Assessment of temporary dialysis catheter performance on the basis of flow and pressure measurements in vivo and in vitro

The efficiency of hemodialysis treatments depends on catheter performance and, consequently, on effective blood flow that can be achieved at maximum extracorporeal pressures. Differences in effective and displayed flow were determined with ultrasound dilution technology, and a mathematical correction function for the MultiFiltrate hemodialysis machine was developed. This algorithm was used to calculate effective blood flow during treatment from displayed flow and arterial pressure. To assess catheter performance over time, we measured effective blood flow as function of extracorporeal pressure in 11 uncuffed, tunneled hemodialysis catheters with shotgun design. Pressure and flow profiles of the catheters were determined, and pressure symmetry was measured. To assess flow resistance over time, pressure trends of the catheters at different blood flow rates were measured for each patient over a mean period of 6.1 +/- 3.0 days. Increases in flow resistance during the study period were found to be small. Mean arterial pressure decreased from -185 mm Hg to -200 mm Hg, and mean venous pressure increased from 197 mm Hg to 215 mm Hg. Effective flow did not change significantly during the study. In conclusion, all catheters investigated easily provided effective flows above 450 mL/min over the study period at maximum extracorporeal pressures below +/-300 mm Hg.     

Neural correlates of transmeatal cochlear laser (TCL) stimulation in healthy human subjects

Transmeatal cochlear laser (TCL) treatment has recently been proposed as a therapeutic procedure for cochlear dysfunction such as chronic cochlear tinnitus or sensorineural hearing loss. The aim of this study was to investigate whether TLC has any influence on the central nervous system using functional MRI with healthy young adults. The laser stimulation device was placed on the tympanic membrane of both ears. A laser stimulation run and a placebo run were performed in random order. The participants were unable to differentiate between verum and placebo stimulation. In the comparison of verum to placebo runs, we observed significant activations within the left superior frontal gyrus, the right middle and medial frontal gyrus, the right superior parietal lobule, the left superior occipital gyrus, the precuneus and cuneus bilaterally, the right anterior and the left and right middle and posterior cingulate gyrus and the left thalamus. This network of brain areas corresponds well to results from previous PET studies of patients with tinnitus. Though TCL seems to have a clinically measurable effect on the central nervous system the neurophysiological mechanism leading to the observed activated neuronal network remains unknown.     

In vivo regulation of plasminogen function by plasma carboxypeptidase B

The major functions of plasminogen (Plg) in fibrinolysis and cell migration depend on its binding to carboxy-terminal lysyl residues. The ability of plasma carboxypeptidase B (pCPB) to remove these residues suggests that it may act as a suppressor of these Plg functions. To evaluate this role of pCPB in vivo, homozygote pCPB-deficient mice were generated by homologous recombination, and the resulting pCPB(-/-) mice, which were viable and healthy, were mated to Plg(-/-) mice. Plg(+/-) mice show intermediate levels of fibrinolysis and cell migration compared with Plg wild-type and deficient mice, reflecting the intermediate levels of the Plg antigen in their plasma. Differences in Plg-dependent functions between pCPB(+/+), pCPB(+/-), and pCPB(-/-) mice were then analyzed in a Plg(+/-) background. In a pulmonary clot lysis model, fibrinolysis was significantly increased in mice with partial (pCPB(+/-)) or total absence (pCPB(-/-)) of pCPB compared with their wild-type counterparts (pCPB(+/+)). In a thioglycollate model of peritoneal inflammation, leukocyte migration at 72 hours increased significantly in Plg(+/-)/pCPB(+/-) and Plg(+/-)/pCPB(-/-) compared with their wild-type counterparts. These studies demonstrate a definitive role of pCPB as a modulator of the pivotal functions of Plg in fibrinolysis and cell migration in vivo.     

A chemokine receptor CCR-1 antagonist reduces renal fibrosis after unilateral ureter ligation

The expression of chemokines and their receptors is thought to contribute to leukocyte infiltration and progressive renal fibrosis after unilateral ureter obstruction (UUO). We hypothesized that blocking the chemokine receptor CCR1 using the nonpeptide antagonist BX471 could reduce leukocyte infiltration and renal fibrosis after UUO. UUO kidneys from BX471-treated mice (day 0-10 and day 6-10) revealed a 40-60% reduction of interstitial macrophage and lymphocyte infiltrate compared with controls. Treated mice also showed a marked reduction of CCR1 and CCR5 mRNA levels, and FACS analysis showed a comparable reduction of CD8+/CCR5+ T cells. Markers of renal fibrosis, such as interstitial fibroblasts, interstitial volume, mRNA and protein expression for collagen I, were all significantly reduced by BX471-treatment compared with vehicle controls. By contrast treatment was ineffective when the drug was supplied only from days 0 to 5. In summary, blockade of CCR1 substantially reduces cell accumulation and renal fibrosis after UUO. Most interestingly, late onset of treatment is also effective. We therefore conclude that CCR1 blockade may represent a new therapeutic strategy for reducing cellular infiltration and renal fibrosis as major factors in the progression to end-stage renal failure.     

Angiographic outcome after intracoronary X-Sizer helical atherectomy and thrombectomy: first use in humans.

The objective of this study was to evaluate the early angiographic outcome in the first human subjects who underwent intracoronary atherectomy and thrombectomy using the X-Sizer helical cutting and aspiration system. Percutaneous coronary interventions in patients with thrombo-occlusive disease or friable degenerative saphenous vein grafts are associated with considerable periprocedural morbidity and mortality, predominantly related to microscopic distal embolization. X-Sizer catheter system is a novel atherectomy and thrombectomy device that consists of a helix cutter connected to a handheld motor drive unit and a vacuum collection chamber for aspiration of excised atheroma, thrombus, and debris. Quantitative coronary angiography was obtained in 14 patients before and after X-Sizer extraction atherectomy with adjunctive balloon angioplasty and stenting. Thirteen native coronary arteries and one saphenous vein graft were treated. Mean preprocedural reference vessel diameter was 3.06 +/- 0.66 mm. There were 71.4% AHA/ACC type B2 and C lesions. Preprocedural thrombus was present in nine patients and total occlusion in 64% of cases. Minimal luminal diameter was increased from 0.29 +/- 0.47 mm to 1.32 +/- 0.64 mm, a gain of 1.04 +/- 0.69 mm after atherectomy. Final total gain was 1.47 +/- 0.61 mm. Mean diameter stenosis was reduced from 89.3% to a final residual stenosis of 14.4%. Postatherectomy distal embolization occurred in one patient who had heavy preprocedural thrombus burden. No episodes of perforation, distal coronary spasm, abrupt closure, or slow/no-reflow occurred. The angiographic analysis of the first cohort of human subjects suggests that X-Sizer helical atherectomy is a feasible method of removing occlusive tissue or thrombus in coronary artery disease with a low angiographic complication rate. A large-scale randomized phase II clinical trial is underway to determine the ultimate safety and efficacy of this device in thrombo-occlusive native coronary arteries and saphenous vein grafts.     

The validity of rating patch test reactions based on digital images

BACKGROUND: The proper reading of patch test (PT) reactions, based on morphological criteria, is of utmost importance. Digital images are increasingly used for medical training. OBJECTIVES: To assess the diagnostic validity of readings of 20 digital images of various PT reaction grades by congress attendants. METHODS: 122 volunteers took a PT quiz offered during the 8th ESCD meeting, September 2006, Berlin. No information on the respective allergen was given, nor the gold standard grading determined by an European Environmental and Contact Dermatitis Research Group (EECDRG) expert panel was disclosed while the quiz was open. RESULTS: Overall, 63.5% of all ratings agreed 'exactly' with the gold standard, and 87.8% 'grossly', that is, with regard to the distinction between non-positive [doubtful or irritant (IR)] and positive (+, ++, and +++) reactions. Most images prompted a fair proportion of correct classifications. The distinction between doubtful and + and between +++, and strong bullous IR reactions proved partly difficult, probably because of blinding of the test substance. The least experienced in particular tended to misclassify IR reactions. CONCLUSIONS: The rating of digital images of PT reactions represents just 1 particular, isolated aspect of PT evaluation. Results were largely valid. Thus, the method could be used for continuing medical education, and for standardization in multicentre networks.     

Optical coherence tomography as an orientation guide in cochlear implant surgery?

CONCLUSION: With optical coherence tomography (OCT) it is basically possible to reveal parts of the cochlear morphology without opening its enveloping membranes. Thus, it may serve as a helpful guide for the surgeon to localize the scala tympani precisely before opening the fluid-filled inner ear to insert the electrode array. OBJECTIVE: To improve anatomical orientation in cochlear implant surgery before definitively opening the fluid-filled inner ear. The question was whether a new imaging technique, OCT, might provide information about the site of the underlying inner ear structures (scala tympani, scala vestibuli) and could, consequently, guide the surgeon towards the scala tympani. MATERIALS AND METHODS: In a preliminary study, OCT was carried out on human temporal bone preparations, in which a cochleostomy ('fenestration') was performed leaving the endosteum and the fluid-filled inner ear intact. OCT was applied via a prototype of a specially equipped operating microscope. The mode of OCT used in this context was spectral-domain (SD)-OCT. RESULTS: On scans, which can be read analogous to B-mode sonography, OCT provides information about structures on the inner surface of the partly exposed but still intact membranous cochlear lining - such as scala tympani or scala vestibuli.     

Sphingosine‐1‐phosphate modulators in inflammatory skin diseases – lining up for clinical translation

The bioactive lysophospholipid sphingosine‐1‐phosphate (S1P) is best known for its activity as T‐cell‐active chemoattractant regulating the egress of T cells from the lymph node and, consequently, the availability of T cells for migration into peripheral tissues. This physiological role of S1P is exploited by the drug fingolimod, a first‐line therapy for multiple sclerosis, which “detains” T cells in the lymph nodes. In recent year, it has been elucidated that S1P exerts regulatory functions far beyond T‐cell egress from the lymph node. Thus, it additionally regulates, among others, homing of several immune cell populations into peripheral tissues under inflammatory conditions. In addition, evidence, mostly derived from mouse models, has accumulated that S1P may be involved in the pathogenesis of several inflammatory skin disorder and that S1P receptor modulators applied topically are effective in treating skin diseases. These recent developments highlight the pharmacological modulation of the S1P/S1P receptor system as a potential new therapeutic strategy for a plethora of inflammatory skin diseases. The impact of S1P receptor modulation on inflammatory skin diseases next requires testing in human patients.