DEXTER C.

CORRALES, RN, RM
September 9, 2013

Stem Cell Treatments Overtake Science

personal miracle. (Some foreign operators offer creative variations on the theme, like cells from sharks and sheep.) Domestic providers, too, can push the limits. In July, for example, a former pathologist at the Medical University of South Carolina pleaded guilty to illegally processing and shipping stem cells for treatment without approval from the university or the Food and Drug Administration. The number of clinics and products has reached the point that scientists fear repercussions for their own work. Dr. Hesham Sadek of the University of Texas Southwestern Medical Center in Dallas, who is studying heart muscle regeneration, worries that the marketing deluge now makes it hard for patients to tell science from swindle, and all that lies on the spectrum in between. It really has the potential to undermine the legitimacy of the whole field, he said. Trial or Treatment? Even though Tijuana has perhaps 20 clinics offering adult stem cell therapy, Dr. Javier Lopez, founder of the Regenerative Medicine Institute, says it is his that has become the poster company to knock down. Born and educated in Tijuana, he has lived and worked across the border, in San Diego, for more than 30 years, mainly as a health care administrator. He became inspired by stem cells after accompanying a physician friend to a conference in Palm Springs, Calif., in 2008. It was eye-opening, he said. I immediately thought, This is the future of medicine, and I want to be a part of it.

By LAURA BEIL
TIJUANA, Mexico Maggie Alejos arrived here in June from St. Anne, Ill., with her husband, her daughter and a cashiers check for $13,500, payable to the Regenerative Medicine Institute. Rail-thin, with an oxygen tube anchored above her upper lip, Ms. Alejos, a retired Army nurse, has coped with emphysema for a dozen of her 65 years. Once she came close enough to a lung transplant that doctors prepared her for surgery, only to discover that the donor lung was unfit. At a hospital here, doctors affiliated with the institute extracted about seven ounces of fat from her thighs, hoping to harvest about 130 million stem cells and implant them in her failing lungs. Across the Internet where Ms. Alejos learned about the Tijuana institute adult stem cells are promoted as a cure for everything from sagging skin to severed spinal cords. On the surface, the claim is plausible. Scientists have discovered that fat, bone marrow and other parts of the body contain stem cells, immature cells that can rejuvenate themselves, at least in the tissue they are naturally found. But it has yet to be proved that these cells can regenerate no matter where they are placed, or under what conditions this might occur. Moreover, questions about safety remain unanswered. These sober realities do not appear to have slowed the rise of an international industry catering to customers who may pay tens of thousands of dollars in cash for their shot at a

He says he runs the institute within the accepted framework of clinical trials: Patients sign consent forms acknowledging that the treatment is experimental. Studies are registered with the National Library of Medicine in the United States. Being accepted for treatment requires more than cash. Protocols and procedures are approved by the institutional review board, or I.R.B., at Hospital Angeles Tijuana, and are administered by physicians at the hospital. The focus of our trial, from Day 1, has been safety, Dr. Lopez said. Still, skeptics in the United States are not convinced. Leigh Turner, a bioethicist at the University of Minnesota, says the Regenerative Medicine Institute blurs the boundary between trial and treatment. The institutes patient consent form would not pass muster with a competent American I.R.B., Dr. Turner said, and the testimonials on its Web site place the emphasis squarely on results. Moreover, studying patients who pay undermines the trials scientific validity, Dr. Turner said. The patient sample is skewed toward those with the means to travel, and their financial investment may amplify an already strong placebo effect. Dr. Lopez says that scientists in Mexico lack the government research support available in the United States, leaving establishments like his no choice but to charge patients. He agrees that many stem cell providers are dubious, and says he works with the Mexican authorities to try to establish uniform standards. As for his own institute, he said, Im very proud of what we are doing, and added, I get upset when people start talking trash about what is done south of the border.

A Gray Area In the United States, too, it is easy to conduct business outside government oversight, said Dr. George Q. Daley, who studies stem cells for blood diseases at Harvard Medical School. Close down one shady operation, he went on, and more seem to randomly pop up. Even questionable publicity does not necessarily hurt business. Regnocyte, a company in Florida, posted an unflattering CNN report about iton its Web site under the heading special coverage. If the stem cell business continues to flourish without proper scrutiny, Dr. Daley and others fear research progress will suffer. Clinical trials depend on patients who are willing to sign on even though they know they might be given a placebo, while competing clinics are offering what seems to be a sure thing. In addition, patients who have already had stem cell therapy could be ineligible for trials. And if too many patients try stem cells unsuccessfully, the public may come to see the entire field as a failure, said Dr. Sadek, the heart cell scientist in Dallas. Many comments on articles about his last paper, published in the journal Nature, were skeptical and jaded, he continued. One said, Ive gotten stem cell therapy and nothing happened. If the public loses faith in regenerative medicine in general, funding can be affected. A Lack of Data Beyond the online testimonials, there is little evidence to indicate whether adult stem cell treatments on offer are working. Paul Knoepfler, a stem cell researcher at the University of California, Davis, says the lack of data is vexing. There is absolutely no legitimate reason for such clinics to be not publishing their data, he wrote on his stem cell

blog this year. Yet they almost never do it.Stem cell businesses say they have other priorities. Im not that interested in doing a lot of research for publication purposes only, said Maynard A. Howe, the chief executive of Stemedica Cell Technologies in San Diego, which is developing a drug made from donated stem cells. Dr. Howe and his brother Roger started the company in 2005 after a sister-in-law received stem cells in Russia for a spinal cord injury. Dr. Howe says that his company publishes just enough data to meet F.D.A. requirements, but that he would rather his scientists spend their time getting a product to market. He also defends the practice of foreign trials largely on economic grounds. Outside the United States, he said, I can do a PET scan for $500, a fraction of the typical American rate. Why wouldnt I do my clinical trial overseas? For his part, Dr. Lopez says he is trying to publish data from the 125 patients he has treated so far, but he faces a struggle. Nobody wants to talk to us because we are from Tijuana, he said of medical journals. He has managed to get just a case description accepted for publication. So for now, he does not have much to show in the way of science. He believes in stem cells and in that, he and

his critics share common ground. The challenge for scientists is to promote the promise of stem cells with both excitement and restraint. It can be a hard line to walk. I understand how difficult it is how many years and sometimes decades it takes before you discover a new therapy, said Dr. Daley, of Harvard. We have a tremendous enthusiasm about the potential of stem cell therapy. That said, these arent magical agents that run around your body and fix things. Its frustrating to watch other people who, even well intentioned, arent acting in their patients best interest. This week, the International Society for Stem Cell Research is to release a statement declaring the use of stem cells outside scientific settings to be a threat to patient welfare, patient autonomy and to the scientific process, according to its public policy chairman, Jonathan Kimmelman, a bioethicist at McGill. This is the same group that once tried to offer an online guide to stem cell clinics, but the journal Nature reported that the effort was abruptly abandoned under threat of lawsuits.

Acute Pancreatitis Overview

Acute pancreatitis is sudden swelling and inflammation of the pancreas. CAUSES The pancreas is an organ located behind the stomach that produces chemicals called enzymes, as well as the hormones insulin and glucagon. Most of the time, the enzymes are only active after they reach the small intestine, where they are needed to digest food. When these enzymes somehow become active inside the pancreas, they eat (and digest) the tissue of the pancreas. This causes swelling, bleeding (hemorrhage), and damage to the pancreas and its blood vessels. Acute pancreatitis affects men more often than women. Certain diseases, surgeries, and habits make you more likely to develop this condition. The condition is most often caused by alcoholism and alcohol abuse (70% of cases in the United States). Genetics may be a factor in some cases. Sometimes the cause is not known, however. Other conditions that have been linked to pancreatitis are: Autoimmune problems (when the immune system attacks the body) Blockage of the pancreatic duct or common bile duct, the tubes that drain enzymes from the pancreas Damage to the ducts or pancreas during surgery High blood levels of a fat called triglycerides (hypertriglyceridemia) Injury to the pancreas from an accident Other causes include: Complications of cystic fibrosis Hemolytic uremic syndrome Hyperparathyroidism Kawasaki disease Reye syndrome Use of certain medications (especially estrogens, corticosteroids, thiazide diuretics, and azathioprine) Viral infections, including mumps, coxsackie B, mycoplasma pneumonia, and campylobacter

SYMPTOMS The main symptom of pancreatitis is abdominal pain felt in the upper left side or middle of the abdomen. The pain: May be worse within minutes after eating or drinking at first, especially if foods have a high fat content Becomes constant and more severe, lasting for several days May be worse when lying flat on the back May spread (radiate) to the back or below the left shoulder blade People with acute pancreatitis often look ill and have a fever, nausea, vomiting, and sweating. Other symptoms that may occur with this disease include: Clay-colored stools Gaseous abdominal fullness Hiccups Indigestion Mild yellowing of the skin and whites of the eyes (jaundice) Skin rash or sore (lesion) Swollen abdomen EXAMS AND TESTS The doctor will perform a physical exam, which may show that you have: Abdominal tenderness or lump (mass) Fever Low blood pressure Rapid heart rate Rapid breathing (respiratory) rate Laboratory tests will be done. Tests that show the release of pancreatic enzymes include: Increased blood amylase level Increased serum blood lipase level Increase urine amylase level

Other blood tests that can help diagnose pancreatitis or its complications include: Complete blood count (CBC) Comprehensive metabolic panel Imaging tests that can show inflammation of the pancreas include: Abdominal CT scan Abdominal MRI Abdominal ultrasound TREATMENT Treatment often requires a stay in the hospital and may involve: Pain medicines Fluids given through a vein (IV) Stopping food or fluid by mouth to limit the activity of the pancreas Occasionally a tube will be inserted through the nose or mouth to remove the contents of the stomach (nasogastric suctioning). This may be done if vomiting or severe pain do not improve, or if a paralyzed bowel (paralytic ileus) develops. The tube will stay in for 1 - 2 days to 1 - 2 weeks. Treating the condition that caused the problem can prevent repeated attacks. In some cases, therapy is needed to: Drain fluid that has collected in or around the pancreas Remove gallstones Relieve blockages of the pancreatic duct In the most severe cases, surgery is needed to remove dead or infected pancreatic tissue. Avoid smoking, alcoholic drinks, and fatty foods after the attack has improved. OUTLOOK (PROGNOSIS) Most cases go away in a week. However, some cases develop into a life-threatening illness. The death rate is high with: Hemorrhagic pancreatitis

Liver, heart, or kidney impairment Necrotizing pancreatitis Pancreatitis can return. The likelihood of it returning depends on the cause, and how successfully it can be treated. POSSIBLE COMPLICATIONS Acute kidney failure Acute respiratory distress syndrome (ARDS) Buildup of fluid in the abdomen (ascites) Cysts or abscesses in the pancreas Heart failure Low blood pressure Repeat episodes of acute pancreatitis can lead to chronic pancreatitis. WHEN TO CONTACT A MEDICAL PROFESSIONAL Call your health care provider if:

You have intense, constant abdominal pain You develop other symptoms of acute pancreatitis PREVENTION You may lower your risk of new or repeat episodes of pancreatitis by taking steps to prevent the medical conditions that can lead to the disease:

Avoid aspirin when treating a fever in children, especially if they may have a viral illness, to reduce the risk of Reye syndrome. Do NOT drink too much alcohol. Make sure children receive vaccines to protect them against mumps and other childhood illnesses (see: Immunizations - general overview). REFERENCES Banks PA, Freeman ML; Practice Parameters Committee of the American College of Gastroenterology. Practice guidelines in acute pancreatitis. Am J Gastroenterol . 2006;101:2379-2400. Frossard JL, Steer ML, Pastor CM. Acute pancreatitis. Lancet . 2008;371:143-152. Owyang C. Pancreatitis. In: Goldman L, Ausiello D, eds. Cecil Medicine . 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 147.