Sonographic detection of mobile echogenic foci within the main portal vein and its branches or within the liver parenchyma extending along the portal triads to the periphery of the liver is an alarming finding that has been associated with portal venous gas in the setting of bowel ischemia. Ultrasound-enhancing agents (UEAs) have been widely utilized in abdominal ultrasound for evaluation of organ neoplasms and vascular patency as well as in echocardiography for the evaluation of cardiac function. The appearance of UEAs on abdominal ultrasound can resemble gas like that seen in the portal venous system and liver in patients with bowel ischemia; therefore, UEA residuals should always be a part of the differential diagnosis of echogenic foci when seen on abdominal ultrasounds with preceding recent UEA administration.
View Article and Find Full Text PDFPortal venous gas on abdominal ultrasound classically represents an indirect indicator of bowel ischemia, a critical condition which poses a high patient mortality and therefore warrants emergent corrective action. While the classic appearance of portal venous gas on ultrasound is well-described in the literature, the characteristic descriptors are nonspecific and may actually represent other less emergent mimics. Therefore, while radiologists should remain vigilant for the detection of findings corresponding to portal venous gas, they should also be aware of similar-appearing entities in order to provide the most accurate diagnosis.
View Article and Find Full Text PDFAims: Atrial fibrillation (AF) is associated with atrial enlargement, mitral annulus (MA) and tricuspid annulus (TA) dilation, and atrial functional regurgitation (AFR). However, less is known about the impact of AF on both atrioventricular valves in those with normal and abnormal ventricular function. We aimed to compare the remodelling of the TA and MA in patients with non-valvular AF without significant AFR.
View Article and Find Full Text PDFPercutaneous left atrial appendage (LAA) occlusion is increasingly performed in patients with atrial fibrillation and long-term contraindications for anticoagulation. Our aim was to evaluate the effects of LAA occlusion with the Watchman device on the geometry of the LAA orifice and assess its impact on the adjacent left upper pulmonary vein (LUPV) hemodynamics. We included 50 patients who underwent percutaneous LAA occlusion with the Watchman device and had acceptable three-dimensional transesophageal echocardiography images of LAA pre- and post-device placement.
View Article and Find Full Text PDFAims: Atrial fibrillation (AF) has been associated with tricuspid annulus (TA) dilation in patients with severe functional tricuspid regurgitation (TR); however, the impact of AF is less clear in patients without severe TR. Our aim was to characterize TA remodelling in patients with AF in the absence of severe TR using 3D transoesophageal echocardiography (TOE).
Methods And Results: Ninety patients underwent clinically indicated transthoracic and TOE: non-structural (NS)-AF (n = 30); AF with left heart disease (LHD) (n = 30), and controls in sinus rhythm (n = 30).
Background: Right ventricle (RV) evaluation requires dedicated imaging to achieve a comprehensive functional and anatomical assessment. Right ventricular imaging could be technically difficult which results in suboptimal visibility and inconsistent assessment between observers. The aim of this study was to assess feasibility and the additive value of contrast enhancement for right ventricular evaluation.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
March 2018
Cerebral malaria (CM) is a severe and rapidly progressing complication of infection by parasites that is associated with high rates of mortality and morbidity. Treatment options are currently few, and intervention with artemisinin (Art) has limited efficacy, a problem that is compounded by the emergence of resistance to Art in parasites. Rocaglates are a class of natural products derived from plants of the genus that have been shown to interfere with eukaryotic initiation factor 4A (eIF4A), ultimately blocking initiation of protein synthesis.
View Article and Find Full Text PDFThe diagnosis of malaria, caused by Plasmodium spp., still remains a challenging process. Especially in low-income countries, a rapid user-friendly method is needed for the efficient care of the patient.
View Article and Find Full Text PDFThe aim of the present study was to determine the effect of different pretest pedaling cadences on power outcomes obtained during the Wingate Anaerobic Test (WAnT). Vigorously exercising adult men (n = 14, 24.9 ± 1.
View Article and Find Full Text PDFBackground: Drug resistance, absence of an effective vaccine, and inadequate public health measures are major impediments to controlling Plasmodium falciparum malaria worldwide. The development of antimalarials to which resistance is less likely is paramount. To this end, we have exploited the chaperone function of P.
View Article and Find Full Text PDFA series of compounds structurally related to astemizole were designed and synthesized with the goal of determining their anti-Plasmodium activity. Several modifications of the astemizole structure, namely the removal of the 4-fluorobenzyl and/or 4-methoxyphenethyl moieties, substitution of the benzene ring of the benzimidazole scaffold, replacement of the fluorine atom in the 4-fluorobenzyl group, and variation of the 4-aminopiperidine moiety, were explored. In vitro evaluation of the anti-Plasmodium activity of these compounds using the ItG strain showed that astemizole and some of its structurally similar derivatives have IC50 values in the nanomolar range and exhibit toxicity towards the parasite over Chinese ovarian hamster (CHO) cells with a selectivity as high as 200.
View Article and Find Full Text PDFResistance by Plasmodium falciparum to almost all clinically used antimalarial drugs requires the development of new classes of antimalarials. 6-Iodouridine (15), a novel and potent inhibitor of orotidine 5'-monophosphate decarboxylase (ODCase), exhibited efficacy in a mouse model infected by P. chabaudi chabaudi.
View Article and Find Full Text PDFThe interaction between DNA and members of series of bivalent imidazole compounds, monovalent and bivalent imidazolium compounds, and monovalent and bivalent tetrazolium compounds, which had been synthesized and evaluated for their anti-Plasmodium activity, has been examined using the displacement of SYBR Green I as a measure of competitive binding. The degree of interaction with DNA appears to be dependent on both hydrophobic and charge-pairing interactions.
View Article and Find Full Text PDFOrotidine-5'-monophosphate decarboxylase (ODCase) is an interesting enzyme with an unusual catalytic activity and a potential drug target in Plasmodium falciparum, which causes malaria. ODCase has been shown to exhibit unusual and interesting interactions with a variety of nucleotide ligands. Cytidine-5'-monophosphate (CMP) is a poor ligand of ODCase, and CMP binds to the active site of ODCase with an unusual orientation and conformation.
View Article and Find Full Text PDFAntimicrob Agents Chemother
August 2012
Previous studies have shown an antimalarial effect of total alkaloids extracted from leaves of Guiera senegalensis from Mali in West Africa. We independently observed that the beta-carboline alkaloid harmine obtained from a natural product library screen inhibited Plasmodium falciparum heat shock protein 90 (PfHsp90) ATP-binding domain. In this study, we confirmed harmine-PfHsp90-specific affinity using surface plasmon resonance analysis (dissociation constant [K(d)] of 40 μM).
View Article and Find Full Text PDFEnterohemorrhagic Escherichia coli serotype O157:H7 is a food borne enteric bacterial pathogen that causes significant morbidity and mortality in both developing and industrialized nations. E. coli O157:H7 infection of host epithelial cells inhibits the interferon gamma pro-inflammatory signaling pathway, which is important for host defense against microbial pathogens, through the inhibition of Stat-1 tyrosine phosphorylation.
View Article and Find Full Text PDFA series of compounds containing bivalent imidazolium rings and one triazolium analog were synthesized and evaluated for their ability to inhibit the replication of Plasmodium falciparum cultures. The activity and selectivity of the compounds for P. falciparum cultures were found to depend on the presence of electron-deficient rings that were spaced an appropriate distance apart.
View Article and Find Full Text PDFFluorinated nucleosides and nucleotides are of considerable interest to medicinal chemists because of their antiviral, anticancer, and other biological activities. However, their direct interactions at target binding sites are not well understood. A new class of 2'-deoxy-2'-fluoro-C6-substituted uridine and UMP derivatives were synthesized and evaluated as inhibitors of orotidine 5'-monophosphate decarboxylase (ODCase or OMPDCase).
View Article and Find Full Text PDFAm J Respir Crit Care Med
March 2011
Rationale: Stenotrophomonas maltophilia is one of the more common multidrug-resistant organisms isolated from the respiratory tract of patients with cystic fibrosis (CF), but the effect of chronic S. maltophilia infection on CF lung disease is unknown.
Objectives: To determine the impact of chronic S.
Background: A large fraction of anti-malaria medicines (and indeed many other medicines classes) used in developing countries are inadequately identified. Framing this problem as one of misidentification rather than the more common framing of criminal misrepresentation leads to new solutions sets not currently being considered.
Method: That reframing led to consideration and analysis of 4 new problems that informed design of a digital platform technology for delivering a distributed medicine characterization system: 1) problematic interests associated with a focus on preventing counterfeiting, 2) the complexity of the many ways that medicines can deviate from expected identities, 3) the challenge of choosing amongst a diversity of attribute characterization technologies, and 4) the need for a flexible and distributed data aggregation mechanism.
We have previously reported that tetrazolium salts were both potent and specific inhibitors of Plasmodium replication, and that they appear to interact with a parasite component that is both essential and conserved. The use of tetrazolium salts in vivo is limited by the potential reduction of the tetrazolium ring to form an inactive, neutral acyclic formazan. To address this issue imidazolium and triazolium salts were synthesized and evaluated as Plasmodium inhibitors.
View Article and Find Full Text PDFBackground: Deficits in clinical microbiology infrastructure exacerbate global infectious disease burdens. This paper examines how commodity computation, communication, and measurement products combined with open-source analysis and communication applications can be incorporated into laboratory medicine microbiology protocols. Those commodity components are all now sourceable globally.
View Article and Find Full Text PDF