Nucleic acid-based therapy has become an increasingly important strategy for treating a variety of human diseases. In systemic therapy, a therapeutic gene must be delivered efficiently to its target tissues without side effects. To deliver a therapeutic gene such as plasmid DNA (pDNA) or small interfering RNA (siRNA) to target tissues by systemic administration, cationic carriers such as cationic liposomes and polymers have been commonly used as a non-viral vector. However, the binary complex of therapeutic gene and cationic carrier must be stabilized in the blood circulation by avoiding agglutination with blood components, because electrostatic interactions between positively charged complexes and negatively charged erythrocytes can cause agglutination, and the agglutinates contribute to high entrapment of the therapeutic genes in the highly extended lung capillaries. One promising approach for overcoming this problem is modification of the surface of cationic complexes with anionic biodegradable polymers such as hyaluronic acid, chondroitin sulfate, or polyglutamic acid. As another approach, we recently developed a sequential injection method of anionic polymer and cationic liposome/therapeutic gene complex (cationic lipoplex) for delivery of a therapeutic gene into the liver or liver metastasis. In this review, we describe recent advances in the delivery of therapeutic genes by lipid- and polymer-based carrier systems using anionic polymers.
Acute and subacute ischemia of the lower limbs represents a major emergency with a high in-hospital mortality, complication, and leg amputation rates.
Treatment options for acute limb ischemia include systemic anticoagulation, followed by various catheter based options including infusion of fibrinolytic agents (pharmacological thrombolysis), pharmacomechanical thrombolysis, catheter-mediated thrombus aspiration, mechanical thrombectomy, and any combination of the above or open surgical intervention (thromboembolectomy or surgical bypass).
Minor and major bleeding complication during catheter directed thrombolysis (CDT) especially at access site are frequent. Bleeding complications require often an interruption or termination of CDT affecting clinical outcome of the patients. Recently we examined a new access site bleeding protection device during CDT.
Dissecting aortic aneurysm with ST segment elevation, and pulmonary embolism with ST segment elevation are two of a number of clinical entities which can simulate ST segment elevation myocardial infarction.
Objective: The purpose of this review is to analyse clinical features in anecdotal reports of 138 dissecting aortic aneurysm patients with STEMI-like presentation, and 102 pulmonary embolism patients with STEMI-like presentation in order to generate insights which might help to optimise triage of patients with STEMI-like clinical presentation.
Methods: Reports were culled from a literature search covering the period January 2000 to March 2020 using Googlescholar, Pubmed, EMBASE and MEDLINE. Reports were included only if there was a specification of the location of ST segment elevation and an account of the clinical signs and symptoms. Search terms were “ST segment elevation”,”aortic dissection”, “pulmonary embolism”, “myocardial infarction”, and “paradoxical embolism”. Fisher’s exact test was utilised for two-sided comparison of proportions. Proportion was calculated for each group as the number of patients with that parameter relative to the total number of patients assessed for that parameter.
Findings: There were 138 patients with aortic dissection, 91 of whom were either fast-tracked to coronary angiography (81 patients) or fast-tracked to thrombolytic treatment (10 patients). There were 47 patients managed with neither of those strategies. There were 102 patients with pulmonary embolism, 71 of whom were fast tracked to coronary angiography, and 31 who did not receive that evaluation. Compared with their dissecting aortic aneurysm counterparts, those dissecting aortic aneurysm patients initially managed by percutaneous coronary intervention or by thrombolysis were significantly (p = 0.0003) more likely to have presented with chest pain, and significantly (p = 0.018) less likely to have presented with breathlessness. The preferential fast-tracking to coronary angiography prevailed in spite of comparable prevalence of back pain in fast tracked and in non-fast tracked subjects. Use of transthoracic echocardiography was also comparable in the two subgroups of dissecting aortic aneurysm patients. Pulmonary embolism patients fast tracked to percutaneous coronary intervention were significantly (p = 0.0008) more likely to have presented with chest pain than their pulmonary embolism counterparts who were not fast-tracked. The prevalence of paradoxical embolism was also significantly (p = 0.0016) higher in fast-tracked patients than in counterparts not fast-tracked. Cardiac arrest was significantly (p = 0.0177) less prevalent in fast-tracked pulmonary embolism patients than in pulmonary embolism patients who were not fast-tracked. Preferential fast-tracking to coronary angiography prevailed in spite of the fact that prevalence of documented deep vein thrombosis was comparable in fast-tracked subjects and in subjects not fast-tracked. The prevalence of use of transthoracic echocardiography was also similar in fast-tracked pulmonary embolism patients vs counterparts not fast tracked. Overall, however, transthoracic echocardiography had been utilised significantly (p = 0.007) less frequently in dissecting aneurysm patients than in pulmonary embolism patients.
Conclusion: Given the high prevalence of STEMI-like presentation in aortic dissection there is a need for greater use of point-of-care transthoracic echocardiography to mitigate risk of inappropriate percutaneous coronary intervention(which might delay implementation of aortic repair surgery) and inappropriate thrombolysis(which might precipitate hemorrhagic cardiac tamponade) (75) during triage of patients presenting with ST segment elevation simulating ST segment elevation myocardial infarction (STEMI). Furthermore, during triage of patients with STEMI-like clinical presentation, the combined use of point-of -care echocardiography and evaluation for deep vein thrombosis will facilitate the differentiation between acute myocardial infarction, STEMI-like aortic dissection, and STEMI-like pulmonary embolism. Among STEMI-like patients in whom DAA has been ruled out by point of care TTE, fast tracking to PCI might generate an opportunity to identify and treat paradoxical coronary artery embolism by thrombectomy. Thereby mitigating the mortality risk associated with coronary occlusion. Concurrent awareness of PE as the underlying cause of paradoxical embolism also generates an opportunity to relieve the clot burden in the pulmonary circulation, either by pulmonary embolectomy or by thrombolysis. Above all, frontline clinicians should have a greater awareness of the syndrome of STEMI-like presentation of aortic dissection and STEMI-like pulmonary embolism so as to mitigate the risk of inappropriate thrombolysis and inappropriate percutaneous coronary angiography which seems to prevail even in the presence of red flags such as back pain (for aortic dissection) and deep vein thrombosis(for pulmonary embolism).
CRISPR technology has presented a path forward for genomic engineering and gene modification. The framework for the use of CRISPR technology to manipulate the human genome is of great interest and the form of its development and application has excited the researchers and biotech communities as the number of publications citing CRISPR gene targeting system has rose predominantly as indexed in PubMed. From a technical standpoint of view, most of us think that this would be relatively straightforward process, but technical feasibility is never the only consideration in doing experiments. Much of the discussion about CRISPR engineering has revolved mostly around its ability for treating disease or editing the genes of human embryos. In the real sense, what the biologists desire about CRISPR is its specificity: the ability to target and determine particular DNA sequences in the genome circuit.
Pulmonary embolism (PE) is an age-related disorder which is potentially fatal, but frequently misdiagnosed. However, the true prevalence of pulmonary embolism is unknown. Inaccurate estimates of PE prevalence might, in part, be attributable to underrecognition of atypical presentations of this disorder. If true prevalence is unknown, the positive predictive values of both typical and atypical symptoms and signs of PE will be unreliable. The negative predictive value of those parameters will, likewise, be unreliable. The aim of this review is to make clinicians more aware of atypical manifestations of PE, thereby increasing the likelihood of correct diagnosis and, hence, ascertainment of the true prevalence of PE. The range of atypical manifestations was explored by a literature search, using MEDLINE from 1946 to February 2019, and EMBASE, from 1947 to February 2019, and Pubmed, from February 2014 to February 2019, using the search terms atypical, uncommon, unusual, pulmonary embolism, lung embolism, pulmonary thromboembolism.
This search revealed atypical presenting features such as non pleuritic retrosternal pain, abdominal pain, atypical breathing patterns, pulmonary oedema, Dressler’s syndrome, atypical radiographic manifestations, atypical electrocardiographic features, manifestations associated with oxygen saturation of 95% or more, coexistence of acute myocardial infarction and pulmonary embolism, coexistence of thoracic aortic dissection and pulmonary embolism, neurological manifestations other than stroke, paradoxical embolism, acute venous thrombosis of atypical location, and pulmonary embolism with normal D-dimer levels.
Although the classical surgical treatment methods of chronic venous insufficiency are successful to relieve perfectly the cause (reflux) and result (varicose veins), the new ablation techniques such as endogenous laser ablation therapy (EVLT), radiofrequency (RF) and foam ablation come into currency more and more with their advantage of being performed with only local anesthesia. However, these techniques, still have the potential for residual saphenofemoral reflux due to incomplete ablation of all side branches of the saphenofemoral junction. As an alternative technique ligation + foam sclerotherapy is not only comfortable like EVLT or RF but also safe and effective as much as classic stripping.
Background: The plant Artemisia annua has been used in traditional Chinese medicine for many years. Rich in bioactive molecules, the A. annua plant is used to extract the anti-malaria compound artemisinin (< 1%), which results in most of the plant being unutilized. One byproduct of artemisinin extraction is artemisia naphtha (AN), which has yet to be studied extensively.
Aims: Study the activity of a novel AN oil extract against microbes, pro-inflammatory cytokines, and dermatological endpoints that are key for eczema and acne pathogenesis to determine if an effective A. annua extract for these skin conditions can be developed.
Methods: Gas chromatography-mass spectrometry was performed to determine the composition of AN oil. P. acnes, S. aureus, M. furfur, and C. albicans were cultured to determine minimal inhibitory concentration. in vitro studies utilizing keratinocytes and macrophages were treated with AN oil and gene expression measured by quantitative RT-PCR. A 13-subject clinical trial was performed with 1% AN oil Gel to assess its potential benefits for sensitive and acne prone skin.
Results: AN oil upregulates filaggrin gene expression and possesses antimicrobial and anti-inflammatory activity inhibiting LPS, S. aureus and "Th2 induced" pro-inflammatory mediator release (IL-6, IL-8 and TSLP). Clinical assessment of 1% AN Gel shows it reduces acne blemishes and the appearance of redness.
Conclusion: Previously an underutilized and unpurified byproduct, AN is now the source to develop the first topical AN oil for cosmetic use with an activity profile that suggests it is effective for those with sensitive and/or acne prone skin.
In 2007, Professor Breijo-Márquez described an electrocardiographic pattern, consisting of the presence of a short PR interval (or PQ) together with a short QT interval in the same individual. It was published with the headline “Decrease in cardiac electrical systole” in International Journal of Cardiology (IJC) [1].
Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematologic condition which could be revealed by deep venous thrombosis. It could be fatal unless correctly treated.
Case report: We report here the case of a 28 year-old male with no medical history who was admitted to the emergency room for severe abdominal pain. Computerized Tomography angiography (CT) scan revealed portal vein thrombosis. Laboratory findings showed pancytopenia with severe regenerative normocytic anemia resulting in PNH. Because of the lack of Eculizumab, treatment was first based on curative anticoagulation until bone marrow transplant, with no success.
Conclusion: PNH remains a severe disease with bad prognosis unless treated with Eculizumab.
Follicular psoriasis is an uncommon diagnosis and probably the least well-known subtype of psoriasis. Hence, we report the clinical and histological findings of follicular psoriasis in one patient to raise awareness of this rare entity.
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