Critical Limb Ischemia - Potential Solution and Treatment?

Medical Quarterly
Metro Magazine
August 2009
Duke Testing New Stem Cell Therapy
By Rick Smith


The name is not commonly known and is difficult to pronounce, but the disease afflicts an estimated 12 million Americans. It’s called critical limb ischemia. Treatments are lacking and often require amputation, but help may be on the way: A potential solution for people afflicted with diabetes and obesity who are facing amputation of a limb due to circulatory problems caused by ischemia is soon to begin clinical testing at Duke Uni versity.
The disease causes narrowing and hardening of arteries, thus reducing blood flow. If not treated, victims can suffer nerve and tissue damage. The disease can also trigger gangrene, which often requires amputation.
In lab tests on animals, the use of stem cells not only improved blood flow, but also grew new blood vessels. Dr. Chris Kontos, co-director of the Duke Heart and Vascular Group, will be coordinating the trial that focuses on the stem cell regime developed by Pluristem Thera peutics.
But these are not embryonic stem cells, which have created so much controversy within the medical community. Rather, Pluristem, an Israeli biotherapeutics company whose stock is traded on the Nasdaq, is pioneering the use of stem cells derived from the placenta.
“There is no good medical therapy for critical ischemia,” said Dr. William Prather, who is a consultant with Pluri stem and helped pick Duke as one of the sites for the test. “There are surgical therapies that can clean out the vessels, but there is no medication or procedure to grow new blood vessels around the obstruction. That is what we have proved in animals.”
Duke is currently enrolling subjects for the trials for the Phase I tests of Pluristem’s PLX-PAD solution. A similar trial will take place in Alabama. “Both locations have used other companies’ cells in the past, so they are familiar with stem cell therapy,” Prather said.
Allogeneic Method
Pluristem is working on a variety of products that would enable stem cell transplants between unrelated donors and patients. The concept is called allogeneic, or “taken from different individuals.” The company wants to treat both severe ischemic and autoimmune disorders; it recently received funding support from the Israeli government.
The Pluristem method is not the first to use stem cells as a potential treatment for ischemia, Prather pointed out. How ever, the other choice is stem cells taken from bone marrow. Placenta cells are much more widely available, less expensive and don’t require donors to go through the surgical process to extract cells from the hip.
“We don’t have to do any of that with our cells,” Prather explained. “Our cells come off the shelf, they are one size fit all, they come from material that is thrown away, and outpatients can be injected in a process that takes 30 minutes. They are observed for six hours and then sent home.”
In late July, the first patient was injected with the proposed treatment in a clinical trial in Germany being run in parallel with the US tests. As many as 12 patients will be injected, with a mix of smokers, diabetics and obese subjects to be tested in the US.
Phase I trials focus on safety. If the treatment is found to be safe, Phase II trials would begin. The US Food and Drug Administration granted Pluristem approval for the Phase I trials earlier this year.
The treatment is intended for victims of “late stage” ischemia who have not responded to other treatments or surgery and face the prospect of amputation. People selected for the trial will already have a condition related to ischemia, such as an ulcer or nerve pain.
All test patients will receive one injection and half will receive a second, Prather said. There will be no placebos. Pluristem will track both safety and efficacy data over a three-month period following the injections. Although the primary “end point,” or goal of the Phase I trial, is safety, Prather said doctors also will be able to track whether the patients show improvement.
“In animal trials, we saw improvement in blood flow in about three weeks,” Prather explained. “I’m not sure we can equate that to three weeks in humans, though. We could get efficacy in blood flow within a month or two months of injection.”
Even if the treatment proves safe and ultimately is granted FDA approval for sale, Prather pointed out the healing process would not be a quick one. “If these cells are going to be effective, blood flow improvement will be a matter of weeks and months, not inject today and improve tomorrow,” he said. “It just takes time for a new blood vessel to grow.”
Duke and Pluristem agreed to partner on the trial after Pluristem came in contact with Dr. Brian Annex, a former physician at Duke. “He is a world-renowned leader in angiogenesis (the growth of new blood vessels),” Prather said. “He was in transition at the time when we talked last year, and he recommended that we work with Dr. Kontos. Annex later joined the Pluristem Scientific Advisory Board.
“We are very excited about the possibilities,” said Kontos, who hopes for the first patient injections to be made by the end of August.

Peripheral Vascular Disease

There has to be knowledge in order to bring awareness...


From Wikipedia, the free encyclopedia


Peripheral vascular disease (PVD), also known as peripheral artery disease (PAD) or peripheral artery occlusive disease (PAOD), includes all diseases caused by the obstruction of large arteries in the arms and legs. PVD can result from atherosclerosis, inflammatory processes leading to stenosis, an embolism or thrombus formation. It causes either acute or chronic ischemia (lack of blood supply), typically of the legs.

Shammi Kapoor speaks about his battle with the little-known disease

By: Hemal Ashar Date: 2009-08-06 Place: Mumbai




Celebrities are notorious for keeping their guard up, not letting the world see that their star (literally) has dimmed, that they are human after all. So former star Shammi Kapoor deserves a double yahoo for letting his defences down and giving the world a peek into his frailties.

The actor was at the Breach Candy hospital on Tuesday afternoon, along with a clutch of doctors to raise awareness about peripheral vascular disease. The relatively little known disease occurs when there is a blockage of blood flow from the artery to organs other than the heart.


In familiar territory

The SoBo hospital is familiar territory for the actor, (also a kidney patient) who takes regular dialysis at the hospital. Shammi is also a Chronic Obstructive Pulmonary Disorder (COPD) sufferer, where his lungs have been compromised. He arrived in a wheelchair; and ribbed the docs at the press conference, "Ah, you all are wearing ties today." He then asked in jest, "What do you want me to talk about? The last time I winked at a girl? Okay, okay, I will tell you about my experience with vascular disease."

Lost toes

The flamboyant Kapoor was afflicted with the disease last year. He said, "I lost a toe on each of my feet to vascular disease. I was saved from losing my limbs by timely medical treatment." He then revealed how he heard the doctors who were operating on him in the operation theatre. "I was given local anaesthesia, so I could hear the docs speaking: "Here I found it, hey milaa vein, oh artery.

The pain was so bad, I started shrieking, an anaesthetist clamped my mouth shut." He said gesticulating wildly to laughter by the docs. The docs admitted that Shammi started bleeding while the operation was on and his thigh had swelled to twice the size, underlining the gravity of this disease.

Finally, Shammi when urged to give a message to mark Vascular Awareness Day on August 6, told people to take timely medical help, with the same flourish he delivered lines like Chahe koi mujhe jungli kahe on screen.

What is peripheral vascular disease?

Peripheral artery disease (PAD) is a heart condition similar to that of coronary artery disease and carotid artery disease. In PAD, the fatty deposits build up in the inner linings of the artery walls. These blockages restrict the blood flow circulation, mainly in arteries leading to the kidneys, stomach, arms, legs and feet.
In its early stages, a common symptom is cramping, or fatigue in the legs and buttocks during activity. Such cramping subsides when the person stands still. This is called “intermittent claudication.” People with PAD often have fatty buildup in the arteries of the heart and brain. Because of this association, most people with PAD have a higher risk of death from heart attack and stroke.
There are two types of these circulation disorders:
Functional peripheral vascular diseases don’t have an organic cause. They don’t involve defects in blood vessels’ structure. They’re usually short-term effects related to “spasm” that may come and go. Raynaud’s disease is an example. It can be triggered by cold temperatures, emotional stress, working with vibrating machinery or smoking.
Organic peripheral vascular diseases are caused by structural changes in the blood vessels, such as inflammation and tissue damage. Peripheral artery disease is an example. It’s caused by fatty buildups in arteries that block normal blood flow.
How is peripheral artery disease diagnosed and treated?
Techniques used to diagnose PAD include a medical history, physical exam, ultrasound, X-ray angiography and magnetic resonance imaging angiography (MRA).
Most people with PAD can be treated with lifestyle changes, medications or both. Lifestyle changes to lower your risk include stopping smoking, diabetes control and blood pressure. Become physically active; eat a low-saturated-fat, low-cholesterol diet.
PAD may require drug treatment, too. Drugs include medicines to help improve walking distance, antiplatelet agents and cholesterol-lowering agents (statins).

Alternatives to Amputation

Amputation of an arm or leg should always be a last resort. That’s why Florence Davis of Hillside, NJ sought the help of a talented team of doctors at Newark Beth Israel Medical Center in an effort to save her leg.

For over a year, Davis struggled with a persistent foot wound that restricted blood circulation in her leg. The problem became so severe that doctors were considering amputating the leg. However, the vascular specialists at Beth Israel had other plans for their 81 year-old patient. Doctors applied a new ultra-cold catheter technique to open several blockages in the arteries—a technique that would save her leg without any surgery.

If you’ve ever sough medical advice for the treatment of a wound, you know that wound care can be a tricky ailment that can often spiral into other diseases due to complications and infections. Davis suffered from peripheral artery disease (PAD), but wasn’t aware that the condition could be life-threatening and seriously debilitating. If left untreated, people who exhibit symptoms of PAD are four to five times more likely to get a heart attack or stroke. The pain in Ms. Davis’ foot became so severe that she could barely walk. To make matters worse, she got a cut on her toe that refused to heal, so she turned to the Advanced Wound Care and Hyperbaric Institute at Newark Beth Israel Medical Center for help.

Doctors began aggressive wound treatment, but tests show that she had three blockages in the artery that runs from her hip to her toe. Circulation had to be restored, but Davis was not a candidate for the traditional vascular bypass surgery that transplants blood vessels from a healthy limb to replace blocked vessels. The wound care specialists at Beth Israel referred Davis to Madhu Salvaji, DO, one of a handful of New Jersey doctors who uses the Polarcath system to treat patients. This sophisticated form of treatment combines cold therapy and angioplasty (a procedure that involves using a balloon to open clogged arteries) to help prevent future blockages.

“Cooling the blood vessel down to -10 degrees Celsius as the balloon is inserted in the clogged artery, causes targeted cell death and alters the new cells that will replace them, greatly reducing the chances of a future blockage,” explained Dr. Salvaji. Altogether, Dr. Salvaji opened three blockages using a combination of cold catheter, stent placement and artherectomy, a delicate process of removing plaque from the artery walls.

“All I had to do was lie still,” said Mrs. Davis about the three minimally invasive procedures that were performed in stages. Within two weeks, the swelling in her foot disappeared, her toe was healed and she was back to her daily walking, shopping, and gardening.

For more information about advanced wound care or treatment for peripheral artery disease at Newark Beth Israel Medical Center, please call 1-888-SBHS-123.

Peripheral Arterial Disease (PAD)

Peripheral Arterial Disease (PAD) is also known as atherosclerosis, poor circulation, or hardening of the arteries. PAD progresses over time at variable rates in each individual depending on the area of circulation effected and one's health and family history. The signs and symptoms of PAD may not arise until later in life. For many, the outward indications will not appear until the artery has narrowed by 60 percent or more.

One method the body uses to adapt to the narrowed arteries is the development of smaller peripheral arteries that allow blood flow around the narrowed area. This process is known as collateral circulation and may help explain why many can have PAD without feeling any symptoms.

When a piece of cholesterol, calcium or blood clot abruptly breaks from the lining of the artery or a narrowed artery blocks off completely, blood flow will be totally obstructed and the organ supplied by that artery will suffer damage. The organs in PAD most commonly affected and researched are the legs.

What happens if the disease worsens?

The severity of PAD depends on when it is detected and any pre-existing health factors; especially smoking, high cholesterol, heart disease or diabetes. In the later stages, leg circulation may be so poor that pain occurs in the toes and feet during periods of inactivity or rest. This is especially true at night. This is known as rest pain, which usually worsens when the legs are elevated and is often relieved by lowering the legs (due to the effects of gravity on the blood flow).

Critical Limb Ischemia

The most advanced stages of PAD can lead to Critical Limb Ischemia (CLI) . Here the legs and feet have such severe blockage that they do not receive the oxygen rich blood required for growth and repair of painful sores and even gangrene (dead tissue). This condition, if left untreated, may require amputation.

Workshop on Surgery cure for Peripheral Vascular Disease organised by Ruby Hall

(I-Newswire) - Workshop on Surgery cure for Peripheral Vascular Disease organised by
Ruby Hall
- Surgeries performed on five patients -
Pune, Tuesday 20th July 2009: In a bid to spread awareness about breakthrough treatments of Peripheral Vascular Disease ( PVD ), also known as Peripheral Arterial Disease, Ruby Hall had organised a day-long workshop recently.
The workshop, conducted under the supervision of Dr Bhagat Reddy from Georgia, USA. Dr Shirish ( M.S ) Hiremath, Dr Dhanesh Kamerkar and Dr Chandrashekhar Makhale actually performed Endo vascular procedures on five patients, who were suffering from PVD.
For cases of PAD, someone requiring surgery the newly developed device called the Frontrunner is now available which works in a similar way like an excavator, which bore through the mud and sludge causing the blockage. “It is like an angioplasty and a by-pass surgery performed on the leg,” says Dr Kamerkar.
Dr. Shirish ( M.S. ) Hiremath, Director, Ruby Hall Clinic said, “Lower limb PVD is a serious threat to the Indian population especially because of our susceptibility to Diabetes. Since people with diabetes frequently have high blood pressure and high cholesterol levels, it further accelerates the development of atherosclerosis. Given that PVD in diabetes is largely asymptomatic, patient education plays a key role in preventing major complications later. While 82,000 people have diabetes-related leg and foot amputations each year in India, timely treatment can significantly reduce this number”.

The new technique of surgery, prevalent in the West for a couple of years has now been brought to India to help patients who have a high risk of surgery. By the use of a Frontrunner, surgeons can avoid major cuts and incisions on the patient’s body and open up the blockage with just a puncture, as in conventional Coronary Angioplasty.
The workshop, which has already been held at major cities like Bengaluru, Hyderabad etc. aimed to instruct doctors about new tools and techniques that they can learn to deal effectively with the threat of PVD .
PVD, a widely prevalent, progressive atherosclerotic disease that carries a high risk of limb loss, stroke, and premature death, which can affect anyone. It occurs when the arteries ( blood vessels ) that supply blood to various parts of the body become narrow because of the buildup of fatty deposits on the inside walls of the blood vessels of the heart ( coronary artery disease ), brain ( cerebrovascular disease ) and kidney ( renal artery disease ). Because of this, people with PVD have a higher risk of heart attack, stroke or kidney failure.
Dr. Shirish ( M.S. ) Hiremath who has the largest volume of Angioplasties, explained how cardiologists have got involved in managing leg issues.” Basically the process of atherosclerosis ( aging of the arteries ) is same all over the body. Measures taken to avoid atherosclerosis help both “Heart and Health.” Also, with enormous expertise in Heart arteries, Dr. Shirish ( M.S. ) Hiremath, feels they are very adapt to performing leg Angioplasties.
The doctors warn that people with PVD, if not treated are likely to undergo amputation of the limbs. “If people have better tools available to them, the results in treating patients can improve drastically. Thus, the workshop is beneficial not just to doctors and a boon to patients suffering from PVD, but to the whole society at large,” acts Dr Kamerkar.
One of the patients, Suhas Patil, who got operated said, “ I was suffering from daibetes from a very long time but I was not aware of PVD. When the doctors informed me about it, I had lost all hopes. There are many such people like me who are not aware of such consequences Such kind of workshops should be organized on a regular basis to make people aware about the disease. I would like to thank all the doctors who helped me in understanding the effects of the disease and guided in the right direction.”