Depletion of BAFF cytokine exacerbates infection in Pseudomonas aeruginosa infected mice

BackgroundCystic fibrosis (CF) is a genetic disease characterized by chronic inflammation of the lungs that is ineffective at clearing pathogens. B-cell activating factor (BAFF), a cytokine involved in the development of B-cells, is known to be elevated in CF patients with subclinical infections. We postulate that the elevated BAFF levels in CF patients might be triggered by Pseudomonas aeruginosa infection and it might play a protective role in the regulation of lung responses to infection.MethodsTo address this hypothesis, we used a well characterized model of CFTR.KO mice infected with a clinical strain of P. aeruginosa (PA508). We quantified cell types with flow cytometry, concentration of cytokines by ELISA tests, bacterial load by colony counting and lung physiology by metacholine-induced lung resistance.ResultsOur data demonstrates that BAFF is not elevated in uninfected CF mice, and infection with Pseudomonas leads to significant induction of this regulatory cytokine. We also demonstrate that the maintenance of BAFF levels and its induction during the infection is important for clearance of Pseudomonas infection as its depletion during the course of infection leads to decrease in the resolution of infection both in WT and CFTR-KO mice. Interestingly, the depletion of BAFF not only results in a depletion of B cells numbers but also to a significant decrease in the number of regulatory T cells in the non-infected lungs.ConclusionsOverall, our data demonstrate for the first time that BAFF is an important regulatory molecule helping to maintain the immunological response to infection and clearance of lung infection.     

Comparison of Ultrasound-Accelerated versus Pigtail Catheter–Directed Thrombolysis for the Treatment of Acute Massive and Submassive Pulmonary Embolism

Purpose

To compare the technical and clinical effectiveness of ultrasound-accelerated endovascular thrombolysis (USAT) versus pigtail catheter–directed thrombolysis (PCDT) for the treatment of acute pulmonary embolism (PE).

A cribriform urothelial neoplasm of the renal pelvis: an adenoid cysticlike variant of inverted urothelial papilloma or florid ureteritis cystica?

Tumors with cribriform appearance, similar to that of salivary gland adenoid cystic carcinoma, have been described at various anatomic sites. We present an unusual polypoid tumor, discovered incidentally, in the renal pelvis of an elderly man. The mass displayed a prominent cribriform architecture, akin to adenoid cystic carcinoma with an immunophenotype that supported a urothelial origin. Because of its lack of significant invasive growth and other adverse morphologic features, this lesion will likely behave in a banal fashion. This cribriform urothelial neoplasm of the renal pelvis may, in fact, represent a variant of an inverted urothelial neoplasm with a prominent cystic component or florid ureteritis cystica. It is important for pathologists to recognize this growth pattern as a possible variant of urothelial tumors.     

Clofarabine in the treatment of poor risk acute myeloid leukaemia

Clofarabine is a second generation nucleoside analogue. It inhibits DNA repair and activates the mitochondrial apoptotic pathway leading to cell death. In vitro clofarabine has demonstrated synergy with daunorubicin and Ara‐C and in phase II clinical trials has shown promising activity in poor risk Acute myeloid leukaemia (AML) patients. In our institution over a 24 month period 22 AML patients (11 M, 11 F) with poor risk features, deemed unsuitable for standard therapy, were treated with clofarabine, alone (eight patients) or in combination (14 patients) for up to three cycles of treatment. The median age was 67.5 years (24–76) with 16 patients > 60 years. At the time of treatment 18 patients had active AML. Four patients intolerant of standard induction received clofarabine as consolidation. The overall response rate (ORR) for the 18 patients with active AML was 61%, nine patients (50%) achieving a complete response (CR). Induction and consolidation were well tolerated with no unexpected toxicities. Predictably, all patients developed grade 4 neutropenia but the median duration was only 20 days (17–120). Induction mortality was acceptable at 17%. In conclusion, clofarabine (alone or in combination) is active in poor risk AML with an acceptable safety profile and should be considered a potential option in poor risk AML patients. Copyright © 2009 John Wiley & Sons, Ltd.     

Genetic analysis of four Pakistani families with achromatopsia and a novel S4 motif mutation of <Emphasis Type="Italic">CNGA3</Emphasis>

Background  

To identify the causative variants of achromatopsia (ACHM) in four Pakistani families presenting autosomal recessive ACHM.     

Risk and protection in prodromal schizophrenia: ethical implications for clinical practice and future research

Over the last decade schizophrenia researchers have turned their attention to earlier identification in the prodromal period of illness. A greater understanding of both risk and protective factors can lead to improved prevention and treatment strategies in this vulnerable population. This research, however, has far-reaching ethical implications. One year follow-up data from 50 individuals who met established criteria for a prodromal state is used to illustrate ethical issues that directly affect clinicians and future research strategies. At 1-year follow-up, the psychotic transition rate was 13%, but it increased in subsequent years with smaller sample sizes. One-half developed an affective psychosis. The converted sample was older (p > 0.05) than the nonconverted sample and more likely to have a premorbid history of substance abuse, as well as higher clinical ratings on "subsyndromal" psychotic items (delusional thinking, suspiciousness, and thought disorder). Despite a lack of conversion, the nonconverted sample remained symptomatic and had a high rate of affective and anxiety disorders with evidence of functional disability. This conversion rate is relatively low compared to similar studies at 1 year. Specific risk factors were identified, but these findings need to be replicated in a larger cohort. By examining the rate of conversion and nonconversion in this sample as an example, we hope to contribute to the discussion of implications for clinical practice and the direction of future research in the schizophrenia prodrome. Finally, our data strengthen the evidence base available to inform the discussion of ethical issues relevant to this important research area.