Diagnostic Splenectomy for Visceral Leishmaniasis

A 57-year-old-man with a history of malaise, fever,night sweats and shortness of breath presented a diagnostic challenge to his medical team. He was pancytopaenic and had splenomegaly on admission but other investigations, including bone marrow aspiration, proved inconclusive. After the patient deteriorated clinically, the general surgical team was requested to perform a diagnostic splenectomy. The histology of this showed infection with visceral leishmaniasis. He recovered completely with Amphotericin treatment. Although this is a rare condition, particularly for the general surgeon, this case highlights the difficult position surgeons are often put in when performing major surgery diagnostically.     

Effect of high-dose methylprednisolone infusion on polymorphonuclear leukocyte function in patients with systemic lupus erythematosus

We have studied the effect of high-dose (1 gm) methylprednisolone infusion on polymorphonuclear leukocyte (PMN) function in 11 patients with active systemic lupus erythematosus (SLE). The only alteration of polymorphonuclear leukocyte function produced consistently by methylprednisolone was decreased adherence to plastic surfaces when tested 2 hours after infusion. This steroid-induced abnormality, however, was transient. Cells obtained from patients 24 hours after a single dose of drug exhibited normal adhesiveness. These results indicate that single, large doses of methylprednisolone do not produce long-lasting abnormalities of PMN function in patients with lupus.     

The development of an instrument to evaluate interprofessional student team competency

Healthcare institutions, accreditation agencies for higher learning, and organizations such as the National Academy of Medicine in the United States, support interprofessional education (IPE) opportunities. However, incorporating IPE opportunities into academic settings remains difficult. One challenge is assessing IPE learning and practice outcomes, especially at the level of student performance to ensure graduates are “collaboration-ready”. The Creighton-Interprofessional Collaborative Evaluation (C-ICE) instrument was developed to address the need for a measurement tool for interprofessional student team performance. Four interprofessional competency domains provide the framework for the C-ICE instrument. Twenty-six items were identified as essential to include in the C-ICE instrument. This instrument was found to be both a reliable and a valid instrument to measure interprofessional interactions of student teams. Inter-rater reliability as measured by Krippendorff’s nominal alpha (nKALPHA) ranged from .558 to .887; with four of the five independent assessments achieving nKALPHA greater than or equal to 0.796. The findings indicated that the instrument is understandable (Gwet’s alpha coefficient (gAC) 0.63), comprehensive (gAC = 0.62), useful and applicable (gAC = 0.54) in a variety of educational settings. The C-ICE instrument provides educators a comprehensive evaluation tool for assessing student team behaviors, skills, and performance.     

Impact of Physical Activities on Frailty in Community-Dwelling Older Women

Aims: The aim of the study was to determine whether increased physical activities (PA) affect frailty for old women, 75 years and older (OO), compared to 60–74 years old (YO). Methods: This cross-sectional study measured 19 frailty indicators (muscle strength and endurance, balance, gait characteristics, and function), using 46 community-dwelling women. PA were divided into three levels by caloric expenditure per week (<2,000 kcal/week, 2,000–3,999 kcal/week, >4,000 kcal/week). Results: As PA level increased, a gap (=difference) between OO and YO narrowed for step length and function, but for quadriceps strength and endurance, a gap widened. Conclusions: Frailty progresses with aging but older women who engage in a high level of physical activity (>4,000 kcal/week) can increase mobility and functional capacity, but not for muscle strength and endurance. Starting regular resistance training activities early in the aging process is critical to improve or maintain muscle quality to offset age-related frailty.     

Elevated blood viscosity in patients with borderline essential hypertension

In patients with borderline hypertension, total peripheral resistance (TPR) is either elevated or abnormally related to cardiac output. Since blood viscosity is one determinant of TPR, we compared various components of blood viscosity in 25 patients with borderline hypertension and 25 normal subjects. Under all experimental blood flow conditions examined, blood viscosity directly correlated with systolic and diastolic blood pressure (p less than 0.05 or better) and was greater in the hypertensive than in normal subjects. Venous hematocrit and plasma viscosity were higher in the hypertensive patients. These latter rheologic abnormalities accounted for the increased blood viscosity at higher shear rates. At lower shear rates, increased red cell aggregation, primarily mediated by elevated fibrinogen concentration, accounted for the higher blood viscosity in the hypertensive subjects. We conclude that even relatively small elevations in arterial pressure are associated with increased viscous resistance of blood to flow, and that the increased blood viscosity is a consequence of increased hematocrit, plasma viscosity, and red cell aggregation.     

Ultra‐deep T cell receptor sequencing reveals the complexity and intratumour heterogeneity of T cell clones in renal cell carcinomas

The recognition of cancer cells by T cells can impact upon prognosis and be exploited for immunotherapeutic approaches. This recognition depends on the specific interaction between antigens displayed on the surface of cancer cells and the T cell receptor (TCR), which is generated by somatic rearrangements of TCR α‐ and β‐chains (TCRb). Our aim was to assess whether ultra‐deep sequencing of the rearranged TCRb in DNA extracted from unfractionated clear cell renal cell carcinoma (ccRCC) samples can provide insights into the clonality and heterogeneity of intratumoural T cells in ccRCCs, a tumour type that can display extensive genetic intratumour heterogeneity (ITH). For this purpose, DNA was extracted from two to four tumour regions from each of four primary ccRCCs and was analysed by ultra‐deep TCR sequencing. In parallel, tumour infiltration by CD4, CD8 and Foxp3 regulatory T cells was evaluated by immunohistochemistry and correlated with TCR‐sequencing data. A polyclonal T cell repertoire with 367–16 289 (median 2394) unique TCRb sequences was identified per tumour region. The frequencies of the 100 most abundant T cell clones/tumour were poorly correlated between most regions (Pearson correlation coefficient, –0.218 to 0.465). 3–93% of these T cell clones were not detectable across all regions. Thus, the clonal composition of T cell populations can be heterogeneous across different regions of the same ccRCC. T cell ITH was higher in tumours pretreated with an mTOR inhibitor, which could suggest that therapy can influence adaptive tumour immunity. These data show that ultra‐deep TCR‐sequencing technology can be applied directly to DNA extracted from unfractionated tumour samples, allowing novel insights into the clonality of T cell populations in cancers. These were polyclonal and displayed ITH in ccRCC. TCRb sequencing may shed light on mechanisms of cancer immunity and the efficacy of immunotherapy approaches. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Hyperspectral imaging and spectral unmixing for improving whole-body fluorescence cryo-imaging

Whole-animal fluorescence cryo-imaging is an established technique that enables visualization of the biodistribution of labeled drugs, contrast agents, functional reporters and cells in detail. However, many tissues produce endogenous autofluorescence, which can confound interpretation of the cryo-imaging volumes. We describe a multi-channel, hyperspectral cryo-imaging system that acquires densely-sampled spectra at each pixel in the 3-dimensional stack. This information enables the use of spectral unmixing to isolate the fluorophore-of-interest from autofluorescence and/or other fluorescent reporters. In phantoms and a glioma xenograft model, we show that the approach improves detection limits, increases tumor contrast, and can dramatically alter image interpretation.