Immunologic privilege in the central nervous system and the blood–brain barrier

The brain is in many ways an immunologically and pharmacologically privileged site. The blood–brain barrier (BBB) of the cerebrovascular endothelium and its participation in the complex structure of the neurovascular unit (NVU) restrict access of immune cells and immune mediators to the central nervous system (CNS). In pathologic conditions, very well-organized immunologic responses can develop within the CNS, raising important questions about the real nature and the intrinsic and extrinsic regulation of this immune privilege. We assess the interactions of immune cells and immune mediators with the BBB and NVU in neurologic disease, cerebrovascular disease, and intracerebral tumors. The goals of this review are to outline key scientific advances and the status of the science central to both the neuroinflammation and CNS barriers fields, and highlight the opportunities and priorities in advancing brain barriers research in the context of the larger immunology and neuroscience disciplines. This review article was developed from reports presented at the 2011 Annual Blood-Brain Barrier Consortium Meeting.     

Factors associated with silent myocardial ischemia,autonomic or peripheral neuropathies,and survival in diabetes mellitus type 2 patients without cardiovascular symptoms

International Journal of Diabetes in Developing Countries - Complications from diabetes mellitus (DM) include cardiovascular system, peripheral neuropathy (PN), and autonomic dysfunction (AD)....     

Gene expression profiles of breast cancer metastasis according to organ site

In advanced breast cancer, biomarker identification and patient selection using a metastatic tumor biopsy is becoming more necessary. However, the biology of metastasis according to the organ site is largely unknown. Here, we evaluated the expression of 771 genes in 184 metastatic samples across 11 organs, including liver, lung, brain, and bone, and made the following observations. First, all PAM50 molecular intrinsic subtypes were represented across organs and within immunohistochemistry‐based groups. Second, HER2‐low disease was identified across all organ sites, including bone, and HER2 expression significantly correlated with ERBB2 expression. Third, the majority of expression variation was explained by intrinsic subtype and not organ of metastasis. Fourth, subtypes and individual subtype‐related genes/signatures were significantly associated with overall survival. Fifth, we identified 74 genes whose expression was organ‐specific and subtype‐independent. Finally, immune profiles were found more expressed in lung compared to brain or liver metastasis. Our results suggest that relevant tumor biology can be captured in metastatic tissues across a variety of organ sites; however, unique biological features according to organ site were also identified and future studies should explore their implications in diagnostic and therapeutic interventions.     

GenoType MTBDRplus assay for molecular detection of rifampin and isoniazid resistance in Mycobacterium tuberculosis strains and clinical samples

The purpose of this study was to evaluate the GenoType MTBDRplus assay (Hain Lifescience GmbH, Nehren, Germany) for its ability to detect resistance to rifampin (RIF) and isoniazid (INH) in Mycobacterium tuberculosis clinical strains and directly in clinical samples. A total of 62 clinical strains characterized with the Bactec 460TB system were included. For the INH-resistant strains, the MIC was measured and sequencing was performed. Sixty-five clinical samples from 28 patients (39 smear-positive samples and 26 smear-negative samples) were also tested directly. The corresponding isolates of the clinical specimens were studied with the Bactec 460TB system. The overall rates of concordance of the MTBDRplus assay and the Bactec 460TB system for the detection of RIF and INH susceptibility in clinical strains were 98.3% (61/62) and 79% (49/62), respectively. The rate of concordance between the Bactec 460TB system and the MTBDRplus test for the detection of INH resistance in the group of 27 strains with low-level resistance was 62.9% (17/27), and that for the detection of INH resistance in the group of 21 strains with high-level resistance was 85.71% (18/21). Valid test results were obtained for 78.45% (51/65) of the clinical samples tested. The rates of concordance between both assays for the detection of drug resistance in these samples were 98% (50/51) for RIF and 96.2% (49/51) for INH. Taking into account only one sample per patient, the overall rate of concordance between both tests was 92.85% (26/28). The GenoType MTBDRplus assay is easy to perform and is a useful tool for the management of tuberculosis, as it allows the detection of resistance to RIF and INH in M. tuberculosis strains and also in clinical samples.     

Endoscopic management of pancreatic fistula after distal pancreatectomy and enucleation

Background

Preoperative endoscopic pancreatic sphincterotomy (EPS) has been proposed to prevent postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP) or enucleation (EN). The use of EPS as a curative treatment for POPF has been scarcely reported. We reported 10 consecutive patients who were successfully treated by EPS for a prolonged POPF.

Study design

Ten patients underwent EPS for prolonged POPF (median duration = 40 days, range 20-114; median daily output = 80 mL, range 50-250) after 6 DPs, 2 ENs, and 2 medial pancreatectomies.

Results

EPS was performed in all patients, with stent insertion in 4. No patient developed a specific complication because of EPS. POPF healed within a median delay of 4 days (range 1-12). One patient underwent a repeated endoscopy to treat stent malposition. The median delay of discharge after EPS was 13 days (range 8-15). With a 20-month median follow up, 1 patient developed early transient POPF recurrence because of spontaneous stent migration.

Conclusions

EPS is indicated for prolonged POPF after DP or EN because it is highly feasible, shortens healing, and is well tolerated.