Perisaccadic mislocalization of visual targets by head-free gaze shifts: visual or motor?

Such perisaccadic mislocalization is maximal in the direction of the saccade and varies systematically with the target-saccade onset delay. We have recently shown that under head-fixed conditions perisaccadic errors do not follow the quantitative predictions of current visuomotor models that explain these mislocalizations in terms of spatial updating. These models all assume sluggish eye-movement feedback and therefore predict that errors should vary systematically with the amplitude and kinematics of the intervening saccade. Instead, we reported that errors depend only weakly on the saccade amplitude. An alternative explanation for the data is that around the saccade the perceived target location undergoes a uniform transient shift in the saccade direction, but that the oculomotor feedback is, on average, accurate. This "visual shift" hypothesis predicts that errors will also remain insensitive to kinematic variability within much larger head-free gaze shifts. Here we test this prediction by presenting a brief visual probe near the onset of gaze saccades between 40 and 70° amplitude. According to models with inaccurate gaze-motor feedback, the expected perisaccadic errors for such gaze shifts should be as large as 30° and depend heavily on the kinematics of the gaze shift. In contrast, we found that the actual peak errors were similar to those reported for much smaller saccadic eye movements, i.e., on average about 10°, and that neither gaze-shift amplitude nor kinematics plays a systematic role. Our data further corroborate the visual origin of perisaccadic mislocalization under open-loop conditions and strengthen the idea that efferent feedback signals in the gaze-control system are fast and accurate.     

Exploring Tai Chi in rheumatoid arthritis: a quantitative and qualitative study

Background  

Rheumatoid arthritis (RA) is a chronic, inflammatory and systemic disease which affects the musculoskeletal system. Exercise programmes are reported to improve physical functioning in patients with RA. Tai Chi is a traditional Chinese martial art which combines slow and gentle movements with mental focus. The purpose of this study was to study in which way Tai Chi group exercise impacted on disease activity, physical function, health status and experience in RA patients, applying quantitative and qualitative methods.     

Downregulation of the antioxidant protein peroxiredoxin 2 contributes to angiotensin II-mediated podocyte apoptosis

Podocytes have a significant role in establishing selective permeability of the glomerular filtration barrier. Sustained renin-angiotensin-aldosterone system activation is crucial to the pathogenesis of podocyte injury, but the mechanisms by which angiotensin II modulates podocyte survival due to physiological or injurious stimuli remain unclear. Here, we used proteomic analysis to find new mediators of angiotensin II-induced podocyte injury. Antioxidant protein peroxiredoxin 2 expression was decreased in cultured podocytes stimulated with angiotensin II. Peroxiredoxin 2 was found to be expressed in podocytes in vivo, and its expression was decreased in the glomeruli of rats transgenic for angiotensin II type 1 receptors in a podocyte-specific manner, or in rats infused with angiotensin II. Downregulation of peroxiredoxin 2 in podocytes resulted in increased reactive oxygen species release, protein overoxidation, and inhibition of the Akt pathway. Both treatment with angiotensin II and downregulation of peroxiredoxin 2 expression led to apoptosis of podocytes. Thus, peroxiredoxin 2 is an important modulator of angiotensin II-induced podocyte injury.     

Post-transplant survival after lowering fixed pulmonary hypertension using left ventricular assist devices.

OBJECTIVE: We have previously shown that fixed pulmonary hypertension in cardiac transplant candidates can be lowered using left ventricular assist devices (LVADs). The post-transplant survival of these patients is uncertain as pulmonary hypertension may reappear, possibly affecting post-transplant survival. MATERIALS AND METHODS: Between 01/2000 and 01/2005 a total of 26 cardiac transplant candidates (92% male; mean age 56.2 years) in whom fixed pulmonary hypertension was lowered by LVAD implantation (pulmonary vascular resistance (PVR) before implantation: 5.1+/-2.8wood units (WU); PVR before cardiac transplantation: 2.0+/-.9WU) underwent cardiac transplantation at our institution. These patients were age and sex matched with 52 cardiac transplant candidates without pulmonary hypertension undergoing cardiac transplantation during the same time period. Study endpoints were peri-transplant complications and long-term survival. Mean follow-up was 36+/-14 months. RESULTS: Peri-transplant mortality was 5% in patients after LVAD therapy and 7% in patients without prior LVAD therapy (p=.089). We observed 2 cases (4%) of acute right heart failure requiring mechanical support in patients without prior LVAD therapy. None of the patients with LVAD therapy developed peri-transplant right heart failure requiring mechanical support. Incidence of other peri-transplant complications was comparable between the two groups. Log-rank (p=.124) revealed comparable long-term survival between patients with (1 year: 85%, 2 year: 85%, 3 year: 85%) and without (1 year: 90%, 2 year 82%, 3 year prior 79%) prior LVAD therapy. CONCLUSION: LVAD therapy lowers fixed pulmonary hypertension in cardiac transplant candidates with fixed pulmonary hypertension. Thereafter, long-term post-transplant survival is comparable to cardiac transplant recipients without pulmonary hypertension.     

Predictive Value of Four Kallikrein Markers for Pathologically Insignificant Compared With Aggressive Prostate Cancer in Radical Prostatectomy Specimens: Results From the European Randomized Study of Screening for Prostate Cancer Section Rotterdam

Background

Treatment decisions can be difficult in men with low-risk prostate cancer (PCa).

Objective

To evaluate the ability of a panel of four kallikrein markers in blood—total prostate-specific antigen (PSA), free PSA, intact PSA, and kallikrein-related peptidase 2—to distinguish between pathologically insignificant and aggressive disease on pathologic examination of radical prostatectomy (RP) specimens as well as to calculate the number of avoidable surgeries.

Design, setting, and participants

The cohort comprised 392 screened men participating in rounds 1 and 2 of the Rotterdam arm of the European Randomized Study of Screening for Prostate Cancer. Patients were diagnosed with PCa because of an elevated PSA ≥3.0 ng/ml and were treated with RP between 1994 and 2004.

Outcome measurements and statistical analysis

We calculated the accuracy (area under the curve [AUC]) of statistical models to predict pathologically aggressive PCa (pT3–T4, extracapsular extension, tumor volume >0.5 cm³, or any Gleason grade ≥4) based on clinical predictors (age, stage, PSA, biopsy findings) with and without levels of four kallikrein markers in blood.

Results and limitations

A total of 261 patients (67%) had significant disease on pathologic evaluation of the RP specimen. While the clinical model had good accuracy in predicting aggressive disease, reflected in a corrected AUC of 0.81, the four kallikrein markers enhanced the base model, with an AUC of 0.84 (p < 0.0005). The model retained its ability in patients with low-risk and very-low-risk disease and in comparison with the Steyerberg nomogram, a published prediction model. Clinical application of the model incorporating the kallikrein markers would reduce rates of surgery by 135 of 1000 patients overall and 110 of 334 patients with pathologically insignificant disease. A limitation of the present study is that clinicians may be hesitant to make recommendations against active treatment on the basis of a statistical model.

Conclusions

Our study provided proof of principle that predictions based on levels of four kallikrein markers in blood distinguish between pathologically insignificant and aggressive disease after RP with good accuracy. In the future, clinical use of the model could potentially reduce rates of immediate unnecessary active treatment.     

Randomized placebo‐controlled human pilot study of cold atmospheric argon plasma on skin graft donor sites

Cold atmospheric plasma has already been shown to decrease the bacterial load in chronic wounds. However, until now it is not yet known if plasma treatment can also improve wound healing. We aimed to assess the impact of cold atmospheric argon plasma on the process of donor site healing. Forty patients with skin graft donor sites on the upper leg were enrolled in our study. The wound sites were divided into two equally sized areas that were randomly assigned to receive either plasma treatment or placebo (argon gas) for 2 minutes. Donor site healing was evaluated independently by two blinded dermatologists, who compared the wound areas with regard to reepithelialization, blood crusts, fibrin layers, and wound surroundings. From the second treatment day onwards, donor site wound areas treated with plasma (n = 34) showed significantly improved healing compared with placebo‐treated areas (day 1, p = 0.25; day 2, p = 0.011; day 3, p < 0.001; day 4, p < 0.001; day 5, p = 0.004; day 6, p = 0.008; day 7, p = 0.031). Positive effects were observed in terms of improved reepithelialization and fewer fibrin layers and blood crusts, whereas wound surroundings were always normal, independent of the type of treatment. Wound infection did not occur in any of the patients, and no relevant side effects were observed. Both types of treatment were well tolerated. The mechanisms contributing to these clinically observed effects should be further investigated.     

No association of the -2518 MCP-1 A/G promoter polymorphism with incidence and clinical course of IgA nephropathy.

BACKGROUND: The clinical course of IgA nephropathy is highly variable, ranging from complete remission to progression with end-stage renal disease. Although the mechanisms involved in disease progression are not characterized in detail, loss of renal function is positively correlated with mononuclear cell infiltration. In general, chemokines play an important role in the directional recruitment of inflammatory cells. Recently, a polymorphism in the distal 5' regulatory region of the chemokine monocyte chemoattractant protein-1 (MCP-1), which affects gene expression, has been described (A/G at position -2518). The aim of our study was to evaluate a possible association of this polymorphism with disease progression in patients with IgA nephropathy, as well as susceptibility to this form of glomerulonephritis. METHODS: Blood samples from 207 patients with biopsy proven IgA nephropathy and 140 ethnically, age and sex-matched healthy controls were collected and genomic DNA was extracted. MCP-1 -2518 genotype was assessed by PCR, followed by restriction fragment length polymorphism analysis. Genotype distribution between the two groups was compared by chi(2) test. Cumulative renal survival was assessed by Kaplan-Meier plot and log-rank analysis. RESULTS: 111 (53.6%) patients had the MCP-1 -2518 wild-type A/A, 83 (40.1%) were heterozygous for the G allele and 13 (6.3%) patients showed homozygosity. The allelic distribution was not significantly different in the control group of 140 healthy blood donors (P = 0.71). Renal survival analysis of patients did not reveal statistically significant differences in cumulative survival (P = 0.32), median survival time and 5 year survival rate between the wild-type group and carriers of the G allele. Furthermore, the number of infiltrating CD68-positive monocytes/macrophages into the kidneys of patients with IgA nephropathy was not statistically different between the groups. CONCLUSION: Our data indicate that no association exists between the -2518 A/G polymorphism and susceptibility to IgA nephropathy or its clinical course.     

Methods to monitor response to chemotherapy in non-small cell lung cancer with 18F-FDG PET.

PET using 18F-FDG is a promising technique to monitor response in oncology. Unfortunately, a multitude of analytic methods is in use. To date, it is not clear whether simplified methods could replace complex quantitative methods in routine clinical practice. The aim of this study was to select those methods that would qualify for further assessment in a future prospective response-monitoring study by comparing results with patient outcome. METHODS: Dynamic 18F-FDG PET scans were obtained on 2 groups of patients. First, 10 patients with advanced non-small cell lung cancer (NSCLC) were scanned on consecutive days before treatment to assess test-retest variability. Second, 30 scans were obtained on 19 patients with locally advanced NSCLC as part of an ongoing response-monitoring study. These scans were analyzed by 2 observers to assess observer variability. In addition, these studies were used to compare various methods with the gold standard, full kinetic analysis (nonlinear regression [NLR]). RESULTS: Using an image-derived input function, NLR showed excellent test-retest and observer agreement confirming that it could be used as a gold standard method. From a total of 34 analytic methods, 10 showed good correlation with NLR. Taking into account the degree of complexity of the methods, 4 remain for further evaluation. CONCLUSION: The optimal method for analysis of 18F-FDG PET data was determined for several levels of complexity. Four methods need to be evaluated further to determine the optimal trade-off between simplicity and accuracy for routine clinical practice.