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Stem Cell Treatment – Stem Cell Therapy – Stem Cell …

By adminJanuary 21, 2014Stem Cell Treatment

Stem Cell Therapy

Stem cell treatment and stem cell therapy may be considered controversial and are, perhaps, viewed as akin to science fiction by some people. However, stem cell treatments have been used regularly in veterinary practice since 2003 for the repair of bone and tissue damage, and have a wealth of research highlighting their efficacy in both humans and other animals. Stem cells are found in plentiful supply in embryonic tissue, but are also found in adult tissues. These cells have the ability to self-renew, giving rise to countless generations of new cells with varying abilities to differentiate into specific cell types. By introducing stem cells into an area of damage or pathology, the body can be encouraged to repair and renew regardless of how old the trauma is. Stem cells also show application for inhibiting the death of cells (apoptosis) through disease, making them candidates for use in treating degenerative illnesses such as Lou Gehrigs disease, Multiple Sclerosis, Parkinsons disease and Alzheimers.

Stem cells from embryos are considered more flexible in terms of their ability to become either new liver cells, new neurons, new skin cells, and so on, whereas adult stem cells tend to be more restricted to the tissue type from which they were taken. New research is showing that this might not necessarily have to remain the case however, with the plasticity of adult stem cells now under investigation. Stem cell use carries little risk of the resulting tissues being rejected, it appears safe, efficient, and almost endless in its possibilities for application.

Potential Stem Cell Treatments

Conditions such as cardiovascular disease, diabetes, spinal cord injury, and cancer, among others, are considered possible candidates for stem cell treatment. Cures for some of these diseases could be closer than previously thought with clinical trials already showing impressive results where stem cells have been used in cases thought intractable. The rapid rate of progression in research and clinical use means that some of the controversial issues, such as the use of embryos as a source of stem cells, have been overcome, with governments around the globe subtly altering their legal policies in order to accommodate new scientific advances. In the US, Bill Clinton was the first president to have to consider the legal issues surrounding stem cells, and subsequent presidents have been forced to readdress the issues time and again in line with medical discoveries. Worldwide, governments have remained generally cautious over the use of this technology but are gradually improving funding access, whilst keeping an eye on the ethics of stem cell treatment, in order to explore the tremendous benefits that appear possible. The credibility of research remains a concern, with some stem cell studies discredited by ethics committees after initial general acceptance of their veracity.

Stem cells may be garnered from living adult donors and, indeed, already are in the case of bone marrow transplants. More usually they are taken from discarded embryos leftover after IVF treatment, or from the placenta after birth. Previously the removal of stem cells resulted in the destruction of these embryos, but now it is possible for scientists to remove the stem cells without this occurring. This development negates some of the criticism faced by the technology from religious groups and ethical bodies over the sanctity of life and the attribution of sentience and autonomy to embryos, gametes, and the foetus. Clearly, some debate remains about these issues in relation to stem cell research, but recent improvements in methodology may remove the need for these considerations completely. Clinicians have demonstrated the possibility of taking adult stem cells and seemingly teaching them to become cells of a different type to their site of removal, effectively returning them to a similar state to that of the embryonic stem cell. Whilst stem cells from embryos remain more reliable and more economical to work with, the use of adult tissue-derived stem cells could revolutionize the research in this field.

As well as stem cell use in pathology and disease, there are also applications in personal aesthetics such as the regeneration of hair follicles and an end to baldness through stem cell treatment. Stem cells are also considered useful in regenerating the skin after injury, without the scarring usually associated with repair. There are reports of paralyzed patients becoming mobile after years in a wheelchair through the use of stem cells injected into the spinal cord, and the rapid disappearance of tumors in brain tissue after stem cells were injected.

Stem cell treatment provides an exciting possibility to change the face of modern medicine, alleviating pain and suffering, and improving the prognosis for millions withe diseases previously thought incurable.

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Stem Cell Treatment – Stem Cell Therapy – Stem Cell ...

Stem Cell Therapies for Celiac Disease and IBD Now Offered in the United States

By adminJanuary 21, 2014Stem Cell Treatment

Tampa, FL (PRWEB) January 21, 2014

Regenerative Medicine Solutions (RMS), a global provider of stem cell treatments for degenerative diseases, is now offering Regenerative ColoTherapy (RCT), a proprietary stem cell treatment for people suffering with celiac and inflammatory bowel disease (IBD). Crohns disease and ulcerative colitis (UC) are two of the most notable conditions that fall under the IBD umbrella, affecting millions of people across the United States and the world.

It is estimated that there are 1.4 million cases of Crohns and colitis in the United States, which roughly translates to the population size of Philadelphia. Although Crohns, colitis, and celiac disease are very different conditions, affecting different areas of the intestines, treatment options are similar and mainly consist of diet modification, anti-inflammatories, and immunosuppressants.

In severe cases, sufferers use the restroom over 20 times a day and may require surgery to remove part of their intestine or colon. As you can imagine, symptoms of these disorders take a heavy toll on sufferers quality of life. Andrew, a 26-year-old RMS patient that suffers from ulcerative colitis underwent the Regenerative ColoTherapy.

For three years, I suffered from diarrhea, bleeding, painful stomach cramping, and being completely drained of energy, Andrew said. 90 days following the RCT procedure, I noticed considerable improvements in my symptoms. My bowel movements went from upwards of 20 times a day to less than five. This procedure was invaluable and in my opinion the best option for treating this disease.

As stem cells have the ability to differentiate into many different types of tissues and have been found to be immunomodulatory and anti-inflammatory in nature, their intrinsic healing capacity is highly beneficial for sufferers of celiac disease and IBD. RMS has harnessed the natural properties of stem cells in the form of Regenerative ColoTherapy, a unique stem cell treatment that utilizes stem cells from a patients own body for the regeneration and repair of damaged tissues in the intestines and colon.

Regenerative ColoTherapy treatments are being performed RMSs headquarters in Tampa, FL where it also operates its subsidiary company Lung Institute. To learn more about RCT or to schedule a free consultation call today at 1-855-469-5864.

About Regenerative Medicine Solutions

Regenerative Medicine Solutions (RMS) is a leading global provider of stem cell treatments for the treatment of an array of debilitating medical conditions. Notably, RMS performs Regenerative ColoTherapy an innovative treatment for people with celiac disease and IBD. For more information, visit MyRegenMed.com or call us today at 1-855-469-5864.

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Stem Cell Therapies for Celiac Disease and IBD Now Offered in the United States

Pluristem Gains Most in 17 Months on Stem-Cell Study

By adminJanuary 21, 2014Stem Cell Treatment

Pluristem Therapeutics Inc. (PSTI), the Israeli developer of stem-cell therapies, rose the most in more than 17 months after an experimental treatment showed promise in a study of 20 patients with muscle injuries.

The stock surged 22 percent to 16.18 shekels ($4.63) at 11:04 a.m. in Tel Aviv. Earlier it gained as much as 27 percent, the biggest increase since Aug. 6, 2012. The shares fell 15 percent yesterday ahead of the study results.

The early-stage clinical trial assessing Pluristems placental-expanded, or PLX-PAD, cells in people who had a buttock muscle injured during hip-replacement surgery found the treatment was safe, the company said in a statement today. Patients getting the injection also fared better in a muscle-contraction exercise six months later.

These are remarkable results that signal advances in the cell-therapy industry, Jason Kolbert, an analyst with Maxim Group LLC in New York, said at a press conference organized by Pluristem in Tel Aviv.

The study results suggest the stem-cell therapy could help treat a broader range of muscle and tendon injuries, according to the Haifa-based company. We intend to move forward with implementing our strategy towards using PLX cells in orthopedic indications and muscle trauma, Chief Executive Officer Zami Aberman said in the statement.

The results come after the U.S. Food and Drug Administration in June placed one of Pluristems most advanced studies on hold after a patient suffered an allergic reaction. The hold was lifted in September.

To contact the reporter on this story: David Wainer in Tel Aviv at dwainer3@bloomberg.net

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Pluristem Gains Most in 17 Months on Stem-Cell Study

Inhaled Stem Cells Might Replace Lost Neurons

By adminJanuary 21, 2014Stem Cell Treatment

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Intranasal stem cell therapy may one day treat brain disorders

Image: Jim Kopp

Many diseases of the central nervous system involve the death of neuronsso, theoretically, the replacement of dead cells should improve symptoms of degenerative disorders such as Parkinson's, Huntington's, amyotrophic lateral sclerosis (ALS) and Alzheimer's, as well as stroke and brain tumors. Stem cell therapy may do just that even though evidence of its effectiveness is mixed.

In any cell transplant procedure, the host organin this case, the brainmay reject its new additions. Further, it is unclear whether grafted cells can truly integrate into complex neural circuitry. Finally, current procedures require invasive surgical implantation, which can be expensive and risky. The surgery can cause neural inflammation, and the implanted cells may quickly die.

Intranasal administration may address at least some of these issues. Most important, it eliminates the need for surgery. Further, some research suggests that stem cells delivered intranasally are smartthey do not spread through the brain indiscriminately but instead target damaged cells.

Although it is difficult to predict when medical practice will adopt stem cell therapy for the brain, animal studies have produced some promising results. In a rat model of Parkinson's, for example, treatment with intranasal stem cells appeared to improve motor function and slow the neurological deterioration associated with the disease.

2014 Scientific American, a Division of Nature America, Inc.

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Inhaled Stem Cells Might Replace Lost Neurons

Art imitating life: Cancer center fetes sculptor whose work is now permanently featured

By adminJanuary 18, 2014Stem Cell Medical Center

Click photo to enlarge

A sculpture by Jan Martin Bopp sits center-stage at its unveiling party in the Southwestern Vermont Regional Cancer Center Wednesday. Bopp, a volunteer and cancer survivor, created the sculpture to symbolize his battle with myeloma. (Derek Carson)

BENNINGTON - The Southwestern Vermont Regional Cancer Center honored and celebrated local educator, sculptor, and volunteer Jan Martin Bopp on Wednesday.

Bopp was diagnosed with multiple myeloma, a cancer of plasma cells in which collections of abnormal plasma cells accumulate in bone marrow, where they interfere with the production of normal blood cells. Throughout his battle with cancer, he was also challenged with cardiovascular dysfunctions, a stem-cell transplant, chemotherapy, coronary artery stent implants, a carotid endarterectomy, a pacemaker implant, and what one speaker called the worst case of shingles he had ever seen.

Yet Bopp persevered through everything, and eventually decided to create a sculpture to symbolize his battle with myeloma. The result was "My Medical Journey: Trauma to Transcendence," a 17-inch wide, 16-inch tall, and 10-inch deep ceramic sculpture, which is on permanent display in the atrium of the cancer center.

The sculpture, which was completed in 2009, "embodies the story of my journey through extensive medical trauma and treatment to better health and a life coping with chronic illness," said Bopp in a written description that was displayed next to the sculpture. "It is a story of some of my physiological ambushes and health challenges and how I have responded, with much professional help, medicine and procedures, fortitude, and good fortune."

Bopp was born and raised near Lansing, Mich., completed his undergraduate studies at Hope College in Holland, Mich., and worked toward a graduate degree at Miami University of Ohio. In the 1970s he began teaching at Mount Greylock High School in Williamstown, Mass.

"My sculpture is a therapeutic expression of my resilience, positive energy and spirit, and eternal optimism. It has been given to the Southwestern Vermont Regional Cancer Center to symbolize my deep gratitude for the profound help of expert health care providers and to inspire others afflicted with cancer," said Bopp.

While 92 people officially RSVP'd to Wednesday's reception, the total number of attendees may very well have been higher. "Certainly tonight's turnout is a reflection of the impact Jan has made on all of us, on our lives," said Thomas Dee, CEO of Southwestern Vermont Health Care.

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Art imitating life: Cancer center fetes sculptor whose work is now permanently featured

Stem Cell Clinics USA | Stem Cell Treatment

By adminJanuary 18, 2014Stem Cell Clinic

Stem Cells....Snake Oil or Reality?

Searching for stem cell treatment online will give you a huge number of results often offering unproven, and ill-explained, therapies at overseas clinics. Finding a clinic that offers such services in the US is nigh on impossible as the FDA controls the use of stem cells for both research and therapeutic application very carefully. To some this is a problem because it necessarily slows down the rate of availability of treatments, but for others it can, quite literally, save their lives. Whatever problems the FDA has, you can be pretty confident that undergoing stem cell treatment in the US means having a dedicated, experienced, and professional team of qualified scientists and doctors administering the treatment and handling follow-up care as appropriate. You can also be fairly sure that the stem cell treatments you undergo will have been researched professionally and reviewed extensively before being made available to patients.

Clinics overseas are often unregulated or so transient that they simply move from country to country as the authorities catch up with them. The staff at such clinics may well be highly regarded doctors or scientists who are practicing therapies they feel should be made available to all patients in the US now rather than when the FDA decides they are appropriate. However, in many cases these clinics are more concerned with convincing vulnerable patients to part with their money for treatments that are unlikely to offer any health benefits other than a placebo effect and may in fact be downright dangerous.

Controls on health, hygiene, and safe medical practices may not be followed in countries where the government turns a blind eye to such health tourism. Treatments using embryonic stem cells have been, and still are being used in clinics overseas despite safety concerns regarding the uncontrolled differentiation of these stem cells once injected into the body. The origins of such biological material is also questionable in many cases with the Ukraine implicated, a number of years ago, in a scandal involving dubious procurement of foetuses and infants for stem cell therapies.

Clinical trials exist not in order to frustrate patients awaiting treatment but to safeguard patients from potentially dangerous and mishandled therapy. Even after clinical trials have been carried out and a treatment approved there are still many potential problems that can arise in the much larger number of patients treated than those in the trials themselves. Clinical trials can at least avoid some of the more overt contraindications and highlight the need for further research. They also allow patients to receive treatments which are likely to be efficacious and can be covered by medical insurance.

Travelling overseas for treatments often means invalidating the health-care plan in the US and any complications (such as infection, tumor growth, or paralysis) requiring further treatment or hospitalization when back home are often excluded from such plans. Although many clinics in the US offer stem cell treatments the reality is that patients only have their consultation on US soil and then must travel to a clinic in the Caribbean, Ukraine or other country to actually undergo the treatment as it is not approved by the FDA.

Research trials conducted overseas may offer patients a way of accessing treatment but these should be approached cautiously as the regulation of standards in such trials can vary widely. Again, some researchers are perfectly professional and are simply looking to further the field of regenerative medicine without having to adhere to the seemingly overly stringent restrictions put in place by US regulators. Others however, are adept at engaging in methodologically unsound trials which prove to be little more than anecdotal observation and publishing these in a non-peer-reviewed trade journal of their own making. Claiming that a therapy has been proven to work and has had research published to such effect means very little unless the journal, the paper, and the raw data are readily available for other scientists to review and confirm through repeated experiment.

Stem Cell Treatment overseas is often unregulated and downright dangerous

Clinics in Russia, India, Mexico, and Panama are offering treatments with little, if any, clinical evidence to merit their use. Even in the US there are doctors who are using a loophole in regulations to treat patients with their own stem cells despite there being limited evidence proving any benefit from such treatment. These doctors extract stem cells from fatty tissue using liposuction and minimal processing techniques and then inject the stem cells back into the patient all in an outpatient procedure taking around seven hours or so. This treatment is unlikely to be harmful to a patient but is far from proven to be effective for any disease condition. Indeed, the clinics offering such treatment maintain that it is not intended to treat any pathology and is at best a cosmetic procedure. Clearly the establishment of such clinics and the marketing practices defies this supposed intention and is much more geared toward ill and vulnerable patients.

China, well known for offering stem cell treatments to patients despite a lack of evidence for safety or efficacy, passed a law last May requiring clinical trials prior to such treatments being offered to patients. The degree to which this law is being enforced remains unknown, and, as yet, there have been no public announcements of clinics shut down under the new regulations. There are thought to be around 150 clinics in China which offer stem cell therapy for conditions ranging from spinal cord injuries to Multiple Sclerosis, and diabetes. Patients from the US would expect to pay around $25,000 for treatments in Chinese stem cell clinics although the cost of follow-up treatments and possible rehabilitative care in the US is not included in this price.

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Stem Cell Clinics USA | Stem Cell Treatment

New Assessment Tool Shows Potential of Stem Cells in Restoring LSCD Patients’ Sight

By adminJanuary 18, 2014Stem Cell Clinic

Durham, NC (PRWEB) January 17, 2014

A new assessment tool is helping scientists determine which treatments might benefit patients with a type of eye disorder called limbal stem cell deficiency (LSCD). The tool, developed by researchers at University College London and Moorfields Eye Hospital in London and funded by the UKs National Institute for Health Research Biomedical Research Centre at these institutions, has already shown that the majority of these patients can benefit in the short term from a stem cell transplantation and up to 30 percent are still experiencing better sight three years later, according to the study published in the current issue of STEM CELLS Translational Medicine.

LSCD is an eye disorder in which the stem cells responsible for forming the surface skin of the cornea are destroyed by injury or disease. This results in pain, loss of vision and a cosmetically unpleasant appearance. Many new treatments, including limbal stem cell transplants, are emerging for this condition but their effectiveness remains to be proven.

Assessing how well they perform has been severely hampered by the lack of biomarkers for LSCD and/or validated tools for determining its severity, said Alex Shortt, M.D., Ph.D., of University College Londons Institute of Ophthalmology and lead investigator in the study. In virtually all studies of limbal stem cell transplantation to date the clinical outcome has been assessed subjectively by the investigating clinician. This is clearly open to significant measurement and reporting bias.

His teams aims, then, were to design and test the reliability of a new tool for grading LSCD, to define a set of core outcome measures to use in evaluating treatments and to demonstrate the treatments impact on two common types of LSCD: a genetic disorder called aniridia and Stevens-Johnson syndrome (SJS), an inflammatory disorder.

They began developing an assessment tool by paring down a list of clinical signs taken from previously published studies to four key LSCD indicators: corneal epithelial haze, superficial corneal neovascularization, corneal epithelial irregularity and corneal epithelial defect. A standardized grading plate was then produced for each of these parameters, ranging from normal to severe. They named their assessment method the Clinical Outcome Assessment in Surgical Trials of Limbal stem cell deficiency [COASTL] tool and validated its performance in 26 patients with varying degrees of LSCD.

Once they had the COASTL tool in place, they used it to evaluate treatment outcomes in 14 patients with aniridia or SJS. All had undergone a limbal epithelial transplantation (allo-CLET), using cells taken from a deceased donor, cultivated in the lab before being transplanted into the recipient.

The COASTL tool showed that following allo-CLET there was a decrease in LSCD severity and an increase in visual acuity up to 12 months post-treatment, but thereafter LSCD severity and visual acuity progressively deteriorated, Dr. Shortt said. However, despite a recurrence of clinical signs, the visual benefit persisted in 30 percent of aniridic and 25 percent of SJS patients at 36 months.

A reliable method of obtaining objective outcome data for surgical trials of limbal stem cell deficiency will greatly contribute to the effective evaluation of current and new treatments, said Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine.

The full article, Three-Year Outcomes of Cultured Limbal Epithelial Allografts in Aniridia and Stevens-Johnson Syndrome Evaluated Using the Clinical Outcome Assessment in Surgical Trials Assessment Tool, can be accessed at http://www.stemcellstm.com.

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New Assessment Tool Shows Potential of Stem Cells in Restoring LSCD Patients’ Sight

SmartChoice® Adult Stem Cell Procedures – Incredible pain relief in just one treatment – Video

By adminJanuary 18, 2014Stem Cell Treatment

SmartChoice Adult Stem Cell Procedures - Incredible pain relief in just one treatment
Patient Testimonial: Donna was a patient with severe knee and back pain. After just one treatment at SmartChoice, her life has significantly improved. Learn...

By: Hardesh Garg

New Development in Stem Cell Treatment

By adminJanuary 18, 2014Stem Cell Treatment

Physicians and researchers have used Hematopoietic Stem Cell Therapgy for more than 50 years to treat many diseases according to the National Institutes of Health. You ask, "What is Hematopoietic Stem Cell? The National Institutes of Health states it is a stem cell that is isolated from the blood or bone marrow and it can renew itself. Cells have long term and short term replicating ability. The classic source of these cells is through bone marrow. I recall a friend of mine dying at a young age, while waiting for a bone marrow transplant. It is sad to hear of those unable to find a donor while they wait for a transplant.

Have you ever asked, "Where do you find stem cells?" Well, they can come from several places such as bone marrow, the bloodstream, or the umbilical cord after it has been detached from the baby. Stem cells for transplant can come from your own body or from a donor's body. If they come from your body, they are generally taken and frozen before chemotherapy and radiation. This type of transplant is called autologous transplant. Then after chemotherapy and radiation treatment they are put back in your body to increase the number of good cells. If the transplant is from a donor, there must be testing to be sure of a perfect match.

Stem Cell Studies

Did you know there may be a stem cell treatment for the cure of baldness? If the clinical trials are successful, women can benefit from this as well as men. This new approach could increase the hair follicles. It would require fewer hair cells to grow in a lab culture, then the multiplied cells would be transplanted back into the bald or thinning hair area. Sounds like a plan to me.

Vet-Stem, Inc. is Proud to Announce Its 10,000th Animal in 10 Years of Stem Cell Therapy

By adminJanuary 18, 2014Stem Cell Treatment

Poway, California (PRWEB) January 18, 2014

The leading Regenerative Veterinary Medicine Company, Vet-Stem, Inc., is proud to announce that its regenerative stem cell therapy has been used to treat 10,000 animals in the last 10 years of offering tissue processing services to veterinarians. Vet-Stem was founded in 2002, seeking to discover a successful treatment for horses with potentially fatal injuries to tendons and ligaments.

Dr. Robert Harman, CEO and Founder of Vet-Stem has spoken at many human and veterinary conferences sharing the results of real treatments. He has also authored or co-authored numerous peer-reviewed papers on stem cells as well as written book chapters on stem cells.

In 2003 Vet-Stem signed a worldwide exclusive license for adipose-derived (fat derived) stem cell technology for veterinary application, and the first horse was treated. Shortly after, the first dogs were treated with Vet-Stem Regenerative Cell Therapy. Vet-Stem started providing stem cell banking to their clients from the beginning so that cells could be stored for future use. By August of 2005 500 horses had been treated. Vet-Stem had effectively introduced a new, natural, injectable treatment to the equine and small animal veterinary industry that could serve as an alternative to euthanasia for some conditions.

By April 2006, 1000 animals had been treated using Vet-Stem cell therapy, including the first cat. Another milestone was the first ever randomized double-blinded placebo-controlled multi-centered study that was published reporting that using Vet-Stem processing, intra-articular injection of adipose-derived stem cells into the hip joint of a dog decreases patient discomfort and increases patient functional ability in relation to arthritis.

Only nine months after formally launching a Small Animal application, over 1,000 dogs had been treated for orthopedic conditions. At the same time Veterinary Therapeutics published a peer-reviewed study on the use of stem cells for treatment of chronic osteoarthritis in the elbow of dogs. The clinical trial reported significant improvement in lameness, range of motion, and functional ability in dogs treated with Vet-Stem Regenerative Cell Therapy.

Although the large majority of animals treated have been horses, dogs and cats, Vet-Stem has provided services for exotic species as well. The U.S. Navy, Office of Naval Research, awarded Vet-Stem a contract to engage in a collaborative study of stem cell biology in marine mammals in 2009. From this, the first peer-reviewed article was published showing successful isolation of stem cells from dolphin fat. Several media outlets featured a story on a panther from the Tallahassee Museum who received stem cell therapy by Vet-Stem for arthritis of the elbow in 2011. After the therapy he was able to stand up and scratch on his favorite tree with both front paws.

I started Vet-Stem in order to help horses with career ending injuries to their tendons and ligaments but so many more animals have been saved from a life of pain or even from euthanasia. I feel privileged and excited to be a part of this therapy that has changed how veterinary medicine is practiced as well as contributing to changes in human medicine, Robert Harman, DVM, CEO and Founder of Vet-Stem, Inc.

About Vet-Stem, Inc. Vet-Stem, Inc. was formed in 2002 to bring regenerative medicine to the veterinary profession. The privately held company is working to develop therapies in veterinary medicine that apply regenerative technologies while utilizing the natural healing properties inherent in all animals. As the first company in the United States to provide an adipose-derived stem cell service to veterinarians for their patients, Vet-Stem, Inc. pioneered the use of regenerative stem cells in veterinary medicine. The company holds exclusive licenses to over 50 patents including world-wide veterinary rights for use of adipose derived stem cells. In the last decade over 10,000 animals have been treated using Vet-Stem, Inc.s services, and Vet-Stem is actively investigating stem cell therapy for immune-mediated and inflammatory disease, as well as organ disease and failure. For more on Vet-Stem, Inc. and Veterinary Regenerative Medicine visit http://www.vet-stem.com or call 858-748-2004.