Causa rara de doença pericárdica

Among cardiovascular diseases, pericardial disease has specific characteristics. Its etiology, diagnosis and medical management are not as well understood as in coronary and valvular heart disease. In most cases, its cause is benign, although the proportion decreases with more severe clinical presentation.The authors present the case of a 35-year-old man with no relevant past medical history, who went to the emergency department with what appeared to be an idiopathic case of acute pericarditis. However, over the following five months, there was an unfavorable evolution to constrictive pericarditis, requiring pericardiectomy. The final diagnosis was only made following surgery – a rare case of a primary pericardial tumor, a mesothelioma.     

Temperature-responsive cationic block copolymers as nanocarriers for gene delivery

Cationic block copolymers have been regarded as promising alternatives to the use of viral vectors for gene delivery. In this work, poly(N-isopropylacrylamide)_n-block-poly((3-acrylamidopropyl)trimethylammonium chloride)_m (PNIPAAM_n-b-PAMPTMA(+)_m) block copolymers with n = 48 or 65 and m = 6, 10 or 20 were synthesized and evaluated in terms of their potential for in vitro transfection of HeLa cells. These block copolymers collapse above a phase transition temperature, allowing the entrapment of the DNA molecules they are adsorbed to. The transfection efficiency increased with polymer concentration and was higher in the presence of a long PNIPAAM block and for a short charged block. In general, increasing the length of the charged block decreased the transfection efficiency. Additionally, polymer–DNA complexes (polyplexes) formed at lower polymer/DNA charge ratios caused lower cell toxicity levels. All polymers were shown to efficiently protect the DNA, even when they were present at low concentrations. At 37 °C, the polyplexes mostly formed structures with size ranging from 100 to 500 nm. The results also showed that the thermoresponsive contraction of PNIPAAM causes the charged block segments to be pressed out to the surface. The formation of compact structures seems to be a key factor in achieving high transfection efficiency.     

Fluid balance and urine volume are independent predictors of mortality in acute kidney injury

Introduction

In ICUs, both fluid overload and oliguria are common complications associated with increased mortality among critically ill patients, particularly in acute kidney injury (AKI). Although fluid overload is an expected complication of oliguria, it remains unclear whether their effects on mortality are independent of each other. The aim of this study is to evaluate the impact of both fluid balance and urine volume on outcomes and determine whether they behave as independent predictors of mortality in adult ICU patients with AKI.

Methods

We performed a secondary analysis of data from a multicenter, prospective cohort study in 10 Italian ICUs. AKI was defined by renal sequential organ failure assessment (SOFA) score (creatinine >3.5 mg/dL or urine output (UO) <500 mL/d). Oliguria was defined as a UO <500 mL/d. Mean fluid balance (MFB) and mean urine volume (MUV) were calculated as the arithmetic mean of all daily values. Use of diuretics was noted daily. To assess the impact of MFB and MUV on mortality of AKI patients, multivariate analysis was performed by Cox regression.

Results

Of the 601 included patients, 132 had AKI during their ICU stay and the mortality in this group was 50%. Non-surviving AKI patients had higher MFB (1.31 ± 1.24 versus 0.17 ± 0.72 L/day; P <0.001) and lower MUV (1.28 ± 0.90 versus 2.35 ± 0.98 L/day; P <0.001) as compared to survivors. In the multivariate analysis, MFB (adjusted hazard ratio (HR) 1.67 per L/day, 95%CI 1.33 to 2.09; <0.001) and MUV (adjusted HR 0.47 per L/day, 95%CI 0.33 to 0.67; <0.001) remained independent risk factors for 28-day mortality after adjustment for age, gender, diabetes, hypertension, diuretic use, non-renal SOFA and sepsis. Diuretic use was associated with better survival in this population (adjusted HR 0.25, 95%CI 0.12 to 0.52; <0.001).

Conclusions

In this multicenter ICU study, a higher fluid balance and a lower urine volume were both important factors associated with 28-day mortality of AKI patients.     

Amide conjugates of the DO3A‐N‐(α‐amino)propionate ligand: leads for stable,high relaxivity contrast agents for MRI?

A novel synthetic methodology for preparing amide conjugates of the DO3A‐N‐(α‐amino)propionate chelator is described, using the synthesis of the DO3A‐N‐(α‐benzoylamido)propionate chelator as an illustrative example. The model Gd[DO3A‐N‐(α‐benzoylamido)propionate] chelate displays accelerated water exchange, stability in a wide pH range and inertness towards transmetallation by Zn²⁺. The Gd[DO3A‐N‐(α‐benzoylamido)propionate] complex is mainly excreted via the kidneys, producing a significant increase in the kidney medulla/cortex enhancement ratio in MR images of Wistar rats, reflecting probably its higher lipophilicity compared with Gd(DTPA). The results presented suggest that Gd[DO3A‐N‐(α‐amido)propionate] chelates can be valuable leads for preparing potentially safe high relaxivity MRI contrast agents. Copyright © 2012 John Wiley & Sons, Ltd.     

Expectancies and Hypnotic Responsiveness: An Experimental-Design Flaw Revealed

Recent research suggests that expectancies about being hypnotized have a determinant role in the hypnotic experience. The authors analyzed the relationship between expectancies and the phenomenology of hypnosis using the Phenomenology of Consciousness Inventory and Hypnotic Assessment Procedure. Participants (115) were assigned either to the imagination (hypnosis labeled as imagination) or the hypnosis conditions. Results revealed only a minor influence of expectancies and none on the label “hypnosis” across all variables. These findings indicate that the methodology commonly used to study the influence of expectancies on hypnotic responsiveness and phenomenology might represent a flaw in favor of a causal relationship between expectancies and hypnotic experience.     

Influence of aging on the synthesis and morphology of the aggrecans synthesized by differentiated human articular chondrocytes

OBJECTIVE: Synthesis rates of aggrecans by phenotypically stable human articular chondrocytes and the immobilization of these aggrecans in large aggregates were used as variables reflecting the capability of these cells of restoring the extracellular matrix of articular cartilage in vivo in an aging population. DESIGN: Human articular chondrocytes were isolated from articular cartilage obtained from 33 different donors at autopsy. The chondrocytes were cultured in gelled agarose. Synthesis of aggrecans was investigated using Na(2)(35)SO(4)as a radioactive precursor after a 2-week culture period. Electron microscopic study of aggrecan aggregates was done on the macromolecules accumulated over 3 weeks in culture by the chondrocytes obtained from eight other donors with increasing ages. RESULTS: Sulfate incorporation rates into aggrecans correlated inversely with the age of the donor. The value of sulfate incorporation in aggrecans for chondrocytes obtained from mature cartilage of a 20-year-old individual in this system drops to 50% and 25% for chondrocytes obtained from 45- and 69-year-old individuals respectively. Electron microscopic study of aggrecan aggregates showed that the 'de novo' synthesized hyaluronan molecules were fully loaded with aggrecans. Mature human articular cartilage cells were found to synthesize an aggrecan aggregate which carried an average number of 11.7 to 13.1 aggrecans. Cells obtained from immature donors synthesized aggrecan aggregates of which the hyaluronan chain carried twice the amount of aggrecans. These immature human articular cartilage cells were also found to synthesize significant proportions of large aggrecan aggregates with 20 to over 100 aggrecans immobilized on a single hyaluronan chain. The proportions of these large aggrecan aggregates decreased with increasing age of the donors of the chondrocytes. CONCLUSION: The declining aggrecan synthesis rates and the decreased capability of assembling large molecular size aggregates with increasing age in humans illustrates a progressive failure of the repair function of articular cartilage cells in humans.     

Revision of meniscal transplants: long-term clinical follow-up

Purpose

The primary aim is to document objective and subjective clinical outcome after knee arthroplasty for failed meniscal allograft transplantation; secondly, to investigate the influence of previous meniscal allograft surgery on the clinical outcome after a knee arthroplasty procedure; thirdly, to identify possible prognostic factors for the failure of meniscal allograft, such as potential number of concomitant procedures or pre-transplantation HSS-scores. The study population was compared to a control group of primary total knee arthroplasties.

Methods

The pre-operative phase, prior to meniscal allograft transplantation, was evaluated by the HSS questionnaire. At final follow-up, the clinical outcome was evaluated by the HSS, KOOS and SF-36 questionnaires. The mean follow-up was 16 years and 2 months. The control group, matched for age and sex, comprised patients with primary total knee arthroplasty.

Results

Statistical analysis showed that for the HSS-scores, there was no significant difference between the study population and the control group. KOOS data showed that the control group scored better overall. There was no significant difference between the HSS-scores after the transplantation and after the knee prosthesis. However, both showed a significant improvement regarding the clinical condition before meniscal transplantation.

Conclusions

The clinical results after revised meniscal transplantation by means of knee prosthesis are highly variable with a tendency to have a lower score than patients with a primary knee prosthesis. Patients who underwent a revision of their meniscal allograft transplantation by means of a knee arthroplasty still had a significant better clinical outcome than prior to the meniscal allograft transplantation. There were no prognostic factors found by which one can determine whether a meniscal allograft will have a good survival or not.

Level of evidence

IV.     

Expression of AMPA/kainate receptors during development of chick embryo retina cells: in vitro versus in vivo studies

The activity and the subunit expression of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate ionotropic glutamate receptors were studied in retina cells developing in chick embryos and in retina cells cultured as retinospheroids, at the same stages of development. In the retinospheroids, the activity of the AMPA/kainate receptors was monitored by following the changes in the intracellular free calcium concentration ([Ca(2+)](i)), in response to AMPA, kainate or to L-glutamate, and the expression of the receptor subunits GluR1, GluR2/3, GluR4 and GluR6/7 was determined in the retinospheroids and in chick retinas by immunodetection using polyclonal antibodies. The changes in [Ca(2+)](i) in response to 400 microM kainate increased from 5h in vitro to 3 days, and remained constant until day 14, whereas the [Ca(2+)](i) in response to 500 microM L-glutamate or 400 microM AMPA increased from 5h in vitro to 3 days, and thereafter decreased slightly until day 14. The [Ca(2+)](i) responses to kainate are mainly due to AMPA receptor stimulation, since the signals were abolished by LY303070, the AMPA receptor antagonist, and were not affected by MK-801, the NMDA receptor antagonist. In retinospheroids, the levels of expression of GluR1 subunit increased from 5h in vitro until day 7, then decreased until day 14. The levels of expression of GluR2/3 and GluR4 subunits increased from 5h in vitro until day 10, and remained constant until day 14. The levels of kainate receptor subunits GluR6/7 increased from 5h in vitro until day 3, and thereafter decreased slightly until day 14. In the retinas, the expression of GluR1 and GluR6/7 subunits increased from day 8 until day 15, and then decreased until day 22 (post-natal 1). The subunits GluR2/3 and GluR4 increased from day 8 until day 18, and remained constant until day 22. The results suggest that AMPA/kainate receptors are expressed at early embryonic stages, although at low levels and before synapse formation (E12). However, the AMPA receptors are not completely functional at the first stage studied since they do not respond to the agonist AMPA. Also, the patterns of AMPA/kainate receptor subunit expression in retinospheroids of chick embryo retina cells cultured in vitro and in retina cells developing in the embryo (in vivo) were similar, indicating that the AMPA/kainate receptor subunits expression in these primary cultures mimics their expression in the developing chick retina.