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Stem Cell Therapy: Helping the Body Heal Itself
Stem cells are nature's own transformers. When the body is injured, stem cells travel the scene of the accident. There, they help heal damaged tissue. They do this by transforming themselves into whatever type of cell has been injured. Stem cells can become bone, skin – even heart tissue. When your heart muscle is damaged in a heart attack, stem cells are summoned from the bone marrow to make repairs. Stem cells do a good job. But they could do better – for some reason, the heart stops signaling for heart cells after only a week or so after the damage has occurred, leaving the repair job mostly undone. The partially repaired tissue becomes a burden to the heart, forcing it to work harder and less efficiently, leading to heart failure.
Researchers believe that we can we can boost the efficiency of stem cells and help the body recover faster and better from heart attacks, even after the heart has stopped signaling for them. They've developed methods to enhance the body's natural repair function, both in the setting of heart attack and congestive heart failure. Now these methods are being tested in clinical trials. Some of them are enrolling patients now. If you're interested, read about some of these clinical trials below.
Clinical trials using stems cells to heal the heart:
ATHERSYS MULTISTEM: Following an acute myocardial infarction (AMI), the body automatically recruits stem cells from the bone marrow to repair damaged heart tissue. The problem, however, is the molecular signals that recruit the new stem cells stay on for only a short period. Consequently, damage to the myocardium is never repaired, which weakens its functionality and leads to chronic heart failure.
Cleveland Clinic also enrolled the first AMI patient who was treated with a multipotent adult progenitor cell developed by Cleveland-based biotech firm Athersys Inc. The first cohort of the Phase I clinical trial thus far suggests the Athersys MultiStem cell was administered safely and was well tolerated by the patients. This Phase I trial is continuing to recruit patients.
In preclinical AMI models, MultiStem has shown the potential to improve heart function. The MultiStem cells are derived from bone marrow of qualified donors.
"MultiStem is being developed as an off-the-shelf product so that it can be administered in the catheterization lab at any hospital while the patient is undergoing a stent procedure to open the artery," says Marc S. Penn, MD, PhD, Department of Stem Cell Biology and Regenerative Medicine and the Robert and Suzanne Tomsich Department of Cardiovascular Medicine. "A Cricket Micro-Infusion Catheter, a proprietary device developed by Mercator Med Systems, enables physicians to rapidly and efficiently deliver the MultiStem cells in to the damaged region of the heart."
Cleveland Clinic's Department of Stem Cell Biology and Regenerative Medicine also is a key clinical site for national stem cell trials currently recruiting patients including trials being run by the National Institutes of Health Cardiovascular Cell Therapy Research Network. They include:
IMPACT-DCM: Led at Cleveland Clinic by Nicholas Smedira, MD, Cardiothoracic Surgery, this Phase II trial will examine intramyocardial delivery of autologous bone marrow cells in ischemic and non-ischemic patients with chronic heart failure due to dilated cardiomyopathy (DCM). Patients randomized into the treatment group of the IMPACT-DCM trial are treated with Cardiac Repair Cells (CRCs), an autologous, mixed-cell product (Aastrom Biosciences) containing expanded populations of stem and early progenitor cells produced from a small sample of the patient's own bone marrow. The CRCs are injected into the heart muscle through minimally invasive surgery. The IMPACT-DCM trial will determine the safety and tolerability of CRCs compared to standard-of-care in patients with DCM.
MARVEL: This Phase II/III trial will assess safety and efficacy of MyoCell (Bioheart) autologous clinical cell therapy into myocardium post myocardial infarction to determine if adult stem cells can improve heart function. After autologous myoblasts are harvested from a patient's skeletal muscle tissue, they are isolated and expanded in culture in a closed system. When a sufficient number of cells are estimated, they are taken from culture, packaged in a suspension and injected directly into the myocardium via the femoral artery.
TIME: The trial, led by site PI Stephen G. Ellis, MD, Cardiovascular Medicine, will provide stem cell infusions to patients three days or seven days after they receive percutaneous coronary intervention (PCI) for AMI. The study will evaluate the safety and effectiveness of placing bone marrow derived stem cells into the myocardium to improve its function following an AMI after successful revascularization. What's more, the study will help determine the best time to deliver the stem cells after MI.
Late TIME: Also led by Dr. Ellis, this trial is similar to the TIME study. The only difference is that patients will receive their own bone marrow derived stem cells two to three weeks following AMI and PCI. For some patients, delaying the delivery of stem cells two to three weeks after AMI may be better than initiating treatment during the acute phase.
FOCUS: This trial will assess the effectiveness of bone marrow derived stem cell treatment for adults with chronic heart failure due to a history of myocardial infarction. Some patients with this condition, especially those with substantial scar tissue on the myocardium's wall, or patients with a particular heart structure, may not be eligible to receive standard treatments of coronary artery bypass grafting or coronary angioplasty and stent placement. The trial, led by Dr. Ellis, will evaluate whether bone marrow derived stem cells may be an effective way to achieve therapeutic angiogenesis and improvement in heart function.
Coming Soon in 2010:
In January 2010, Dr. Penn expects to launch a new Phase I clinical trial to determine the safety and efficacy of stromal derived factor-1 (SDF-1) proprietary technology developed by Cleveland Clinic. In preclinical studies, animals that were injected with genes that express SDF-1 protein showed definite improvement in cardiac function over those animals that were given control genes.
Dr. Penn says the goal of this new gene therapy is to stimulate the recruitment of the patient's own stem cells to repair the damaged heart tissue and to induce angiogenesis (new blood vessel growth). This trial is rather unique because most research involves harvesting stem cells from patients and delivering them directly into the heart via minimally invasive procedures and specially designed catheters.
Dr. Ellis, Dr. Penn, Dr. Smedira and their colleagues in the Heart & Vascular Institute are working hard to bring these developing stem cell therapies to the patient's bedside in a safe and timely fashion.
Important information about stem cell trials:
All stem cell studies have strict protocols, approved by the FDA and the Cleveland Clinic Institutional Review Board for inclusion and exclusion criteria. To insure you meet the criteria, patients need to be evaluated by a physician and may require specific testing at the Cleveland Clinic. This testing may take more than one day to complete if you require studies or consultations with multiple physicians.
Stem cell trials are randomized controlled studies – not all patients who undergo evaluation for stem cell trials will receive stem cell therapy.
Each study has different protocols and the stem cells are accessed and administered differently, and have different criteria for follow-up. The research team will discuss all aspects of the trial with you in detail prior to signing consent and participating in the trial.
Patients are not given monetary compensation for testing to determine enrollment into the different studies. Once a patient meets the screening baseline criteria and informed consent has been reviewed and signed, patients are not charged for any therapy or monitoring that is directly related to the research. Travel, lodging and meals are not covered by the studies.
Cleveland Clinic is a large referral center for advanced heart disease and heart failure – we offer a wide range of therapies – including medications, devices and surgery. Patients will be evaluated for the treatments that best address their condition. Whether patients meet the criteria for stem cell therapy – or not, they will be offered the most advanced array of treatment options.
Adult Stem Cells Repair Heart Attack Damage
Adult stem cells may help repair heart tissue damaged by heart attack according to the findings of a new study to be published in the December 8 issue of the Journal of the American College of Cardiology. Results from the Phase I study show stem cells from donor bone marrow appear to help heart attack patients recover better by growing new blood vessels to bring more oxygen to the heart.
Rush University Medical Center was the only Illinois site and one of 10 cardiac centers across the country that participated in the 53-patient, double-blind, placebo-controlled Phase I trial. Rush is now currently enrolling patients for the second phase of the study.
Researchers say it is the strongest evidence thus far indicating that adult stem cells can actually differentiate, or turn into heart cells to repair damage. Until now, it has been believed that only embryonic stem cells could differentiate into heart or other organ cells.
"The results point to a promising new treatment for heart attack patients that could reduce mortality and lessen the need for heart transplants," said Dr. Gary Schaer, head of the Rush Cardiac Catheterization Laboratory and study principal investigator at Rush.
In phase I of the study, a group of 53 patients who had heart attacks in the previous ten days received adult mesenchymal stem cells and were kept under close study for two years.
The mesenchymal stem cells (MSC) were harvested from the bone marrow of healthy adult donors. These cells have the potential to develop into mature heart cells and new blood vessels. Similar to Blood Type O, mescenchymal stem cells have the advantage that they can be taken from the bone marrow of an unrelated donor without needing to be matched by blood type.
After the stem cells were extracted, they were purified by drug manufacturer Osiris Therapeutics into a formulation for intravenous delivery called Prochymal. Patients were administered an infusion of either Prochymal or placebo as an injection into a vein in the arm or leg. To prevent bias, neither the patient nor the physician knew who received the stem cell treatment and who received the placebo.
In the study, patients who received the adult stem cells were compared to similar patients who received inert placebo injections. Both were followed by MRI and echocardiogram.
After six months, patients who received the adult stem cells were four times as likely to have improved overall condition, were able to pump more blood with each heartbeat than untreated patients, had only one-quarter as many dangerous heart arrhythmias, and suffered no toxicity or other serious adverse side effects from the treatment.
"It is suspected that these stem cells may take part in the growth of new blood vessels to bring more oxygen to the heart and help reduce the scarring from a heart attack," said Schaer.
Echocardiograms showed patients had improved heart function, particularly in those patients with large amounts of cardiac damage. Patients also have improvements in lung function.
According to Schaer, one reason the study results are so promising is that these stem cells can be used without tissue typing and do not trigger an immune response, and are available for every patient.
A unique benefit of the stem cell product is that it is given to patients through a standard intravenous (IV) line which is simple and easy for the patient compared to other therapies that require delivery to the site of the disease through catheterization or open surgical procedures,
Adult stem cells are designed by nature to perform tissue repair in a mature adult. It is believed that these cells can be used in patients unrelated to the donor, without rejection, eliminating the need for donor matching and recipient immune suppression. Once transplanted, the cells promote healing of damaged or diseased tissues.
"It is possible that in the future, hospitals might be able to keep frozen adult stem cells on hand for speedy use in treating heart attacks," said Schaer.
"This study suggests that adult bone marrow derived stem cells are more flexible than previously thought," said Schaer. "If the benefits and safety are confirmed in the oingoing Phase II trial, we may soon have a remarkable new therapy for patients with a large heart."
Rush is currently seeking participants for the second phase of the study.
About Rush University Medical Center
Rush University Medical Center is an academic medical center that encompasses the more than 600 staffed-bed hospital (including Rush Children's Hospital), the Johnston R. Bowman Health Center and Rush University. Rush University, with more than 1,270 students, is home to one of the first medical schools in the Midwest, and one of the nation's top-ranked nursing colleges. Rush University also offers graduate programs in allied health and the basic sciences. Rush is noted for bringing together clinical care and research to address major health problems, including arthritis and orthopedic disorders, cancer, heart disease, mental illness, neurological disorders and diseases associated with aging.
Source: Rush University Medical Center
Stem Cells Repair Heart Attack Damage
'Off-the-Shelf' Stem Cell Product Safe, May Mend Hearts
By Daniel J. DeNoon
WebMD Health News
Reviewed by Louise Chang, MD
Dec. 1, 2009 -- Can stem cells safely repair heart attack damage? Yes, a clinical trial suggests.
Bone marrow stem cells are supposed to home in on damaged parts of the heart. Once there, they send out signals that help the body repair the injury. There's also evidence, from animal studies, that the stem cells themselves engraft to the heart and help repopulate dead cells with new, living cells.
Now there's evidence from actual patients who suffered heart attacks. It comes from a study led by cardiologist Joshua M. Hare, director of the stem cell institute at the University of Miami Miller School of Medicine, and colleagues at nine other medical centers.
"Stem cell-treated patients had ... significant improvements in heart, lung, and global function," Hare said in a news release. "Echocardiography showed improved heart function, particularly in those patients with large amounts of cardiac damage."
It's not the first time heart attack patients have been treated with stem cells. But previous studies used bone marrow cells extracted from the patient and then injected directly into the heart.
Hare's team used an "off-the-shelf" stem cell product -- Prochymal -- containing stem cells harvested from a single healthy donor and grown to large numbers in laboratories. Prochymal is given by intravenous infusion. It's made by Osiris Therapeutics Inc., which sponsored the study, and which currently seeks FDA approval of the product as a treatment for graft-versus-host disease in transplant recipients.
"Many have argued that it's premature to test stem cells in patients," Hare said. "This trial ... lays the foundation for a brand new cell-based therapy for the human heart."
The Hare study enrolled 53 heart attack patients treated within 10 days of their first heart attack. None of the patients required bypass. A fourth of the patients got infusions of an inactive placebo; the others got various doses of the Prochymal cells.
The main goal of the study was to see if Prochymal was safe. It had been feared that the cells might cause growth of unwanted tissue in the arteries or the lungs; this did not happen. Patients receiving the stem cells had fewer adverse events than those who received placebo.
The secondary goal of the study was to gather some evidence that the treatment actually helped. There was such evidence -- particularly in the patients with the largest infarcts (patches of heart tissue killed during a heart attack).
Why? Emergency signals sent out by wounded heart tissue attract help from stem cells. It's probable that the stronger signal from the more damaged hearts attracted more of the stem cells to the site of injury, suggest Cleveland Clinic researchers Marc S. Penn, MD, PhD, and colleagues in an editorial accompanying the Hare report in the Dec. 8 issue of the Journal of the American College of Cardiology.
Warning that the Hare study is only a first step, Penn and colleagues call the findings "important."
"Many questions remain, but there is excitement in what the future holds with regard to advances in this field," they write.
A phase 2 clinical trial, also sponsored by Osiris, is enrolling heart attack patients.
Can Stem Cells Repair a Damaged?
Heart attacks and congestive heart failure remain among the Nation's most prominent health challenges despite many breakthroughs in cardiovascular medicine. In fact, despite successful approaches to prevent or limit cardiovascular disease, the restoration of function to the damaged heart remains a formidable challenge. Recent research is providing early evidence that adult and embryonic stem cells may be able to replace damaged heart muscle cells and establish new blood vessels to supply them. Discussed here are some of the recent discoveries that feature stem cell replacement and muscle regeneration strategies for repairing the damaged heart.
For those suffering from common, but deadly, heart diseases, stem cell biology represents a new medical frontier. Researchers are working toward using stem cells to replace damaged heart cells and literally restore cardiac function.
Today in the United States, congestive heart failure—the ineffective pumping of the heart caused by the loss or dysfunction of heart muscle cells—afflicts 4.8 million people, with 400,000 new cases each year. One of the major contributors to the development of this condition is a heart attack, known medically as a myocardial infarction, which occurs in nearly 1.1 million Americans each year. It is easy to recognize that impairments of the heart and circulatory system represent a major cause of death and disability in the United States [5].
What leads to these devastating effects? The destruction of heart muscle cells, known as cardiomyocytes, can be the result of hypertension, chronic insufficiency in the blood supply to the heart muscle caused by coronary artery disease, or a heart attack, the sudden closing of a blood vessel supplying oxygen to the heart. Despite advances in surgical procedures, mechanical assistance devices, drug therapy, and organ transplantation, more than half of patients with congestive heart failure die within five years of initial diagnosis. Research has shown that therapies such as clot-busting medications can reestablish blood flow to the damaged regions of the heart and limit the death of cardiomyocytes. Researchers are now exploring ways to save additional lives by using replacement cells for dead or impaired cells so that the weakened heart muscle can regain its pumping power.
How might stem cells play a part in repairing the heart? To answer this question, researchers are building their knowledge base about how stem cells are directed to become specialized cells. One important type of cell that can be developed is the cardiomyocyte, the heart muscle cell that contracts to eject the blood out of the heart's main pumping chamber (the ventricle). Two other cell types are important to a properly functioning heart are the vascular endothelial cell, which forms the inner lining of new blood vessels, and the smooth muscle cell, which forms the wall of blood vessels. The heart has a large demand for blood flow, and these specialized cells are important for developing a new network of arteries to bring nutrients and oxygen to the cardiomyocytes after a heart has been damaged. The potential capability of both embryonic and adult stem cells to develop into these cells types in the damaged heart is now being explored as part of a strategy to restore heart function to people who have had heart attacks or have congestive heart failure. It is important that work with stem cells is not confused with recent reports that human cardiac myocytes may undergo cell division after myocardial infarction [1]. This work suggests that injured heart cells can shift from a quiescent state into active cell division. This is not different from the ability of a host of other cells in the body that begin to divide after injury. There is still no evidence that there are true stem cells in the heart which can proliferate and differentiate.
Researchers now know that under highly specific growth conditions in laboratory culture dishes, stem cells can be coaxed into developing as new cardiomyocytes and vascular endothelial cells. Scientists are interested in exploiting this ability to provide replacement tissue for the damaged heart. This approach has immense advantages over heart transplant, particularly in light of the paucity of donor hearts available to meet current transplantation needs.
What is the evidence that such an approach to restoring cardiac function might work? In the research laboratory, investigators often use a mouse or rat model of a heart attack to study new therapies (see Figure 9.1. Rodent Model of Myocardial Infarction). To create a heart attack in a mouse or rat, a ligature is placed around a major blood vessel serving the heart muscle, thereby depriving the cardiomyocytes of their oxygen and nutrient supplies. During the past year, researchers using such models have made several key discoveries that kindled interest in the application of adult stem cells to heart muscle repair in animal models of heart disease.
Recently, Orlic and colleagues [9] reported on an experimental application of hematopoietic stem cells for the regeneration of the tissues in the heart. In this study, a heart attack was induced in mice by tying off a major blood vessel, the left main coronary artery. Through the identification of unique cellular surface markers, the investigators then isolated a select group of adult primitive bone marrow cells with a high capacity to develop into cells of multiple types. When injected into the damaged wall of the ventricle, these cells led to the formation of new cardiomyocytes, vascular endothelium, and smooth muscle cells, thus generating de novo myocardium, including coronary arteries, arterioles, and capillaries. The newly formed myocardium occupied 68 percent of the damaged portion of the ventricle nine days after the bone marrow cells were transplanted, in effect replacing the dead myocardium with living, functioning tissue. The researchers found that mice that received the transplanted cells survived in greater numbers than mice with heart attacks that did not receive the mouse stem cells. Follow-up experiments are now being conducted to extend the posttransplantation analysis time to determine the longer-range effects of such therapy [8]. The partial repair of the damaged heart muscle suggests that the transplanted mouse hematopoietic stem cells responded to signals in the environment near the injured myocardium. The cells migrated to the damaged region of the ventricle, where they multiplied and became "specialized" cells that appeared to be cardiomyocytes.
A second study, by Jackson et al. [3], demonstrated that cardiac tissue can be regenerated in the mouse heart attack model through the introduction of adult stem cells from mouse bone marrow. In this model, investigators purified a "side population" of hematopoietic stem cells from a genetically altered mouse strain. These cells were then transplanted into the marrow of lethally irradiated mice approximately 10 weeks before the recipient mice were subjected to heart attack via the tying off of a different major heart blood vessel, the left anterior descending (LAD) coronary artery. At two to four weeks after the induced cardiac injury, the survival rate was 26 percent. As with the study by Orlic et al., analysis of the region surrounding the damaged tissue in surviving mice showed the presence of donor-derived cardiomyocytes and endothelial cells. Thus, the mouse hematopoietic stem cells transplanted into the bone marrow had responded to signals in the injured heart, migrated to the border region of the damaged area, and differentiated into several types of tissue needed for cardiac repair. This study suggests that mouse hematopoietic stem cells may be delivered to the heart through bone marrow transplantation as well as through direct injection into the cardiac tissue, thus providing another possible therapeutic strategy for regenerating injured cardiac tissue.
More evidence for potential stem cell-based therapies for heart disease is provided by a study that showed that human adult stem cells taken from the bone marrow are capable of giving rise to vascular endothelial cells when transplanted into rats [6]. As in the Jackson study, these researchers induced a heart attack by tying off the LAD coronary artery. They took great care to identify a population of human hematopoietic stem cells that give rise to new blood vessels. These stem cells demonstrate plasticity meaning that they become cell types that they would not normally be. The cells were used to form new blood vessels in the damaged area of the rats' hearts and to encourage proliferation of preexisting vasculature following the experimental heart attack.
Like the mouse stem cells, these human hematopoietic stem cells can be induced under the appropriate culture conditions to differentiate into numerous tissue types, including cardiac muscle [10] (see Figure 9.2. Heart Muscle Repair with Adult Stem Cells). When injected into the bloodstream leading to the damaged rat heart, these cells prevented the death of hypertrophied or thickened but otherwise viable myocardial cells and reduced progressive formation of collagen fibers and scars. Control rats that underwent surgery with an intact LAD coronary artery, as well as LAD-ligated rats injected with saline or control cells, did not demonstrate an increase in the number of blood vessels. Furthermore, the hematopoietic cells could be identified on the basis of highly specific cell markers that differentiate them from cardiomyocyte precursor cells, enabling the cells to be used alone or in conjunction with myocyte-regeneration strategies or pharmacological therapies. (For more about stem cell markers see Appendix E.i. How Do Researchers Use Markers to Identify Stem Cells?)
Exciting new advances in cardiomyocyte regeneration are being made in human embryonic stem cell research. Because of their ability to differentiate into any cell type in the adult body, embryonic stem cells are another possible source population for cardiac-repair cells. The first step in this application was taken by Itskovitz-Eldor et al. [2] who demonstrated that human embryonic stem cells can reproducibly differentiate in culture into embryoid bodies made up of cell types from the body's three embryonic germ layers. Among the various cell types noted were cells that had the physical appearance of cardiomyocytes, showed cellular markers consistent with heart cells, and demonstrated contractile activity similar to cardiomyocytes when observed under the microscope.
In a continuation of this early work, Kehat et al. [4] displayed structural and functional properties of early stage cardiomyocytes in the cells that develop from the embryoid bodies. The cells that have spontaneously contracting activity are positively identified by using markers with antibodies to myosin heavy chain, alpha-actinin, desmin, antinaturietic protein, and cardiac troponin—all proteins found in heart tissue. These investigators have done genetic analysis of these cells and found that the transcription-factor genes expressed are consistent with early stage cardiomyocytes. Electrical recordings from these cells, changes in calcium-ion movement within the cells, and contractile responsiveness to catecholamine hormone stimulation by the cells were similar to the recordings, changes, and responsiveness seen in early cardiomyocytes observed during mammalian development. A next step in this research is to see whether the experimental evidence of improvement in outcome from heart attack in rodents can be reproduced using embryonic stem cells.
These breakthrough discoveries in rodent models present new opportunities for using stem cells to repair damaged heart muscle. The results of the studies discussed above are growing evidence that adult stem cells may develop into more cell types than first thought. In those studies, hematopoietic stem cells appear to be able to develop not only into blood, but also into cardiac muscle and endothelial tissue. This capacity of adult stem cells, increasingly referred to as "plasticity," may make such adult stem cells a viable candidate for heart repair. But this evidence is not complete; the mouse hematopoietic stem cell populations that give rise to these replacement cells are not homogenous. Rather, they are enriched for the cells of interest through specific and selective stimulating factors that promote cell growth. Thus, the originating cell population for these injected cells has not been identified, and the possibility exists for inclusion of other cell populations that could cause the recipient to reject the transplanted cells. This is a major issue to contend with in clinical applications, but it is not as relevant in the experimental models described here because the rodents have been bred to be genetically similar.
What are the implications for extending the research on differentiated growth of replacement tissues for damaged hearts? There are some practical aspects of producing a sufficient number of cells for clinical application. The repair of one damaged human heart would likely require millions of cells. The unique capacity for embryonic stem cells to replicate in culture may give them an advantage over adult stem cells by providing large numbers of replacement cells in tissue culture for transplantation purposes. Given the current state of the science, it is unclear how adult stem cells could be used to generate sufficient heart muscle outside the body to meet patients' demand [7].
Although there is much excitement because researchers now know that adult and embryonic stem cells can repair damaged heart tissue, many questions remain to be answered before clinical applications can be made. For example, how long will the replacement cells continue to function? Do the rodent research models accurately reflect human heart conditions and transplantation responses? Do these new replacement cardiomyocytes derived from stem cells have the electrical-signal-conducting capabilities of native cardiac muscle cells?
Stem cells may well serve as the foundation upon which a future form of "cellular therapy" is constructed. In the current animal models, the time between the injury to the heart and the application of stem cells affects the degree to which regeneration takes place, and this has real implications for the patient who is rushed unprepared to the emergency room in the wake of a heart attack. In the future, could the patient's cells be harvested and expanded for use in an efficient manner? Alternatively, can at-risk patients donate their cells in advance, thus minimizing the preparation necessary for the cells' administration? Moreover, can these stem cells be genetically "programmed" to migrate directly to the site of injury and to synthesize immediately the heart proteins necessary for the regeneration process? Investigators are currently using stem cells from all sources to address these questions, thus providing a promising future for therapies for repairing or replacing the damaged heart and addressing the Nation's leading causes of death.
Scientists find master heart cell
Harvard discovery gives new tools for drug development
By Carolyn Y. Johnson
Harvard University scientists said yesterday they discovered a master human heart cell that gives rise to three major types of heart tissue, providing new tools for drug development and an important advance toward the ultimate goal of repairing damaged hearts.
Using human embryonic stem cells, the researchers have unraveled part of the process by which the human heart is built during development - insight they hope could be used to understand congenital heart disease and create new therapies for cardiovascular disease, the top cause of death in the United States.
"Since these [cells] are entirely human, you can use this system now to study the role of specific genes in human heart disease, and as ways to screen drugs for cardiotoxicity and for therapeutic effect,'' said Dr. Kenneth R. Chien, director of the Cardiovascular Research Center at Massachusetts General Hospital and principal faculty member at the Harvard Stem Cell Institute. He is senior author of the paper, published in Nature yesterday.
The work points to new applications for regenerative medicine. For years, attempts to repair damaged heart tissue using different types of cells have come back with "ambiguous, disappointing, marginal, and, in certain cases, negative'' results, Chien said. For example, Genzyme Corp. of Cambridge stopped enrolling patients in a clinical trial for a heart cell therapy three years ago because it was deemed to have little chance of success.
Because the new work reveals progenitor cells that naturally create specific types of heart tissue during development, Chien thinks they might have a better chance of repairing damaged hearts.
But the greatest near-term promise of the work might be in routine drug development. It could now be possible, for example, to create large numbers of heart muscle cells to test drugs.
"Add one drug, two drugs, or all combinations of drugs a heart patient would take'' to test how effective or toxic compounds are in actual human heart cells, said Christine Mummery, a professor of developmental biology at Leiden University Medical Center who was not involved with the work. "It's really a kind of tool to bring us a step further.''
Drug companies are especially interested in such applications. Using the actual human cells affected by a disease, instead of mice, dogs, or other stand-ins, could potentially speed up drug development by giving com panies a more accurate template for screening potential drugs. Animal cells and other types of assays have been invaluable for testing and screening drugs, but the new cells could give scientists a chance to see how the human cells they are interested in react to drugs.
Such cells could also prevent companies from spending too much time on a drug that ultimately fails. One big concern at pharmaceutical companies is that drugs might have a side effect on the heart that only emerges late in the drug development process, said John D. McNeish, executive director of Pfizer Regenerative Medicine. Testing the drug on human heart cells might alert scientists to side effects before they begin administering the drug to patients in clinical trials.
Stem Cells From Skin Cells Can Make Beating Heart Muscle Cells
ScienceDaily (Feb. 13, 2009) — A little more than a year after University of Wisconsin-Madison scientists showed they could turn skin cells back into stem cells, they have pulsating proof that these "induced" stem cells can indeed form the specialized cells that make up heart muscle.
In a study published online Feb. 12 in Circulation Research, UW-Madison School of Medicine and Public Health professor of medicine Tim Kamp and his research team showed that they were able to grow working heart-muscle cells (cardiomyocytes) from induced pluripotent stem cells, known as iPS cells.
The heart cells were originally reprogrammed from human skin cells by James Thomson and Junying Yu, two of Kamp's co-authors on the study.
"It's an encouraging result because it shows that those cells will be useful for research and may someday be useful in therapy,'' said Kamp, who is also a cardiologist with UW Health. "If you have a heart failure patient who is in dire straits — and there are never enough donor hearts for transplantation — we may be able to make heart cells from the patient's skin cells, and use them to repair heart muscle. That's pretty exciting."
It's also a few more discoveries away. The researchers used a virus to insert four transcription factors into the genes of the skin cell, reprogramming it back to an embryo-like state. Because the virus is taken up by the new cell, there is a possibility it eventually could cause cancer, so therapies from reprogrammed skin cells will likely have to wait until new methods are perfected.
Still, the iPS cardiomyocytes should prove immediately useful for research. And Kamp said the speed at which knowledge is progressing is very encouraging.
Jianhua Zhang, lead author on the study, noted that it took 17 years, from when a mouse embryonic stem cells were first created in 1981, to 1998, when Thomson created the first human embryonic stem cells. In contrast, the first mouse iPS stem cells were created in 2006, and Thomson and Yu published their paper in November 2007, announcing the creation of human iPS stem cells that began as a skin cells.
While research on embryonic stem cells is controversial, because it destroys a human embryo, lessons learned through such research apply to current work with iPS cells made from adult cells.
"That's one of the important things that have come out of the research with embryonic stem cells, it taught us how human pluripotent stem cells behave and how to work with them,'' Kamp says. "Things are able to progress much more quickly thanks to all the research already done with embryonic stem cells."
Many types of heart disease have known genetic causes, so creating cardiomyocytes grown from patients who have those diseases will likely be some of the next steps in the research. One of Kamp's colleagues, Clive Svendsen, a UW-Madison School of Medicine and Public Health professor of neurology and anatomy, has grown the iPS cells into disease-specific neural cells. Kamp and Svendsen are also on the faculty of the Waisman Center and the Stem Cell and Regenerative Medicine Center.
Kamp's latest research, proving that iPS cells can become functional heart cells, is just one step along the way to better understanding and treatment of disease.
"We're excited about it, because it's the some of the first research to show it can be done, but in the future, we'll probably say, 'Well, of course it can be done,'" he says. "But you don't know until you do it. It's a very mysterious and complicated dance to get these cells to go from skin cells to stem cells to heart cells."
Scientists have moved a step closer to creating functioning heart tissue for transplants in the lab.
They have grown three types of human heart cells from cultures derived from embryonic stem cells.
When a mix of the cells was transplanted into mice with simulated heart disease, the animals' heart function was significantly improved.
The study, by a team of Canadian, US and UK scientists, features in the journal Nature.
In the future, these cells may be very effective in developing new strategies for repairing damaged hearts.
Dr Gordon Keller
McEwen Centre for Regenerative Medicine
The researchers created the cells by supplying embryonic stem cell cultures with a cocktail of growth factors and other molecules involved in development.
By supplying the right growth factors at the right time, they encouraged the cells to grow into immature versions of three different types of cardiac cell.
The three cell types they created - cardiomyocytes, endothelial cells and vascular smooth muscle cells - are each important constituents of heart muscle.
Researcher Dr Gordon Keller, from the McEwen Centre for Regenerative Medicine in Toronto, said: "This development means that we can efficiently and accurately make different types of human heart cells for use in both basic and clinical research.
"The immediate impact of this is significant as we now have an unlimited supply of these cells to study how they develop, how they function and how they respond to different drugs.
"In the future, these cells may also be very effective in developing new strategies for repairing damaged hearts, following a heart attack."
Jeremy Pearson, associate medical director at the British Heart Foundation, said: "This research provides another promising indication that we are steadily getting closer to the day when stem cells will be used successfully to repair damaged hearts in patients."
From stem cells to heart muscle
'This moves us closer to heart stem cell therapy'
A team of Harvard Stem Cell Institute (HSCI) scientists at Massachusetts General Hospital (MGH) and collaborators at Harvard's School of Engineering and Applied Sciences (SEAS) has taken a giant step toward the possibility of using human stem cells to repair damaged hearts.
The researchers, led by HSCI principal faculty member Kenneth Chien, report using a mouse version of a human cardiac master stem cell to create a functioning strip of mouse heart muscle with technology developed by Kevin Kit Parker, the Thomas Dudley Cabot Associate Professor of Applied Science in Harvard's School of Engineering and Applied Sciences and a faculty member at the University's Wyss Institute for Biologically Inspired Engineering.
"This is the beginning of making heart parts for heart disease," said Chien, the director of the MGH Cardiovascular Research Center and the Charles Addison and Elizabeth Ann Sanders Professor of Basic Science at Harvard Medical School (HMS).
The new work by the HSCI-SEAS team, being published in tomorrow's edition of the journal Science, raises the possibility of someday using induced pluripotent stem cell (iPS) technology to take a skin cell from a patient with heart disease to use in generating muscle tissue to repair the diseased heart — avoiding the need to suppress the immune system and the possibility of rejection, a major issue in organ transplantation.
"This is an initial step in moving beyond heart stem cell biology towards a different level — finding a rare cardiomyogenic cell from embryonic stem cells that can proliferate on its own and could potentially be therapeutic. This work moves us closer to heart stem cell therapy," Chien explained. "The beauty of the system our team has developed relates to the almost pure population of the exact cells, ventricular heart cells, which we're trying to replace in a damaged heart, and then expanding and assembling them into a functioning strip of pure ventricular muscle. That has not been done to my knowledge."
We've "been able to take these very rare populations of muscle progenitors that were isolated because we were able to color code the cells," Chien continued. "We look for the cells that have a mixed-color read out. We've been able to take those cells and put them one layer thick on something that is almost like saran wrap. When they contract, they flex the film. We have the pure cells; they can be expanded, and they can make a fully functional strip of muscle."
Parker, whose lab developed the technology that produces a strip of muscle from the cardiac cells, said, "We try to develop technologies that are cell-agnostic — technologies that can work with Ken's cardiac progenitors, or anyone else's stem cells. These techniques are not limited to cardiac cells, or even to stem cells for that matter."
The bioengineer explained that the best way to visualize the construction of the muscle strip might be to think of a "Fruit Roll-up," but with cells taking the place of the pressed fruit.
Chien called the new findings "the latest in a chain of scientific discoveries that have come out of our lab here at Mass General and the Harvard Stem Cell Institute that have been a collaboration of physicians, scientists and bioengineers. For the first time we report the identification of a cell that could be viewed as perhaps an optimal cell type to promote cardiac muscle regeneration because the cells that we use come from embryonic stem cells and then have been induced to form an intact strip of functioning ventricular muscle." Chien said the work takes the most basic form of undifferentiated stem cell and directs its differentiation and development "to ventricular muscle — and that's the type of muscle in the heart we're trying to regenerate."
"What we think we have right now are the exact cell types to do this type of repair," said Ibrahim Domian, first author on the Science paper and an HMS instructor in medicine. "One way or another we have to get to three-dimensional muscle, which is made up of multiple layers of cells. The amazing thing about these strips we have now is that they are generating the right amount of force, but as you want to generate more force, you have to increase the thickness of the strips, and they have to have their own blood supply. There are two ways you could do this; rely on tissue engineering to produce a strip like that, or find a way to use the natural architecture of the heart to regenerate the muscle. We're now working hard in our lab, and with Kit Parker, to see how we could produce the thicker strip."
There are a number of approaches to solving the delivery problem, Chien said. One might be to incorporate the cells into a gel of some kind, which could be applied to the damaged muscle. Another might be to simply inject the cells into the damaged tissue, hoping that they would proliferate and create new muscle. In Chien's view, novel technology for cell delivery will be required in either case.
Over the past two years Chien and his team have published a series of "leap-frogging" studies, first making a discovery in mice, then replicating it in human embryonic stem cells, then taking the next step in mice, then moving on to human cells. Next comes the attempt to actually repair cardiac damage in animals and then on to clinical studies in the next five years.
"In mice we're in a position to attempt the repair right now," Domian said. "We can cause a heart attack, and then look for ways to repair the tissue. The simplest way is to inject the cells into the tissue – we can do that right now in a mouse. If that doesn't work, we have to rely on other technologies." But, he added, "this is direct proof of concept that a similar approach will work" with human embryonic stem cells.
"Now we're actually in the core of the next level of challenges that face all of regenerative medicine," said Chien. "In essence, I think we're moving quite quickly now from stem cell biology all the way through towards regenerative medicine."
Human stem cells fix heart damage in lab rats
By Carol M. Ostrom
Seattle Times health reporter
Human embryonic stem cells have been used to regrow the heart muscles of rats that had survived lab-induced heart attacks, scientists from the University of Washington and a private biotechnology company reported Sunday.
Because the rebuilt heart muscle halted the progression of heart failure, the findings offer encouragement that treatments based on embryonic stem cells someday might be used to help people who suffer heart attacks, a leading cause of death in the U.S., said Chuck Murry, a UW researcher and an author of the study.
Unlike many tissues in the body, heart muscle cells don't regenerate. So when heart attacks cause heart cells to die, they are replaced by scar tissue, which doesn't beat. Often, that leads to outright heart failure and death.
Murry, director of the Center for Cardiovascular Biology at the UW's Institute for Stem Cell and Regenerative Medicine, has long struggled to use adult stem cells to re-create heart muscle. He and UW colleague Michael Laflamme, the lead researcher on this study, knew from other studies that human embryonic stem cells could become heart muscle cells in rats — an encouraging first step.
But in practice, only a tiny percentage of the stem cells were actually becoming heart-muscle cells. And most died quickly after being injected into rats' hearts.
After four years of research, Murry and his colleagues at Geron, a biotechnology company in Menlo Park, Calif., had a breakthrough: They found a process to coax as many as half the cells into becoming heart-muscle cells, and second, a way to keep the cells alive.
Not only did all the rats start getting new heart muscle, but they were protected from the progression of heart failure, Murry said.
"No one had ever grown human heart muscle back in an injured animal," Murry said. "We're pretty pleased."
The research is published in the September issue of Nature Biotechnology.
Like most research in this area, Murry's is incremental, building on his own previous findings and those of other researchers.
Funding for this study came partially from Geron, which hopes to develop medical products to help heart-attack survivors. Other funding came from the federal National Institutes of Health.
"There's an epidemic of heart failure coming on as baby boomers age," Murry said.
Stem cells are promising to researchers because they have the ability to turn into any kind of cell in the body. The challenge has been finding ways to control their transformations.
So for Murry and his colleagues, the problem was to get the cells to become heart-muscle cells instead of cells for livers, kidneys or something else. At first, they had little success, but then found certain proteins would trigger the right growth.
When they put the cells into damaged hearts, however, the cells died en masse.
"Almost everything we put in died," Murry said. "It's a very harsh environment. It's what killed the heart muscle cells to begin with, so maybe it's not surprising that it killed those cells."
The researchers tried one intervention after another. "We were trying to be very scientific, trying one approach at a time, but nothing worked," Murry said.
Finally, they hit on a "pro-survival cocktail" of chemicals and also applied heat to the cells to make them behave. "Lo and behold, in 100 percent of the animals we delivered the cells to, we saw grafts," Murry said.
About 10 percent of a damaged heart area was restored, enough to stop the progression of the heart failure.
That came as a surprise, Murry said. "The fact that if you can grow human heart muscle back, that prevents heart failure — we didn't know that."
The study, which ran for four weeks, didn't reveal what would have happened in the long run to the rats that got the stem cells.
To make the breakthrough, Murry and his colleagues used the so-called "presidential lines" of stem cells. Those cells are generated from a group of embryos that already had been destroyed before the Bush administration limited research on embryonic stem cells.
"We're pleased to be able to provide an example of something that can be done with embryonic cells that can't be done with adult stem cells," Murry said.
Murry hopes someday to work with newer lines that would be more suitable for human transplantation.
Stem cell treatment of Cardiovascular diseases
Heart Disease
Coronary heart disease (CHD) is a narrowing of the small blood vessels that supply blood and oxygen to the heart. CHD is also called coronary artery disease (CAD). Angina (chest pain) is the most common symptom of CHD. Other common symptoms include shortness of breath and fatigue with activity.
Heart Failure is a life-threatening condition in which the heart can no longer pump enough blood throughout the body. Cardiomyopathy, (weakening of the heart muscle or a change in its structure) is often associated with heart failure.
Standard treatments for CHD and heart failure are diet control, medications and surgical procedures such as stenting to open up clogged arteries or coronary artery bypass grafting (CABG) to build detours around clogged portions of the arteries.
The XCell-Center Heart Treatment
The XCell-Center's heart treatment differs from standard methods because it is a drug-free alternative focused on repairing heart muscle and increasing blood flow within the heart muscle itself.
The entire procedure requires patients to stay in Germany for 4 or 5 nights.
Bone Marrow Collection
On the first day, bone marrow is collected from the patient's iliac crest (hip bone) using thin-needle mini-puncture under local anesthesia. Although some pain is felt when the needle is inserted, most patients do not find the bone marrow collection procedure particularly painful. The entire procedure normally takes about 30 minutes.
Once the bone marrow collection is complete, patients may return to their hotel and go about normal activities.
More detailed information on the bone marrow collection procedure is available in the Bone Marrow Informed Consent document (PDF file).
Laboratory Processing
The next day, the stem cells are processed from the bone marrow in a state-of-the-art, government approved (cGMP) laboratory. In the lab, both the quantity and quality of the stem cells are measured. These cells have the potential to transform into multiple types of cells and are capable of regenerating or repairing damaged heart tissue.
Stem Cell Implantation
On the third day, the stem cells are implanted back into the patient by angiography under local anesthesia. A special catheter (thin hollow wire) is inserted into the femoral artery and then guided forward under x-ray scanning until it reaches the targeted areas where the stem cells are then injected. During this procedure, additional treatments such as coronary artery stenting can be performed if necessary. The angiography procedure takes about 90 minutes.
Once all the cells have been successfully implanted, patients stay at the hospital overnight for monitoring and to allow the catheter entry point to close properly. They may return home after being released from the hospital the following day.
Patient Stories
Aaron Wood, Age 60 - 3 heart attacks and heart failure
"I no longer have any angina pain or no shortness of breath - no symptoms whatsoever. I am walking 3 miles per day and lifting heavy weights again. I consider this a complete reversal. I saw my cardiologist 2 weeks ago for more testing and he is still shaking his head!"
The price of the heart angiography treatment is 11,500 Euros.
Evaluation Process
To begin the treatment evaluation process, you must complete an online medical history form. Once you've completed the online medical history and submitted it, a patient relations consultant will contact you within 3 business days. He or she will assist you with the rest of the evaluation process. Upon treatment approval, your consultant will also assist you with treatment scheduling and trip preparation.
If you will be in Germany, you may also schedule an in-person consultation/evaluation with an XCell-Center physician. You may also request a "fast-track" evaluation and treatment schedule.
Abu Zubair meriwayatkan dari Jabir bin Abdullah bahwa Nabi Muhammad SAW bersabda:
"Setiap penyakit ada obatnya. Jika obat yang tepat diberikan dengan izin Allah, penyakit itu akan sembuh".
(HR. Muslim, Ahmad dan Hakim).
Rabu, 30 Desember 2009
Stem Cells for Heart Muscle Cells
Stem Cell Therapy: Helping the Body Heal Itself
Diposting oleh FX di 19.26
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The Holy Al-Qur'an (English version)
- Surah 1 - Al Fatiha THE OPENING
- Surah 2 - Al Baqarah THE HEIFER
- Surah 3 - Ali 'Imran - THE FAMILY OF 'IMRAN
- Surah 4 - Al-Nisa' THE WOMEN
- Surah 5 - Al Ma'idah THE REPAST
- Surah 6 - Al An'am THE CATTLE
- Surah 7 - Al A'raf THE HEIGHTS
- Surah 8 - Al Anfal THE SPOILS OF WAR
- Surah 9 - Al Tawbah THE REPENTANCE
- Surah 10 - Yunus JONAH
- Surah 11 - Hud THE PROPHET HUD
- Surah 12 - Yusuf JOSEPH
- Surah 13 - Al Ra'd THE THUNDER
- Surah 14 - Ibrahim ABRAHAM
- Surah 15 - Al Hijr THE ROCKY TRACT
- Surah 16 - Al Nahl BEES
- Surah 17 - Al Isra' THE NIGHT JOURNEY
- Surah 18 - Al Kahf THE CAVE
- Surah 19 - Maryam MARY
- Surah 20 - TA HA
- Surah 21 - Al Anbiya THE PROPHETS
- Surah 22 - Al Hajj THE PILGRIMAGE
- Surah 23 - Al Mu'minun THE BELIEVERS
- Surah 24 - Al Nur THE LIGHT
- Surah 25 - Al Furqan THE CRITERION
- Surah 26 - Al Shu'ara' THE POETS
- Surah 27 - Al Naml THE ANTS
- Surah 28 - Al Qasas THE NARRATIONS
- Surah 29 - Al 'Ankabut THE SPIDER
- Surah 30 - Al Rum THE ROMANS
- Surah 31 - Luqman LUQMAN
- Surah 32 - Al Sajdah THE PROSTRATION
- Surah 33 - Al Ahzab THE CONFEDERATES
- Surah 34 - Saba' SHEBA
- Surah 35 - Fatir THE ORIGINATOR OF CREATION
- Surah 36 - Ya Sin YA SIN
- Surah 37 - Al Saffat THOSE RANGED IN RANKS
- Surah 38 - Sad SAD
- Surah 39 - Al Zumar CROWDS
- Surah 40 - Ghafir FORGIVER
- Surah 41 - Fussilat EXPOUNDED
- Surah 42 - Al Shura CONSULTATION
- Surah 43 - Al Zukhruf THE GOLD ADORNMENTS
- Surah 44 - Al Dukhan THE SMOKE
- Surah 45 - Al Jathiyah THE KNEELING DOWN
- Surah 46 - Al Ahqaf WINDING SAND-TRACTS
- Surah 47 - Muhammad MUHAMMAD
- Surah 48 - Al Fath THE VICTORY
- Surah 49 - Al Hujurat THE CHAMBERS
- Surah 50 - Qaf QAF
- Surah 51 - Al Dhariyat THE WINDS THAT SCATTER
- Surah 52 - Al Tur THE MOUNT
- Surah 53 - Al Najm THE STAR
- Surah 54 - Al Qamar THE MOON
- Surah 55 - Al Rahman THE MOST GRACIOUS
- Surah 56 - Al Waq'iah THE INEVITABLE
- Surah 57 - Al Hadid IRON
- Surah 58 - Al Mujadilah THE WOMAN WHO PLEADS
- Surah 59 - Al Hashr THE MUSTERING
- Surah 60 - Al Mumtahinah THAT WHICH EXAMINES
- Surah 61 - Al Saff THE BATTLE ARRAY
- Surah 62 - Al Jumu'ah FRIDAY
- Surah 63 - Al Munafiqun THE HYPOCRITES
- Surah 64 - Al Taghabun THE MUTUAL LOSS AND GAIN
- Surah 65 - Al Talaq DIVORCE
- Surah 66 - Al Tahrim PROHIBITION
- Surah 67 - Al Mulk THE DOMINION
- Surah 68 - Al Qalam THE PEN
- Surah 69 - Al Haqqah THE SURE REALITY
- Surah 70 - Al Ma'arij THE WAYS OF ASCENT
- Surah 71 - Nuh NOAH
- Surah 72 - Al Jinn THE SPIRITS
- Surah 73 - Al Muzzammil THE ENFOLDED ONE
- Surah 74 - Al Muddaththir THE ONE WRAPPED UP
- Surah 75 - Al Qiyamah THE RESURRECTION
- Surah 76 - Al Insan MAN
- Surah 77 - Al Mursalat THOSE SENT FORTH
- Surah 78 - Al Naba' THE GREAT NEWS
- Surah 79 - Al Nazi'at THOSE WHO TEAR OUT
- Surah 80 - 'Abasa HE FROWNED
- Surah 81 - Al Takwir THE FOLDING UP
- Surah 82 - Al Infitar THE CLEAVING ASUNDER
- Surah 83 - Al Mutaffifin THE DEALERS IN FRAUD
- Surah 84 - Al Inshiqaq THE RENDING ASUNDER
- Surah 85 - Al Buruj THE CONSTELLATIONS
- Surah 86 - Al Tariq THE NIGHT STAR
- Surah 87 - Al A'la THE MOST HIGH
- Surah 88 - Al Ghashiyah THE OVERWHELMING EVENT
- Surah 89 - Al Fajr THE DAWN
- Surah 90 - Al Balad THE CITY
- Surah 91 - Al Shams THE SUN
- Surah 92 - Al Layl THE NIGHT
- Surah 93 - Al Duha THE GLORIOUS MORNING LIGHT
- Surah 94 - Al Sharh THE EXPANSION OF THE BREAST
- Surah 95 - Al Tin THE FIG
- Surah 96 - Al Alaq THE CLINGING CLOT
- Surah 97 - Al Qadr THE NIGHT OF POWER
- Surah 98 - Al Bayyinah THE CLEAR EVIDENCE
- Surah 99 - Al Zalzalah THE EARTHQUAKE
- Surah 100 - Al 'Adiyat THOSE THAT RUN
- Surah 101 - Al Qari'ah THE GREAT CALAMITY
- Surah 102 - Al Takathur THE PILING UP
- Surah 103 - Al 'Asr TIME THROUGH THE AGES
- Surah 104 - Al Humazah THE SCANDALMONGER
- Surah 105 - Al Fil THE ELEPHANT
- Surah 106 - Quraysh THE TRIBE OF QURAYSH
- Surah 107 - Al Ma'un THE NEIGHBOURLY ASSISTANCE
- Surah 108 - Al Kawthar THE ABUNDANCE
- Surah 109 - Al Kafirun THOSE WHO REJECT FAITH
- Surah 110 - Al Nasr THE HELP
- Surah 111 - Al Masad THE PLAITED ROPE
- Surah 112 - Al Ikhlas THE PURITY OF FAITH
- Surah 113 - Al Falaq THE DAYBREAK
- Surah 114 - Al Nas MANKIND
- Acute Coronary Syndromes
- Angina Pectoris
- Anomalous Left Coronary Artery From the Pulmonary Artery
- Aortic Coarctation
- Aortic Dissection
- Aortic Regurgitation
- Aortic Stenosis
- Aortic Stenosis, Subaortic
- Aortic Stenosis, Supravalvar
- Aortitis
- Ashman Phenomenon
- Atherosclerosis
- Atrial Fibrillation
- Atrial Flutter
- Atrial Myxoma
- Atrial Septal Defect
- Atrial Tachycardia
- Atrioventricular Block
- Atrioventricular Dissociation
- Atrioventricular Nodal Reentry Tachycardia (AVNRT)
- Benign Cardiac Tumors
- Brugada Syndrome
- Complications of Myocardial Infarction
- Coronary Artery Atherosclerosis
- Coronary Artery Vasospasm
- Digitalis Toxicity
- Dissection, Aortic
- Ebstein Anomaly
- Eisenmenger Syndrome
- First-Degree Atrioventricular Block
- HACEK Group Infections (Infective Endocarditis)
- Heart Failure - Decompensatio Cordis
- Holiday Heart Syndrome
- Hypertensive Heart Disease
- Junctional Rhythm
- Loeffler Endocarditis
- Long QT Syndrome
- Lutembacher Syndrome
- Mitral Regurgitation
- Mitral Stenosis
- Mitral Valve Prolapse
- Myocardial Infarction
- Myocardial Rupture
- Paroxysmal Supraventricular Tachycardia
- Patent Ductus Arteriosus
- Patent Foramen Ovale
- Pericardial Effusion
- Pericarditis Acute
- Pericarditis, Constrictive
- Pericarditis, Constrictive-Effusive
- Pulmonic Regurgitation
- Pulmonic Stenosis
- Right Ventricular Infarction
- Saphenous Vein Graft Aneurysms
- Second-Degree Atrioventricular Block
- Sinus of Valsalva Aneurysm
- Sudden Cardiac Death
- Syncope
- Tetralogy of Fallot
- Third-Degree Atrioventricular Block
- Torsade de Pointes
- Tricuspid Regurgitation
- Tricuspid Stenosis
- Unstable Angina
- Ventricular Fibrillation
- Ventricular Septal Defect
- Ventricular Tachycardia
- Wolff-Parkinson-White Syndrome


text:
The last two weeks we've been on the road visiting family. We drove to see some cousins, then up to a family reunion, then to my sister's house, then to my in-laws'. Seeing as we had no car in England, I've never been on a road trip whilst pregnant and the kids aren't used to long road trips. We'd driven up with them for Christmas, though, and learnt their limits, so this time we broke the trip up more, stopping at hotels along the way and then staying with family when we arrived. As it turns out, breaking it up was really good for me, too. I ended up driving the entire time because I get motion sick more easily when pregnant. I have the ability to make myself motion sick whilst driving when pregnant, so having me drive made it less likely that I'd feel ill.
So, what else did I learn? My children have a holiday limit of about a week before asking to go home. Of course, going from place to place every few days and meeting loads of family make for overwhelmed kids, even though they had fun.
I was also reminded of how much I love cooking my own food instead of eating out. Of course we had home-cooked meals when staying its family, but when on the road of course we had to eat at restaurants. Dear restaurants: salt is used as a flavour enhancer. If you cannot taste the real flavours of the food, you're using too much. Now, I know I like a lot less salt than many Americans and in fact I don't cook with salt; because of this, I'm sure I'm more sensitive to salt than many, and I find that I really can't tolerate much salt (all my college friends can now laugh at the irony, since I used to eat loads of salt). Also, portion sizes are fairly ridiculous when I'm unable to take the rest with me because of being on the road. Oh well. And of course not all restaurants are bad at this. This one, for example, was wonderful.
All in all, it was a nice holiday, though it's good to be back, too.

subset: commoncrawl


text:
By Mark E. Wilson, MD
We have an epidemic in the Birmingham area that is killing an alarming number of people, mostly young adults, and even a few teenagers. Although it is not initially fatal in every case, it is very hard to eradicate and it tends to relapse. It also increases the risk of several other diseases. The risk of precipitous death is always there. It affects people from all socioeconomic groups. It causes extraordinary suffering and disruption in families. It negatively impacts our schools and our neighborhoods, and its economic toll on society is enormous.
What is it? A resurgence of heroin: cheaper, more potent and more widely available than ever before. Deaths from heroin overdose in Jefferson County increased from 13 in 2008 to 30 in 2011, and then jumped to 58 in 2012 and 58 again in 2013. The confirmed death count so far in 2014 is 36. Shelby County reported no heroin overdose deaths in 2008, but in 2011 there were 10, climbing to 16 in 2012. Seven heroin-related deaths have been confirmed for 2013; four more deaths are believed to be heroin related, pending confirmation by toxicology reports. Tuscaloosa County has seen several deaths as well.
Many users start with prescription painkillers (opiates) and then move on to heroin. Teenagers often get their start with medicines taken from home medicine cabinets. But some are trying heroin without first using prescription pain medicines. Because the heroin supply is of variable potency but sometimes very pure, it's like playing Russian roulette. Any outbreak of disease with a death rate this high would call for swift public health intervention, but the heroin epidemic is much more complex than most disease outbreaks. We need a multimodal approach with involvement of multiple sectors of the community to successfully reverse the current trend.
Federal, state and local law enforcement launched an coordinated effort to dismantle and disrupt the heroin supply chain beginning in September 2012. They have had some notable successes which appear to have checked the dramatic increase in deaths. A major drug bust in September 2013 resulted in the arrests of about 50 heroin dealers. But more drug dealers are surely filling the void. The effort to limit the supply must be paired with a robust effort to curb the demand. We must all wake up to the problem of addiction in our own families and throughout our community and take action.
First, we need to increase awareness and overcome the naive assumption that "this couldn't happen to my child" or "this isn't a problem in our school." We need to listen to the stories of families who struggle with heroin addiction or have lost a loved one to heroin overdose. These stories can help us all approach the problem with humility and with compassion for the addicts and their families. Addicts have made bad decisions, for sure. But most people, once they become addicted actually want to quit, but feel trapped. Heroin addiction alters the brain so that the drug seems as essential as food and water. For those who try to quit without medical assistance, the withdrawal symptoms are horrible: nausea and vomiting, diarrhea, abdominal pain, severe body aches - they often say it feels like they are going to die.
We need to take specific, pragmatic steps to prevent deaths from overdose. We should adopt "911 Good Samaritan" policies that provide limited immunity from arrest or prosecution for minor drug law violations for people who summon help to the scene of an overdose.
The vast majority of heroin use is in the company of other people, but the majority of people who have died from overdose are found alone, abandoned out of fear of arrest. These policies protect only the caller and the overdose victim from arrest and/or prosecution for simple drug possession, possession of drug paraphernalia, and/or being under the influence, but not those who traffic drugs or commit other crimes. Naloxone (Brand names Narcan and Evzio; generic available) is a drug that can be given by injection or via nasal spray to temporarily reverse an overdose of heroin or other opiate, buying time for emergency responders to arrive.
Many lives have been saved in Alabama by emergency medical personnel who carry naloxone in their ambulances. Several states have passed laws that allow naloxone to be used by police officers, or prescribed to family members or friends of addicts as a rescue medicine. While this is not without controversy, we need to at least have a meaningful policy discussion about what is most appropriate. We need to strengthen and expand effective prevention efforts and increase access to addiction treatment. Prevention is obviously preferable to treatment after heroin use has begun, but it's not simple or easy. Treatment of heroin addiction is challenging and failure is common. There is not a one-size-fits-all approach; we need to pursue a variety of evidence-based approaches. Some addicts have been successful with non-pharmacological treatment programs. Others are able to lead safe, law-abiding and productive lives with the help of drug replacement therapies such as methadone or Suboxone.
We need to engage parents, educators, medical professionals, policy-makers, addiction treatment specialists and others in a community-wide discussion to develop these and other strategies. The United States Attorney's Office for the Northern District of Alabama, the UAB School of Public Health, and the Jefferson County Department of Health are hosting an all-day community awareness summit on June 10, 2014 at the UAB Alumni House, titled "Pills To Needles: The Pathway to Rising Heroin Deaths – A Community Alert and Call to Action." U.S. Deputy Attorney General James M. Cole will be the keynote speaker, and there will be multiple other speakers and panelists. The summit will end with a draft community action plan, and there will be smaller follow-up meetings to further develop specific strategies. For more information about the summit, or to get involved in the action plan, contact Lyndon Laster at email@example.com.
Mark E. Wilson, MD is the Jefferson County Health Officer. He can be contacted at email@example.com
By Special to AL.com AL.com
on June 02, 2014 at 7:00 AM, updated June 02, 2014 at 7:11 AM
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In June 2017, Saudi Arabia, UAE, Bahrain and Egypt imposed land, sea and air blockade on Qatar, accusing the latter of financing terrorist groups like Hamas and Hezbollah and its growing relations with Iran. One year later, Qatar seems to be steadily reviving from the sanctions. Qatar has refused to give in to the demands of Arab nations which include: reducing ties with Iran significantly, shutting down of state run media house Al-Jazeera, and stop financing terrorism. How did Qatar manage and what comes next?
Qatar's Crisis management: International Engagement
Ninety percent of Qatar's import of regular goods, including food, medicine and water came from Saudi Arabia before the blockade; the move blocked Qatar's only land border with the country. Since then, Qatar has helped itself to become self-reliant and grow diplomatic ties with alternative international partners – not only the US but also Russia and Turkey.
When the crisis erupted, Turkey sent cargo planes full of dairy products and basic food to mitigate the food crisis. Because of no direct land route between Turkey and Qatar and longer import routes, the food and beverage prices jumped 4.2 percent within three months of the crisis, but as an alternative – Turkey, Iran and Qatar have been cooperating to open a new route. The trade route via Iran will bring down the transportation cost of Turkish and Iranian goods significantly. Moreover, regarding the Turkish investment in Qatar, Qatar's Chamber of Commerce Vice Chairman Mohamed bin Twar said: "Turkish companies here are handling projects worth about $11.6bn in Qatar, most of which is put into FIFA World Cup 2022 projects." Besides being one of the top suppliers of non-oil exports to Turkey, Qatar investment in Turkey is over $20 bn, which is second highest investment in Turkey by any country.
Outside Turkey, Qatar has been exploring options with Russia. Doha and Moscow signed a military cooperation agreement on air defence and military supplies in October 2017 when Russian Defence Minister visited Qatar. Based on this, Doha is planning to buy Russian missile defence system S – 400. Although Saudi king Salman has threatened to take military action to eliminate the defence system, Qatari ambassador to Moscow Fahad bin mohammed Al-Attiyah has confirmed the deal to be at an advanced stage. This could lower its dependence on US weapon import and diversify its options for future requirements.
The blockade did not affect Qatar's LNG exports much. Qatar's geographic position helped it to maintain its trade relation, which has been stable during last one year and added to the much needed revenue. Beijing is also helping Doha; Qatar's export to the China has grown significantly in recent past. In September 2017, Qatar's newly built Hamad port became operational which is creating job opportunities for Qatari youths, as well as skilled labour. The port is 14 times larger than Doha port and managing much of Qatar's increasing trade with China and the rest of the world, decreasing dependence on the Arab neighbours. The port was partly built by China Harbour Engineering Company by bringing in various components from China, which is helping Qatar to boost manufacturing sector and diversify its economy.
Another major external player at the region, the US, was vocal about Qatar's support to Islamic terrorist groups at the beginning of the crisis, but what changed with the US position in last few months is that White House has stopped accusing Qatar on financing terrorism. On January, 2018 during a strategic dialogue with Qatari Emir at the US State Department President Trump thanked the Emir for "Qatari action to counter terrorism and extremism in all forms." This can be seen as Doha's major diplomatic win over Washington's position at the start of the crisis. Also, during the April 2018, meeting at White House, Trump said that the US and Qatar "have been great friends in so many ways" and "are working very well together". Trump has offered to play a mediator to find a diplomatic solution to the GCC crisis as he added "we're working on unity in that part of the Middle East and I think it's working out very well". Although no significant progress has been observed towards resolving the crisis, the addition of new external players like Russia and Turkey can make the crisis more intricate, which can be Washington's one of the main concerns. Also, the shift in the US weapon export market as Qatar and Saudi Arabia has made few arms deal with Russia recently, can make Washington think seriously to increase pressure on the Arab nations to bring them at the negotiation table before it impacts GCC significantly.
Doha's Domestic Changes
The blockade has forced Qatar to change many policies and as a result the share of hydro carbon in economy has significantly reduced to 40 percent from 60 percent in last year, signifying growth of non-hydrocarbon sector. To draw labour and talent to work in these sectors, recently, Qatar has approved a draft law allowing permanent residence to non-Qataris under certain conditions.
Although inflation rate has increased to 0.5 per cent in May 2018 from 0.1 per cent in April 2018, in a recent report IMF has forecasted Qatar's economic growth to accelerate in 2019 According to the report Qatar's real GDP will grow from 2.6 percent in 2018 to 2.7 percent in 2019 with both hydro carbon and non–hydrocarbon sectors contributing to the growth. The report also states, Qatar's total revenue was $ 26.3 billion in 2017 and it is expected to rise to $ 28.9 billion and $ 31.5 billion in 2018 and 2019 respectively. With gradual decrease in country's expenditure, it is expected that the fiscal balance would turn positive in 2019 to $ 3.4 billion.
With the highest per capita GDP in the world, proper use of its gas and oil revenue to diversify the economy and creation of active sovereign wealth fund to make high return investments overseas has helped Qatar to overcome the effects of the blockade. It has also innovatively increased self sufficiency, one of the examples of which is Baladna air conditioned dairy farm, which was built just after the blockade. The farm was built in the middle of the desert and imported nearly 8000 cows by air and ship from US, Australia and Germany to attain self sufficiency in dairy products. It is expected that by 2019, Qatar will be the exporter of dairy products.
Although, the blockade was meant to curtail Qatar's political and diplomatic influence in the region, after one year of the crisis Qatar's current status reinforces the fact that amid hostile neighbours Qatar has become self-sufficient. Doha has diversified the economy away from oil and gas by increasing the non-oil sector's contribution to the economy and by relying lesser on hydrocarbon revenues. In spite of some problems that Qatar is facing in terms of Qatar airlines and the US sanctions on Iran, the crisis seems to be a blessing in disguise for the emirate.


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School's (mostly) out! (Sorry year round friends- it's almost your turn!)
And I'm soooo glad!
Welcome Summer in with these happy & FREE cactus prints!
A few different options:
Print them on cardstock and use as cards. Or maybe print & frame them & cheer up your space.
Either way- celebrate summer!!


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Resurrecting the Street Walker
The digital video technology that led to a boom in cheaply shot indie horror over the last few years, also chanced to come in the wake of the critical and commercial success of "The Blair Witch Project" and its predecessor "The Last Broadcast": two films which made the horror 'mockumentary' format by far the most obvious way for aspiring film-makers to circumvent the limitations of budget and the aesthetic roughness inherent in the new medium by utilising these very qualities for their own ends -- instantly transforming them into the authentic qualities of the diegetic texture of the fictional work supposedly being offered to the viewer. In other words: it no longer mattered if your film looked like a piece of crap -- you could simply claim it as a deliberate mimicry of the amateur standards commonly found in low budget film-making.
Unfortunately, tempting though this sub-genre must now be for the budding indie film-maker, the mockumentary is still one of the most difficult genres to execute properly. Not least because you're having to follow two of the best attempts in the style, particularly with the atmospheric and ultra-scary "The Last Broadcast". The problem is that both that film and the following "The Blair Witch Project" addressed our inherent trust in the documentary form and undermined it in clever, sometimes subtle ways to unnerve and wrong-foot viewer expectations, that there seems little left to be done with the format. "The Last Broadcast" undermined the authority of the investigative documentary form itself, making everything it showed us the build up to a magnificently executed twist at the very end; while "The Blair Witch Project" created an unnervingly realistic atmosphere with its imitation of raw, 'found footage', that worked on the imagination by offering no resolution or documentary structure other than that which the fictional subjects of the 'work' had allegedly filmed themselves.
"Resurrecting the Street Walker" is pitched more in the style of "The Last Broadcast", but also includes echoes of "The Blair Witch Project" in purporting to be a documentary about an aspiring film-maker who has discovered the only copy of a legendary, unfinished horror film from the Video Nasty era, and his subsequent attempts to complete the project himself. Thus, we are presented with several layers of artifice over which the real director, Ozgur Uyanik, provides his own narration -- just to bring an extra level of post modern cleverness to the project.
The film is ostensibly presented to the viewer as a documentary made by film-school attendee Marcus Grady (Tom Shaw) about what happened to his friend James Parker (James Powell): a film-obsessed horror fan struggling to make it in the film business by working his way up from a lowly position as a runner for an insignificant production company called Portland Pictures, based in Soho. We know from the get-go that something horrible must have happened to James because Grady's fictional film foregrounds the fact straight away; but Grady's film started life as a co-project between the two aspiring film-makers, the idea being that Parker's experiences as a runner would form material for a documentary about the struggling British Film Industry in the Noughties.
Throughout its 80 minute running time, footage supposedly shot by Grady for his documentary in fact captures Parker's unpleasant experiences as an unpaid dogsbody, constantly harassed and abused by spiteful production executive Dorothy Thistle (Lorna Beckett), inter-cut with subsequently filmed Talking Head shots of Parker's friends, family and colleagues which ominously intimate at the disaster to come. Not only is Parker the subject of abuse and bullying at work, but his parents aren't keen on his choice of career either, his father threatening to kick him out of the house unless he starts earning a proper wage. Parker also keeps his own secret video diary in conjunction with Grady's documentary. In the light of subsequent events, the diary footage illustrates a man close to the edge -- in marked contrast to the public persona he attempts to convey in everyday life captured in Grady's film record.
The turning point comes when, after being assigned to make an inventory of the contents of an old film storage facility in London, Parker stumbles upon the materials for a legendry lost video nasty "The Street Walker". This is a film about a serial killer who trawls the pubs and clubs of London, picking up young girls and leading them back to his flat where he drugs, tortures and murders them in a dingy, soundproof basement room. The plot starts to get interesting when he meets a woman called Catherine who seems to get to him in a way no one else ever has, but here the footage just stops before the story is completed. The film is unfinished and consists only of endless footage of women being murdered in grainy black & white. Parker becomes obsessed with both the film and the mythology surrounding the footage: why did the film's writer and director David Foreshaw commit suicide before the movie was completed? And are the rumours that the whole thing is in fact a snuff movie true? While re-running some of the footage, Parker becomes convinced that one of the actresses was accidently killed during the filming of one of the murder scenes -- but by now not only is everyone at his production office fed up with his obsession, but even Marcus has had enough.
But then Parker hits on a new idea. What if he re-edits all the surviving footage and combines it with his own to complete the project? This could be his big break in the film industry at last: he could complete the story begun by Foreshaw with his own written material and use the infamy and controversy surrounding "The Street Walker" to kick-start his career and escape the abuses and indignities of his wretched life as an unpaid nobody for a backstreet production office.
Parker's obsession with this idea then becomes the main focus of Marcus Grady's fictional film. He needs to convince the head of his production company to provide the money to complete the project. Marcus documents his attempts. But after giving him half of what he asks for and allowing Parker to cast a new lead to play Catherine, his boss also assigns Parker's nemesis Dorothy to oversee the project. Her sneering presence on the mock-up set of the new Street Walker shoot soon starts to tip the pressurised young film-maker over the edge, but an on-set accident which threatens to derail the whole project is the final straw and terrible consequences result.
"Resurrecting the Street Walker" starts well by evoking the Video Nasty panic of the mid eighties and filling the viewer in on the real historical background of the day: there was real outrage and public fear about these kinds of films, most of which quite simply seem unbelievably tame by today's standards. The recreation of the fictional James Parker's early 8 mm work looks convincing also; but the minute the mock documentary switches to presenting the raw footage Parker finds in the storage vault, depicting clips of the murders from the supposedly lost "The Street Walker", we're instantly taken out of the illusion since there is no way this looks anything like a film that would have been shot in the 1980s. Uyanik's recreation of standard documentary techniques and familiar tropes is quite well executed, but from here on in you are never really fooled into thinking you could be watching a real documentary in the way you are by "The Last Broadcast", for instance; and while it aims to build up a sense of dread and nervous anticipation for Parker's final meltdown, when it finally comes it does tend to feel more like watching someone having a tantrum on Big Brother than a dangerous explosion of murderous aggression accidentally caught on film: actor James Powell simply isn't menacing enough. It's left to Lorna Becket as the spiteful and aggressive Dorothy Thistle to provide the film's most captivating performance. The big finish finally arrives as something of an anticlimax, not least because it is so completely expected and predictable. Nonetheless, Ozgur Uyanik's film is better made than the majority of indie features of this ilk -- the idea simply hasn't been developed thoroughly enough to provide the full intended effect.
As a final word I should mention that the UK DVD disc from Kaleidoscope Home Entertainment is set to arrive with a number of special features which were not included on my screener so I cannot comment upon them. Apparently it will also have some deleted scenes; test footage; a cast & crew Interview and an audio commentary.


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SOLID! The
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TackleTour's 2010 Spinnerbait Shootout! (continued)
Picasso Flip Side: Picasso is the non-tungsten division of Fish Harder Companies offering almost a carbon copy catalog of products from the TruTungsten side except made out of the more traditional lead. However, one product TruTungsten no longer offers is a spinnerbait. Picasso takes up that slack and more with their collection of bladed products. Today, we look at their Flip Side Spinnerbait.
Introducing the Flip Side Spinnerbait from Picasso.
The Blades: The story with the Picasso Flip Side Spinnerbait is all in the blades. Finished in nickel or gold on one side and painted on the other side, the blades on the Flip Side Spinnerbait give off the unique benefit of color and flash in an effort to give the fish something just a little different from your prototypical spinnerbait.
This bait gets its name for the two tone blades with color on one side and gold or silver on the other depending upon the bait's overall color combination.
The Skirt: The skirts on the Picasso Flip Side are silicone fastened to the bait via a rubber band and are available in up to seven different colors including white pearl, white/red, chartreuse/white, orange crystalina/chartreuse, gizzard shad, chartreuse, and chartreuse/blue.
A lot of the Picasso skirts are cut with longer skirting in the center, like
a trailer.
The Flip Side features a silicone skirt fastened by a thick rubber band ...
The Hook: Surprisingly, Picasso makes no mention of their hook brand of choice leading us to believe it is an
in-house brand. We know that TruTungsten has partnered with Daiichi to produce hooks for many of their products, so perhaps they are the suppliers for this hook as well? Regardless, we ran into no issues with the hook on our Flip Side Spinnerbaits.
Zander, our Editor-in-Chief, loves spinnerbaits with long shanked hooks and
Picasso spinnerbaits fit the bill nicely here.
... an unspecified hook ...
The Head: Of all the spinnerbaits in this year's shootout, the Picasso's head design is
among least intricate featuring a shad-like, teardrop shape and molded eyes.
Though simple Zander really likes the profile of the head as well as the
flared out gill which he believes does help displace the water a bit when
... and these simple, molded eyes painted black.
Ratings: (We've re-calibrated our ratings standard for 2008 and have included a key at the bottom of the following matrix as a guide):
Picasso Flip Side Ratings (?/10)
Total Score
Pluses and Minuses:
The bait itself fishes very well out of the package as a whole. In fact, on my very first cast with this bait, I hooked up with a quality fish experiencing no issues with the hook and certainly no issues with the head design. The Flip Side Spinnerbait comes with an intriguing blade design and it's a bait we will likely continue to throw.
The Flip Side may
not have the most realistic head/eyes but it is a good performing bait nonetheless
Looking for Picasso Spinnerbaits? Try
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Revenge Baits: Revenge is the last of our small, custom bait manufacturing companies and the company we first noticed as having that realistic head design in their spinnerbaits and jig heads. There are no catchy names for their spinnerbait products, but these spinnerbaits flat out catch fish.
Introducing Revenge Bait's take on the spinnerbait.
The Blades: Revenge offers their spinnerbait in four different blade combinations including double willow, tandem, single Colorado and double Colorado. Not many manufacturers offer the double Colorado option any longer so it's nice to see this option still available from Revenge. Fishing a double Colorado can be akin to throwing a deep diving crankbait – it can really wear you out!
The Revenge spinnerbait is available in several different blade combinations.
The Skirt: The skirt on these baits is a quality silicone product held in place by a thick rubber band, but protected by the very unique head design. The skirts are available in one of thirteen different colors ranging from basic white and white/chartreuse, to the more intricate and unique orange crush, bluegill, and craw. Revenge receives extra bonus points for their intricate array of custom colors.
They are built on the foundation of a Mustad Ultra Point hook.
The Hook: Revenge makes use of the second most popular branded hook in our shootout and that's the Mustad Round Bend Ultra Point Hook. These are very sharp, very stout, very reliable hooks.
But the real differentiator with Revenge is their signature head.
The Head: But again, where the story lies with these baits is in the head. The Revenge product features a very intricate head design exemplified by the flaring gills that server as protection to the bait's skirt while providing a surface against which the skirt actually gets bent back towards the rear of the bait. As a result, the Revenge spinnerbaits all feature a unique, and consistent skirt flare.
Notice how the base of the head turns out... on the backside is the skirt, protected by the gills from the head and made to splay out evenly as the skirt is held up against the backside of the head by the thick rubber band.
The finish on these heads is intricate as well providing a slight change in hue as you adjust the angle by which you're viewing the bait. Deep set, lifelike eyes complete the design which only serves to give you confidence this bait will work right out of the package.
Revenge Spinnerbait
Ratings (?/10)
Revenge Spinnerbaits are a proven winner.
Effectiveness: As with most things but especially in fishing, confidence is the key. If you have confidence in your bait, you'll work it more effectively whether you realize it or not. You'll also keep it tied to the end of your line longer increasing the chances you'll get bit by staying consistent in your approach and presentation. Revenge baits are all about inspiring confidence and their spinnerbaits are about as confidence inspiring as they come.
for Revenge Spinnerbaits? Try
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Section: War Eagle and the Wrap! ...