Estrogens and Glucocorticoids in Mammary Adipose Tissue: Relationships with Body Mass Index and Breast Cancer Features.

CONTEXT: Adipose tissue is an important site for extragonadal steroid hormone biosynthesis through the expression and activity of P450 aromatase, 11ß-hydroxysteroid dehydrogenase (HSD) 1, and 17ß-HSDs. The contribution of steroid hormones produced by adjacent adipose tissue for the progression and survival of breast tumors is unknown. OBJECTIVE: To quantify estrogens (estradiol, estrone) and glucocorticoids (cortisol, cortisone) in breast adipose tissue from both healthy and diseased women and their relationships with adiposity indices and breast cancer prognostic markers. DESIGN AND SETTING: Breast adipose tissue was collected at time of surgery. PATIENTS: Pre- and postmenopausal women undergoing partial mastectomy for treatment of breast cancer (n = 17) or reduction mammoplasty (n = 6) were studied. INTERVENTIONS: Relative estrogen and glucocorticoid amounts were determined by liquid chromatography tandem mass spectrometry. RESULTS: The targeted steroids were reliably detected and quantified in mammary adipose tissues. Women with ER+/PR+ tumor had higher relative estradiol amount than women with ER-/PR- tumor (P < .05). The ratio of estradiol-to-estrone was higher in lean women than in women with a body mass index (BMI) ≥ 25 kg/m2 (P < .05). Mixed-model analyses showed that estradiol, cortisone, and cortisol were negatively associated with tumor size (P < .05). Relationships between glucocorticoids and tumor size remained significant after adjustment for BMI. The cortisol-to-cortisone ratio was negatively associated with tumor stage (P < .05) independently of BMI. CONCLUSIONS: We reliably quantified estrogens and glucocorticoids in breast adipose tissue from healthy women and women suffering from breast cancer. Our findings suggest that smaller breast tumors are associated with higher relative amounts of estradiol and cortisol in adipose tissue.

Simultaneous quantification of estrogens and glucocorticoids in human adipose tissue by liquid-chromatography-tandem mass spectrometry.

The presence of estrogens, androgens and glucocorticoids as well as their receptors and steroid converting enzymes in adipose tissue has been established. Their contribution to diseases such as obesity, diabetes and hormone-dependent cancers is an active area of research. Our objective was to develop a LC-MS/MS method to quantify bioactive estrogens and glucocorticoids simultaneously in human adipose tissue. Estrogens and glucocorticoids were extracted from adipose tissue samples using solid-phase extraction. Estrogens were derivatized using 1-(2,4-dinitro-5-fluorophenyl)-4-methylpiperazine (PPZ) and methyl iodide to generate a permanently charged molecule (MPPZ). Steroids were separated and quantified by LC-MS/MS. The limit of quantitation for the steroids was between 15 and 100 pg per sample. Accuracy and precision were acceptable (<20%). Using this method, estradiol, estrone, cortisone and cortisol were quantified in adipose tissue from women with and without breast cancer. This novel assay of estrogens and glucocorticoids by LC-MS/MS coupled with derivatization allowed simultaneous quantification of a panel of steroids in human adipose tissue across the endogenous range of concentrations encountered in health and disease.

Simplified Criteria Using Pleural Fluid Cholesterol and Lactate Dehydrogenase to Distinguish between Exudative and Transudative Pleural Effusions.

BACKGROUND: An important part of the investigation of pleural effusion is the identification of markers that help separate exudate from transudate. OBJECTIVES: The purposes of this study were to compare the accuracy of published and new sets of criteria to distinguish between exudative and transudative pleural effusions, and to determine whether serum biochemical analysis is necessary. METHODS: An externally validated cohort study was performed. Pleural effusions were determined to be transudative or exudative on the basis of an assessment of the medical record by two clinicians blinded to biochemical results. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and area under the receiver operating characteristic curve were determined for each proposed combination of criteria. RESULTS: Pleural fluid analysis was available for 311 thoracenteses in the main cohort and for 112 thoracenteses in the validation cohort. The best sensitivity (97% [95% CI 94-99]) and negative likelihood ratio (0.04 [95% CI 0.02-0.08]) for identifying exudative effusions were observed with criteria combining pleural fluid lactate dehydrogenase greater than 0.6 the upper limit of normal serum lactate dehydrogenase and pleural fluid cholesterol greater than 1.04 mmol/L (40 mg/dL). The overall diagnostic accuracy was similar to Light's criteria. Findings were similar in the validation cohort. CONCLUSIONS: Our proposed criteria using simultaneously pleural fluid lactate dehydrogenase and pleural fluid cholesterol can identify an exudate with a sensitivity and an overall diagnostic accuracy similar to Light's criteria. It avoids simultaneous blood sampling, thus reducing patient discomfort and potential costs.

Reoperation Rate After Primary Augmentation With Smooth, Textured, High Fill, Cohesive, Round Breast Implants (RANBI-I Study).

BACKGROUND: Reoperation after primary breast augmentation remains an important clinical issue. OBJECTIVE: The authors sought to evaluate incidence and causes of reoperation in patients who underwent primary augmentation. METHODS: This retrospective, noninterventional study conducted at 16 Canadian sites reviewed medical records and patient-completed questionnaires of women who underwent primary breast augmentation with smooth or textured Natrelle Inspira implants containing TruForm 1 or TruForm 2 gel. Patients were aged ≥22 years, received implants via inframammary fold incision, and returned for follow-up at 2 to 4 years. RESULTS: A total of 319 women received Inspira implants (smooth TruForm 2, n = 205; textured TruForm 2, n = 99; smooth or textured TruForm 1, n = 15). At follow-up, 30 women (9.4%) had undergone reoperation, including 19 (9.3%) in the smooth TruForm 2 subgroup and 9 (9.1%) in the textured TruForm 2 subgroup. The mean time to reoperation was 1.2 years; the risk rate for reoperation was 9.9% at 3 years. The most common reasons for reoperation were implant malposition (36.7%), capsular contracture (33.3%), and the patient's request for a change in implant size or style (20.0%). Most women were very or somewhat satisfied with the initial surgery (89.3% overall; 90.7% smooth TruForm 2; 86.9% textured TruForm 2). Thirty-four women (10.7%) reported adverse events, including 20 (9.8%) in the smooth TruForm 2 subgroup and 14 (14.1%) in the textured TruForm 2 subgroup. CONCLUSIONS: This analysis suggests that Natrelle Inspira TruForm 2 implants are safe when used in primary breast augmentation, resulting in low reoperation rates that are consistent with those for other breast implants.

Influence of trainee involvement on procedural characteristics for linear endobronchial ultrasound.

BACKGROUND: Linear endobronchial ultrasound (EBUS) is a safe and effective method for the diagnostic sampling of mediastinal lymph nodes. However, there is a learning curve associated with the procedure and operator experience influences diagnostic yield. We sought to determine if trainee involvement during EBUS influences procedural characteristics, complication rate, and diagnostic yield. METHODS: We performed a retrospective analysis of 220 subjects who underwent an EBUS procedure at our center from December 2012 to June 2013. Procedures were performed by six different interventional pulmonologists with substantial experience with EBUS or by a trainee under their direct supervision. Procedural characteristics and complications were recorded. Diagnostic yield and specimen adequacy were compared between groups. RESULTS: EBUS was performed in 220 patients with a trainee involved (n = 116) or by staff physician alone (n = 104). Patient characteristics, and the number and size of lymph node stations sampled were similar. EBUS duration was longer (16.0 vs. 13.7 minutes; P = 0.002) and the total dose of lidocaine used was higher (322.3 vs. 304.2 mg; P = 0.045) when a trainee was involved. The rate of adequate specimens sampled was comparable between the groups (92.0 vs. 92.0%; P = 0.60). Diagnostic yield was lower when a trainee was involved in the EBUS procedure (52.6 vs. 68.3%; P = 0.02). CONCLUSION: Trainee involvement significantly increased EBUS duration and the dose of local anesthesia used for the procedure. Diagnostic yield was lower when a trainee was involved. Factors accounting for this difference in yield, despite adequate samples being obtained, warrant further investigation.

Occupational asthma phenotypes identified by increased fractional exhaled nitric oxide after exposure to causal agents.

BACKGROUND: The added value of fractional exhaled nitric oxide (Feno) remains controversial in the investigation of occupational asthma (OA). OBJECTIVE: We sought to assess whether or not the increase of Feno levels following positive specific inhalation challenge (SIC) was restricted to phenotypes of subjects sharing common clinical characteristics by using a statistical cluster analysis. METHODS: Subjects were investigated for possible OA in a tertiary center using SICs from 2006 to 2012. Feno levels and sputum eosinophil counts were assessed at baseline and 24 hours after SIC. We performed a 2-step cluster analysis of the subgroup of subjects with OA. A multivariate logistic regression was performed in order to identify the variables associated with an increase in Feno in subjects with OA. RESULTS: One hundred and seventy-eight subjects underwent SIC; 98 had a positive test. The cluster analysis performed in the OA subgroup identified 3 clusters. Despite a positive SIC, there was no increase in the Feno levels after exposure to occupational agents in Cluster 3, in which subjects were only exposed to low-molecular-weight (LMW) agents. The molecular weight of the agent (high molecular weight vs LMW) was the only factor associated with an increase in Feno (OR: 4.2 [1.1-16.8]) in subjects with a positive SIC. CONCLUSION: An increase in Feno after exposure to agents causing OA seems to occur more consistently in subjects with OA caused by high molecular weight than in those with OA due to LMW.

Integrated approach to diagnosis of associated occupational asthma and rhinitis.

Patients with coexisting work-related rhinitis and asthma would benefit from an adequate and simultaneous recognition of both diseases. The present case illustrates the advantages and importance of using an integrated approach to confirm a diagnosis of occupational rhinitis (OR) and occupational asthma (OA). A 38-year-old woman, who worked as an animal laboratory technician since 2004, first noticed the appearance of rhinitis and conjunctivitis symptoms in 2007 when she was exposed to rats. A skin-prick test with rat extract was strongly positive. A specific inhalation challenge with parallel assessment of nasal and bronchial responses was conducted. After 10 min of exposure, she developed rhinitis and conjunctivitis symptoms, her forced expiratory volume in 1 s dropped by 27.5% and her nasal volume, measured by acoustic rhinometry, decreased by 80% from baseline values. After allergen exposure, induced sputum and nasal lavage examination demonstrated an increase in eosinophils (11% and 20%, respectively). A diagnosis of associated allergic OA and OR was confirmed and she was advised to stop working with rats. A systematic and parallel diagnostic approach enables confirmation of a diagnosis of OA and OR in patients complaining of work-related rhinitis and asthma symptoms.

Congenital Amusia (or Tone-Deafness) Interferes with Pitch Processing in Tone Languages.

Congenital amusia is a neurogenetic disorder that affects music processing and that is ascribed to a deficit in pitch processing. We investigated whether this deficit extended to pitch processing in speech, notably the pitch changes used to contrast lexical tones in tonal languages. Congenital amusics and matched controls, all non-tonal language speakers, were tested for lexical tone discrimination in Mandarin Chinese (Experiment 1) and in Thai (Experiment 2). Tones were presented in pairs and participants were required to make same/different judgments. Experiment 2 additionally included musical analogs of Thai tones for comparison. Performance of congenital amusics was inferior to that of controls for all materials, suggesting a domain-general pitch-processing deficit. The pitch deficit of amusia is thus not limited to music, but may compromise the ability to process and learn tonal languages. Combined with acoustic analyses of the tone material, the present findings provide new insights into the nature of the pitch-processing deficit exhibited by amusics.

Tone language fluency impairs pitch discrimination.

Here we present evidence that native speakers of a tone language, in which pitch contributes to word meaning, are impaired in the discrimination of falling pitches in tone sequences, as compared to speakers of a non-tone language. Both groups were presented with monotonic and isochronous sequences of five tones (i.e., constant pitch and intertone interval). They were required to detect when the fourth tone was displaced in pitch or time. While speakers of a tone language performed more poorly in the detection of downward pitch changes, they did not differ from non-tone language speakers in their perception of upward pitch changes or in their perception of subtle time changes. Moreover, this impairment cannot be attributed to poor musical abilities since the impairment remains unchanged when individual differences in musical pitch-based processing is taken into account. Thus, the impairment appears highly specific and may reflect the influence of statistical regularities of tone languages.

Tonal language processing in congenital amusia.

Twenty amusic and 20 control speakers of French were presented with pairs of Mandarin lexical tones to discriminate as same or different. Results revealed that even if the amusic group performed significantly below the control group, the scores of the two groups largely overlapped, with only 15% of the amusic group performing outside the normal variations. Thus, the findings suggest a modest transfer of deficit between music and speech, which in turn calls for further work in order to identify the nature of the mediating factors.

Expression of the self-marker CD47 on dendritic cells governs their trafficking to secondary lymphoid organs.

Dendritic cells (DCs) capture and process Ag in the periphery. Thus, traffic through lymphatic vessels is mandatory before DCs relocate to lymph nodes where they are dedicated to T-cell priming. Here, we show that the ubiquitous self-marker CD47 selectively regulates DC, but not T and B cell trafficking across lymphatic vessels and endothelial barriers in vivo. We find an altered skin DC migration and impaired T-cell priming in CD47-deficient mice at steady state and under inflammatory conditions. Competitive DC migration assays and active immunization with myeloid DCs demonstrate that CD47 expression is required on DCs but not on the endothelium for efficient DC trafficking and T-cell responses. This migratory defect correlates with the quasi-disappearance of splenic marginal zone DCs in nonmanipulated CD47-deficient mice. Nonetheless, CCR7 expression and CCL19-driven chemotaxis remain intact. Our data reveal that CD47 on DCs is a critical factor in controlling migration and efficient initiation of the immune response.