The Registro Informatizado de Enfermedad TromboEmbólica (RIETE Registry) is an ongoing, international, prospective registry of consecutive patients with acute venous thromboembolism (VTE) designed to gather and analyze data on treatment patterns and outcomes in patients with acute VTE. It started in Spain in 2001, and 6 years later the database was translated into English with the aim to expand the Registry to other countries. In contrast to randomized controlled trials, there is no imposed experimental intervention: the management is determined solely by physicians. Thus, it provides data on patients with VTE in a real-world situation with an unselected patient population. Data from RIETE are hypothesis-generating and provide feedback from real-world clinical situations. So far, we learned about the natural history of VTE in patients with relative or absolute contraindications to anticoagulant therapy. We also learned interesting aspects on the natural history of VTE, and we built a number of prognostic scores to identify VTE patients at low, moderate, or high risk for adverse outcome.
In the absence of immortality, the human species has over the millennia developed rites and rituals to help in the passing of life to honor the person who is dying or has died or in some way demonstrate their “courage” and perseverance as well as duty even in the face of almost certain death. The centuries-old traditions of the gathering of loved ones, the chanting of prayers, the ritual religious blessings are in the process of being replaced by the “miracles” of modern medical technology.
Heparanase, a β-D-endoglucuronidase abundant in platelets that was discovered 30 years ago, is an enzyme that cleaves heparan sulfate side chains on the cell surface and in the extracellular matrix. It was later recognized as being a pro-inflammatory and pro-metastatic protein. We had earlier demonstrated that heparanase may also affect the hemostatic system in a non-enzymatic manner. We had shown that heparanase up-regulated the expression of the blood coagulation initiator tissue factor (TF) and interacted with the tissue factor pathway inhibitor (TFPI) on the cell surface membrane of endothelial and tumor cells, leading to dissociation of TFPI and resulting in increased cell surface coagulation activity. Moreover, we have demonstrated that heparanase directly enhanced TF activity which led to increased factor Xa production and subsequent activation of the coagulation system. Recently, heparanase inhibitory peptides derived of TFPI-2 were demonstrated by us to inhibit heparanase procoagulant activity and attenuate sepsis in mouse models.
Venous thromboembolism (VTE), the third most frequent acute cardiovascular syndrome, may cause life-threatening complications and imposes a substantial socio-economic burden. During the past years, several landmark trials paved the way towards novel strategies in acute and long-term management of patients with acute pulmonary embolism (PE). Risk stratification is increasingly recognized as a central cornerstone for an adequate diagnostic and therapeutic management of the highly heterogeneous population of patients with acute PE. Recently published European Guidelines emphasize the importance of clinical prediction rules in combination with imaging procedures (assessment of right ventricular function) and laboratory biomarkers (indicative of myocardial stress or injury) for identification of normotensive PE patients at intermediate risk for an adverse short-term outcome. In this patient group, systemic full-dose thrombolysis was associated with a significantly increased risk of intracranial bleeding, a complication which discourages its clinical application unless hemodynamic decompensation occurs. A large-scale clinical trial program evaluating new oral anticoagulants in the initial and long-term treatment of venous thromboembolism showed at least comparable efficacy and presumably increased safety of these drugs compared to the current standard treatment. Research is continuing on catheter-directed, ultrasound-assisted, local, low-dose thrombolysis in the management of intermediate-risk PE.
Intelligent Design (ID) burst onto the scene in 1996, with the publication of Darwin’s Black Box by Mi-chael Behe. Since then, there has been a plethora of articles written about ID, both pro and con. How-ever, most of the articles critical of ID deal with peripheral issues, such as whether ID is just another form of creationism or whether ID qualifies as science or whether ID should be taught in public schools. It is our view that the central issue is whether the basic claim of ID is correct. Our goal is fourfold: (I) to show that most of the proposed refutations of ID are unconvincing and/or incorrect, (II) to describe the single fundamental error of ID, (III) to discuss the historic tradition surrounding the ID controversy, showing that ID is an example of a “god-of-the-gaps” argument, and (IV) to place the ID controversy in the larger context of proposed proofs for the existence of God, with the emphasis on Jewish tradition.
Parkinson’s disease (PD) and Alzheimer’s disease (AD) are severe neurodegenerative disorders, with no drugs that are currently approved to prevent the neuronal cell loss characteristic in brains of pa-tients suffering from PD and AD, and all drug treatments are symptomatic and monomodal in their action. Due to the complex pathophysiology, including a cascade of neurotoxic molecular events that result in neuronal death and predisposition to depression and eventual dementia, and etiology of these disorders, an innovative approach towards neuroprotection or neurorestoration (neurorescue) is the development and use of multifunctional pharmaceuticals which can act at different brain regions and neurons. Such drugs target an array of pathological pathways, each of which is believed to contribute to the cascades that ultimately lead to neuronal cell death. In this short review, we discuss examples of novel multifunctional ligands that may have potential as neuroprotective-neurorestorative therapeutics in PD and AD, some of which are under development. The compounds discussed originate from synthetic chemistry as well as from natural sources.
KEY WORDS: Rasagiline multimodal drugs, antiapoptotic, neuroprotection, neurorestoration, Parkinson’s disease, Alzheimer’s disease
Moses Maimonides, the illustrious medieval rabbi and philosopher, dedicated the last decade of his life primarily to medicine. His strong interest in medicine was an integral component of his religious-philosophical teachings and world view. In this paper various sources from his rabbinic writings are presented that explain Maimonides’ motivation regarding and deep appreciation for medicine: (A) The physician fulfills the basic biblical obligation to return lost objects to their owner, for with his knowledge and experience the physician can restore good health to his sick fellow human being; (B) medicine provides a unique opportunity to practice imitatio dei, as it reflects the religious duty to maintain a healthy life-style; (C) as an important natural science, medicine offers tools to recognize, love and fear God. These three aspects address man’s relationship and obligation towards his fellow man, himself and God. Biographical insights supported by additional sources from Maimonides’ writings are discussed.
The contributions of Jewish American surgeons in the nineteenth and early twentieth century at a time in which prejudice against ethnic and religious minorities was commonplace in the United States are detailed. The contributions of Jewish American surgeons and the positions they attained subsequent to a change in attitude toward religious minorities in the United States are presented as a comparison.
I present a realistic view of what Darwinian evolution is in its current form and what it is not. I argue that the Torah is not a source of scientific knowledge and all attempts to reconcile its plain text with the data of science are an exercise in futility. The article argues the position that science and the Torah are incommensurable. I argue against using the Torah for attaining knowledge about the nature of the world, or using science for enhancing or denying the truth of the Torah.
Heparanase that was cloned from and is abundant in the placenta is implicated in cell invasion, tumor metastasis, and angiogenesis. Recently we have demonstrated that heparanase may also affect the hemostatic system in a non-enzymatic manner. Heparanase was shown to up-regulate tissue factor (TF) expression and interact with tissue factor pathway inhibitor (TFPI) on the cell surface, leading to dissociation of TFPI from the cell membrane of endothelial and tumor cells, resulting in increased cell surface coagulation activity. More recently, we have shown that heparanase directly enhances TF activity, resulting in increased factor Xa production and activation of the coagulation system. Data indicate increased levels and possible involvement of heparanase in vascular complications in pregnancy. Taking into account the prometastatic and proangiogenic functions of heparanase, overexpression in human malignancies, and abundance in platelets and placenta, its involvement in the coagulation machinery is an intriguing novel arena for further research.
