Parieto-Occipital Injury on Diffusion MRI Correlates with Poor Neurologic Outcome following Cardiac Arrest.

BACKGROUND AND PURPOSE: MR imaging of the brain provides unbiased neuroanatomic evaluation of brain injury and is useful for neurologic prognostication following cardiac arrest. Regional analysis of diffusion imaging may provide additional prognostic value and help reveal the neuroanatomic underpinnings of coma recovery. The purpose of this study was to evaluate global, regional, and voxelwise differences in diffusion-weighted MR imaging signal in patients in a coma after cardiac arrest. MATERIALS AND METHODS: We retrospectively analyzed diffusion MR imaging data from 81 subjects who were comatose for >48 hours following cardiac arrest. Poor outcome was defined as the inability to follow simple commands at any point during hospitalization. ADC differences between groups were evaluated across the whole brain, locally by using voxelwise analysis and regionally by using ROI-based principal component analysis. RESULTS: Subjects with poor outcome had more severe brain injury as measured by lower average whole-brain ADC (740 [SD, 102] × 10-6 mm2/s versus 833 [SD, 23] × 10-6 mm2/s, P < .001) and larger average volumes of tissue with ADC below 650 × 10-6 mms/s (464 [SD, 469] mL versus 62 [SD, 51] mL, P < .001). Voxelwise analysis showed lower ADC in the bilateral parieto-occipital areas and perirolandic cortices for the poor outcome group. ROI-based principal component analysis showed an association between lower ADC in parieto-occipital regions and poor outcome. CONCLUSIONS: Brain injury affecting the parieto-occipital region measured with quantitative ADC analysis was associated with poor outcomes after cardiac arrest. These results suggest that injury to specific brain regions may influence coma recovery.

Exercise-induced alterations and loss of sarcomeric M-line organization in the diaphragm muscle of obscurin knockout mice.

We recently reported that skeletal muscle fibers of obscurin knockout (KO) mice present altered distribution of ankyrin B (ankB), disorganization of the subsarcolemmal microtubules, and reduced localization of dystrophin at costameres. In addition, these mice have impaired running endurance and increased exercise-induced sarcolemmal damage compared with wild-type animals. Here, we report results from a combined approach of physiological, morphological, and structural studies in which we further characterize the skeletal muscles of obscurin KO mice. A detailed examination of exercise performance, using different running protocols, revealed that the reduced endurance of obscurin KO animals on the treadmill depends on exercise intensity and age. Indeed, a mild running protocol did not evidence significant differences between control and obscurin KO mice, whereas comparison of running abilities of 2-, 6-, and 11-mo-old mice exercised at exhaustion revealed a progressive age-dependent reduction of the exercise tolerance in KO mice. Histological analysis indicated that heavy exercise induced leukocyte infiltration, fibrotic connective tissue deposition, and hypercontractures in the diaphragm of KO mice. On the same line, electron microscopy revealed that, in the diaphragm of exercised obscurin KO mice, but not in the hindlimb muscles, both M-line and H-zone of sarcomeres appeared wavy and less defined. Altogether, these results suggest that obscurin is required for the maintenance of morphological and ultrastructural integrity of skeletal muscle fibers against damage induced by intense mechanical stress and point to the diaphragm as the skeletal muscle most severely affected in obscurin-deficient mice.

Human pericytes isolated from adipose tissue have better differentiation abilities than their mesenchymal stem cell counterparts.

Multi-potent mesenchymal stem/progenitor cells are present in almost all organs and tissues, although their identity remains elusive. Several isolation strategies have been pursued to identify these cells prospectively, leading to the isolation of various cell populations endowed with multi-lineage mesodermal potential. Historically, mesenchymal stem cells (MSCs) were the first cell population to be isolated from the stromal fraction of most connective tissues. These cells are able to differentiate towards various mesodermal lineages and are currently the most studied adult mesodermal progenitors. Recently, the isolation of a subpopulation of microvascular pericytes (PCs) endowed with multi-lineage mesodermal potential has led to the identification of mesenchymal progenitors that reside in a defined anatomical location, namely the wall of small blood vessels. To gain insight into these two related cell populations, we performed a detailed analysis of the mesodermal potential of isogenic human MSCs and PCs isolated from white adipose tissue. Although both cell populations expressed known mesodermal markers at similar levels and displayed a comparable growth rate, PCs differentiated towards osteocytes, adipocytes and myocytes more efficiently than their MSC counterparts, as revealed by both histological and molecular assays. Our results show that microvascular PCs are more prone to mesenchymal differentiation than MSCs and therefore represent a preferable source of human adult mesenchymal progenitors when adipose tissue is used as a cell source.

The KSR2-calcineurin complex regulates STIM1-ORAI1 dynamics and store-operated calcium entry (SOCE).

Store-operated calcium entry (SOCE) is the predominant Ca(2+) entry mechanism in nonexcitable cells and controls a variety of physiological and pathological processes. Although significant progress has been made in identifying the components required for SOCE, the molecular mechanisms underlying it are elusive. The present study provides evidence for a direct involvement of kinase suppressor of Ras 2 (KSR2) in SOCE. Using lymphocytes and fibroblasts from ksr2(-/-) mice and shKSR2-depleted cells, we find that KSR2 is critical for the elevation of cytosolic Ca(2+) concentration. Specifically, our results show that although it is dispensable for Ca(2+)-store depletion, KSR2 is required for optimal calcium entry. We observe that KSR2 deficiency affects stromal interaction molecule 1 (STIM1)/ORAI1 puncta formation, which is correlated with cytoskeleton disorganization. Of interest, we find that KSR2-associated calcineurin is crucial for SOCE. Blocking calcineurin activity impairs STIM1/ORAI1 puncta-like formation and cytoskeleton organization. In addition, we observe that calcineurin activity and its role in SOCE are both KSR2 dependent.

Contrast-enhanced ultrasound of hepatocellular carcinoma: correlation between enhancement pattern and cellular differentiation on histopathlogy.

The aim of this study was to evaluate and correlate the enhancement pattern of hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS) and tumour cellular differentiation on histopathology. Patients underwent hepatic CEUS, performed with SonoVue and contrast pulse sequencing. The correlation between enhancement time and enhancement level of the lesions in different vascular phases and tumour cellular differentiation was determined. The tumours were graded according to the Edmondson grading system. Then, diagnosis was obtained by histopathological examination following surgery or percutaneous ultrasound-guided biopsy. 189 patients with HCC were examined with CEUS and histopathological examination between 2003 and 2009: 159 had a solitary lesion (85 %), 24 had 2 lesions (12 %) and 6 had multiple lesions (3 %). The final histological grading of the tumours was as follows: 22, 114, 49, 4 grade I-IV, respectively. Significant differences were shown between the time that HCC become hypoenhancing or remained echogenic in late phase and tumour cellular differentiation (p = 0.006, p = 0.036). The timing of HCC becoming hypoenhancing was correlated with tumour cellular differentiation, with better differentiated HCCs washing out more slowly than poorly differentiated ones (p = 0.164, p = 0.113; p = 0.186, p = 0.070). The enhancement pattern of HCC by CEUS correlates with the cellular differentiation. In late phases, hyperechoic lesions are likely to be better differentiated, whereas hypoechoic lesion is more likely to be poorly differentiated.

Long-term environmental exposure to metals (Cu, Cd, Pb, Zn) activates the immune cell stress response in the common European sea star (Asterias rubens).

The common sea star Asterias rubens represents a key-species of the North-Eastern Atlantic macro benthic community. The cells of their immune system, known as coelomocytes, are the first line of defence against environmental hazards. Here, we report the results of investigations on the immune cells response of sea stars exposed to marine environmental pollution for long periods. We show that levels of the heat shock cognate protein 70 (HSC70) in coelomocytes from A. rubens, which were collected during a field study in the SÇ¿rfjord (North Sea, SW coast of Norway) along a contamination gradient, are directly associated with the long-term accumulation of Cd, Cu heavy metals exclusively in the tegument. Conversely, Pb and Zn accumulation in the tegument did not relate to HSC70 levels and none of the metals were found accumulated in the pyloric coeca. In addition the coelomocytes from A. rubens, collected in high and low metal impacted stations were examined by a proteomic approach using two-dimensional electrophoresis (2DE). By comparison of the proteomic maps, we observed that 31 protein spots differed in their relative abundance, indicating a gene expression response to the metal mixture exposure. All together, our results confirm that the echinoderm immune cells are a suitable model for the assessment of long-term exposure to environmental pollution, moreover that the increased level of HSC70 can be considered a signal of an acquired tolerance within a large spectrum of protein profile changes occurring in response to metal contamination.

Feasibility of photopheresis to reduce the occurrence of restenosis after percutaneous transluminal coronary angioplasty: a clinical pilot study.

BACKGROUND: Photopheresis was evaluated as a means of preventing restenosis on the basis of immune modulation. METHODS: This was a prospective, randomized, controlled clinical trial analyzing clinical restenosis at 6 months after percutaneous transluminal coronary angioplasty (PTCA). Seventy-eight patients with single-vessel angioplasty were randomly assigned to a control group of 41 patients and a treatment group of 37 patients. At 6 months, there were 72 evaluable patients: 39 control patients and 33 treated. Twenty-nine control patients received balloon PTCA only and 10 patients received stents. Twenty treated patients received PTCA only and 13 patients received stents. Baseline clinical characteristics of both groups were similar. The treatment group received photopheresis for a total of 5 treatments. Primary end points were death from any cause, myocardial infarction, ischemia, and repeat revascularization procedures. RESULTS: By intention-to-treat analysis, clinical restenosis occurred in 27% of control patients versus 8% of treated patients (P =.040, relative risk = 0.30). CONCLUSIONS: Photopheresis therapy in patients undergoing balloon PTCA with and without stent deployment has been shown to be effective in reducing restenosis. The use of photopheresis in such patients merits further investigation.

Efficient polycyclic aromatic hydrocarbons dihydroxylation in direct micellar systems.

Optimization of whole-cell bioconversion of the polycyclic aromatic hydrocarbons (PAHs) anthracene, phenanthrene, and naphthalene to the enantiomerically pure corresponding cis-dihydroxydihydro derivatives by the Escherichia coli JM109 (pPS1778) recombinant strain, carrying the naphthalene dioxygenase and corresponding regulatory genes cloned from Pseudomonas fluorescens N3, in micellar systems, is presented. We show that direct microemulsion systems, where a nonionic surfactant such as 1.5% (v/v) Triton X-100 plus 0.6% to 1.0% (v/v) selected oils are able to solubilize the PAHs tested at relatively high concentrations (initial concentrations in the reaction medium > or =10 mM for naphthalene and phenanthrene and > or =2 mM for anthracene), and allow for more efficient substrate bioconversion. These media, while not affecting bacteria viability and performance, provide increased efficiency and final product yields (100% for naphthalene, >30% for anthracene, >60% for phenanthrene). The phase behavior of the direct microemulsion systems for the different substrates and oils utilized was monitored as a function of their volume fraction by light scattering experiments, and related to the bioconversion results. For anthracene and phenanthrene, the dihydroxylated products have an inhibitory effect on the conversion reactions, thus hindering complete turnover of the substrates. We ascertain that such inhibition is reversible because removal of the products formed allowed the process to start over at rates comparable to initial rates. To allow for complete conversion of the PAHs tested a stepwise or continuous separation of the product formed from the micellar reaction environment is being developed.

Direct micellar systems as a tool to improve the efficiency of aromatic substrate conversion for fine chemicals production.

Whole-cell bioconversion of naphthalene to (+)-cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene by Escherichia coli JM109(pPS1778) recombinant strain, carrying naphthalene dioxygenase and regulatory genes cloned from Pseudomonas fluorescens N3, in direct micellar systems is optimized as an example of fine chemicals bioproduction from scarcely water-soluble substrates. The oxygen insertion into the aromatic substrate, which stops at the enantiomerically pure cis dihydroxylated product, is performed in direct microemulsion systems, where a non-ionic surfactant stabilizes naphthalene containing oil droplets in an aqueous medium. These media provide an increased substrate solubility so that a homogeneous reaction can be carried out, while not affecting bacteria viability and performances. The influence of the chemical nature of the oil is investigated. The phase behavior of the direct microemulsion system was monitored for three different oils as a function their volume fraction and characterized through light scattering. The addition of isopropyl palmitate, oleic acid, or glyceryl trioleate, 0.6-1.2% v/v to the micellar systems, led to an increase of the substrate concentration in the solution and particularly its bioavailability, allowing faster catalytic conversions. All these systems resulted in being suitable for catalytic conversions of aromatic compounds. Although the nature of the oil does have a deep effect on the phase behavior of the micellar systems, in the present investigation no differences in the yields and in the rates of product formation of the enzymatic system were observed on changing the oil, thus showing that in this case the substrate concentration or bioavailability is not the rate-limiting step.

Obstructive sleep apnea-induced supraventricular tachycardia.

Obstructive sleep apnea has been associated with various cardiac arrhythmias; however, supraventricular tachycardia has not been reported to occur in this disorder. This case report describes a patient who developed episodes of supraventricular tachycardia during periods of apnea and oxygen desaturation. With the initiation of nasal continuous positive airway pressure during sleep, the arrhythmia was abolished. The etiology and possible mechanisms responsible for the supraventricular tachycardia are discussed.

Complete atrioventricular block with ventricular asystole following infusion of intravenous phenytoin.

A case of complete atrioventricular block with ventricular asystole in a patient receiving intravenous phenytoin is presented. Although the potential for hypotension is generally recognized with the intravenous administration of phenytoin, conduction abnormalities are rarely reported. The differential diagnosis of atrioventricular block and the effects of phenytoin on cardiac conduction are discussed.

[Controlled trabeculectomy and incidence of postoperative choroidal detachment]. / Kontrollierte Trabekulektomie und Häufigkeit der postoperativen Aderhautamotio.

In this study the authors report their experience with titrated trabeculectomy. It is performed as follows: tight scleral flap trabeculectomy, five or more 10/0 nylon sutures, argon laser lysis of one or more sutures (depending on the eye's postoperative condition) by means of the Hoskins lens. The aim of this technique, performed by the authors for 3 years, is to decrease atalamia and choroidal detachment. Results obtained in 70 eyes of 62 patients with chronic open-angle glaucoma are compared by means of statistical analysis with those in 70 eyes of 66 patients operated on by means of the traditional technique. The incidence of choroidal detachment is significantly reduced (P < 0.001). There is no important difference in ocular pressure and visual acuity. In conclusion, this technique is very useful in controlling and titrating the filtration rate, avoiding an excessive lowering of IOP after trabeculectomy and decreasing the complications.

Flecainide induced atrial tachycardia with 1:1 ventricular conduction during exercise testing.

Wide complex tachycardias may represent a rare proarrhythmic effect of some antiarrhythmic agents. The authors describe a patient who developed a wide complex tachycardia developing during stress testing while on therapy with flecainide, and the difficulty in interpreting the electrocardiogram. This article reviews potential proarrhythmic effects of flecainide in the treatment of atrial dysrhythmias and the difficulty in differentiating associated wide complex tachycardias.

[Determination of contrast sensitivity in patients with silicone oil tamponade]. / Bestimmung der Lichtunterschiedsempfindlichkeit bei Patienten mit Silikonölfüllung.

UNLABELLED: The issue of whether silicone oil has a toxic effect on the retina is still being debated. In order to verify possible retinotoxic effects, the authors studied the variations of retinal function by means of computerized perimetry on patients who had undergone a vitreoretinal operation with injection of silicone oil in the vitreous cavity. Silicone oil remained in the eyes for a period of 120 days +/- 15. PATIENTS AND METHODS: 14 patients under treatment for vitreoretinal pathologies sparing the macula underwent five examinations (Macular Threshold Test of the Humphrey Field analyzer): two examination during the period silicone oil was in the vitreous cavity (30 days after injection and 10 days before removal) and three examinations after its removal (at 30, 90, and 180 days). RESULTS: When the paired t-test and ANOVA test were applied to our results, there were no significant differences in the light-difference sensitivity. CONCLUSIONS: These data do not indicate that silicone oil a retinotoxic effect (revealed by means of computerized perimetry) when it is removed within 4 months.

Comparison of antibodies for rapid detection of cytomegalovirus.

Antibodies were compared for use in the spin-amplified shell vial method for rapid cytomegalovirus detection. Commercial antibodies by Du Pont Co., Whittaker M.A. Bioproducts, Bartels Immunodiagnostic, Virostat, and Serono Diagnostics were compared at incubation times of 16 to 48 h on 22 patient specimens. Only the Du Pont antibody showed 100% sensitivity and specificity and no nonspecific reactions.

Topical vitamin A acid in the treatment of acne vulgaris (a controlled multicenter trial).

A controlled non-blind multicenter trial was conducted in 211 acne patients to test the activity of topical retinoic acid against sulfur-resorcinol--salicylic acid and placebo. Uniform evaluation criteria were used. After 8 weeks' treatment in comparable groups of patients, retinoic acid proved to be superior to the standard and to the placebo. The difference was statistically significant. Side effects were present in a number of patients treated with the active substances and with the placebo (mainly erythema), but rarely was the treatment discontinued.