Fortified hyperbranched PEGylated chitosan-based nano-in-micro composites for treatment of multiple bacterial infections.

Bacterial resistance is a real threat to human health. One of the most common strategies used to overcome this problem is the combination therapy. This study proposes a new chitosan-based nano-in-microparticles (NIMs) antibacterial platform that can deliver multiple antibacterial therapeutics at the same time. Chitosan (CS) was PEGylated to overcome its limited water solubility. Then, the antibacterial activity of the resulting PEG-CS was fortified via conjugation with dendritic polyamidoamine hyperbranches (HB) as well as in-situ immobilization of silver nanoparticles (AgNPs) to be efficient against multiple bacterial strains. Montmorillonite nanoclay (MMT) was prepared and used to encapsulate ibuprofen (IBU) as anti-inflammatory drug to reduce any concomitant inflammatory response during bacterial infection. The successful synthesis of PEG-HBCS-AgNPs as well as IBU-MMT nanocomplex was confirmed using FTIR, 1H NMR, DSC, TGA and EDX. SEM micrographs showed a complete formation of NIM spherical particles with a size around 13 µm. Besides, the newly developed drugs-loaded CS-based NIM formulation showed a better widespread activity on the tested aerobic and anaerobic bacterial species, and it may represent, after further optimization, a promising approach for overcoming multiple-bacterial infection.

Should AFP (or any biomarkers) be used for HCC surveillance?

A PURPOSE OF REVIEW: To address the controversy around the use of biomarkers for hepatocellular carcinoma (HCC) surveillance in individuals with cirrhosis or chronic hepatitis B who are at risk for development of liver cancer. B RECENT FINDINGS: Recent studies suggest that surveillance for hepatocellular carcinoma is beneficial, even after adjustment for lead time and other biases. Alpha fetoprotein (AFP) is complementary to ultrasound (US) in surveillance, particularly in obese patients and patients with infiltrative tumors. US and AFP are both associated with harms to patients from false positive over-diagnosis, with US appearing to cause greater harms. Including patient demographic characteristics and additional biomarkers into diagnostic models is beneficial. Recent studies emphasize the advantage of time trends in biomarkers over single cross-sectional measurements. C SUMMARY: AFP and other biomarkers are complementary to US in surveillance for HCC, especially when applied in models including patient variables and incorporating time trends in biomarker levels. With advances in genetic and molecular analysis of tumors, we may be poised at the cusp of a revolution in HCC surveillance.

Very late mesenteric bare metal stent thrombosis in the setting of cessation of antiplatelet agents.

We report a case of a 73 year-old man admitted for acute mesenteric ischaemia. Eight years before, he had a first mesenteric ischaemic event treated by left colectomy and angioplasty of both main coeliac artery (MCA) and superior mesenteric artery (SMA); the patient was discharged on lifelong clopidogrel and aspirin. One month before his admission for the index event, he had a major haematuria; clopidogrel was stopped first, then aspirin because of recurrent haematuria. Five days after withdrawal of both antiplatelet drugs, the patient presented with acute mesenteric ischaemia. Urgent aortography showed in-stent occlusion of SMA and in-stent restenosis of MCA; we performed ad hoc thrombus aspiration of SMA and balloon angioplasty of MCA. The patient was discharged seven days after, without complications. This case shows that very late stent thrombosis in digestive artery can occur in the setting of antiplatelet arrest and urgent endovascular intervention constitutes a seductive alternative for surgery when performed early after symptoms onset.

SU-E-T-267: Construction and Evaluation of a Neutron Wall to Shield a 15 MV Linac in a Low-Energy Vault.

PURPOSE: To design and quantify the shielding efficacy of an inner Borated Polyethylene (BPE)wall for a 15 MV linac in a low energy vault. METHODS: A Varian TrueBeam linac with a maximum photon energy of 15 MV was installed in asmaller, preexisting vault. This vault originally housed a low-energy machine and did not havesufficient maze length recommended for neutron attenuation. Effective dose rate calculationswere performed using the Modified Kersey's Method as detailed in NCRP Report No. 151 andfound to be unacceptably high. An initial survey following the machine installation confirmedthese calculations. Rather than restrict the linac beam energy to 10 MV, BPE was investigatedas a neutron moderating addition. An inner wall and door were planned and constructed using4'×8'×1″ thick 5% BPE sheets. The resulting door and wall had 2″ of BPE; conduits and ductwork were also redesigned and shielded. A survey was conducted following construction of thewall. RESULTS: The vault modification reduced the expected effective dose at the vault door from 36.23to 0.010 mSv/week. CONCLUSION: As specific guidelines for vault modification are lacking, this project quantitativelydemonstrates the potential use of BPE for vault modification. Such modifications may provide alow-cost shielding solution to allow for the use of high energy modes in smaller treatment vaults.

Dosimetric characterization of an image-guided stereotactic small animal irradiator.

Small animal irradiation provides an important tool used by preclinical studies to assess and optimize new treatment strategies such as stereotactic ablative radiotherapy. Characterization of radiation beams that are clinically and geometrically scaled for the small animal model is uniquely challenging for orthovoltage energies and minute field sizes. The irradiator employs a commercial x-ray device (XRAD 320, Precision x-ray, Inc.) with a custom collimation system to produce 1-10 mm diameter beams and a 50 mm reference beam. Absolute calibrations were performed using the AAPM TG-61 methodology. Beam's half-value layer (HVL) and timer error were measured with an ionization chamber. Percent depth dose (PDD), output factors (OFs) and off-axis ratios were measured using radiochromic film, a diode and a pinpoint ionization chamber at 19.76 and 24.76 cm source-to-surface distance (SSD). PDD measurements were also compared with Monte Carlo (MC) simulations. In-air and in-water absolute calibrations for the reference 50 mm diameter collimator at 19.76 cm SSD were measured as 20.96 and 20.79 Gy min(-1), respectively, agreeing within 0.8%. The HVL at 250 kVp and 15 mAs was measured to be 0.45 mm Cu. The reference field PDD MC simulation results agree with measured data within 3.5%. PDD data demonstrate typical increased penetration with increasing field size and SSD. For collimators larger than 5 mm in diameter, OFs measured using film, an ion chamber and a diode were within 3% agreement.

Olanzapine- and clozapine-induced stuttering. A case series.

Drug-induced stuttering has been described in association with several drugs, in particular antidepressants and low-potency neuroleptics. Here we describe a case series of stuttering induced by the atypical neuroleptics olanzapine and clozapine. Patients receiving neuroleptic treatment were carefully screened for stuttering as a possible side effect. We have studied all patients in the outpatient department (800 per year) as well as most inpatients (1300 per year) within 3 years. Seven cases of drug-induced stuttering were observed. Six patients suffered from stuttering in association with olanzapine treatment, and one received clozapine. Stuttering arose on average 2-21 days after initiation of treatment and ceased 2-5 days after discontinuation. Most patients suffered from additional diseases, such as brain pathology due to cortical atrophy or celiac disease, or received concomitant medication (i.e. intrathecal morphine pump). Our case series suggests that the atypical neuroleptic olanzapine can induce stuttering in the absence of a history of stuttering without accompanying akathisia or general decline of function. It appears that preexisting brain pathology or concomitant anti-depressant medication might predispose some patients to this side effect.

Time estimation in schizophrenia: an fMRI study at adjusted levels of difficulty.

fMRI was performed in nine male schizophrenia patients and 15 healthy male controls during an auditory time estimation (timing), a frequency (i.e. pitch) discrimination task, and rest. An adaptive psychophysical approach, the weighted up-down method, was used to adjust individual performance to a level of 75% probability for correct answers. Although performing on the same level of individual difficulty, schizophrenia patients revealed less activations in prefrontal cortex and caudate nucleus, comparing time vs rest. Timing specific differences (i.e. timing vs pitch) between patients and controls were found in the posterior putamen, anterior thalamus, and right medial prefrontal cortex, with patients showing relative hypoactivity. Impairment in time estimation in schizophrenia might be mediated by specific fronto-thalamo-striatal dysfunction.

[The role of lymph nodes in colon carcinoma]. / Die Rolle der Lymphknoten beim Kolonkarzinom.

Metastatic spread of colon cancer to intermediate lymph nodes is found, depending on tumor stage, in up to 44% of patients and to central lymph nodes in about 10%. The incidence of skip metastases is estimated not to exceed 5%. Tumorous involvement of pericolic lymph nodes occurs almost only within a 10 cm distance from the primary. There is only one prospective randomized controlled trial available comparing hemicolectomy versus radical segmental colectomy in patients with left colonic cancer. In this limited study there was no statistical difference regarding survival, mortality and morbidity between the two groups. However, several large retrospective studies are in favor of extended colon resection with radical clearance of lymphatic tissue. In 198 patients with colon cancer excluding rectal cancer in a 6-year period we performed 151 radical (76%) and 47 segmental (24%) colonic resections. The median length of the specimens in an unstretched and formalin-fixed state was 39 cm and 19 cm, respectively. The mean number of investigated lymph nodes was 16 and 12, respectively. 40% of our patients showed lymph node metastases. In-hospital mortality was 4/198 patients (2%) and surgical morbidity occurred in 29/198 patients (15%). We recommend radical colonic resections in all potentially curable patients with colonic cancer.

Successful conservative surgery of acute ascending aortic dissection occurring during coronary angiography.

We reported the case of an acute aortic dissection complicating right guiding catheter manipulation during engagement in the right coronary ostium. Despite absence of hemodynamic deterioration, dissection progressed rapidly from the sinus of Valsalva to the ascending aorta along its entire length. At surgery, performed in emergency, the aorta was not dilated and the aortic wall did not appear pathologic. Therefore conservative surgery was performed, consisting of suture of the aortic tear and incollage of the false lumen, with good immediate and mid-term results.

Left ventricular lead insertion using a modified transseptal catheterization technique: A totally endocardial approach for permanent biventricular pacing in end-stage heart failure.

This article describes a new technique of LV lead insertion, using transseptal catheterization performed through the right internal jugular vein, to obtain a totally endocardial biventricular chronic pacing in end-stage heart failure. Three patients with QRS widening (> 180 ms) linked to complete left bundle branch block (n = 2) or right ventricular pacing (n = 1) were included in this preliminary study. Catheterization was performed under fluoroscopy and transesophageal echocardiography guidance. Transseptal catheterization was achieved by puncture of the right internal jugular vein at the base of the neck and by using a Brockenbrough needle, the tip curve of which was more curved than the standard model. A flexible long sheath was advanced in the left atrium through the interatrial septum and then a unipolar electrode was placed easily in the LV. The proximal tip of the LV lead was tunneled from the neck to the subclavian area and connected to the ventricular channel of a dual (n = 1) or simple (n = 2) chamber pacemaker. Efficient acute sensing (V wave amplitude = 13 +/- 3 m V) and pacing (acute pacing threshold = 0. 7 +/- 0.4 V) were obtained in the three patients. Early loss of capture occurred in two patients requiring lead replacement. Functional status dramatically improved in all three patients. At 6-month follow-up, biventricular pacing was maintained in all patients (mean threshold 1.4 V) who were free of clinical embolic event with oral anticoagulation therapy. This modified technique of jugular transseptal catheterization appears promising for the development of left heart pacing.

Decreased frontal activation in schizophrenics during stimulation with the continuous performance test--a functional magnetic resonance imaging study.

The Continuous Performance Test (CPT) has become an essential constituent of the neuropsychological investigation of schizophrenia. Also, a vast number of brain imaging studies, mostly PET investigations, have employed the CPT as a cognitive challenge and established a relative hypofrontality in schizophrenics compared to controls. The aim of the present investigation was to clarify whether this predescribed hypofrontality could also be verified using functional magnetic resonance imaging (fMRI). 20 healthy volunteers and 14 schizophrenics on stable neuroleptic medication were included. Imaging was performed using the CPT-double-T-version and a clinical 1.5 T MRI-scanner with a single slice technique and a T(2)*-weighted gradient-echo-sequence. The schizophrenics exhibited a decreased activation in the right mesial prefrontal cortex, the right cingulate and the left thalamus compared to controls. These results obtained by fMRI are discussed in relation to published findings using PET.

Combined assessment of reflow and collateral blood flow by myocardial contrast echocardiography after acute reperfused myocardial infarction.

OBJECTIVE: To evaluate the combined assessment of reflow and collateral blood flow by myocardial contrast echocardiography after myocardial infarction. DESIGN: Myocardial contrast echocardiography was performed in patients with acute myocardial infarction shortly after successful coronary reperfusion (TIMI 3 patency) by direct angioplasty. Collateral flow was assessed before coronary angioplasty, and contrast reflow was evaluated 15 minutes after reperfusion. The presence of contractile reserve was assessed by low dose dobutamine echocardiography (5 to 15 micrograms/kg/min) at (mean (SD)) 3 (2) days after myocardial infarction. Recovery of segmental function (myocardial viability) was evaluated by resting echocardiography at a two month follow up. The study was prospective. PATIENTS: 35 consecutive patients referred for acute transmural myocardial infarction. RESULTS: Contrast reflow was observed in 20 patients (57%) and collateral flow in 14 (40%). Contrast reflow and collateral contrast flow were both correlated with reversible dysfunction on initial dobutamine echocardiography and at follow up (p < 0.05). The presence of reflow or collateral flow on myocardial contrast echocardiography was a highly sensitive (100%) but weakly specific (60%) indicator of segmental dysfunction recovery. Simultaneous presence of contrast reflow and collateral flow was more specific of reversible dysfunction than reflow alone (90% v 60%). CONCLUSIONS: Combined assessment of reflow and collateral blood flow enhanced the sensitivity of myocardial contrast echocardiography in predicting myocardial viability after acute, reperfused myocardial infarction. The simultaneous presence of reflow and collateral blood flow was highly specific of recovery of segmental dysfunction.

Challenging the anterior attentional system with a continuous performance task: a functional magnetic resonance imaging approach.

Combining the Continuous Performance Test (CPT) with a modern functional imaging technique provides a powerful tool for investigating neurophysiological processes in the human brain. There is increasing evidence from single photon emission tomography (SPECT), positron emission tomography (PET) and presently also functional magnetic resonance imaging (fMRI) studies proposing the existence of a distributed large-scale attentional network, mediated by the dorsolateral prefrontal and mesial frontal cortex, thalamus, basal ganglia and posterior parietal and superior temporal lobe. The aim of this study is to show that fMRI is a useful tool for in vivo localization of attentional tasks and to compare the results with established imaging techniques. Functional MRI was performed on a clinical 1.5-T system using gradient-echo acquisition. For data processing, the Statistical Parametric Mapping (SPM96) package was used. A right lateralized activation pattern in the dorsolateral prefrontal and mesial frontal cortex, the thalamus and the basal ganglia was found in a group of 12 male subjects. These findings support theories suggesting right hemispheric dominance of human attention.

[Present concepts of accessory pathways]. / Conception actuelle des faisceaux accessoires.

The possibility of ablation of arrhythmias has revived interest in accessory atrioventricular pathways. The authors propose a classification based on their electrophysiological properties, the nature of the arrhythmias which they induce, their anatomy and localisation. Classical accessory pathways have a rapid "all or nothing" type of conduction and are responsible for the WPW syndrome. They are called bundles of Kent although Kent's description does not correspond exactly to our present concept of their structures. However, some classical accessory pathways do have unidirectional conduction properties. When only retrograde reciprocating orthodromic tachycardia may occur but not preexcitation is observed in sinus rhythm: they have to be differentiated from reciprocating nodal tachycardias. Atypical accessory pathways show decremential conduction and are composed of specific tissues. When the conclusion is mainly or exclusively anterograde, tachycardias may be observed which were generally attributed to nodoventricular Mahaim fibres. When the conduction is essentially retrograde, they usually give rise to chronic junctional tachycardias.

Cognitive stimulation with the Wisconsin Card Sorting Test: functional MR imaging at 1.5 T.

PURPOSE: To determine whether functional magnetic resonance (MR) imaging can demonstrate a specific pattern of cerebral activation during cognitive stimulation by using a high-level cognitive task such as the Wisconsin Card Sorting Test. MATERIALS AND METHODS: Thirty-one healthy volunteers underwent functional MR imaging with a 1.5-T MR imager with a standard head coil (100/50 [repetition time msec/echo time msec], 230-mm field of view, 40 degrees flip angle, 256 x 256 matrix). For stimulation, a personal computer version of the Wisconsin Card Sorting Test was used. Image analysis was done off-line, and cross-correlation coefficients between the stimulus function and the signal intensity response were calculated on a pixel-by-pixel basis and overlaid onto the corresponding anatomic MR image for each volunteer. RESULTS: Stimulation resulted in strongly frontal activation, which included the mesial and the dorsolateral prefrontal cortexes, interconnected with Brodmann areas 44, 45, and 46. While activation was often bilateral, the largest area of activation was in the right hemisphere. Activation also was found in the basal ganglia and the mesial thalamic nuclei. CONCLUSION: Functional MR imaging can demonstrate a specific pattern during activation with a cognitive task. Functional MR imaging has promise for more precise anatomic and functional imaging studies of brain interaction than have other imaging modalities.

Brain activation during cognitive stimulation with the Wisconsin Card Sorting Test--a functional MRI study on healthy volunteers and schizophrenics.

It has been demonstrated by single photon emission computed tomography (SPECT) and positron emission tomography (PET) that frontal brain regions are stimulated during performance of the Wisconsin Card Sorting Test (WCST). The WCST is also regarded as one of the standard tests for the assessment of frontal activity in brain imaging studies of schizophrenia. In this study cerebral activation was assessed by means of functional magnetic resonance imaging (fMRI). In healthy volunteers WCST stimulation resulted in a right lateralized frontal activation. In 13 chronic schizophrenics on stable neuroleptic medication, a lack of activation in the right prefrontal cortex and--as a trend--an increased left temporal activity during execution of the WCST was noted compared to controls. Since a one-slice technique was used, no information about the activation pattern in adjacent brain regions was obtained. However, as fMRI possesses a superior spatial resolution compared to SPECT and PET, the anatomical localization of the activation effect in the measured slice can be defined more precisely. Beside these methodological considerations, the results are discussed in relation to prior findings of a reduced ability of schizophrenics to coordinate cerebral function.

[Color-coded Doppler sonography of the male urethra: studies in vivo and experimental results]. / Farbkodierte Dopplersonographie der männlichen Urethra: Untersuchungen in vivo und experimentelle Ergebnisse.

The so-called ureter jet is a well known phenomenon, which consists of echoes due to turbulent urine flow emanating from the ureteral orifices during forced diuresis. These motion phenomena are also visible in colour Doppler examinations. In analogy to the ureter jet we could demonstrate different colour phenomena in the normal (n = 20) and stenosed (n = 14) male urethra during voiding by using colour coded Doppler sonography. These observations are obviously caused by turbulent urine flow. In an experimental study, this hypothesis could be verified. Because certain intraurethral colour phenomena are related to stenoses of the urethra, and because their intensity depends on the degree of stenosis and on urine flow (in ml/s), it seems to be possible to draw conclusions on the urodynamic consequences of a stenosis in the urethra by means of colour coded Doppler sonography.