Performance of a New MicroScan WalkAway PC30 panel and disk diffusion method for detection of oxacillin resistance in Staphylococcus spp

The performance of the MicroScan WalkAway PC30 panel for detection of oxacillin resistance was evaluated by use of a collection of 420 staphylococcus isolates. The addition of a cefoxitin test (4 mg/liter) to the oxacillin MIC determination increased its raw performance for Staphylococcus aureus; additional data were required for coagulase-negative staphylococci.     

Cytological, histological, and immunohistochemical findings of pulmonary carcinomas with basaloid features

Pulmonary basaloid carcinoma (BC), a variant of large cell, nonsmall cell carcinoma (NSCC), and basaloid squamous cell carcinoma (BSQCC) can show features similar to small cell carcinoma (SCC) and large cell neuroendocrine carcinoma (LCNEC). Distinction from SCC, especially on FNA, is therapeutically relevant. We describe cytological, histological, and immunohistochemical features of BC and BSQCC. Numerous cytologic features were documented in cytologic preparations. Similar features and architecture were evaluated in the resections. Immunohistochemical results were recorded. Histologically confirmed BC (n = 3) and BSQCC (n = 3) were included. Five FNAs of SCC, (four with histologic follow-up) were studied for comparison of cytological, histological, and immunohistochemical findings. In cytologic preparations of BC/BSQCC, cells were arranged mostly as tightly cohesive clusters (n = 4) or singly and in clusters (n = 2) with a predominance of clusters. Cytologic features of BC and BSQCC were similar: palisading (n = 6), crush artifact (n = 6), hyperchromasia (n = 5), focal nuclear molding (n = 6; very rare in 2/6), nucleoli, usually pinpoint (n = 3), scant cytoplasm (n = 6), necrosis (n = 5), apoptosis (n = 4), squamous differentiation (n = 1). BSQCC tended to have occasional larger cells, including keratinizing cells in one case. Histologic sections (n = 6) showed neuroendocrine features, including organoid arrangements, nests, and palisading. BC and BSQCC show overlapping features with SCC and LCNEC in cytological and histological specimens. Unlike SCCs, BC/BSQCC lack prominent nuclear molding, show tightly cohesive cell clusters, and demonstrate palisading. However, immunostains were the very helpful and probably necessary to accurately diagnosing BC/BSQCC, which show the immunostaining pattern of p63 (+), HMWCK (+), and TTF-1 (-).     

Value of PCA3 urinary test for prostate biopsy decision: the Lyon-Sud University Hospital experience

The poor specificity of diagnostic strategy for prostate cancer (digital rectal examination and seric PSA) induces both a great number of useless prostate biopsies and diagnosis of non evolutive cancers. A urinary test (Progensa PCA3(?), Gen-Probe) measuring the expression of PCA3, a prostate cancer-specific gene, has recently be proposed to indicate re-biopsy. The aim of this prospective study was to evaluate diagnostic value of urinary PCA3 test for prostate cancer. In the urines of 245 patients submitted to prostate biopsy, expression of the PCA3 gene was measured and reported to that of PSA to calculate PCA3 score using a method amplifying and detecting RNA. Patients with informative samples (98%) were classified depending of the presence (n?=?126) or absence (n?=?114) of cancer tissue on biopsies. The median PCA3 score was significantly higher in the group with positive biopsies (p?相似文献   

Determinants and Reference Ranges of Serum Immunoglobulins in Middle-Aged and Elderly Individuals: a Population-Based Study

Purpose

In clinical practice, currently one reference range for serum immunoglobulin (Ig) A, G, and M is applied to all adults, although various factors may influence Ig serum levels. Population-based data on determinants of IgA, IgG, and IgM and recommendations for subgroup specific reference ranges are lacking. We aimed to provide an overview of determinants of IgA, IgG, and IgM in community-dwelling middle-aged and elderly individuals and explore determinants that influence Ig reference ranges.

Methods

Within the Rotterdam Study, we performed linear regression analyses for the association of demographic, lifestyle, and cardiovascular factors with serum IgA, IgG, and IgM. We furthermore calculated Ig reference ranges (based on percentiles), both overall and within relevant subgroups.

Results

We included 8768 participants (median age 62 years). IgA and IgG increased non-linearly with higher age (P?<?.0001 for both). Women had lower IgA (beta:???0.24; 95% confidence interval [95% CI]:???0.29;???0.20) and IgG (beta:???0.33; 95% CI:???0.44;???0.23), but higher IgM levels (beta: 0.08; 95% CI: 0.04;0.13) than men. Former and particularly current smoking were associated with lower IgA and IgG (betas between???0.07 and???1.03). Higher alcohol consumption was associated with lower IgG (beta for heavy drinking:???0.70; 95% CI:???0.91;???0.48). Corticosteroid use was associated with lower IgG (beta:???1.12; 95% CI:???1.58;???0.66). Associations with cardiovascular factors were heterogeneous and differed between sexes.

Conclusion

Age, sex, smoking, alcohol consumption, corticosteroid use, and cardiovascular factors are determinants that should be considered when interpreting serum Ig levels in middle-aged and elderly individuals and may require adjusted reference ranges.

     

The role of weight bias and role-modeling in medical students’ patient-centered communication with higher weight standardized patients

ObjectivePatients with obesity may experience less patient-centered care. We assessed whether medical students’ implicit/explicit weight-related attitudes and perceptions of normative attitudes are associated with patient-centered care for patients with obesity.MethodsThird and fourth year medical students (N = 111) at one medical school completed a survey and participated in a patient care scenario with a standardized patient with obesity. Encounters were coded for patient-centered behavior. Predictors of patient-centered behaviors were assessed.ResultsStudent perceptions that negative attitudes about patients with obesity are normative in medical school were significantly associated with poorer patient-centered behaviors, including lower attentiveness (b=?0.19, p = 0.01), friendliness (b=?0.28, p < 0.001), responsiveness (b=?0.21, p = 0.002), respectfulness (b=?0.17, p = 0.003), interactivity (b=?0.22, p = 0.003), likelihood of being recommended by observers (b=?0.34, p < 0.001), and patient-centeredness index scores (b=?0.16, p = 0.002). Student reported faculty role-modeling of discrimination against patients with obesity predicted lower friendliness (b=?0.16, p = 0.03), recommendation likelihood (b=?0.22, p = 0.04), and patient-centeredness index score (b=?0.12, p = 0.03).ConclusionsNegative normative attitudes and behaviors regarding obesity in the medical school environment may adversely influence the quality of patient-centered behaviors provided to patients with obesity.Practice implicationsEfforts to improve patient-centered communication quality among medical trainees may benefit from intervention to improve group normative attitudes about patients with obesity.     

Plasma membrane Ca2+ ATPase 1 (PMCA1) but not PMCA4 is critical for B-cell development and Ca2+ homeostasis in mice

The amplitude and duration of Ca²⁺ signaling is crucial for B-cell development and self-tolerance; however, the mechanisms for terminating Ca²⁺ signals in B cells have not been determined. In lymphocytes, plasma membrane Ca²⁺ ATPase (PMCA) isoforms 1 and 4 (PMCA1 and PMCA4, aka ATP2B1 and ATP2B4) are the main candidates for expelling Ca²⁺ from the cell through the plasma membrane. We report here that Pmca4 (Atp2b4) KO mice had normal B-cell development, while mice with a conditional KO of Pmca1 (Atp2b1) had greatly reduced numbers of B cells, particularly splenic follicular B cells, marginal zone B cells, and peritoneal B-1a cells. Mouse and naïve human B cells showed only PMCA1 expression and no PMCA4 by western blot, in contrast to T cells, which did express PMCA4. Calcium handling was normal in Pmca4^−/− B cells, but Pmca1 KO B cells had elevated basal levels of Ca²⁺, elevated levels in ER stores, and reduced Ca²⁺ clearance. These findings show that the PMCA1 isoform alone is required to ensure normal B-cell Ca²⁺ signaling and development, which may have implications for therapeutic targeting of PMCAs and Ca²⁺ in B cells.     

Positive and negative selection of antigen-specific B cells in transgenic mice expressing variant forms of the V(H)1 (T15) heavy chain

Four variant forms of the V1 (T15-H chain) gene are synthesized in mice. Each V1 variant pairs with a distinct L chain to produce a binding site having specificity for phosphocholine (PC). Transgenic mice expressing variant forms of the V1 gene were analyzed to elucidate the factors driving B cell selection into the peripheral repertoire. In all four lines of H chain transgenic mice analyzed, transgene expression caused complete allelic exclusion of endogenous H chains in the bone marrow (BM), whereas most splenic B cells expressed endogenous H chains. The number of sIgM(+) BM B cells and their sIg receptor number was reduced compared to that of normal transgene-negative controls, suggesting that B cells expressing transgene-encoded H chains were being negatively selected in the BM. Mice expressing autoreactive forms of the V1 transgene with lower affinity for PC (M603H and M167H) exhibit positive selection of PC-specific B cells into the spleen, whereas mice expressing the higher affinity T15H variant exhibited elevated PC-specific B cells in the peritoneal cavity but few V(H)1(+) splenic B cells. These data suggest that the higher affinity T15-id(+) B cells preferentially survive in the peritoneal cavity. When these H chain transgenes were crossed into the mu MT knockout mouse in which surface expression of endogenous H chains is blocked, the percent of splenic V(H)1(+) PC-specific B cells increased up to 5-fold and T15-id(+) B cells were detectable in the spleen of T15H mice. This implies that T15-id(+) PC-specific B cells can be selected into the periphery, but they compete poorly with follicular B cells expressing endogenous Ig.     

Generation of antibodies directed against the low-immunogenic peptide-toxins microcystin-LR/RR and nodularin

The preparation of antibodies against the liver toxin microcystin, as described here, is of major importance for its detection and purification in food and water, and for a therapeutic approach to neutralize the toxin by passive immunization. Microcystin-LR (MLR) and microcystin-RR (MRR) were purified from cyanobacterial cell materials by extraction, Sephadex LH-20-, ODS silica gel-, ionic exchange and RP-HPLC-chromatography. In order to reduce the toxicity for parenteral administration, microcystins were coupled by the carbodiimide method to poly-L-lysine (PLL(50.000)). Mice and rabbits were immunized with the conjugates in the presence of two lipopeptide immunoadjuvants (P(3)CSK(4) and P(3)CS-T(h)). High MLR-specific antibody levels were observed after parenteral coadministration of antigen and lipopeptides, whereas no anti-MLR antibodies were obtained with free microcystin or the microcystin-PLL(50.000)-conjugate in the absence of lipopeptide. In oral immunization, coadministration of antigen and adjuvants resulted in an accelerated development of anti MLR-specific antibodies and high antibody levels. Using the antisera, we could detect different microcystins and nodularin down to a concentration range of 10-50 ng/ml by a competitive inhibition ELISA; detection of microcystins in crude cell preparations was also possible. Furthermore, microcystins from different sources could be detected and discriminated from cyclic cyanopeptolines.