LASERS AND TCAD UPDATE
FDA Announces Approval of PLC Laser Therapy
Laser May Reduce Chest Pain When Drugs, Surgery Fail
A new surgical laser system will offer an alternative for patients whose severe and frequent chest pain doesn't respond to traditional therapies.
FDA approved in August the Heart Laser System to treat people with coronary heart disease whose angina (chest pain) cannot be adequately controlled by medicine or effectively treated with balloon angioplasty or other surgical methods. (See "Balloons, Lasers and Scrapers: Help for Hearts and Blood Vessels" in the April 1991 FDA Consumer.) For use only by specially trained surgeons, the laser makes tiny holes in areas of the heart muscle with inadequate blood flow.
Clinical studies showed that 72 percent of patients treated with the laser reported significant reduction in angina pain, an effect that remained when patients were followed up one year later. Only 13 percent of angina patients treated with medicine alone reported the same reduction in pain. Patients were not studied beyond a year.
Risks associated with the laser treatment include major heart arrhythmia's (irregular heartbeat), which affected 10 percent of patients in the study, and early death, affecting 3 percent of patients in the study within one month of the procedure. Because of these risks, patients who plan to undergo treatment with the Heart Laser System must sign an informed consent form.
Overall death rate one year after the procedure was performed was similar for patients who received the laser treatment and patients who did not. The treatment had no effect on the progression of heart disease. At FDA's request, the manufacturer, PLC Medical Systems Inc., of Franklin, Mass., will conduct a follow-up study to gather additional information on death rates and long-term benefits related to the laser system.
How the laser treatment works is not understood, but it may relate to reduction in perception of pain, formation of new small blood vessels, or increased blood flow to the heart.
FDA News and Updates
It must be noted here that there are two systems for treating TCAD using lasers. There is the PLC system which literally punches tiny holes through the heart muscle as described in the January '96 issue of UpBeat. In addition there is the C02 assisted laser used from within the heart to literally "blast" away plaque accumulations. Now please remember, it is from amateur material such as right here that rumors of "cures "for TCAD begin. By the time a patient gets to a point whereby one of these treatments might be considered, it's not in any way a cure, but rather a case by case consideration of what might extend quality of life just a bit longer.
The following are abstracts from the most recent research work with the Heart Laser System and the C02 Laser used in place of balloon angioplasty:
Application Of Solid-State Pulsed-Wave, Mid-Infrared Laser For Percutaneous Revascularization In Heart Transplant Recipients.
Topaz O; Bailey NT; Mohanty PK, Medical College of Virginia
J Heart Lung Transplant, 1998 May, 17:5,505-10
BACKGROUND: Severe allograft coronary artery disease is a significant cause of death in heart transplant recipients. Percutaneous revascularization has thus far been attempted with balloon angioplasty and, to a lesser extent, with directional atherectomy. The new, investigational, solid-state pulsed-wave mid-infrared laser (holmium:YAG) can vaporize and remove atheromatous and thrombotic plaques. This mechanism of plaque ablation may be useful for allograftcoronary artery disease associated with focal stenoses deemed unsuitable for standard balloon angioplasty, especially thrombus-containing lesions.
METHODS: Five adult heart transplant recipients with severe focal stenoses related to allograft coronary artery disease underwent six laser angioplasty procedures. Lasercatheters (2.1 micron, 250 to 600 ml, 5 Hz) varying from 1.2 mm to 2.0 mm delivered 45+/-7.4 pulses(mean+/-SD).Five laser procedures were completed with adjunct balloon angioplasty and one with directional atherectomy.
RESULTS: Laser success (defined as stenosis reduction > 20%, no cardiac catheterization laboratory or in-hospital major complication) was achieved in six of seven lesions (85%), and the overall (laser and adjunct balloon) procedural success rate was 100%. No major complications occurred. Laser-assisted angioplasty reduced mean stenosis from 90% +/- 3% to 9% +/ - 11%. All five patients recovered and were discharged. Angiographic follow-up demonstrated a 50% restenosis rate.
CONCLUSIONS: In selected heart transplant recipients laser-assisted angioplasty can provide safe and successful acute revascularization. Focal lesions considered "non-ideal" for balloon angioplasty and, in particular, thrombotic lesions can benefit from application of this device; however, long-term reduction of restenosis rates is not expected from this modality.
Minimally Invasive Direct Coronary Artery Bypass Grafting Without Cardiopulmonary Bypass In Revascularization Procedures In Patients With Transplant Coronary Artery Disease.
Patel VS, Colley DA et al, Texas Heart Institute at St. Luke's Episcopal Hospital, Houston
Eur J Cardiothorac Surg, 1997 May, 11:5,895-901
OBJECTIVE: To assess the efficacy of revascularization in cardiac transplant patients who developed de novo coronary artery disease.
METHODS: Eighteen patients underwent one or more of four methods of revascularization: percutaneous transluminal coronary angioplasty (PTCA),percutaneoustransluminalcoronary rotational atherectomy (PTCRA), coronary artery bypass grafting (CABG), and transmyocardial laser revacularization (TMLR). Eleven PTCA procedures were performed in 10 patients 55.3 +/- 6.6 months after transplantation. Six patients underwent PTCRA 83.3 +/- 11.2 months after transplantation. Five patients underwent CABG 54.0 +/12.6 months after transplantation; the mean left ventricular ejection fraction was 49.6 +/- 16.9 (20-65%); hypertrophy was present in two of these patients. One patient with distal coronary artery disease and New York Heart Association class IV symptoms underwent TMLR only. One patient underwent both CABG and TMLR because of triple vessel proximal disease, diffuse distal disease, and New York Heart Association class IV symptoms.
RESULTS: PTCA was successful in 10 procedures with decrease in mean stenosis from 87.7 +/ - 2.7 to 24.3 +/- 6.0%. Follow-up, at 16.9 +/- 4.0 months, showed restenosis in two patients. PTCRA was successful in all patients with a decrease in mean stenosis from 83.4 +/- 4.4 to 11.7 +/- 1.9%. Short-term follow-up did not reveal reocclusion. Two CABG patients who had hypertrophy died of heart failure 2 and 9 days after their operations. One CABG patient with excellent cardiac function died after 15 days because of pulmonary failure. In one patient, left ventricular ejection fraction improved from 35 to 50%, and he is alive 64 months later. Six months after TMLR, the New York Heart Association class in one patient improved from IV to II, and his left ventricular ejection fraction improved from 29 to 42%. The ejection fraction in the patient who underwent both CABG and TMLR improved from 20 to 56% but the patient expired 7 weeks later.
CONCLUSIONS: It appears that revascularization procedures can be effective in patients with coronary artery disease after cardiac transplantation and that coronary angioplasty or atherectomy would be a therapy of choice for single proximal lesions. CABG should be used cautiously and only reserved for patients with multi-vessel disease without hypertrophy. Laser revascularization with or without bypass grafting has potential to become the therapy of choice for transplant coronary artery disease.
End Stage Coronary Disease Treated With The Transmyocardial CO2 Laser Revascularization: A Chance For The 'Inoperable' Patient.
Vincent JG et al; Herz-Zentrum Bodensee, Kreuzlingen, Switzerland. Eur J Cardiothorac Surg, 1997 May, 11:5,888-94
OBJECTIVE: The aim of this study is to evaluate the short and mid-term efficacy of the Transmyocardial High Power CO2 Laser Revascularisation (TMLR) as a last resource method for end-stage coronary disease patients.
METHOD AND PATIENTS: The High Power CO2 Laser 800 W Heart Laser (PLC Medical Systems) was used since February 1994 to treat 268 patients. In 52% of the cases (140) the indication for TMLR treatment was virtual inoperability by the classical bypass revascularisation. In the other 128 patients (48%), where only an incomplete revascularisation was expected, the TMLR was combined with a feasible bypass revascularisation (CABG). Of all patients, 71% were operated on 1-5 times before and or treated by several percutaneous transluminal coronary angioplasty (PTCA). All patients were sufferers of angina pectoris and most were classified Canadian Cardiac Society (ccs) 3-4, despite the maximal medical treatment. The ejection fraction was normal in 13% of patients only, and in 47% of them it was below 40% (10-68%).
RESULTS: The operation itself was generally well tolerated. We lost only one patient at the table. The hospital survival was 89.2%; 88.2% in the combined group and 90.3 % in the TMLR only group. After the routine follow up screening 3, 6 and 12 months postoperatively (262 patients-131 TMLR and 131 TMRL/CABG), 40% of the TMLR patients upgraded into the functional class CCS 0-1; the combined group of patients scored up even in 84%. All considering their quality of life to be 'better than years ago'. The ergomerry stress test, impossible for most of them before, became feasible and better in 80% of the patients. In the follow up period of the combined group, another 6 (4.7%), and in the TMLR only group, 12 (9.4%) patients died.
CONCLUSION: The short and middle term results of this--until now the largest single institution series of TMLR treated patients-were that patients almost without exception were refused for any kind of surgery by several other centres; this shows an acceptable survival rate and a surprising level of pain relief, increased activity and better quality of life then ever expected. In our experience, TMLR is a suitable method for treatment of end stage coronary disease, if all standard measures, medical therapy, PTCA and redo coronary re-vascularisation possibilities are exhausted. The favourable results imply the question as to whether this method will become an alternative for a second bypass operation in the future. The TMLR as an alternative for heart transplant is already a reality for some of our patients.
MAINSTAY ANTI-GRAFT REJECTION DRUG CAUSES CANCER
CYCLOSPORINE'S TUMOR PATHWAY IN ORGAN TRANSPLANT RECIPIENTS SPELLS GOOD NEWS FOR THERAPY.
By David N. Left Science Editor
No one knows what legendary surgeon first said, "The operation was a success, but the patient died." That epitaph certainly applied to the early decades of Organ transplantation, beginning with the first experimental kidney grafts in 1954. Those pioneer organ recipients succumbed not so much to the surgery as to its aftermath: organ rejection by an outraged immune system. Early immunosuppressant drugs either failed to prevent rejection, or worked all too well at knocking out the patient's shield against lethal infection. This grim Catch-22 held back the entire field of organ transplantation, until the cusp of the 1980s.
In 1975, immunologist Jean Borel, at the then Sandoz Pharma AG, in Basel, Switzerland, discovered a compound synthesized by a fungus named Tolypocladium inflatum Gams. Borel was looking for an antibiotic; instead, he discovered an immunosuppressant with a difference. Rather than clobbering a mouse's entire immune defenses, this novel fungal metabolite - which Sandoz called cyclosporine - inhibited only one subset of one arm of the immune system, namely T lymphocyte helper cells. It left transplant recipients with a decent modicum of immune protection against invading pathogens, while sparing donor organs from instant or delayed graft rejection. Cyclosporine became, and remains, a mainstay of organ transplantation, enabling the field to move boldly from replacing one kidney (where its opposite number served as a safety net) to liver, heart, bone marrow and eventually multiple-organ replacement.
In December 1983, the FDA approved its use as a standard concomitant of organ transplantation. To be sure, cyclosporine had one serious side effect- kidney toxicity. Transplant surgeons had to tailor its dosage to minimize this risk of kidney failure without unduly courting the danger of graft rejection. (See BioWorld Today, June 10, 1998, p. 1) Now, a different consequence of cyclosporine administration has surfaced, in yesterday' s issue of Nature, dated Feb. 11, 1999. The paper' s title spells out the drug' s unsuspected effect: "Cyclosporine induces cancer progression by a cell-autonomous mechanism." Its senior author is transplant physician Manikkam Suthanthiran, at Cornell University's College of Medicine, in New York. He is chief of transplant medicine at the Cornell-affiliated New York Presbyterian Hospital. However, his paper is not a wake-up call to abandon cyclosporine as a premier safeguard against organ rejection. Cyclosporine's Cancer Connection? Not To Worry "We think this is not a cause for alarm," Suthanthiran told BioWorld Today. "It would be terrible if transplant patients read this and get worried. We think our finding is actually a reason for hope, in the sense that there may a metabolic pathway we might want to block.
In particular, inhibiting the hyperexpression of transforming growth factor-beta (TGF-b) may be useful to prevent cancer progression. "And this may not be just for organ transplantation alone," he continued. "In other types of cancer, if the tumor cells make a lot of TGF-b, it may be a way by which a cancer cell evades the immune system." Suthanthiran and his co-authors propose that cyclosporine generates excessive concentrations of TGF-b, "It's a very important cytokine in terms of wound repair," he said. "An excess can give you trouble. In the mouse, when you knock out the TGF-b gene, the animal dies within two to three weeks, of a fatal multifocal inflammatory disease.
But TGF-b is not all bad. I think of it as being like blood pressure. If you have the right levels of TGF-b, it's very beneficial, whereas an excess is harmful. Hypertension or hypotension are both bad; normal blood pressure is good. TGF-b is like that."
Malignancies Common After Transplants "Malignancy is a common and dreaded complication following organ transplantation," the Nature paper starts off. Transplant teams, the article points out, commonly attribute these invasive and aggressive cancers to impairment of the organ recipient's immune surveillance system, which patrols the body for invading antigens. The Cornell co-authors report "a mechanism for the heightened malignancy that is independent of host immunity," and attributable to the effects of cyclosporine. "I think cyclosporine is a very useful drug," Suthanthiran declared. "It has improved patient and graft survival. We are not suggesting that cyclosporine increases the incidence of cancer. What we are suggesting is that maybe the reason transplant patients get cancer is that it, and drugs like it, suppress the immune system, which then is not able to fight the cancer.
Even if a transplant candidate has a past history of cancer, unless he or she is two years free of malignancy, that patient will not be transplanted. "Clearly," he continued, "transplant recipients get more cancer. A recent study showed that 10 years after receiving new organs, maybe 13 percent have a neoplasm, and that risk increases with time. By 15 years, it's 20 percent, and 20 years out, 40 percent. Most of these malignancies are skin cancers, and in these patients, tumors tend to be more aggressive." He said the increased cancer risk "is not very peculiar to cyclosporine alone.
A number of pre-cyclosporine immunosuppressants, such as prednisone and imuran, were also associated with an increased incidence of cancer in transplant patients. In many such cancers, physicians would reduce or stop the immunosuppressive therapy. And that's a double-edged sword, because maybe it would cause the tumor process to regress, but it may be bad for the transplanted organ. Because when you put in a transplant, most recipients require lifelong antirejection therapy." Suthanthiran and his co-authors injected SCID-beige mice, which lack an intact immune system, with human cancer cells, then administered cyclosporine.
"Those tumors obviously grew in these mice," he recounted. "Then, when we treated them with cyclosporine, the number of their tumors went up. Typically, we counted 100 tumor nodules in untreated mice, and 150 nodules in the treated ones." They were able to block this increase, using an antibody to TGF-b. "We interpreted this effect to mean," Suthanthiran said, "that the increase in TGF-b expression, its concentration, contributed at least in part to the rise in tumor nodule number. Because the mice were immunodeficient, this was not a conventional mechanism people think about.
The immuno-surveillance theory holds that your T cells and B cells are keeping the cancer in check. These mice didn't have T cells or B cells or natural killer cells." The Cornell transplanter sees his team's finding as "a new mechanism for cancer progression. We have several ideas how best to inhibit the excess expression of TGF-b, perhaps better than the antibody we reported in the paper. Blocking it may be beneficial to organ recipients, and also to other cancer patients. There may be gene-therapy approaches as well," Suthanthiran concluded, "and other drug candidates that can can block this expression. That's what we plan to do."
BIOWORLD Today, Feb 12, 1999 v 10 i29 p 1
Contributed by M. Porter, Woodbridge, VA (Editor's Comment: Dr. Suthanthiran says,"It would be terrible if transplant patients read this and get worried." It just leaves one speechless, as to how a doctor of medicine could get that far removed from reality. Patients are real people, not statistics, and it's today's patients who are dying doctor, not the next gene ration! Of course we'll worry, thank you very much, but don't let that foul up your study!
Extrapulmonary TB More Common in Heart Recipients.
By Charles W Henderson
Researchers in Spain report the impact of tuberculosis following heart transplantation.
Three cases of tuberculosis occurred in a series of 410 heart transplant recipients in a Spanish hospital, representing a rate of 0.73 percent. Twenty-eight cases reported in the literature were also reviewed.
"In most series reported, tuberculosis occurred in a small percentage of heart transplant recipients, the average rate being 1.25 percent," R.M. Munoz and colleagues wrote ("Three Cases of Tuberculosis of Heart Transplantation in Spain," European Journal of Clinical Microbiology and Infectious Disease, November 1998;17(11);:801-806).
"Compared to the general population, a higher percentage (28 percent) of extrapulmonary and disseminated forms of the disease is seen in these patients. Although a cure without recurrence can usually be achieved with a conventional antituberculous antibiotic regimen, the disease is still associated with a significant mortality rate of I 1 percent."
The corresponding author for this study is R.M. Munoz, Department of Internal Medicine I, Clinica Puerta de Hierro, Madrid, Spain.
Tuberculosis & Airborne Disease Weekly, Feb 15, 1999
Heart Transplant Recipients Have High Rate Of Skin Cancer, Study Finds
Transplant News, Feb 14, 1999 v9 i3 pNA
Australian investigators have confirmed that the high rate of skin cancer previously reported in kidney transplant patients also occurs in recipients of heart transplants.
The cumulative incidence of skin cancer in 400 heart transplant patients was 31% at 5 years and 43% at 10 years, reported Colin Ong, MD of the Skin Cancer Foundation in Darlinghurst and coinvestigators in the January issue of the Journal of the American Academy of Dermatology. Overall, the researchers documented 1,426 skin malignancies--the majority on the head and neck--in 152 of the patients. Squamous cell carcinomas outnumbered basal cell carcinomas by a ratio of 3:1, and after the fourth follow-up year, skin cancer was cited as the cause of 27% of the 41 deaths recorded in the group.
Both older age at transplantation together with length of follow-up correlated significantly with both the number of cancers at different sites as well as the subtypes of cancers. "Our findings reinforce the need to conduct regular skin examinations of heart transplant patients, so that lesions can be treated early," the authors conclude.
Among kidney transplant recipients in Queensland, skin cancer rates of 45% 11 years following transplantation and 70% 20 years after surgery have previously been reported.
Novaills: Cyclosporine Benefits Outweigh Potential Risks
Zurich (Dow Jones 2/12/99)--Pharmaceutical giant Novartis AG (Z.NOV) said Friday the benefits of its transplant drag cyclosporine far outweigh the potential risks associated with immunosuppressive therapy.
"Patients alarmed by reports based on a recent article in Nature, which implies that cyclosporine may change the behavior of existing cancers, should be reassured that hundreds of thousands of patients worldwide have been benefiting from cyclosporine for years," Novartis said in a press release.
Cyclosporine is a drug given to transplant patients to prevent organ rejection and is also used to treat arthritis. Physicians treating organ transplant patients have been well aware for more than 20 years that the mechanism or action which prevents organ rejection can also suppress other immune responses such as the defense mechanisms against some cancerous cells, Novartis said.
"This connection with immunosuppresants was identified before the advent of cyclosporine," Novartis said.
Novartis is one of the world's largest life sciences groups with leading positions in its fields of activity including pharmaceuticals, crop protection, animal health and clinical nutrition. In 1998, Novartis Group posted CHF31.7 billion (Swiss Francs) in sales.
sangStat Vows to Fight AntiCompetitive Actions of Novadis
by Business Editors and Health/Medical Writers
Menlo Park, Calif.--(BW HealthWire)--Feb. 11, 1999--SangStat, The Transplant Company (Nasdaq:SANG), today reiterated its intentions to continue to market the company's recently approved formulation of the immunosuppressive drug cyclosporine, SangCya(tm), and seek approval for additional dosage forms. SangStat's announcement is in response to two lawsuits filed by Novartis Pharmaceuticals Corporation on February 11, 1999, one against the Food and Drug Administration alleging that the FDA did not follow its own regulations in approving SangStat's SangCya in October 1998, and one against SangStat alleging infringement of a cyclosporine technology patented by the Swiss pharmaceutical company. SangStar believes that both suits are without merit.
"This action by Novartis was expected, given its $1.3 billion of worldwide revenue they are trying to protect, and the growing recognition by transplant physicians and recipients of the value of SangStat's offering lower cost therapies," said Philippe Pouletty, MD, SangStat Chairman. "We intend to defend our position vigorously. We believe that the lawsuits against the FDA and SangStar are without merit. They are yet another attempt by Novartis to preserve its monopoly in the marketplace to the potential detriment of transplant recipients who require lifelong treatment with this expensive lifesaving medication."
Jean-Jacques Bienaime, President and CEO noted, "Novartis attempted in 1998 to block the approval of SangCya by filing a citizen's petition with the FDA. The FDA denied Novartis petition on November 2, 1998. We are confident that Novartis' latest action will also fail, and that the transplant community will ultimately be the winner." The lawsuit against the FDA appears to be based on arguments similar to those used in the failed citizen's petition in which Novartis alleged that because Neoral and SangCya, both oral solutions, are based on different formulation technologies, they should be classified as different dosage forms.
On October 31, 1998 the US Food and Drug Administration (FDA) granted marketing clearance and an AB (bioequivalent) rating to SangCya(TM) (Cyclosporine Oral Solution, USP (MODIFIED), 100 mg/mL) for prevention of rejection in solid organ transplant recipients. This rating allows pharmacists to substitute SangCya(TM) for the brand drug Neoral. SangCya(TM) is SangStat's proprietary formulation of cyclosporine. SangCya was also approved in the United Kingdom on January 28, 1999.
SangStat's patent position
The United States Patent and Trademark Office has issued two separate patents owned by SangStat, Patent No. 5,766,629 (June, 1998) and Patent No. 5,827,822 (October 1998), covering SangStat's proprietary cyclosporine formulation technology for developing multiple formulations and dosage forms of cyclosporine including SangCya. SangCya is the company's first cyclosporine product covered by these patents.
The lawsuit filed by Novartis claims that SangStat's product employs a cyclosporine technology invented and patented by Novartis. According to the Novartis press release the patent involved does not cover Neoral but rather an alternative cyclosporine delivery system invented by Novartis.
Based on current pricing, SangCya is significantly cheaper than Neoral, and could potentially save recipients, transplant centers, and healthcare payers, including Medicare, as much as $'1.00 million per year.
Cyclosporine first became available in 1983, and proved to be a significant advance in transplant medicine. The "composition of matter" patent on cyclosporine expired in September 1995, patents covering the process Novartis uses to manufacture the bulk drug substance and patents for the manufacture of multiple formulations remain in effect. These patents relate to Novartis' own products; however they do not cover all other means to make cyclosporine formulations.
More than 240,000 recipients of organ transplants in the US and Europe require daily lifelong treatment with immunosuppressive medication to prevent graft rejection. Cyclosporine is the most commonly prescribed immunosuppressive drug used to prevent rejection of transplanted organs. Currently, it is marketed by Novartis as Sandimmune(R) and Neoral(R) and by SangStat as SangCya(TM). Combined worldwide Novartis sales of cyclosporine exceeded $1.3 billion in 1998. The cost to patients and payers for immunosuppressive therapy currently is estimated at between $9,000 and $12,000 in the first year following transplant and approximately $7,000 to $10,000 annually thereafter.
I've said it before and as would be expected nothing came of it, but it's that time of year again and NOTDAW just doesn't cut it with me. Is there not a better, kinder, more revealing acronym to represent National Organ and Tissue Donor Awareness Day? Is it possible we could go with ODAD, or how about just DAD? Maybe NOD Day? Hey how 'bout that-"Give a NOD to organ and tissue donors."
Just the other day I was doing my thing on the ergometer, ah ha, didn't know I was a deviate did you? Anyway, a nice lady next to me, doing the same thing, finally said,"Aren't you the man who writes for the newspaper about gout?" I thought immediately to myself, "Egad, I know I' m dull as a stone, but a newspaper column about gout? No way."
"Well," she continued," you sure look like him and I just wanted to thank him for curing me." Without expanding too much further, although to say she recognized me after the radiation of my neck is really stretching potential reality (Wow that' s really an in-house pun!), she was referring to black cherry extract and UpBeat's recommendation for it' s use to relieve gout. Now where she got it I don't know, because it's been a long time since we last mentioned it, but she was good for yet another sworn testimony that it does indeed work. Next time you get gout, which is common in transplant recipients, try a couple of teaspoons of black cherry extract twice a day until it's relieved, which can be as quickly as two days. It' s a much more pleasant solution than the transplant center prescribed colchicine with the dosage being, "Take it until the bathroom feels like a second home."
There was a piece on the news this past week about placebo surgery. Apparently in good scientific medical modeling they are now carrying out actual surgical procedures without the key element, just to see if it might be the surgery itself that caused the hoped for improvement, or failure. For instance, the example shown was a new "cure" for Parkinson's disease - they went right ahead and drilled holes in the patient's head, but then closed them up again without inserting whatever device was being tested. Can you imagine being hospitalized waiting for a heart transplant; being rushed to the operating room; and then awaking the next morning with all the tubes and scars of the real thing; only to be told it was just a test - a part of a study to see whether a new Igloo cooler design would keep the new heart cool enough until the moment of transplant, as well as two Cokes and a sandwich for the harvesting technician.
I received a bright red postcard telling me about a new book on Transplantation that is supposed to reveal "the other side". The thing that intrigued me was that a web site was given as the place to get the book (www.1stbooks.com). Being "surfer" of the first order, upon arrival at the site I was somewhat surprised to learn that one doesn't order the book there, one downloads the book from there. Now sad to say, because in no way do I intend to pan a book I haven't even read, I paid my $4.95 via secure credit card transaction and downloaded the book. Unfortunately, my computer refused to look at it upon arrival, so they sent it again, which didn't please my computer any better. So, I have an entire book stuck in my computer somewhere. Maybe one of our fellow computer user readers can do better. (Ed Note: The name of the book is: Transplant - The Other Side and it comes in Adobe Acrobat or MicroSoft Word 97 formats)
Pigs Grown With Human Genes
By Pat Eaton-Robb - Associated Press Writer
NEW HAVEN, Conn. (AP 2/22/99)--At a top-secret farm hidden in the Northeast, scientists are growing pigs whose DNA has been altered with human genes.
It sounds like the stuff of science fiction, yet officials at Alexion Pharmaceuticals Inc. say they are close to figuring out how these pigs can figure in the treatment of human organ failures, spinal cord injuries and illnesses such as Parkinson's disease.
The idea of transplanting animal parts to humans, called xenotransplantation, isn't new. But, until recently, nobody knew how to keep the human body from rejecting the organs.
About 18,000 organ transplants are performed in the United States each year and more than 40,000 patients are waiting for donor organs, according to the United Network for Organ Sharing. About 10 Americans die each day waiting for transplants, network officials say.
Alexion' s first altered pigs, created with the help of researchers at Virginia Tech in the early 1990s, contained a human gene called CD-59. Scientists hoped the grafted gene would trick the human body' s immune system into believing that the pig parts were human.
While transplanted organs from those pigs were able to survive for a couple of days in their new host, the body eventually rejected the parts. A major breakthrough came last year when the small biotechnology firm, working with scientists in Australia, figured out a way to alter a sugar-like molecule in pig cells so that human antibodies would not recognize it as foreign.
The molecule had been acting as a magnet for human antibodies, betraying the fact that the transplanted tissue was not human. Alexion quickly patented the process.
"If you now take cells from those animals and challenge them with human serum, they are almost indestructible in the lab," said Stephen P. Squinto, the chief technology officer at Alexion.
Scientists at Alexion have already transplanted brain cells from their transgenic pigs into rodents with asyndrome similar to Parkinson' s, a degenerative nerve condition that affects motor function. The transplanted cells not only survived, they became neurotransmitters in the animals' brains and helped correct the tremors, Squinto said. The same experiments are now being conducted in baboons. If those experiments work, Alexion hopes to begin human trials by the end of the year. Researchers hope that within 15 years humans will be able to receive permanent organ transplants from swine.
The company also has seen remarkable results by transplanting cells from a pig's snout into the damaged spinal columns of rodents, Squinto said. The cells replace the damaged protective sheath around the spine and allow nerve cells to regenerate.
"Would we expect that we will be able to take a person who is a paraplegic and have them walking or running in the Olympics?"
Squinto said. "No, I don't think that's the case. But restoring some function to that person is certainly a goal."
Xenotransplantation faces stiff opposition from some in the medical community and from animal rights activists. Alexion was unwilling to allow a reporter or photographer to visit their facilities, in part because they could be targeted by animal rights protesters.
Among the medical concerns: the fear that transplanted organs could bring with them new diseases caused by viruses now living only in pigs. A virus originally transmitted from chimpanzees to humans is believed to have caused AIDS.
Because a transplant patient's immune system is suppressed with drugs, xenotransplantation provides an ideal environment for pig viruses to mutate, said Dr. Thomas Murray, director of the Center for Biomedical Ethics at Case Western Reserve University.
"There are risks to third parties here," he said. "If you get an organ from a cadaver, you decide whether to accept that risk for yourself. But if you get an organ from a pig, many more people are put at an unknown risk."
The FDA had temporarily banned animal to-human transplant experiments because of pig viruses, but dropped the ban late in 1997. Scientists now believe they have identified all the so called retroviruses that are unique to pigs and can screen for them, Squinto said.
Dr. David Hull, director of the clinical transplant program at Hartford Hospital, is excited by the idea of farms filled with transplantable organs. The technology could dramatically improve the lives of thousands of people, many of whom can no longer even get out of bed because their own hearts or livers are failing, he said.
"You'd be able to meet the needs of everybody," he said. "You would save a tremendous amount of money and lives."
But animal rights activists say they whole process is unnecessary. Rather than killing animals for organs, they suggest everyone be considered an organ donor unless they specifically request an exemption, the opposite of the current policy.
"That is the way to save a lot of money, and it would save a lot of suffering," said Sandra Larson, with the New England Anti-Vivisection Society.
(Ed. Comment - There's gloom and doom enough in this issue, but didn't l hear somewhere recently the pig barn burned down and most were lost?)
Japan Hails Historic Heart Transplant
By Elaine Lies
TOKYO, March 1 (Reuters) - Japan on Monday hailed its first legal heart transplant from a brain-dead donor as a brave step forward in catching up with other industrialized countries, where such transplants have been carried out for decades.
"We wish this day had come sooner, but there were some unavoidable procedural questions," said Hikaru Matsuda, who led the team that performed the procedure in Osaka.
Preceded by decades of controversy, the historic transplant followed debate last week over whether the donor was legally brain dead, which was not established until Sunday. -;
"I conducted the operation thinking of the many deceased people who fought illness and wished for transplants," Matsuda told a news conference.
The recipient, a man in his 40s, was in stable condition on Monday. Operations to transplant the liver and kidneys from the donor, a 44-year old woman who had been in a coma after suffering a stroke, were successfully completed early on Monday morning.
Transplants of her corneas could be carried out later on Monday, Japanese media said.
"Life for four, sight for two," said the daily Tokyo Shimbun, adding in an editorial: "This is an important first step in regaining the Japanese public's trust towards the idea of organ transplants."
Japan's last heart transplant, carded out in 1968, led to murder charges against Dr Toshiro Wada, who performed the surgery at Sapporo Medical College Hospital on Japan's northernmost main island of Hokkaido.
A court dismissed the charges against Wada, but the case fostered public suspicion about medical ethics.
Public debate about whether death occurs when the heart stops beating or when the brain stops functioning has been further roiled by cultural beliefs that one's body should go into the afterlife intact.
The country's Organ Transplant Law, passed in 1997 after years of debate, requires an unequivocal donor statement expressing the wish to donate organs, along with family consent and two separate tests to determine brain death.
Abiomed Replacement Heart Passes 'Reliability' Test...
NEW YORK (Dow Jones 2/11/99)--Abiomed Inc. (ABMD) said the second pilot production lot of its implantable replacement heart passed a reliability test for use in some bridge-to transplant indications.
In a press release Thursday, the company said it plans to begin initial human trials in 2000. The test is designed to show the product's durability under simulated physiological conditions.
Actual use of the product requires Food and Drug Administration approval.
Abiomed makes cardiovascular products.
Donors must be over 15 years old and children under six cannot legally be declared brain dead, which several editorials mentioned as topics for further discussion.
Another issue raised on Monday was how to preserve the privacy of future donors and recipients.
Japanese media coverage, including scores of reporters camping outside the hospital, was so frenzied that the family almost backed out of their decision.
Calling for a balance between protecting individual privacy and providing transparency to ensure operations are carried out correctly, a Yomiuri Shimbun newspaper editorial said: "Respecting the rights of the family is crucial because we do not want to deter people from donating organs."
New Kidney Transplant Drug
BASEL (Dow Jones 3/4199)--Swiss pharmaceuticals group Roche Holding AG (Z.ROC) said Thursday that its drug Zenapax, which prevents the rejection of transplanted kidneys, has won European Union approval.
The drug blocks only immune cells that a transplanted kidney activates in patients, unlike other anti-rejection medicines that suppress the entire immune system, Roche said.
In two major studies involving 535 kidney transplant patients, Zenapax reduced rejection when used in combination with other drugs and didn't increase serious side effects, Roche said.
"Because Zenapax is a humanized monoclonal antibody, the body is less likely to recognize it as foreign," Roche said.
The company said the drug, which is already available in the US and ten other markets, could generate sales of CHFI00 million a year from 2004.
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