Aortic valve replacement (AVR) is a treatment of choice for patients with symptomatic severe aortic stenosis (AS). However, a significant proportion of these patients do not undergo surgical AVR due to high-risk features. Transcatheter aortic valve implantation (TAVI) has emerged as an alternative for patients with severe AS who are not candidates for open-heart surgery. Since the introduction of TAVI to the medical community in 2002, there has been an explosive growth in procedures. The balloon-expandable Edwards SAPIEN valve and the self-expanding CoreValve ReValvingTM system contribute the largest patient experience with more than 10,000 patients treated with TAVI to date. Clinical out-comes have stabilized in experienced hands, with 30-day mortality less than 10%. Careful patient selection, growing operator experience, and an integrated multidisciplinary team approach contribute to notable improvement in outcomes. In the first randomized pivotal PARTNER trial, in patients with severe AS not suitable candidates for surgical AVR, TAVI compared with standard therapy, significantly improved survival and cardiac symptoms, but was associated with higher incidence of major strokes and major vascular events. The results of randomized comparison of TAVI with AVR among high-risk patients with AS for whom surgery is a viable option are eagerly awaited to provide further evidence on the applicability of TAVI in these patients.
Rasagiline (Azilect) is a highly selective and potent propargylamine inhibitor of monoamine oxidase (MAO) type B. Like other similar propargylamine inhibitors, rasagiline binds covalently to the N5 nitro-gen of the flavin residue of MAO, resulting in irreversible inactivation of the enzyme. Therapeutic doses of the drug which inhibit brain MAO-B by 95% or more cause minimal inhibition of MAO-A, and do not potentiate the pressor or other pharmacological effects of tyramine. Metabolic conversion of the com-pound in vivo is by hepatic cytochrome P450-1A2, with generation of 1-aminoindan as the major me-tabolite. Rasagiline possesses no amphetamine-like properties, by contrast with the related compound selegiline (Deprenyl, Jumex, Eldepryl). Although the exact distribution of MAO isoforms in different neurons and tissues is not known, dopamine behaves largely as a MAO-A substrate in vivo, but follow-ing loss of dopaminergic axonal varicosities from the striatum, metabolism by glial MAO-B becomes increasingly important. Following subchronic administration to normal rats, rasagiline increases levels of dopamine in striatal microdialysate, possibly by the build-up of β-phenylethylamine, which is an ex-cellent substrate for MAO-B, and is an effective inhibitor of the plasma membrane dopamine trans-porter (DAT). Both of these mechanisms may participate in the anti-Parkinsonian effect of rasagiline in humans. Rasagiline possesses neuroprotective properties in a variety of primary neuronal preparations and neuron-like cell lines, which is not due to MAO inhibition. Recent clinical studies have also demon-strated possible neuroprotective properties of the drug in human Parkinsonian patients, as shown by a reduced rate of decline of symptoms over time.
Chronic hepatitis C virus (HCV) infection is a leading cause of liver disease worldwide and remains the most common indication for liver transplantation. The current standard of care leads to a sustained vir-al response of roughly 50% of treated patients at best. Furthermore, anti-viral therapy is expensive, pro-longed, and associated with serious side-effects. Evidence suggests that a poor response to treatment may be the result of a suppressed anti-viral immunity due to the presence of increased numbers and activity of CD4+CD25+Foxp3+ regulatory T cells (Treg cells). We and others have recently identified fi-brinogen-like protein 2 (FGL2) as a putative effector of Treg cells, which accounts for their suppressive function through binding to Fc gamma receptors (FcγR). In an experimental model of fulminant viral hepatitis, our laboratory showed that increased plasma levels of FGL2 pre- and post-viral infection were predictive of susceptibility and severity of disease. Moreover, treatment with antibody to FGL2 fully protected susceptible animals from the lethality of the virus, and adoptive transfer of wild-type Treg cells into resistant fgl2-deficient animals accelerated their mortality post-infection. In patients with HCV infection, plasma levels of FGL2 and expression of FGL2 in the liver correlated with the course and severity of the disease. Collectively, these studies suggest that FGL2 may be used as a biomarker to pre-dict disease progression in HCV patients and be a logical target for the development of novel therapeu-tic approaches for the treatment of patients with HCV infection.
The expanding impact of chronic kidney disease (CKD) due to pandemic diabetes mellitus is recounted emphasizing its epidemiology that has induced global socioeconomic stress on health care systems in industrialized nations now attempting to proffer optimal therapy for end stage renal disease (ESRD). Strategies to delay and perhaps prevent progression of diabetic nephropathy from minimal proteinuria through nephrotic range proteinuria and azotemia to ESRD appear to have decreased the rate of persons with diabetes who develop ESRD. For those with ESRD attributed to diabetes, kidney transplantation affords better survival and rehabilitation than either hemodialysis or peritoneal dialysis. It is likely that advances in genetics and molecular biology will suggest early interventions that will preempt diabetic complications including renal failure.
It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important impli-cations for infectious diseases, Mendelian genetic diseases, and systemic diseases in current human populations. Moreover, evolution proceeds by mechanisms other than natural selection. The recent growth in human population size has greatly increased the reservoir of mutational variants in the hu-man gene pool, thereby enhancing the potential for human evolution. The increase in human popula-tion size coupled with our increased capacity to move across the globe has induced a rapid and ongoing evolutionary shift in how genetic variation is distributed within and among local human populations. In particular, genetic differences between human populations are rapidly diminishing and individual het-erozygosity is increasing, with beneficial health effects. Finally, even when cultural evolution eliminates selection on a trait, the trait can still evolve due to natural selection on other traits. Our traits are not isolated, independent units, but rather are integrated into a functional whole, so selection on one trait can cause evolution to occur on another trait, sometimes with mildly maladaptive consequences.
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.
All possible pro and con arguments regarding the theory of evolution have been discussed and debated in the vast literature—scientific, religious, and lay—in the past 150 years. There is usually great zealotry in all debating parties, with mutual intolerance of ideas and concepts, disrespect toward opposing opi-nions and positions, and usage of very harsh language. This prejudiced approach usually does not allow for a reasonable debate. It is important to look at the facts, assumptions, and beliefs of the theory of evolution in a more calm and humble way.In this article a comparative analysis is offered between the scientific aspects of the theory of evolution and a Judaic approach to these aspects.The two sets of human thought—religion and science—are fundamentally different in their aims and purposes, in their methods of operation, in their scope of interest and issues, and in their origin and ramifications. Whenever science surpasses its limits, or religion exceeds its boundaries, it actually is a form of an abuse of both. This has happened to the theory of evolution in a more powerful mode than any other interaction between science and religion.The agenda of many scientists who promote the theory of evolution is to achieve the goal of under-standing the existence of the universe as a random, purposeless, natural development, evolved slowly over billions of years from a common ancestor by way of natural selection, devoid of any supernatural metaphysical power.Jewish faith perceives the development of the universe in a different way: God created the world, with a purpose known to Him; He established natural laws that govern the world; and He imposed a moral-religious set of requirements upon Man.The discussion and comparative analysis in this article is based upon the current neo-Darwinian theory, although it seems almost certain that even the new and modern assumptions and speculations will continue to be challenged, changed, and revised as new scientific information will be discovered.The theory of evolution is based upon certain facts, many assumptions, speculations, and interpreta-tions, and some fundamental non-evidence-based beliefs.
Stents are widely use in endoscopic urological procedures. One of the most important indications is the treatment of urinary tract strictures. Allium™ Medical has introduced several types of stents for the treatment of different types of urinary tract strictures, based on anatomic location. All the stents are made of nitinol and coated with a co-polymer that reduces encrustations. These stents are self-expandable and have a large caliber and a high radial force. They have different shapes, designed especially for the treatment of each type of stricture. One of the most important features of Allium-manufactured stents is the ease of removal, due to their special unraveling feature. The company has introduced the Bulbar Urethral Stent (BUS) for treatment of bulbar urethral strictures; a rounded stent available in different lengths. Initial data on 64 patients with bulbar urethral stricture treated with the BUS showed a significant improvement in symptoms, with minimal complications and few adverse events. For treatment of prostate obstruction in patients unfit for surgery or unwilling to undergo a classical prostatic surgery, the Triangular Prostatic Stent (TPS) was introduced, which has a triangular shape that fits in the prostatic urethra. Its body has a high radial force attached to an anchor (which prevents migration) through a trans-sphincteric wire (which reduces incontinence rate). Initial data on 51 patients showed significant improvement in symptoms and in urinary peak flow rate, with a relatively small number of complications. The Round Posterior Stent (RPS) was designed for treatment of post radical prostatectomy bladder neck contracture. This short, round stent has an anchor, which is placed in the bladder neck. This stent being relatively new, the clinical data are still limited. Ureteral strictures can be treated with the Ureteral Stent (URS), which is round-shaped, available in different lengths, and has an anchor option (for very distal or very proximal strictures). We have previously published data on 107 URSs inserted in patients with ureteral stricture due to several etiologies, including patients who failed previous treatment. All patients were asymptomatic for a long period of follow-up after stent removal, with only one case of re-stenosis. In this paper, we review the urological “covered” stents produced by Allium Medical with the relevant clinical data available at the present time.
As I shared in my January 2015 editorial, the furor surrounding publication in The Lancet of the open letter by P. Manduca et al. carried potential for bad and for good. Here at Rambam Health Care Campus, we have chosen and will continue to look for the good.
Bladder cancer is a common disease with a stable incidence for the past few decades despite advancements in molecular and genetic determinants of cancer development and progression. Cystoscopy remains the standard for detection and surveillance of bladder cancer, but it is an invasive and potentially costly procedure. With the knowledge of molecular alterations associated with bladder cancer numerous urine-based tumor markers have become commercially available. These urine markers have been evaluated in all clinical scenarios for the detection of bladder cancer including screening, hematuria, atypical cytology evaluation, and surveillance, but given the relative lack of impactful trials they are not routinely utilized. The efforts to develop markers with increased sensitivity to replace cystoscopy for the detection of bladder cancer have thus far been unsuccessful as well. This review addresses role of urine markers for screening, detection, and surveillance of bladder cancer.
