Sunday, November 8, 2009

Welcome back to the NH Pediatric Cardiology blog

We had seen some of the Nobel achievers in Cardiology. We would see the final instalment of this now.

American physician Dickinson Woodruff Richards Jr was born in 1895 in Orange, New Jersey. He received a B.S. degree from Yale University in 1917. Following service in the United States Army in World War I (1914-1918), he entered the College of Physicians and Surgeons of Columbia University, receiving an M.D. degree in 1923. Richard's association with Columbia as a researcher and professor of medicine began in 1928 and continued until his retirement in 1961, after which he became Emeritus Lambert Professor.
In the early 1930s Richards teamed with André Frédéric Cournand at New York's Bellevue Hospital, one of Columbia's teaching facilities, to investigate the interrelated functions of the heart, lungs, and circulatory system. One of Richards's key objectives was to measure precisely the changing levels of oxygen and carbon dioxide in blood as it circulated through the heart and lungs. Richards and Cournand had read of the experiments of Werner Forssmann, who a few years earlier had experimented with cardiac catheterization on himself. Richards and Cournand refined Forssmann's work, performing catheterization first on animals and then, in 1941, on humans. The ability to place a sensing device directly into the heart, where it could be safely left for hours, provided a wealth of new information on heart and lung function. Exact concentrations of carbon dioxide and other gases could be determined in specific locations of the heart. They made it possible to obtain precise measurements of blood pressure and blood volume in the heart and lungs. Richards and his collaborators gained new insight into many disorders such as those caused by malfunctions in the heart's valves. Later, during World War II (1939-1945), they performed crucial research on how the heart, lungs, and blood are affected by shock in reaction to injury.
Through his improvements to the procedure of cardiac catheterization, Richards greatly advanced the knowledge of how the heart and lungs function. Cardiac catheterization was an obscure and largely untried procedure before Richards and his colleagues refined it into the essential diagnostic tool. For their advancements in cardiac catheterization and circulatory system functions, Richards and French American physiologist André Frédéric Cournand were awarded the 1956 Nobel Prize in physiology or medicine, which they shared with German surgeon Werner Forssmann.
Richards also made important studies of the effects of the drug digitalis, given to patients to stimulate a weakened heart.

André Frédéric Cournand , the French-born American physician was born in 1895 at Paris. He received his B.S. degree from the Sorbonne, University of Paris, in 1913. He remained there to begin his medical studies, which were interrupted by World War I (1914-1918). After service in the French Army during the war, Cournand resumed his medical studies, finally receiving his M.D. degree in 1930. He then moved to the United States and an internship in the Columbia University division of Bellevue Hospital in New York City. In 1934 he joined the teaching staff of the Columbia College of Physicians and Surgeons, remaining there until his retirement in 1964. He became a U.S. citizen in 1941.
In the 1930s Cournand, along with his colleague Richards, set out to study how the heart, lungs, and circulatory system work together as an integrated unit. They believed that the technique of cardiac
catheterization, pioneered in Germany a few years earlier by Werner Forssmann, might provide the best tool for their research. Forssmann had demonstrated the safety of inserting a catheter into the heart by performing such procedures on himself. Cournand and Richards worked to improve Forssmann's procedure by experimenting with catheterization on laboratory animals. Within a few years, they had advanced the technique considerably, demonstrating that a catheter could remain in the heart for hours without harmful effect. The way was open to experiment with the procedure on humans. In 1941 Cournand and his colleagues performed their first catheterization on a human patient. Very soon, as their research progressed, their findings were providing a wealth of information on cardiopulmonary function and the interrelated action of the heart and lungs. For example, the catheter permitted the drawing of blood from directly inside the heart, providing samples that had never before been available. Using devices on the tip of the catheter, the researchers could also make precise readings of blood pressure, and measurements of oxygen and carbon dioxide in the circulating blood as it moved through the heart and lungs. Later Cournand and his colleagues used catheterization to study how the heart, lungs, and blood function during the state of shock brought on by traumatic injury. In short, the work of Cournand and his collaborators did much to clarify the workings of the heart and circulatory system in healthy subjects as well as in those suffering from cardiopulmonary disorders. Today cardiac catheterization remains an essential tool in cardiology.
Cournand and his colleagues helped clarify many important aspects of how the heart and lungs function. For their advances, Cournand and American physician Dickinson Woodruff Richards, Jr. received the 1956 Nobel Prize in physiology or medicine, which they shared with German physician Werner Forssmann.
In addition to the Nobel Prize, Cournand's other distinctions include the prestigious Albert Lasker Basic Medical Research Award of the American Public Health Association in 1949.

German physician Werner Forssmann was born in 1904 at Berlin. He completed his medical training at that city's Friedrich Wilhelm University in 1929. He then joined the Eberswalde Surgical Clinic near Berlin, where his key experiments with catheterization took place. Later in his career, as a surgeon specializing in urology, Forssmann was associated with hospitals in Berlin, Dresden, and Düsseldorf.
At Eberswalde, Forssmann was convinced that methods for diagnosing heart disorders and for injecting drugs directly into the heart could be improved. Having read earlier accounts of cardiac catheterization in laboratory animals, he began experimenting with this technique on human cadavers. In 1929 Forssmann performed a cardiac catheterization on himself as its first trial in a living human. Inserting a catheter into a vein in his arm, he pushed the tube up the vein until it entered the right side of his heart, where he observed it by means of a fluoroscope.
After continuing his research, Forssmann published a summary of his findings in 1931. The German medical establishment, however, refused to accept the validity of Forssmann's work, regarding his
experiments as stunts rather than as legitimate research. After being dismissed as a charlatan, Forssmann abandoned his catheterizaton experiments and in 1932 began training as a urological surgeon. Meanwhile, physiologists in the United States, including Cournand and Richards, read Forssmann's writings and continued to develop cardiac catheterizaton, achieving unprecedented insight into the workings of the heart and lungs. For his contribution to cardiac catheterization, Forssmann was jointly awarded the Nobel Prize in physiology or medicine along with French-American physiologist André Frédéric Cournand and American physician Dickinson W. Richards in 1956.

British pharmacologist Sir James Whyte Black was born in 1924. Working at the King's College Medical School in London, he developed several drugs for treating peptic ulcers and heart disease. Black shared the 1988 Nobel Prize in physiology or medicine with American biochemists Gertrude Belle Elion and George Herbert Hitchings.
Propranolol was the drug created by Black and his research team in 1964, binds to beta-receptors. Usually these beta-receptors bind to epinephrine and norepinephrine, hormones that stimulate the heart. For heart patients, too much stimulation of the heart is dangerous, and propranolol relieves this stress. Propranolol is also used to treat heart attacks, high blood pressure, and migraine headaches. Today this class of drugs is known as a beta-blocker. Black also developed cimetidine, for the treatment of ulcers.
In 1981 Black was knighted by Queen Elizabeth II of England for his service to medical research.

American chemist Gertrude Belle Elion was born in 1918 at New York city. Elion received an M.S. degree from New York University and began her long tenure (1944-1983) at the Burroughs Wellcome pharmaceutical company at the height of World War II (1939-1945). Before the 1940s few women worked as scientific researchers, but the war afforded more opportunities for women as men were called to the battlefront. At Burroughs Wellcome, Elion teamed up with American chemist George Herbert Hitchings. Together, they developed many drugs that have been proven effective against previously untreatable diseases. Elion and Hitchings shared the 1988 Nobel Prize in physiology or medicine with British pharmacologist Sir James Whyte Black.
Elion and Hitchings compared the functioning of normal human cells with that of bacteria, viruses, and cancer cells in order to find ways to inhibit or kill harmful invading cells without damaging healthy body cells. Elion and Hitchings concentrated on how cells synthesize the building blocks of deoxyribonucleic acid (DNA) called nucleotides. They successfully blocked the manufacture of new DNA in harmful cells; this stopped the cells from multiplying. The researchers accomplished this feat by developing chemical compounds that would fill in for key nucleotides. Because different sequences of nucleotides are manufactured by different cells, Elion and Hitchings were able to fabricate compounds that would attack the DNA only of the dangerous cells.
Over nearly four decades of research, Elion and Hitchings developed drugs for the treatment of many diseases and conditions, including cancer, malaria, leukemia, herpes, gout, heart disease, autoimmune diseases, bacterial infections, and transplant rejections. Their techniques are now standard in the pharmaceutical industry, but were revolutionary in the 1940s when they were first developed.
After her retirement in 1983, Elion taught, held various advisory positions, and continued consulting for the Burroughs Wellcome Company. In 1991 President Bush presented Elion with the National Medal of Science.

American pharmacologist Robert F. Furchgott was born in 1916 at Charleston, South Carolina, Furchgott earned his bachelor’s degree in chemistry in 1937 at the University of North Carolina and completed his doctoral studies in 1940 at Northwestern University in Illinois. Since 1956 he has been a professor in the Department of Pharmacology at the State University of New York (SUNY) Health Science Center in Brooklyn. In 1988 he earned the title of Distinguished Professor at the center. He is now Distinguished Professor Emeritus.
Furchgott helped demonstrate that nitric oxide (NO), a molecule produced in the form of a gas in the cells of humans and other life forms, can act as a signaling molecule. Signaling molecules are released by cells and transmit messages to other cells. Furchgott found that messages transmitted by NO play essential roles in the regulation of blood pressure and other cardiovascular functions.
His contributions opened an active field of research into the properties and actions of NO. This research has shown that NO is involved in many physiological processes, including memory and other nervous-system functions, as well as certain responses of the immune system to infection.
Furchgott’s breakthrough studies with NO can be traced to the late 1970s, when he investigated the relaxation of smooth muscle in the blood vessels of rabbits. He discovered that the blood vessels would not dilate unless the inner cellular lining of the vessel—a layer called the endothelium—was intact. He surmised that the endothelial cells produced a substance that acted as a signal to the smooth muscle cells surrounding the blood vessels, causing the muscles to relax and the vessels to dilate. Furchgott called this hypothetical agent endothelium-derived relaxing factor (EDRF). He then set out to identify this signaling molecule.
Meanwhile, other researchers were working on pieces of the same puzzle. Among them was American pharmacologist Ferid Murad, whose work at the University of Virginia and at Stanford University had demonstrated that nitroglycerin and other so-called vasodilators cause blood vessels to dilate by releasing NO. During the early 1980s, Furchgott began working on the theory that EDRF and NO were identical. At the time, the NO molecule was known primarily as an air pollutant resulting from the burning of nitrogen, for example, in fumes from automobile exhaust, and Furchgott’s theory seemed farfetched. Nevertheless, he officially proposed the theory at a meeting of biomedical scientists in July 1986. Another American pharmacologist, Louis J. Ignarro of the University of California, Los Angeles, who had been working independently of Furchgott, made the same proposal at the meeting. Subsequent research supported their theory.
Scientists have since intensively investigated NO and its properties. Now NO is known to play many roles in the body. Some types of brain cells, for example, communicate by releasing or receiving NO. White blood cells of the immune system release the gas to fight bacterial infection. Among its many cardiovascular functions, NO is involved in the blood flow involved in penile erection. The drug Viagra, which has helped millions of men overcome impotence, owes its success in part to the NO research sparked by Furchgott.
In 1998, the importance of Furchgott’s work was acknowledged with science’s highest honor, the Nobel Prize. Furchgott shared this prize with Ignarro and Murad. Furchgott’s other distinctions include the Gairdner Foundation International Award in 1991, the Wellcome Gold Medal from the British Pharmacological Association in 1995, and the Albert Lasker Basic Medical Research Award, which he shared with Murad in 1996.

American pharmacologist Louis J. Ignarro was born in 1941 at Brooklyn, New York. Ignarro earned his bachelor’s degree in pharmacy from Columbia University in 1962. He earned his Ph.D. degree in pharmacology in 1966 from the University of Minnesota. Between 1979 and 1985, Ignarro was a professor in the pharmacology department at the Tulane University School of Medicine in New Orleans, Louisiana. Since 1985 he has been a professor in the Department of Molecular and Medical Pharmacology at the University of California, Los Angeles, School of Medicine. Ignarro’s research helped solve a mystery first uncovered in the late 1970s by American pharmacologist Robert F. Furchgott. Furchgott noted that blood vessels would expand, or dilate, only if a specific cellular layer surrounding the vessels—the endothelium—was intact. He proposed that cells in the endothelium released a chemical factor that caused smooth muscle cells around the vessel to relax, with the result that the vessel would dilate and blood flow would increase. Ignarro set out to identify this agent, which Furchgott had named endothelium-derived relaxing factor (EDRF).
Ignarro’s experiments led him to suspect that EDRF might be the gas NO. The prospect seemed unlikely because at the time NO was known primarily as an air pollutant. Ignarro pressed on with his research,however, and at a meeting of biomedical scientists in 1986, he officially proposed his theory that EDRF was NO. Furchgott, who had independently pursued the same theory, presented the same proposal at the meeting. Subsequent research supported their conclusion. In the years following Ignarro and Furchgott’s discovery that EDRF and NO were the same substance, interest in NO virtually exploded. Based on the increasing knowledge of NO and its actions, scientists are pursuing new therapies for heart disease, cancer, septic shock, and other diseases. Even the celebrated anti-impotence drug Viagra owes a debt to Ignarro’s work. Viagra increases the blood flow in the penis, helping to produce an erection.
In 1998 Ignarro’s discoveries were honored with the Nobel Prize in physiology or medicine. He shared the prize with Furchgott and the American pharmacologist Ferid Murad, who had also achieved insights into NO’s cardiovascular function. He helped illuminate the cardiovascular role of nitric oxide. Ignarro was among the first to suggest that NO serves as a molecular signal—a substance that is released by one cell and influences the function of another cell. He also helped identify NO as a crucial agent in the process by which blood vessels widen, or dilate. Scientists now recognize that NO not only regulates blood pressure and other cardiovascular functions but also plays a role in many other processes. These processes are helping the body fight bacterial infection and sending messages between cells in the nervous system.
Other honors received by Ignarro include the Merck Research Award in 1974 and the Lilly Research Award in 1978.

American physician and pharmacologist Ferid Murad was born in 1936 at Whiting, Indiana. He earned his medical degree in 1958 from the medical school at Western Reserve University (now known as Case Western Reserve University). He remained at that institution to complete a doctoral degree in pharmacology, awarded in 1965. Murad has since held academic posts at the University of Virginia School of Medicine, Stanford University, and Northwestern University Medical School. During the early 1990s he served as a corporate officer in two Illinois-based biotechnology companies—first at Abbott Laboratories, and later at Molecular Geriatrics. In 1997 he returned to academic medicine by joining the faculty of University of Texas Medical School at Houston. In 1977, while at the University of Virginia, Murad sought to determine the physiological mechanism by which the drug nitroglycerin helps relieve heart-related chest pain. He found that nitroglycerin and related drugs produce NO in the cells surrounding blood vessels. The NO acts as a signal to other cells, causing the smooth muscle tissue in blood vessels to relax. In the process, the vessels dilate, or widen, increasing the flow of blood. In 1978, Murad formally published his theory that NO is a signalling molecule.
Since Murad’s initial discoveries, the investigation of NO has become an extremely active area of biomedical research. Scientists now recognize that NO is involved in many processes, such as the action of the nervous system and the immune system. Based on this knowledge, new treatments are being developed for heart disease, septic shock, and other diseases. In 1998 Murad received the Nobel Prize in physiology or medicine for his discoveries related to NO. He shared the award with American pharmacologists Robert F. Furchgott and Louis J. Ignarro, who had independently performed key NO research during the early 1980s. His work helped to demonstrate the role in the body of nitric oxide (NO), a gas produced in the cells of humans and other organisms. Murad determined that NO is a signaling molecule—a molecule that transmits messages from one cell to another. Murad investigated the action of NO in the blood vessels of the cardiovascular system. Thanks to extensive research that his findings helped to stimulate, scientists now know that NO plays a role not only in blood pressure and other cardiovascular functions but also in many of the body’s systems.
Murad has also been honored with the Albert Lasker Basic Medical Research Award, which he shared with Furchgott in 1996.

The above list is nowhere complete and exhaustive. They serve only as a matter of information, so that it helps in generating further interest.

On a personal note, our latest meeting on academic publication was a mixture of many sentiments! Although we were all falling short of our given deadlines, there were many who had completely forgotten about their assignment! Few of the team who have left for their future to other places also were not spared. An immediate phone call went to them so as to remind them of their due responsibility! Everyone enjoyed the plight of the other, till their turn came in! Just hope if we had one tenth of enthusiasm of our boss, Dr Sunita. Sometimes I feel how long we would take to match the energies of Dr Sunita!

What are the options in cTGA with VSD, PAH with Ebsteins malformation of TV with severe TR in a 2-month-old? Everything depends on how repairable the TV is. Is the age OK for any kind of repair? What would the plan B be? Let me know your take on it.

We have often come across the VSD and PDA with severe PAH in the same patient. When the VSD shunts bi-directional, the PDA would be predominantly left-to-right in the absence of PS. How to explain this analogy? Is it only the color dominance or any other explanation also exists?
We often come across masses in RA. Are they always pathological? Some of them may be thrombi or fungal mass. Sometime back, we had seen an organized mass in the RA. If it is of an acute origin, does it always require medication even in the absence of systemic symptoms and signs? Any guidelines?

Rheumatics continue to pose both diagnostic and therapeutic challenges. Not every child fulfils the Jones criteria. Many a times, parents would not be intelligent enough to observe and recall the symptoms. There are no clear cut guidelines on diagnosing RHD on echo. The impaired mobility of PML is not always found. Sometimes, children would fulfil Jones criteria, but the heart would show normal mobility of PML with regurgitant mitral valve. The involvement of aortic and mitral valves together in a young child also poses diagnostic challenges. The problems of third world find no guidelines on a regular basis.

Please send your inputs. Feel free to send it to my email drkiranvs@gmail.com I shall post it on your behalf.

Regards

Kiran

2 comments:

  1. Dr Amit Misri, who was a consultant and a team member at NH has placed his views on the VSD and PDA enigma we placed in the recent post. He says,
    "Regarding the shunting in VSD &PDA, I think it is because the diastolic pressure difference b/w the ventricles is little and it equalises early while there is significant diff in diastolic pressure B/w aorta & PA which takes time to equalise and till that time the PDA shunt is predominantly L-R"

    But, what is surprising is that the color difference we have noted is not exclusively diastolic; on the contrary, it is more often systolic. Although Dr Misri has an important and valid point, the explanation still has few more facets to reveal.

    Thanks to Dr Amit Misri for that explanation. More thanks to him for continuing to see the blog!

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