Analyses of phenotypic and functional characteristics of CX3CR1-expressing natural killer cells

We previously demonstrated a correlation between the frequency of CX3CR1-expressing human natural killer (NK) cells and disease activity in multiple sclerosis and showed that CX3CR1(high) NK cells were more cytotoxic than their CX3CR1(neg/low) counterparts. Here we aimed to determine whether human NK cell fractions defined by CX3CR1 represent distinct subtypes. Phenotypic and functional NK cell analyses revealed that, distinct from CX3CR1(high), CX3CR1(neg/low) NK cells expressed high amounts of type 2 cytokines, proliferated robustly in response to interleukin-2 and promoted a strong up-regulation of the key co-stimulatory molecule CD40 on monocytes. Co-expression analyses of CX3CR1 and CD56 demonstrated the existence of different NK cell fractions based on the surface expression of these two surface markers, the CX3CR1(neg) CD56(bright), CX3CR1(neg) CD56(dim) and CX3CR1(high) CD56(dim) fractions. Additional investigations on the expression of NK cell receptors (KIR, NKG2A, NKp30 and NKp46) and the maturation markers CD27, CD62L and CD57 indicated that CX3CR1 expression of CD56(dim) discriminated between an intermediary CX3CR1(neg) CD56(dim) and fully mature CX3CR1(high) CD56(dim) NK cell fractions. Hence, CX3CR1 emerges as an additional differentiation marker that may link NK cell maturation with the ability to migrate to different organs including the central nervous system.     

Glassy cell carcinoma of the urethra

Glassy cell carcinoma is a poorly differentiated form of adenosquamous carcinoma that has never been reported in the urinary tract. We present the first case of primary glassy cell carcinoma of the urethra in a 48-year-old woman. She presented with a newly developed bulky mass protruding from her urethra. A biopsy of this mass revealed sheets of large polygonal cells with a "ground-glass" cytoplasm among a heavy inflammatory infiltrate, establishing the diagnosis of glassy cell carcinoma of the urethra. Treatment of her tumor included a combined surgical and chemotherapeutic approach.     

The capture-mark-recapture technique can be used as a stopping rule when searching in systematic reviews

ObjectiveResearchers have no empirically based search stopping rule when looking for potentially relevant articles for inclusion in systematic reviews. We tested a stopping strategy based on capture–mark–recapture (CMR; i.e., the Horizon Estimate) statistical modeling to estimate the total number of articles in the domain of clinical decision support tools for osteoporosis disease management using four large bibliographic databases (Medline, EMBASE, CINAHL, and EBM reviews).Study Design and SettingRetrospective evaluation of the Horizon Estimate using a systematic review of randomized controlled trials (RCTs) at two levels of article screening: title and abstract (1,246 potentially relevant articles) and full text (42 potentially relevant articles).ResultsThe CMR model suggests that the total number of potential articles was 1,838 for the first level of screening, and 49 for the full-text level. The four databases provided 68% of known articles for the first level of screening and 81% for full-text screening.ConclusionsThe CMR technique can be used in systematic reviews to estimate the closeness to capturing the total body of literature on a given topic. More studies are needed to objectively determine the usefulness of Horizon Estimates as a stopping rule strategy for systematic review searching.     

Mathematical model for wound healing following autologous keratinocyte transplantation

In times of increasing economical pressure on the health care systems, it is important to optimise the outpatient treatment of chronic wounds. Another aim of wound healing research is to discover agents to accelerate healing. Wound healing trajectories or healing velocities can provide information to demonstrate the endpoints for wound healing. A great problem in clinical trials is to specify these parameters. Therefore, we developed a mathematical model for more transparency. In this initial project, we observed 19 wounds to construct the wound healing trajectories after transplantation of autologous keratinocytes, and the results are so encouraging that investigation in this area will continue. The developed mathematical model describes the clinical observed healing process. It was possible to find parameters to distinguish between old and young patients, retrospectively or prospectively calculate the healing rates and to determine exactly the endpoint of healing. Therefore, our model might be very useful in practices or for studies.     

Altered blood flow in terminal vessels after local application of ropivacaine and prilocaine

BACKGROUND: Ropivacaine is primarily a local anesthetic, but it also acts as a vasoactive agent. Case reports have described a critical reduction in blood flow when higher concentrations of ropivacaine were used for peripheral-nerve blocks. One hypothesis is that local application of ropivacaine in tissues supplied by end arteries reduces tissue blood flow because of arterial vasoconstriction. METHODS: Rats were anesthetized by inhalation of isoflurane. The tail vessels were carefully dissected from the ventral side near the radix. Randomly, normal saline, prilocaine 0.5%, prilocaine 0.5% with epinephrine 1:200,000, ropivacaine 0.2%, ropivacaine 0.5%, or ropivacaine 0.75% was applied directly to the artery. Blood flow in the tail was continuously measured by use of laser Doppler flowmetry distal to the surgical site. Changes in temperature in the tail were detected by use of infrared thermography. RESULTS: Blood flow decreased after the application of ropivacaine at all concentrations in comparison with normal saline (P < .01 at t = 10 minutes, P < .001 at t = 20, 30, and 40 minutes). This effect was most pronounced at t = 30 minutes for ropivacaine 0.5% (with a 64.5% decrease in blood flow). Prilocaine 0.5% with epinephrine 1:200,000 reduced blood flow by up to 44.7% (t = 20 minutes, P < .001). In comparison with the placebo, the application of ropivacaine 0.5% and 0.75%, as well as prilocaine 0.5% with epinephrine 1:200,000, caused a significant reduction in tail temperature (P < .001 at t = 20, 30, and 40 minutes). No alteration in blood flow or temperature was seen after application of prilocaine 0.5%. CONCLUSIONS: The application of ropivacaine directly to a rat's tail artery diminished blood flow and lowered regional skin temperature. These effects were dose related. The use of ropivacaine at higher concentrations can, therefore, not be recommended if tissues supplied by end arteries might be affected.