The development of stent has been a major advance in the treatment of obstructive coronary artery disease since the introduction of balloon angioplasty. However, neointimal hyperplasia occurring within the stent leading to in-stent restenosis is a main obstacle in the long-term success of percutaneous coronary intervention (PCI). The recent introduction of drug-eluting stents (DES) contributes a major breakthrough to interventional cardiology. Many large randomized clinical trials using DES have shown a remarkable reduction in angiographic restenosis and target vessel revascularization when compared with bare metal stents. The results of these trials also appear to be supported by evidence from everyday practice and noncontrolled clinical trials. However, the expanded applications of DES, especially in treating complex lesions such as left main trunk, bifurcation, saphenous vein graft lesions, or in-stent restenosis, are still under evaluation with ongoing studies. With the availability of different types of DES in the market, the issue of cost should not be a deterrent and DES will eventually be an economically viable option for all patients. The adoption of DES in all percutaneous coronary intervention may become a reality in the near future. In this review article...
Cancer patients often experience multiple symptoms, and those symptoms can independently predict changes in patient function, treatment failures, and post-therapeutic outcomes. Symptom clusters are defined as two or more concurrent symptoms that are related and may or may not have a common cause. The purpose of the present study was to review, in cancer patients, common symptom clusters and their predictors.
The underlying mechanisms involved in the pathogenesis of acute pancreatitis are ill understood. The mortality rate of this disease has not significantly improved over the past few decades. Current treatment options are limited, and predominantly aimed at supportive therapy. A key feature of severe acute pancreatitis is the presence of extensive tissue necrosis with both local and systemic manifestations of inflammatory response syndromes. A better understanding of the underlying pathophysiology of severe acute pancreatitis may lead to more targeted therapeutic options, potentially leading to improved survival. Animal models of acute pancreatitis are therefore an essential investigative tool for these aims to be achieved. This review discusses the suitability of recent non-invasive models of acute pancreatitis such as hormone-induced, alcohol-induced, immune-mediated, diet-induced, gene knockout and L-arginine; and invasive models including closed duodenal loop, antegrade pancreatic duct perfusion, biliopancreatic duct injection, combination of secretory hyperstimulation with minimal intraductal bile acid exposure, vascular-induced, ischaemia/reperfusion and duct ligation.
This systematic review updates the understanding of the evidence base for balloon kyphoplasty (BKP) in the management of vertebral compression fractures. Detailed searches of a number of electronic databases were performed from March to April 2006. Citation searches of included studies were undertaken and no language restrictions were applied. All controlled and uncontrolled studies were included with the exception of case reports. Prognostic factors responsible for pain relief and cement leakage were examined using meta-regression. Combined with previous evidence, a total of eight comparative studies (three against conventional medical therapy and five against vertebroplasty) and 35 case series were identified. The majority of studies were undertaken in older women with osteoporotic vertebral compression fractures with long-term pain that was refractory to medical treatment. In direct comparison to conventional medical management, patients undergoing BKP experienced superior improvements in pain, functionality, vertebral height and kyphotic angle at least up to 3-years postprocedure. Reductions in pain with BKP appeared to be greatest in patients with newer fractures. Uncontrolled studies suggest gains in health-related quality of life at 6 and 12-months following BKP. Although associated with a finite level of cement leakage...
Considering that short, mainly heterochiral, polypeptides with a high glycine content are expected to have played a prominent role in evolution at the earliest stage of life before nucleic acids were available, we review recent knowledge about polypeptide three-dimensional structure to predict the types of conformations they would have adopted. The possible existence of such structures at this time leads to a consideration of their functional significance, and the consequences for the course of evolution.
The combination of recombinant human bone morphogenetic protein-2 (rhBMP-2) on an absorbable collagen sponge (ACS) carrier has been shown to induce bone formation in a number of preclinical and clinical investigations. In 2002, rhBMP-2/ACS at a 1.5-mg/cc concentration (INFUSE® Bone Graft, Medtronic Spinal and Biologics, Memphis, TN) was FDA-approved as an autograft replacement for certain interbody spinal fusion procedures. In 2004, INFUSE® Bone Graft was approved for open tibial fractures with an intermedullary (IM) nail fixation. Most recently, in March 2007, INFUSE® Bone Graft was approved as an alternative to autogenous bone grafts for sinus augmentations, and for localised alveolar ridge augmentations for defects associated with extraction sockets. The culmination of extensive preclinical and clinical research and three FDA approvals makes rhBMP-2 one of the most studied, published and significant advances in orthopaedics. This review article summarises a number of clinical findings of rhBMP-2/ACS, including the FDA-approved investigational device exemption (IDE) studies used in gaining the aforementioned approvals.
Breastfeeding-associated inflammatory breast diseases appear especially during the first twelve weeks postpartum and are the most common reason for early cessation of breastfeeding. It also becomes increasingly evident that these inflammatory mammary diseases are triggered or perpetuated in a large part by psychosocial stress. Immunological processes taking place during this cascade in the mammary gland and consequences for the breastfeed newborn are mostly yet unknown. This review summarizes insights from studies on modulation of cytokine levels in breast milk during inflammatory processes like milk stasis and mastitis systematically. It also gives an overview on possible pathological effects, which these cytokine changes in the breast milk might have on the newborn.
Activation of the renin–angiotensin system (RAS) is significant in the pathogenesis of cardiovascular disease and specifically coronary atherosclerosis. There is strong evidence that the RAS has effects on the mechanisms of action of atherosclerosis, including fibrinolytic balance, endothelial function, and plaque stability. Pharmacological inhibition of the renin angiotensin system includes angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and renin inhibitors. These agents have clinical benefits in reducing morbidity and mortality in the management of hypertension. In addition, ACE inhibitors and ARBs have shown to be effective in the management of congestive heart failure and acute myocardial infarction. This review article discusses the biochemical and molecular mechanisms involving the RAS in coronary atherosclerosis as well as the effects of RAS inhibition in clinical studies involving coronary atherosclerosis.
Duloxetine is a balanced selective serotonin norepinephrine reuptake inhibitor (SNRI) which, in 2004, became the first agent to receive regulatory approval for the treatment of painful diabetic neuropathy in the US. This compound has no other significant receptor or channel activities other than the serotonin and norepinephrine reuptake inhibition mechanisms and works to diminish or control the symptoms of diabetic neuropathy. Duloxetine has no known neuroprotective or other effects which prevent the development of neuropathy in patients with diabetes. The purpose of this review article is to discuss the background of painful diabetic neuropathy, the pharmacology of duloxetine, and its safety and efficacy in clinical trials and long-term observations. The authors will also comment on its use in clinical practice. Results from controlled clinical trials reveal that duloxetine administered at 60 mg qd or 60 mg bid is efficacious in treating diabetic neuropathic pain relative to placebo. Positive treatment outcomes are also seen for other measures of pain and quality of life. A minor but statistically significant increase in blood glucose compared with placebo treated patients has been observed in controlled clinical trials. Otherwise...
Pediatric migraine is a disabling condition, which can cause a significant impact on quality of life. Currently, no drugs have been approved by the FDA for its preventive treatment. Our aim was to review the medical literature concerning the efficacy and tolerability of topiramate in the prophylactic treatment of migraine in children and adolescents. A total of five papers were reviewed: two randomized controlled trials (RCTs), a post-hoc subset analysis of adolescents who had been included in three RCTs carried out on adults and two open studies. Topiramate has been proven to reduce headache frequency and the accompanying disability. The frequency of side effects varied considerably among studies, the most frequent being weight loss, anorexia, abdominal pain, difficulties in concentrating, sedation and paresthesia. Since these adverse events, although often transitory, may be distressing for the child, we strongly recommend to assess the disability caused by the migraine episodes before deciding to initiate a prophylactic treatment. Nevertheless, dropout rates due to side effects in the studies were very low.
The placebo is an important tool to blind patients to treatment allocation and therefore minimise some sources of bias in clinical trials. However, placebos that are improperly designed or implemented may introduce bias into trials. The purpose of this systematic review was to evaluate the adequacy of placebo interventions used in low back pain trials. Electronic databases were searched systematically for randomised placebo-controlled trials of conservative interventions for low back pain. Trial selection and data extraction were performed by two reviewers independently. A total of 126 trials using over 25 different placebo interventions were included. The strategy most commonly used to enhance blinding was the provision of structurally equivalent placebos. Adequacy of blinding was assessed in only 13% of trials. In 20% of trials the placebo intervention was a potentially genuine treatment. Most trials that assessed patients’ expectations showed that the placebo generated lower expectations than the experimental intervention. Taken together, these results demonstrate that imperfect placebos are common in low back pain trials; a result suggesting that many trials provide potentially biased estimates of treatment efficacy. This finding has implications for the interpretation of published trials and the design of future trials. Implementation of strategies to facilitate blinding and balance expectations in randomised groups need a higher priority in low back pain research.
Contrast media administration during diagnostic and invasive procedures in high risk patients for nephrotoxicity is a common problem in clinical practice. The mechanisms involved in renal function impairment after contrast media administration are not precisely known but are intensively investigated, and new data have emerged in the literature lately. We present the case of a 72-year old male patient with diabetic nephropathy to whom a new generation iso-osmolar contrast medium (iodixanol) was administered during intravenous pyelography. Due to the contrast agent administration, the patient developed irreversible acute renal failure and became dialysis-dependent. This case suggests that even new generation contrast media (including iodixanol) may be severely nephrotoxic, when administered to high risk patients. Additionally we review the complex mechanisms involved in pathogenesis of contrast media nephrotoxicity.
Sarcoidosis is a multi-system granulomatous disorder of unknown aetiology. Symptomatic cardiac involvement occurs in approximately 5% of patients. The prevalence of sarcoidosis in the Netherlands is unknown, but estimated to be approximately 20 per 100,000 population (3200 patients). We report on five patients who presented with different manifestations of cardiac sarcoidosis, and give a brief review on the current management of this condition. Magnetic Resonance Imaging (MRI) can be of great help in diagnosing this condition as well as in the follow-up of the response to therapy.
Gaucher disease is a progressive lysosomal storage disorder caused by the deficiency of glucocerebrosidase, and characterized by intralysosomal storage of glucosylceramide that leads to dysfunction in multiple organ systems. Intravenous enzyme replacement with imiglucerase is the accepted standard for treatment of symptomatic patients and has been effective in reducing many of the signs and symptoms of type I Gaucher disease in the majority of patients without serious adverse effects. An alternative therapeutic approach is substrate reduction therapy with N-butyldeoxynojirimycin (NB-DNJ) (miglustat; Zavesca®), an imino sugar that reversibly inhibits glucosylceremide synthase and reduces intracellular storage of glucosylceramide. Miglustat was recently approved in Europe and the United States for symptomatic patients with mild to moderate clinical manifestations for whom enzyme replacement therapy is not an option. This review article discusses the results of clinical studies and use of miglustat as a therapeutic agent in patients with type I Gaucher disease.
The spleen is the most commonly injured visceral organ in blunt abdominal trauma in both adults and children. Nonoperative management is the current standard of practice for patients who are hemodynamically stable. However, simple observation alone has been reported to have a failure rate as high as 34%; the rate is even higher among patients with high-grade splenic injuries (American Association for the Surgery of Trauma [AAST] grade III–V). Over the past decade, angiography with transcatheter splenic artery embolization, an alternative nonoperative treatment for splenic injuries, has increased splenic salvage rates to as high as 97%. With the help of splenic artery embolization, success rates of more than 80% have also been described for high-grade splenic injuries. We discuss the role of computed tomography and transcatheter splenic artery embolization in the diagnosis and treatment of blunt splenic trauma. We review technical considerations, indications, efficacy and complication rates. We also propose an algorithm to guide the use of angiography and splenic embolization in patients with traumatic splenic injury.
Opiates are the analgesic of choice for the treatment of post-burn, -trauma and -surgical pain, however, it is also well-established that opiates can induce immune complications. These complications, independent of the analgesic regime, are also associated with severe traumatic injuries, such as burns. Recent findings suggest that opiates can contribute to immune and infectious complications in experimental and clinical settings. Based on the immunomodulatory properties of opiate analgesics their therapeutic use/misuse post-injury may contribute to the development of complications leading to increased morbidity and mortality in this patient population. An improved understanding of the relationship(s) between opiates and complications following major injury, such as burn trauma is likely to contribute towards an improvement in existing, as well as the development of new therapeutic regimes. This review will focus on the role of opiate analgesic usage and abuse and in the development of complications following major traumatic injury with a particular emphasis on burn injury.
Thalidomide monotherapy in relapsed/refractory multiple myeloma (MM) has a response rate of 30%. The combination of thalidomide with dexamethasone (Thal/Dex) is expected to improve responses, but it is unknown if the combination increases the rate of adverse events. Here, we conducted a systematic review of studies evaluating Thal/Dex in relapsed/refractory MM. Twelve studies were included, comprising 451 patients. The response rate (CR and PR) was 46% (95% CI 42–51%). Therapy-related toxicity was comparable to thalidomide monotherapy and included somnolence (26%, 95% CI 22–31%), constipation (37%, 95% CI 32–42%) and peripheral neuropathy (27%, 95% CI 23–32%). Only venous thromboembolism appeared to occur more often with Thal/Dex (5%, 95% CI 3–8%). Thus, using Thal/Dex results in an improved response rate in relapsed/refractory MM, with a toxicity rate comparable to thalidomide monotherapy.
Nicotine, the primary psychoactive component of tobacco products, produces diverse neurophysiological, motivational, and behavioral effects through several brain regions and neurochemical pathways. Various neurotransmitter systems have been explored to understand the mechanisms behind nicotine tolerance, dependence, and withdrawal. Recent evidence suggests that glutamate neurotransmission has an important role in this phenomenon. The aim of the present review is to discuss preclinical findings concerning the role of N-methyl-D-aspartate (NMDA) receptor neurotransmission in mediating the behavioral effects of nicotine, tolerance, sensitization, dependence, and withdrawal. Based on preclinical findings, it is hypothesized that NMDA receptors mediate the common adaptive processes that are involved in the development, maintenance, and expression of nicotine addiction. Modulation of glutamatergic neurotransmission with NMDA receptor antagonists may prove to be useful in alleviating the symptoms of nicotine abstinence and facilitate tobacco-smoking cessation.
Prehospital ultrasound has been deployed in certain areas of the USA and Europe. Physicians, emergency medical technicians, and flight nurses have utilized a variety of medical and trauma ultrasound assessments to impact patient care in the field. The goal of this review is to summarize the literature on emergency medical services (EMS) use of ultrasound to more clearly define the potential utility of this technology for prehospital providers.
Apoptosis or programmed cell death is a physiological mechanism, characterized by specific morphological and biochemical changes such as cell shrinkage, chromatin condensation, protein cleavage, DNA breakdown and phagocytosis. Apoptosis is a significant contributor to the morphologic and functional development of multicellular organisms. It is also involved in the pathogenesis of several diseases including degenerative diseases of the central nervous system (CNS) like Alzheimers disease or Parkinsons disease, cancer and immune system dysfunction. There are many factors, mainly proteins, which are involved in the activation, regulation and execution of related events. A fairly detailed outline of apoptotic mechanisms has also started to emerge and to be verified. In this short, focused mini-review, we attempt to outline current evidence regarding the mechanisms and the regulation of apoptosis.