen between the prevalence of former smoking and alcohol intake, while the prevalence of former smoking increased linearly with alcohol intake in women. CONCLUSION: The results show that alcohol consumption is associated with dietary consumption patterns and smoking. Therefore, it will be important to consider dietary patterns and other lifestyle parameters when investigating the health effects of alcohol intake in the future.

Adult↗

Dietary intake of fatty acids, antioxidants and selected food groups and asthma in adults.

OBJECTIVE: Within a prospective study, we explored the associations between dietary intake of fatty acids, antioxidants and relevant food sources of these nutrients on the clinical manifestation of asthma in adulthood. METHOD: A total of 105 newly physician-diagnosed cases of asthma from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort were identified during follow-up and matched with 420 controls. Baseline dietary intake was obtained by means of validated food frequency questionnaires. The association of dietary intake variables and asthma risk was explored by unconditional logistic regression models. RESULTS: A high intake of oleic acid (C18:1 n-9) was positively associated with asthma (P-value for trend 0.035), while no significant associations were found for the other dietary fatty acids. Most prominently, a high margarine intake increased the risk of onset of asthma in adulthood (adjusted odds ratio (OR) 3rd tertile: 1.73 (95% confidence interval (95% CI): 1.05-2.87), P for trend=0.050), the effect being stronger in men (2nd tertile: OR=1.66, 3rd tertile: OR=2.51) than in women (2nd tertile: OR=0.91; 3rd tertile: OR=1.47). The dietary intake of antioxidants and their main food sources had no effect on asthma risk. CONCLUSIONS: In summary, the present results provide evidence that even in adulthood a high margarine intake increases the risk of clinical onset of asthma. Whether oleic acid may serve as a proxy for margarine-derived trans-fatty acids (C18:1 t9) remains to be clarified.

Adult↗

Allergic sensitisation and allergic rhinitis are associated with n-3 polyunsaturated fatty acids in the diet and in red blood cell membranes.

OBJECTIVE: Due to inconsistent results based on dietary intake data, unsaturated fatty acids in red blood cell (RBC) membranes and diet were used to investigate their association with allergic sensitisation and allergic rhinitis. DESIGN: Cross-sectional, population-based study. SETTING: Bavarian Nutrition Survey II (2002-03), Germany. SUBJECTS: A total of 568 adult participants, 325 women and 243 men. METHODS: By means of logistic regression models, the relation of fatty acids to (i) allergic sensitisation as defined by means of specific serum immunoglobulin E analysis (CAPSX1 class > or = 2), and (ii) self-reported allergic rhinitis was examined. RESULTS: A high cell membrane level of eicosapentaenoic acid (EPA, 20:5 n-3) was inversely associated with allergic sensitisation, the adjusted odds ratio (OR) and 95% confidence interval (95% CI) were 0.52 (0.30-0.90) for the highest (vs lowest) quartile. A similar effect was observed for allergic rhinitis with an OR (95% CI) of 0.50 (0.24-1.03; P = 0.027 for trend). A higher dietary intake of alpha-linolenic acid (ALA, 18:3 n-3) was associated with a decreased risk of allergic sensitisation and allergic rhinitis with ORs (95% CIs) of 0.51 (0.28-0.93) and 0.43 (0.20-0.93), respectively, in the highest quartiles. No other dietary or cell membrane unsaturated fatty acid was significantly associated with the outcome variables, nor was the n-6/n-3 ratio. The strongest effects were observed among subjects under the age of 40 y. CONCLUSIONS: In this cross-sectional study among adults, a high content of n-3 fatty acids in RBC membranes (EPA) or in the diet (ALA) is associated with a decreased risk of allergic sensitisation and allergic rhinitis.

Adult↗

Plasma carotenoids as biomarkers of intake of fruits and vegetables: individual-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC).

OBJECTIVE: The aim in this study was to assess the association between individual plasma carotenoid levels (alpha-carotene, beta-carotene, lycopene, beta-cryptoxanthin, lutein, zeaxanthin) and fruit and vegetable intakes recorded by a calibrated food questionnaire (FQ) and 24-h dietary recall records (24HDR) in nine different European countries with diverse populations and widely varying intakes of plant foods. DESIGN: A stratified random subsample of 3089 men and women from nine countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC), who had provided blood samples and dietary and other lifestyle information between 1992 and 2000, were included. RESULTS: beta-Cryptoxanthin was most strongly correlated with total fruits (FQ r = 0.52, 24HDR r = 0.39), lycopene with tomato and tomato products (FQ r = 0.38, 24HDR r = 0.25), and alpha-carotene with intake of root vegetables (r = 0.39) and of total carrots (r = 0.38) for FQ only. Based on diet measured by FQ and adjusting for possible confounding by body mass index (BMI), age, gender, smoking status, alcohol intake, and energy intake, the strongest predictors of individual plasma carotenoid levels were fruits (R(partial)(2) = 17.2%) for beta-cryptoxanthin, total carrots ((partial)(2) = 13.4%) and root vegetables (R(partial)(2) = 13.3%) for alpha-carotene, and tomato products (R(partial)(2) = 13.8%) for lycopene. For 24HDR, the highest R(partial)(2) was for fruits in relation to beta-cryptoxanthin (7.9%). CONCLUSIONS: Intakes of specific fruits and vegetables as measured by food questionnaires are good predictors of certain individual plasma carotenoid levels in our multicentre European study. At individual subject levels, FQ measurements of fruits, root vegetables and carrots, and tomato products are, respectively, good predictors of beta-cryptoxanthin, alpha-carotene, and lycopene in plasma.

Alcohol Drinking↗

Plasma carotenoids as biomarkers of intake of fruits and vegetables: ecological-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC).

OBJECTIVE: The aim of this study was to assess the ability of a single 24-h dietary recall (24HDR) and food questionnaires (FQ) to predict plasma carotenoid levels at the ecological level by assessing the relationship between mean plasma carotenoid levels and mean intake of fruit and vegetables measured by 24HDR and FQ across 16 European regions. DESIGN: A random subsample of 3089 subjects was included, stratified by age and gender. They provided blood samples and dietary information between 1992 and 2000 as part of the European Prospective Investigation into Cancer and Nutrition. RESULTS: Using Spearman's correlation coefficients, the correlations between mean regional 24HDR fruit and vegetable variables and corresponding mean plasma carotenoid levels were generally higher than the correlations using FQ means. The highest correlation was between the 24HDR citrus fruit variable and beta-cryptoxanthin (r = 0.90). For 24HDR, total fruits and vegetables were highly correlated with lutein, zeaxanthin, and beta-cryptoxanthin (r = 0.83-0.87), while vegetables were more closely related with lutein (r = 0.69) and zeaxanthin (r = 0.68), and fruits correlated with zeaxanthin (r = 0.87) and beta-cryptoxanthin (r = 0.84). Root vegetables (r = 0.81) and total carrots (r = 0.71) were well correlated with alpha-carotene. In the multivariate models adjusting for age, body mass index, and season, and using observations of means stratified by sex and region, the association was generally higher for 24HDR compared to FQ. CONCLUSION: Mean regional intakes of fruits and vegetables in several European countries were closely correlated with corresponding mean plasma levels of individual carotenoids. Fruits and vegetables measured by 24HDR were generally better able to predict plasma carotenoids at the ecological level.

Antioxidants↗

Channelrhodopsins: directly light-gated cation channels.

Phototaxis and photophobic responses of green algae are mediated by rhodopsins with microbial type chromophores, i.e. all-trans-retinal in the ground state. The green alga Chlamydomonas reinhardtii was recently completely sequenced and the EST (expressed sequence tag) database was made public. We and others detected overlapping partial cDNA sequences that encode two proteins which we termed channelopsins (Chops). The N-terminal half of chop1 (approximately 300 of 712 amino acids) comprises hypothetical seven-transmembrane segments with sequence similarity to the proton pump bacteriorhodopsin and the chloride pump halorhodopsin. Even though the overall sequence homology is low, several amino acids are conserved that define the retinal-binding site and the H+-transporting network in BR (bacteriorhodopsin). Expression of Chop1, or only the hydrophobic core, in Xenopus laevis oocytes, enriched with retinal, produced a light-gated conductance (maximum at approx. 500 nm), which shows characteristics of a channel [ChR1 (channelrhodopsin-1)] that is selectively permeable for protons. Also ChR2 (737 amino acids) is an ion channel that is switched directly by light and also here the hydrophobic N-terminal half of the protein is sufficient to enable light-sensitive channel activity. The action spectrum is blue-shifted (maximum at approx. 460 nm) with respect to ChR1. In addition to protons, ChR2 is permeable to univalent and bivalent cations. We suggest that ChRs are involved in phototaxis of green algae. We show that heterologous expression of ChR2 is useful to manipulate intracellular pCa or membrane potential of animal cells, simply by illumination.

Amino Acid Sequence↗

Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition.

Considerable experimental and epidemiological evidence suggests that elevated endogenous sex steroids - notably androgens and oestrogens - promote breast tumour development. In spite of this evidence, postmenopausal androgen replacement therapy with dehydroepiandrosterone (DHEA) or testosterone has been advocated for the prevention of osteoporosis and improved sexual well-being. We have conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. Levels of DHEA sulphate (DHEAS), (Delta4-androstenedione), testosterone, oestrone, oestradiol and sex-hormone binding globulin (SHBG) were measured in prediagnostic serum samples of 677 postmenopausal women who subsequently developed breast cancer and 1309 matched control subjects. Levels of free testosterone and free oestradiol were calculated from absolute concentrations of testosterone, oestradiol and SHBG. Logistic regression models were used to estimate relative risks of breast cancer by quintiles of hormone concentrations. For all sex steroids -the androgens as well as the oestrogens - elevated serum levels were positively associated with breast cancer risk, while SHBG levels were inversely related to risk. For the androgens, relative risk estimates (95% confidence intervals) between the top and bottom quintiles of the exposure distribution were: DHEAS 1.69 (1.23-2.33), androstenedione 1.94 (1.40-2.69), testosterone 1.85 (1.33-2.57) and free testosterone 2.50 (1.76-3.55). For the oestrogens, relative risk estimates were: oestrone 2.07 (1.42-3.02), oestradiol 2.28 (1.61-3.23) and free oestradiol (odds ratios 2.13 (1.52-2.98)). Adjustments for body mass index or other potential confounding factors did not substantially alter any of these relative risk estimates. Our results have shown that, among postmenopausal women, not only elevated serum oestrogens but also serum androgens are associated with increased breast cancer risk. Since DHEAS and androstenedione are largely of adrenal origin in postmenopausal women, our results indicated that elevated adrenal androgen synthesis is a risk factor for breast cancer. The results from this study caution against the use of DHEA(S), or other androgens, for postmenopausal androgen replacement therapy.

Aged↗

The impact of comorbidity on the survival of postmenopausal women with breast cancer.

PURPOSE: The aim was to assess the impact of comorbidity on survival of postmenopausal women with breast cancer diagnosis in the period 1995-1997. METHODS: The level of comorbidity was described by the methods suggested by Satariano and Charlson. Cox's proportional hazard models were used to explore the impact of comorbidity on all-cause mortality. RESULTS: After a median follow-up time of 52 months, an increasing level of comorbidity was associated with a higher all-cause mortality. Compared to patients with-out comorbid conditions, the hazard ration of death (HR) was 1.2 (95% CI: 0.8-1.7) for Satariano index 1 and HR 2.3 (95% CI: 1.5-3.5) for Satariano index >or=2, and HR 1.6 and 2.1 for the Charlson comorbidity index, respectively. Independent of comorbidity, the treatment pattern had a strong impact on survival. The level of comorbidity has an influence on the 3-year survival of postmenopausal women with breast cancer. CONCLUSIONS: Long-term follow-up is required to appraise these findings in relation to treatment strategies.

Aged↗

Use of complementary and alternative medicine by patients with breast cancer: observations from a health-care survey.

GOALS OF THE WORK: The aim of this study was to assess the period prevalence and identify predictors of the use of complementary and alternative medicine (CAM) among women with breast cancer. PATIENTS AND METHODS: In a cross-sectional study, 263 women participating in a quality of life survey reported on CAM use. Differences between CAM users and nonusers were evaluated using logistic regression. RESULTS: About 3 years after diagnosis the period prevalence of CAM use among women with breast cancer was 36%. Younger women reported usage of CAM more often than older women. Associations between remote disease, pain and psychosocial variables were found. Involvement in self-help groups and active participation in leisure activities were associated with CAM use; this may indicate differences in the patients' ability to cope with the disease. Most patients were informed of CAM by a physician. CONCLUSIONS: Involvement in self-help groups and leisure activities were associated with CAM use, indicating differences in the patients' ability to cope. Further research is necessary to evaluate the safety of CAM and to determine the value of CAM in health care.

Adult↗