| C O N T A C T | I M P R I N T | L E G A L P A G E | T E R M S / C O N D I T I O N S |  |
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| BIOGRAPHY | ||
| PIONEERING WORK | ||
| LASKER AWARD | ||
| ACCORD SYMPOSIUM | ||
| MEMBRANA BOOTH | ||
| NEPHROLOGY SEMINAR | ||
| VISIT WUPPERTAL | ||
FOR PRINT VERSION  |
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The Artificial Kidney
Encouraged by this 'haemodialysis', Kolff was determined to develop an artificial kidney that would be able to purify the blood in patients with renal failure and thus save their lives. Kolff's first experiments used sausage skins (then made of cellophane) instead of the thick colloid tubes and substituted heparin for the highly antigenic hirudin. Things were looking interesting when a new problem arose - the outbreak of war, soon followed by the occupation of The Netherlands by the Nazis. Kolff moved to the small town of Kampen and its 90-bed hospital, and managed to persuade a local enamel manufacturer to help him source the materials he needed to build his first prototype - the 'rotating drum hemodialyzer'. 130 feet of cellophane sausage skins were wrapped 30 times round a horizontal aluminium drum. As the drum rotated through a bath of salt solution in an enamel tank, the patient's blood was exposed to the dialysis fluid and toxic wastes were removed.
The dialysate brought other problems, including the alarming discovery that leaving potassium out of the electrolyte was likely to paralyse the patient. Machines to prepare dialysate could also prove risky - The Drake Willock machine had a copper heating coil, which unfortunately released copper into the fluid causing breakdown of red blood cells in the patient. Even as these problems (and many others) were gradually overcome, there was still the resistance of the medical profession to contend with. Kolff commented: 'In the beginning, the first remark by physicians when they heard about treating blood outside the body would be, "I would rather be dead." I never heard that remark from a patient.' Nor was the printed word much better. 'When articles were written', says Kolff, 'I remember one in the medical literature condemning the use of the artificial kidney. It was my routine not to respond. By that time I had seen the reversal of uraemia and the life-saving action of the artificial kidney so clearly that I trusted in the long run that the truth would become evident.' It is perhaps not surprising that success did not come immediately. Between 1943 and 1944 Kolff treated 16 patients with acute renal failure: all died. The 17th patient, a 67 year old woman called Sophie Schafstadt, was in a uraemic coma. After 11 hours of haemodialysis she regained consciousness. 'I bent over her and asked if she could hear me,' recalls Kolff. 'She slowly opened her eyes and said, "I'm going to divorce my husband." ' The artificial kidney had saved its first life. By the end of the war Kolff had developed five artificial kidneys, which he donated to hospitals in London, Poland, The Hague, Montreal and New York City. This act of generosity meant that doctors all over the world were able to learn the new technique of dialysis. Kolff also gave blueprints of the rotating drum hemodialyzer to the Peter Bent Brigham Hospital in Boston, USA. This led to the manufacture of the Kolff-Brigham Kidney, an improved stainless steel version of the original that made it possible for a major programme of dialysis to get under way. This in turn paved the way for the first kidney transplant in 1954. Kolff-Brigham kidneys were also vital during the Korean War in treating soldiers with post-traumatic renal failure. Kolff continued to work on renal replacement therapy on his arrival in the USA and the twin-coil artificial kidney he developed in 1956 was the first disposable artificial kidney, making dialysis possible all over the world. The Kolff kidney had proved a lifesaver for patients with acute renal failure, but there was still a problem with the huge numbers of patients suffering from chronic end-stage renal failure. These patients required repeated dialysis for the rest of their lives, but after just a few sessions the access sites to connect the patient to the machine became damaged and unusable. It was not until the invention of the Scribner Shunt in 1960 - a permanently installed U-shaped extension of the patient's circulatory system, which could be connected to the dialyser countless times without the need for new skin incisions - that regular dialysis for ESRD patients became a reality. It is fitting that Belding Scribner who invented this device recently shared the Lasker Award with Willem Kolff - together, the two men must have saved countless lives through their ingenuity. The Heart-Lung machine
Kolff and his colleague Dubbelman produced a number of different designs, including one based on the rotating drum artificial kidney. But Kampen was a small hospital and Kolff realised that there was little chance of these devices being employed there. In 1950 Kolff accepted an invitation to join the staff of the Cleveland Clinic Foundation in Ohio. Knowing that his artificial kidney had been better accepted in the USA than in Europe, and that more funding for research would be available, he accepted and he and his family emigrated. Kolff continued to develop and improve his artificial kidneys and in 1956 he unrolled one of his own twin-coil artificial kidneys in the halls of the clinic, took out the cellophane tubing and replaced it with polyethylene tubing, and rolled the coil up again. The polyethylene prevented ultra-filtrate leakage through the membrane but allowed adequate oxygenation and carbon dioxide exchange. This was the world's first clinically useful oxygenator for a heart-lung machine. Cardiologist Mason F Sones, interested in a membrane oxygenator for paediatric use, was one of the first to congratulate Kolff after seeing the machine tested on a puppy. The first human baby for whom the machine was used died, but the second and third babies survived, and a new world of possibilities had opened up. The experimental work on puppies also included the use of potassium to stop the heart and the introduction of the hear-lung machine led to the first consistently successful use of elective cardiac arrest during open-heart surgery. Procedures that could never have been dreamed of - let alone attempted - in the past now became common place, not only saving countless lives but also improving quality of life, for example through coronary artery bypass grafts. The Intra-Aortic Balloon Pump Of all the cardiac assist devices developed by Dr Kolff and his collaborators, the intro-aortic balloon pump is possibly the most widely used. Developed in his laboratory in 1961 by Dr Spyros Moulopoulos and Stephen Topaz, an estimated 2 million patients are treated with the balloon pump every year in the USA alone. Transapical to Aorta Left Ventricular Bypass Dr Kolff and his colleagues have developed a minimally invasive, novel approach to left ventricular bypass which could be particularly valuable for patients in acute heart failure. It can be inserted in a few minutes, without the need for a heart-lung machine. A small incision is made in the chest wall in the apex of the left ventricle, and a double lumen cannula is introduced through the left ventricle and into the aorta. The 8 mm cannula contains a tiny pump, which remains in the left ventricle, connected to an electric wire. This single pump is likely to be enough to sustain the patient for some hours at least, while in the meantime a second cannula can be introduced into the right atrium to bring blood from the right atrium out of the body to an oxygenator. From the oxygenator the blood flows to a second pump, and then back into the left ventricle via the original cannula, and thus into the aorta. While this system has yet to reach clinical testing in humans, the fact that it is so minimally invasive makes it an exciting prospect for heart failure patients. Dr Kolff has plans to make a model which uses a concentric double lumen cannula and a cylindrical oxygenator to be worn on the left side of the body, under the arm, close to the exit of the trans-apical cannula. Simple peritoneal dialysis Peritoneal dialysis is a relatively simple procedure that in theory can be carried out anywhere in the world, even in countries where there is little or no access to sophisticated medical technology and no funding to buy dialysis machines or commercial fluids. Heat sterilisation is the norm in such situations but it is not possible to heat sterilise a solution that contains calcium chloride, glucose and sodium bicarbonate - as Dr Kolff points out, you end up with caramel and calcium carbonate. He therefore developed a simple two-kettle system for sterilising the fluids in two separate containers, based on the two-compartment enamel tank used back in 1944 in Kampen, The Netherlands. An eight-litre and a two-litre kettle are used to sterilise the fluids on a domestic stove, and after cooling overnight the contents of the two kettles are mixed. The result is eight litres of sterile dialysis fluid which can be used for continuous ambulatory peritoneal dialysis. Subcutaneous Peritoneal Access Device (SPAD) Kolff's experience with peritoneal dialysis led him to develop the subcutaneous peritoneal access device, which made it possible for people with insulin-dependent diabetes to deliver insulin into the peritoneal cavity rather than injecting it into a limb, where high concentrations in the blood can cause long-term problems. From the peritoneal cavity, eighty percent of the insulin goes to the liver where it is needed. Dr Kolff recalls a woman patient in London, England who had to inject herself with thousands of units of insulin per day. When she changed to a SPAD, she was able to reduce her insulin dose dramatically, became pregnant and delivered a normal baby. Cadaver Kidney Transplantation Dr Kolff, with great help from Dr John P Merrill, started kidney transplantation at the Cleveland Clinic in 1960. At this time cadaver kidney transplantation had been almost completely abandoned because of the acute tubular necrosis that occurred in the kidneys of donors who had been dead for some time. However Kolff and his colleague Dr Nakamoto proved that vigorous dialysis of the recipient will reverse the tubular necrosis in the donated kidney, usually in a matter of weeks. In one case Dr Kolff recalls it took as long as 120 days, but the transplanted kidney then functioned for eighteen years. The Artificial Heart Soon after the development of the heart-lung machine, Dr Kolff turned his attention to the idea of a mechanical heart that could temporarily - or even permanently - replace a natural human heart. His first model was implanted in a dog in 1957. The dog lived only one and a half hours, but Kolff was not deterred. In 1967 he hired William C DeVries to help him work on the design and after some years they kept a sheep alive for 50 hours with one of their devices. One of the problems they encountered was the power source. Electricity didn't produce enough power, and Kolff next proposed a nuclear powered heart using a small piece of plutonium. Unfortunately the radiation given off by the plutonium would damage the patient's other organs, and there was a theoretical risk that if a group of people with plutonium powered hearts gathered together, they could cause a nuclear explosion… More options were required. Kolff realised that he was trying to solve two problems at the same time: that of developing a working mechanical pump, and that of inventing an implantable energy source. He decided to concentrate all his energy on the pump, and produced an artificial heart that ran on compressed air. This raised silicone diaphragms, which pumped blood out of the heart. When the compressed air stopped, the diaphragm collapsed and the heart re-filled with blood. The big disadvantage however was that the tubes supplying the compressed air had to stick out of the patient's chest, meaning that this system could only be used in a hospital. However the results were better - animals could now be kept alive for as long as a month. In 1971 Dr Kolff hired Robert Jarvik, then a medical student, to help with his research. Jarvik's father had died of heart disease so he was highly motivated, and had already developed a method of stapling body tissues together during surgery rather than the more time-intensive hand sewing that was the norm. In 1972 Kolff sent Jarvik to Dayton, Ohio to visit a company that had developed a reversible electric motor: Willem Kolff had decided to work on an electro-hydraulic heart. The National Institute of Health (NIH) had requested proposals for such a heart, which would pump a hydraulic fluid from the left to the right ventricle and vice versa, but was doubtful that the motor could be reversed rapidly enough. Kolff and his entire team went to Washington to demonstrate that they could reverse the motor 150 times per minute - but the contract was awarded to a rival team, Abiomed. Despite this setback, and with little funding, Kolff's Laboratory continued to develop the electro-hydraulic heart, with the help of Stephen Topaz. It has only one moving part, the impeller; the hydraulic fluid is saline, and it can pump 12 litres of blood per minute. The device is now commercially available and can be used as an artificial heart or as a left ventricular assist device (LVAD). It was the totally air-driven heart that captured the imagination, however, when it was implanted in 1982. Jarvik had helped to make Kolff's artificial hearts more efficient by replacing silicone diaphragms with polyurethane ones, and the size of the hearts was becoming more like that of a natural human heart. Dr Michael DeBakey in Pennsylvania, working with the Baylor-Rice Artificial heart Program in Houston, Texas, had beaten Kolff to the first human artificial heart implant with a device called the Baylor-Rice artificial heart. A patient with severe heart disease was kept alive with this device for three days, before receiving a donor heart. The heart developed by Kolff and Jarvik, however, was the first artificial heart designed to permanently replace the natural organ. It now weighed about the same as a natural heart - ten ounces - and used compressed air pumped through two six-foot tubes protruding from the patient's ribcage and connected to a large compressor that had to stay at the patient's side. Two years after permission was granted to Dr DeVries to implant the artificial heart - now called the Jarvik-7 - into a human patient, the right candidate was finally found. Barney Clark, a retired dentist from Seattle, received the Jarvik-7 on 1 December 1982, and lived for 112 days. Though he had many complications in that period, most of them did not relate to the artificial heart - and Kolff recalls that Clark maintained his considerable sense of humour, his zest for life, his desire to serve mankind and his love for his wife and family. The second recipient of the Jarvik-7 heart - an improved version with a much smaller, eleven pound compressor which could be carried round - was William Schroeder. DeVries and his team had gained valuable information from the experience with Barney Clark and although Shroeder suffered a number of small strokes caused by blood clots collecting in the artificial heart, he survived for almost two years. He is still the longest survivor on any permanent artificial heart. Work to develop better artificial hearts is still in progress. The air-driven artificial heart (first called the 'Jarvik', then the 'Symbion', and currently the 'Cardio-West' heart) is now mainly used as a bridge to donor heart transplantation when a donor organ is not immediately available, or when the patient is too severely ill to benefit from it. In such patients one in four will die when given a donor heart, but if treated with the artificial heart first to improve their condition, the success rate of the transplantation rises to over 95%. The Artificial Eye In 1968, Dr William Dobelle came to work in Dr Kolff's Laboratory at the University of Utah and instead of working on the artificial heart as he had intended was persuaded to begin work on an artificial eye. Together they proved the feasibility of an artificial eye using direct stimulation of the visual cortex. An array of electrodes made in Kolff's Laboratory in 1972 was implanted into a totally blind patient in Presbyterian Hospital in New York City, after which it was demonstrated that the patient was able to use it as a mobility prosthesis - he was able to recognise a cap on the wall, retrieve it and place it on the head of a mannequin. When the electrodes are stimulated, the appropriate area of the visual cortex responds according and the patient 'sees' a spot of light. The array of electrodes are connected to a pedestal screwed to the patient's skull, and from there to two computers. A map of the visual field for each person is made, to allow the operators to know exactly which electrode will stimulate which spot in the visual field. The computer can then stimulate the electrodes in such a way that the contours of objects can be created. The system has now been developed such that a blind person can wear a pair of glasses, containing on one side a camera that detects the distance of the object the person wishes to see. The other side of the glasses contains a small television camera. William Dobelle travelled with eight blind volunteers to Lisbon, Portugal, where neurosurgeons Dr Antonez, Dr Gervin and Dr Smith, all of whom had worked with Dobelle in the USA, implanted the electrodes. On their return home the visual field for each volunteer was mapped. One of the volunteers looked out of the window and recognised a motor car. He was even able to drive it - though he had to put his head out of the window in order to reverse. Since then three more totally blind people have driven open cars, and demonstrated that they could avoid mannequins placed strategically in a car park. The Artificial Ear Unlike the artificial eye that directly stimulates the cortex of the brain, the artificial ear developed in conjunction with Dr Donald Eddington stimulates the acoustic nerve via six platinum electrodes threaded up into the cochlea of the inner ear of the deaf patient. 60% of totally deaf people provided with the Utah artificial ear are able to have a telephone conversation, a truly remarkable feat. Dr Kolff is enthusiastic about the efficacy of the artificial ear: 'one totally deaf person is able to understand up to 85% of spoken words he has never heard before and without seeing the lips of the speaker. If he sees the speaker face to face, he can hold a near normal conversation. A visitor from Geneva was introduced to a totally deaf bearer of Dr. Eddington's artificial ear. The deaf man told the visitor that although he was from Geneva, his accent sounded as if he came from a German speaking part of Switzerland. Indeed, he came from Zurich.' The Artificial Arm The artificial arm and hand developed with Dr Stephen Jacobsen, a student of Dr Kolff's who became Head of the University of Utah College of Engineering's Center for Engineering Design and renowned as a 'robotics guru', is sensitive enough to peel an orange, and strong enough to crack a nut. Since it was made available in 1981, the Utah Artificial Arm has been the premier myoelectric prosthesis for elbow, hand and wrist, representing the most advanced combination of technology, superior performance and cosmetic appearance for above elbow amputees. Its movements are controlled by myoelectrical pickups attached to either the stump or the muscles of the shoulder girdle, so the arm moves as soon as the amputee thinks he wants to do something. Indeed, it was a particular problem to make sure that this quick moving arm would not knock out the teeth of its owner - so it slows down whenever it approaches the owner's lips. The Utah Artificial Arm now gives renewed dexterity to hundreds of amputees. The Wearable Artificial Lung Dr Kolff is currently, in his 90s, working on the development of a wearable artificial lung, for patients in the last distressing stages of pulmonary disease, when they are very short of breath. With a special cannula system and a very small pump, blood is sucked out of the left ventricle of the heart, passed through an oxygenator, and then returned to the aorta. Only the cannula system leading into the heart is inside the patient's body. The oxygenator comes in two forms. A cylinder device is already available, worn suspended from a girdle on the left side of the body. The oxygen tank and the driving console for the pump and battery can be placed on a small cart enabling the patient to move about relatively freely. A device currently at prototype stage uses a four-channel vacuum-formed housing containing capillary fibres made by Membrana: this can be worn suspended in a reinforced bra for women, or strapped at chest level for men. Dr Kolff is currently in discussions with Membrana GmbH to develop a smaller oxygenator so this device is likely to become an even more practical reality in the near future. The wearable artificial lung, which can make life bearable again for very ill patients, perfectly sums up Dr Kolff's attitude to all the extraordinary devices and developments for which he has been responsible. The main aim of Dr Kolff's endeavours has been, and still is, to restore people to an enjoyable existence. 'If it is not enjoyable, it should not be done.' |
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