Karl Link and Warfarin

Karl Paul Gerhard Link (31 January 1901 - 21 November 1978) was an American biochemist best known for his discovery of the anticoagulant warfarin.



In the subsequent years, most of his research focused on plant carbohydrates. However, the most fruitful period began when Ed Carson, a Wisconsin farmer, attracted Link's attention to sweet clover disease, described in 1924 by veterinarian Frank Schofield. In this condition, cows bled to death after consuming hay made from spoilt sweet clover. Carson's stock had been affected, and he brought a dead cow, blood that would not clot, and 100 pounds of sweet clover hay. Under the direction of Link, PhD students Harold Campbell, Ralph Overman, Charles Huebner, and Mark Stahmann crystallised the putative poison - a coumarin - and synthetised and tested it; it turned out to be dicumarol (3,3'-methylenebis-(4 hydroxycoumarin)).



Dicumarol was subjected to clinical trials in Wisconsin General Hospital and the Mayo Clinic. It was for several years the most popular oral anticoagulant.


Warfarin, one of the several compounds synthesised as part of the coumarin research, was patented in 1945 with the Wisconsin Alumni Research Foundation, Link and researchers Stahlmann and Ikawa jointly owning the patent. Initially marketed as rat poison, warfarin would later, in the 1950s, become the second most important anticoagulant for clinical use (after heparin).

Neisser and the flow of seed

Neisseria gonorrhoeae, a gram-negative intracellular diplococci, was identified in 1879 by the German physician, Albert Neisser, and is the causative agent of gonorrhea, one of the oldest recognized sexually transmitted diseases.

The term "gonorrhea" is derived from the Greek language and literally means "flow of seed"; this term was used to describe the white milky appearance of the purulent urethral discharge, which was mistaken for semen.


Neisser was also the co-discoverer of the causative agent of leprosy. In 1879 the Norwegian physician Gerhard Armauer Hansen gave to young Neisser (who had visited him in Norway to examine some 100 leprosy patients) some tissue samples of his patients. Neisser successfully stained the bacteria and announced his findings in 1880, claiming to have discovered the pathogenesis of leprosy. There was some conflict between Neisser and Hansen, because Hansen had failed to culture the organism and demonstrate unequivocally its link to leprosy, although he had observed the bacterium since 1872.

Charles Richard Drew and Blood Transfusion

Charles Richard Drew (3 June 1904 – 1 April 1950) was an African-American physician, surgeon and medical researcher. He researched in the field of blood transfusions, developing improved techniques for blood storage, and applied his expert knowledge to developing large-scale blood banks early in World War II. This allowed medics to save thousands of lives of the Allied forces. The research and development aspect of his blood storage work is disputed. Drew protested against the practice of racial segregation in the donation of blood, as it lacked scientific foundation, an action which cost him his job. In 1943, Drew's distinction in his profession was recognized when he became the first black surgeon selected to serve as an examiner on the American Board of Surgery.

In late 1940, during World War II before the US entered the war, and just after earning his doctorate, Drew was recruited by John Scudder to help set up and administer an early prototype program for blood storage and preservation. He was to collect, test, and transport large quantities of blood plasma for distribution in Great Britain. Drew went to New York to direct the United States' Blood for Britain project. The Blood for Britain project was a project to aid British soldiers and civilians by giving US blood to Great Britain.

Drew created a central location for the blood collection process where donors could go to give blood. He made sure all blood plasma was tested before it was shipped out. He ensured that only skilled personnel handled blood plasma to avoid the possibility of contamination. The Blood for Britain program operated successfully for five months, with total collections of almost 15,000 people donating blood, and with over 5,500 vials of blood plasma. As a result, the Blood Transfusion Betterment Association applauded Drew for his work

Robert Edwards - Nobel '10

The Nobel Prize in physiology or medicine has been awarded this year to Robert G. Edwards, an English biologist who, with a physician colleague, Patrick Steptoe, developed the in vitro fertilization procedure for treating human infertility.

Since the birth of the first test tube baby, Louise Brown, on July 25, 1978, some four million babies worldwide have been conceived by mixing eggs and sperm outside the body and returning the embryo to the womb to resume development. The procedure overcomes many previously untreatable causes of infertility.

Dr. Edwards, a physiologist who spent much of his career at Cambridge University in England, spent more than 20 years solving a series of problems in getting eggs and sperm to mature and successfully unite outside the body. His colleague, Dr. Steptoe, was a gynecologist and pioneer of laparoscopic surgery, the method used to extract eggs from the prospective mother.

Dr. Steptoe, who presumably would otherwise have shared the prize, died in 1988. Dr. Edwards, who born in 1925, has now retired as head of research from the Bourn Hall Clinic in Cambridge, which he and Dr. Steptoe founded as the world’s first center for in vitro fertilization.

Though in vitro fertilization is now widely accepted, the birth of the first test tube baby was greeted with intense concern that the moral order was subverted by unnatural intervention in the mysterious process of creating a human being. Dr. Edwards was well aware of the ethical issues raised by his research and took the lead in addressing them.

The objections gradually died away, except on the part of the Roman Catholic Church, as it became clear that the babies born by in vitro fertilization were healthy and that their parents were overjoyed to be able to start a family. Long-term follow-ups have confirmed the essential safety of the technique.

The deliberations of the prize-giving committee at the Karolinksa Institute in Sweden are confidential, and it is unclear why it took so long to acknowledge Dr. Edwards’s achievement. The committee routinely ignores the stipulation in Alfred Nobel’s will that the prize should be awarded for a discovery made the preceding year, because it takes longer than that to evaluate most scientific claims, but delays of 30 years or more are unusual. The Lasker Foundation in New York, whose jurors often anticipate the Nobel Prize committee, awarded Dr. Edwards its prize in 2001.

Dr. Edwards’s research proved too controversial for the Medical Research Council, a government financng agency that is the British equivalent of the National Institutes of Health. In 1971 the council rejected an application from Dr. Edwards and Dr. Steptoe to work on in vitro fertilization, but they were able to continue with private funds.

“In retrospect, it is amazing that Edwards not only was able to respond to the continued criticism of in vitro fertilization, but that he also remained so persistent and unperturbed in fulfilling his scientific vision,” Christer Höög, a member of the Nobel Prize committee, writes on the Nobel Foundation’s Web page.

Image: Lesley and Louise Brown with her son Cameron and Professor Robert Edwards

Read more at http://www.nytimes.com/2010/10/05/health/research/05nobel.html?ref=global-home

The Belmont Report

The Belmont Report is a report created by the former United States Department of Health, Education, and Welfare (which was renamed to Health and Human Services) entitled "Ethical Principles and Guidelines for the Protection of Human Subjects of Research," authored by Dan Harms, and is an important historical document in the field of medical ethics. The report was created on April 18, 1979 and gets its name from the Belmont Conference Center where the document was drafted. The conference center, once a part of the Smithsonian Institution, is in Elkridge, Maryland, 10 miles south of Baltimore, and is now operated by Howard Community College.

The Tuskegee Syphilis Study

The Tuskegee syphilis experiment (also known as the Tuskegee syphilis study or Public Health Service syphilis study) was a clinical study conducted between 1932 and 1972 in Tuskegee, Alabama, by the U.S. Public Health Service. Investigators recruited 399 impoverished African-American sharecroppers with syphilis for research related to the natural progression of the untreated disease, in hopes of justifying treatment programs for blacks.

The 40-year study was controversial for reasons related to ethical standards, primarily because researchers failed to treat patients appropriately after the 1940s validation of penicillin as an effective cure for the disease. Revelation of study failures led to major changes in U.S. law and regulation on the protection of participants in clinical studies. Now studies require informed consent (with exceptions possible for U.S. Federal agencies which can be kept secret by Executive Order), communication of diagnosis, and accurate reporting of test results.

By 1947 penicillin had become the standard treatment for syphilis. Choices might have included treating all syphilitic subjects and closing the study, or splitting off a control group for testing with penicillin. Instead, the Tuskegee scientists continued the study, withholding penicillin and information about it from the patients. In addition, scientists prevented participants from accessing syphilis treatment programs available to others in the area. The study continued, under numerous supervisors, until 1972, when a leak to the press resulted in its termination. Victims included numerous men who died of syphilis, wives who contracted the disease, and children born with congenital syphilis.

The Tuskegee Syphilis Study, cited as "arguably the most infamous biomedical research study in U.S. history,"led to the 1979 Belmont Report and the establishment of the Office for Human Research Protections (OHRP).It also led to federal regulation requiring Institutional Review Boards for protection of human subjects in studies involving human subjects. The Office for Human Research Protections (OHRP) manages this responsibility within the US Department of Health and Human Services (HHS).

Gram Stain

Gram stain of mixed Stap aureus (Gram positive cocci) and E. coli (Gram negative bacilli)

The Gram staining method, named after the Danish bacteriologist who originally devised it in 1882 (published 1884), Hans Christian Gram, is one of the most important staining techniques in microbiology. It is almost always the first test performed for the identification of bacteria. The primary stain of the Gram's method is crystal violet. Crystal violet is sometimes substituted with methylene blue, which is equally effective. The microorganisms that retain the crystal violet-iodine complex appear purple brown under microscopic examination. These microorganisms that are stained by the Gram's method are commonly classified as Gram-positive or Gram non-negative. Others that are not stained by crystal violet are referred to as Gram negative, and appear red.

Gram staining is based on the ability of bacteria cell wall to retaining the crystal violet dye during solvent treatment. The cell walls for Gram-positive microorganisms have a higher peptidoglycan and lower lipid content than gram-negative bacteria. Bacteria cell walls are stained by the crystal violet. Iodine is subsequently added as a mordant to form the crystal violet-iodine complex so that the dye cannot be removed easily. This step is commonly referred to as fixing the dye. However, subsequent treatment with a decolorizer, which is a mixed solvent of ethanol and acetone, dissolves the lipid layer from the gram-negative cells. The removal of the lipid layer enhances the leaching of the primary stain from the cells into the surrounding solvent. In contrast, the solvent dehydrates the thicker Gram-positive cell walls, closing the pores as the cell wall shrinks during dehydration. As a result, the diffusion of the violet-iodine complex is blocked, and the bacteria remain stained. The length of the decolorization is critical in differentiating the gram-positive bacteria from the gram-negative bacteria. A prolonged exposure to the decolorizing agent will remove all the stain from both types of bacteria. Some Gram-positive bacteria may lose the stain easily and therefore appear as a mixture of Gram-positive and Gram-negative bacteria (Gram-variable).

Finally, a counterstain of basic fuchsin is applied to the smear to give decolorized gram-negative bacteria a pink color. Some laboratories use safranin as a counterstain instead. Basic fuchsin stains many Gram-negative bacteria more intensely than does safranin, making them easier to see. Some bacteria which are poorly stained by safranin, such as Haemophilus spp., Legionella spp., and some anaerobic bacteria, are readily stained by basic fuchsin, but not safranin. The polychromatic nature of the gram stain enables determination of the size and shape of both Gram-negative and Gram-positive bacteria. If desired, the slides can be permanently mounted and preserved for record keeping.

Besides Gram's stain, there are a wide range of other staining methods available. By using appropriate dyes, different parts of the bacteria structures such as capsules, flagella, granules, and spores can be stained. Staining techniques are widely used to visualize those components that are otherwise too difficult to see under a light microscope. In addition, special stains can be used to visualize other microorganisms not readily visualized by the Gram stain, such as mycobacteria, rickettsia, spirochetes, and others. In addition, there are modifications of the Gram stain that allow morphologic analysis of eukaryotic cells in clinical specimens.

Source: http://www.uphs.upenn.edu/bugdrug/antibiotic_manual/gram1.htm

James Lind and Scurvy

Lind was a Scottish doctor, a pioneer of naval hygiene and expert on the treatment of scurvy. . By conducting the first ever clinical trial,  he developed the theory that citrus fruits cured scurvy

James Lind was born in Edinburgh in 1716. In 1731, he registered as an apprentice at the College of Surgeons in Edinburgh and in 1739 became a surgeon's mate, seeing service in the Mediterranean, Guinea and the West Indies, as well as the English Channel. In 1747, while serving as surgeon on HMS Salisbury, he carried out experiments to discover the cause of scurvy, the symptoms of which included loose teeth, bleeding gums and haemorrhages.

Lind selected 12 men from the ship, all suffering from scurvy, and divided them into six pairs, giving each group different additions to their basic diet. Some were given cider, others seawater, others a mixture of garlic, mustard and horseradish. Another group of two were given spoonfuls of vinegar, and the last two oranges and lemons. Those fed citrus fruits experienced a remarkable recovery. While there was nothing new about his discovery - the benefits of lime juice had been known for centuries - Lind had definitively established the superiority of citrus fruits above all other 'remedies'.

In 1748, Lind retired from the navy and went to Edinburgh University to take professional qualifications. In 1753, he published 'A Treatise of the Scurvy' and in 1757 'An Essay on the Most Effectual Means of Preserving the Health of Seamen in the Royal Navy', which threw much light on the appalling living conditions and diet of seamen. In 1758, he was appointed physician to the Naval Hospital at Haslar in Gosport where he investigated the distillation of fresh water from salt water for supply to ships.

In 1763, Lind published work on typhus fever in ships and in the 1768 publication 'An Essay on Diseases Incidental to Europeans in Hot Climates' he summarised the prevalent diseases in each colony and gave advice on avoiding tropical infections. Lind died in 1794 in Gosport.

Although the importance of Lind's findings on scurvy were recognised at the time, it was not until more than 40 years later that an official Admiralty order was issued on the supply of lemon juice to ships. With this, scurvy disappeared almost completely from the Royal Navy.

Blood groups

Marcello Malpighi

Malpighi was born in Crevalcore near Bologna in Italy, raised on the farm his parents owned and entered the University of Bologna at the age of 17. Malpighi began to study. When his father, mother and paternal grandmother died, he had to abandon his studies for more than two years to settle family affairs. He returned to university after two years, and became a doctor of medicine in 1653. The next year he married Francesca Massari, younger sister of his anatomy professor. She died a year later.

In 1656 Malpighi received a chair of medical practice in the university, three years after he had applied for it, and later the same year University of Pisa created a chair of theoretical medicine for him. He stayed in Pisa for three years and then returned to Bologna. In 1661 he was called to University of Messina where he stayed for four years.

Most of Malpighi's research results were published as articles in the journal of the Royal Society of England. His first article appeared there in 1661 and was about anatomy of a lung of a frog during which he had discovered capillaries. In 1667 Henry Oldenburg invited Malpighi to correspond with the Royal Society regularly and he became a fellow the next year, the first such recognition given to an Italian.

Malpighi used the microscope for studies on skin, kidney, and for the first interspecies comparison of the liver. He greatly extended the science of embryology. The use of microscopes enabled him to describe the development of the chick in its egg, and discovered that insects (particularly, the silk worm) do not use lungs to breathe, but small holes in their skin called tracheae. Later he falsely concluded that plants had similar tubules. However, he observed that when a ringlike portion of bark was removed on a trunk a swelling of the tissues would occur above the ring. He correctly interpreted this as growth stimulated by food coming down from the leaves, and being blocked above the ring. He was the first to see capillaries and discovered the link between arteries and veins that had eluded William Harvey.

Malpighi is regarded as the founder of microscopic anatomy and the first histologist. Many microscopic anatomical structures are named after him, including a skin layer (Malpighi layer) and two different Malpighian corpuscles in the kidneys and the spleen, as well as the Malpighian tubules in the excretory system of insects.

He also studied chick embryo development with detailed drawings and discovered taste buds of human tongue. Some of his studies he made by vivisection. He also studied the anatomy of a brain and concluded that this organ is a gland. In terms of modern endocrinology this deduction is correct because neurotransmitter substances represent paracrine hormones, and the hypothalamus of the brain has long been recognized for its hormone-secreting capacity. He was also among the first to study human fingerprints.

In 1691 Pope Innocent XII invited him to Rome as Papal physician. He taught medicine in the Papal Medical School and wrote a long treatise about his studies which he donated to the Royal Society of London.

Marcello Malpighi died of apoplexy in Rome on September 30, 1694

MRI - Nobel Prize

Prions and Prusiner

                                  

The word prion, coined in 1982 by Dr. Stanley B. Prusiner, is a portmanteau derived from the words protein and infectious.

Stanley Ben Prusiner (born May 28, 1942[1]) is an American neurologist and biochemist. Currently the director of the Institute for Neurodegenerative Diseases at University of California, San Francisco (UCSF). Prusiner discovered prions, a class of infectious self-reproducing pathogens primarily or solely composed of protein. He received the Albert Lasker Award for Basic Medical Research in 1994 and the Nobel Prize in Physiology or Medicine in 1997 for his prion research.

Warren and Marshall

Two Australian scientists who upset medical dogma by discovering a bacterium that causes stomach inflammation, ulcers and cancer won the 2005 Nobel Prize for Physiology or Medicine. The findings by the Australians in the early 1980's went so against medical thinking, which held that psychological stress caused stomach and duodenal ulcers, that it took many more years for an entrenched medical profession to accept it.

In the early 1980's, Dr. Warren noted the bacterium in the lower part of the stomach in about half of the patients who had biopsies. He made a crucial observation that signs of inflammation were always present in the surface lining of the stomach near where he observed the bacterium.


Dr. Marshall joined Dr. Warren in studying biopsies from a series of patients. After several attempts, Dr. Marshall succeeded in growing a bacterium that was unknown then; he named it Campylobacter pyloridis, believing that it was a member of the Campylobacter family. (It was later found to be a member of the Helicobacter family and renamed H. pylori.)

Still, many doctors were unconvinced by the findings, a point recognized by the Nobel committee, which said the award went to Dr. Marshall and Dr. Warren "who with tenacity and a prepared mind challenged prevailing dogmas."

Dr. Marshall carried on a medical tradition in experimenting on himself to test his and Dr. Warren's theory and to show that Helicobacter was the primary cause of gastritis, not a secondary invader.

In earlier interviews, Dr. Marshall described how at age 32, he swallowed a gastroscope tube to allow another doctor to look at his stomach and take several biopsies. These procedures and examinations were needed to document that Dr. Marshall had no H. pylori in his stomach and did not suffer from gastritis or another abnormality.

Dr. Marshall waited 10 days for the areas that had been biopsied to heal and then swallowed a pure culture of H. pylori. A week later, he had an unusual sensation of fullness after eating supper and felt ill. Friends told him that his breath was "putrid."

Ten days after the onset of symptoms, Dr. Marshall underwent the first of an additional three gastroscopies. Biopsies obtained through them showed that he had developed gastritis or inflammation of the stomach, but he did not continue the experiment long enough to develop an ulcer. His symptoms quickly disappeared after treatment.
Source:http://www.nytimes.com/2005/10/04/science/04nobe.html?pagewanted=2

The First Nobel in Medicine

Behring was the discoverer of diphtheria antitoxin and attained a great reputation by that means and by his contributions to the study of immunity. He won the first Nobel Prize in Physiology or Medicine in 1901 for developing a serum therapy against diphtheria (this was worked on with Emile Roux) and tetanus.

Discovery of Vitamin B12

B12 deficiency is the cause of pernicious anemia, an anemic disease that was usually fatal and has unknown etiology when it was first described in medicine. The cure, and B12, were discovered by accident. George Whipple had been doing experiments in which he induced anemia in dogs by bleeding them, and then fed them various foods to observe which diets allowed them fastest recovery from the anemia produced. In the process, he discovered that ingesting large amounts of liver seemed to most-rapidly cure the anemia of blood loss. Thus, he hypothesized that liver ingestion might treat pernicious anemia. He tried this and reported some signs of success in 1920.

After a series of careful clinical studies, George Richards Minot and William Murphy set out to partly isolate the substance in liver which cured anemia in dogs, and found that it was iron. They also found that an entirely different liver substance cured pernicious anemia in humans, that had no effect on dogs under the conditions used. The specific factor treatment for pernicious anemia, found in liver juice, had been found by this coincidence. Minot and Murphy reported these experiments in 1926. This was the first real progress with this disease. Despite this discovery, for several years patients were still required to eat large amounts of raw liver or to drink considerable amounts of liver juice.

In 1928, the chemist Edwin Cohn prepared a liver extract that was 50 to 100 times more potent than the natural liver products. The extract was the first workable treatment for the disease. For their initial work in pointing the way to a working treatment, Whipple, Minot, and Murphy shared the 1934 Nobel Prize in Physiology or Medicine.

These events in turn eventually let to discovery of the soluble vitamin, called vitamin B12, in the liver juice. The vitamin in liver extracts was not isolated until 1948 by the chemists Karl A. Folkers of the United States and Alexander R. Todd of Great Britain. The substance proved to be cobalamin—the most complex of all the vitamins. It could also be injected directly into muscle, making it possible to treat pernicious anemia more easily

Dorothy Hodgkin completed the elucidation of B12's chemical structure by using x-ray crystallography, receiving the 1964 Nobel Prize in chemistry for her work. Vitamin B12 was finally synthesized by Robert Burns Woodward in 1971, after a ten year effort.

Ephedra

Ephedra, from the plant Ephedra sinica, has been used as a herbal remedy in traditional Chinese medicine for the treatment of asthma and hay fever, as well as for the common cold. Known in Chinese as ma huang ephedra is a stimulant that constricts blood vessels and increases blood pressure and heart rate. Several additional species belonging to the genus Ephedra have traditionally been used for a variety of medicinal purposes and are a possible candidate for the Soma plant of Indo-Iranian religion. Native Americans and Mormon pioneers drank a tea brewed from an Ephedra, called Mormon Tea, but North American ephedras lack the alkaloids found in species such as E. sinica.

Ephedra-containing dietary supplements have been linked to a high rate of serious side effects and a number of deaths, leading to concern from the U.S. Food and Drug Administration (FDA), the National Center for Complementary and Alternative Medicine, and the medical community. However, initial efforts to test and regulate ephedra were defeated by lobbying and political pressure from the dietary supplement industry. Ultimately, in response to accumulating evidence of adverse effects and deaths related to ephedra, the FDA banned the sale of ephedra-containing supplements on April 12, 2004.



Following a legal challenge by an ephedra manufacturer, the U.S. Court of Appeals for the Tenth Circuit upheld the FDA's ban of ephedra in 2006.[14] The sale of ephedra-containing dietary supplements remains illegal in the United States due to evidence of adverse ephedra-related effects. Following the FDA's ban, the supplement industry has marketed "ephedrine-free" or "legal" ephedra products, in which the ephedra is replaced with other herbal stimulants such as bitter orange

James W. Black

Sir James Whyte Black, OM, FRS, FRSE, FRCP (14 June 1924 – 22 March 2010) was a Scottish doctor and pharmacologist. He spent his career both as researcher and as an academic at several universities. Black established the physiology department at the University of Glasgow, where he became interested in the effects of adrenaline on the human heart. He went to work for ICI Pharmaceuticals in 1958 and, while there, developed propranolol, a beta blocker used for the treatment of heart disease. Black was also responsible for the development of cimetidine, a drug used in a similar manner to treat stomach ulcers. He was awarded the Nobel Prize for Medicine in 1988 for work leading to the development of propranolol and cimetidine

St Barbara and Barbiturates

Barbituric acid was first synthesized on December 6, 1864, by German researcher Adolf von Baeyer. This was done by condensing urea (an animal waste product) with diethyl malonate (an ester derived from the acid of apples). There are several stories about how the substance got its name. The most likely story is that Von Baeyer and his colleagues went to celebrate their discovery in a tavern where the town's artillery garrison were also celebrating the feast of Saint Barbara — the patron saint of artillerists. An artillery officer is said to have christened the new substance by amalgamating Barbara with urea.[1] No substance of medical value was discovered, however, until 1903 when two German chemists working at Bayer, Emil Fischer and Joseph von Mering, discovered that barbital was very effective in putting dogs to sleep. Barbital was then marketed by Bayer under the trade name Veronal. It is said that Von Mering proposed this name because the most peaceful place he knew was the Italian city of Verona.[1] It was not until the 1950s that the behavioural disturbances and physical dependence potential of barbiturates became recognised

Selman Waksman and Streptomycin

Selman Abraham Waksman (22 July 1888 – 16 August 1973) was an American biochemist and microbiologist whose research into organic substances—largely into organisms that live in soil—and their decomposition promoted the discovery of Streptomycin, and several other antibiotics. A professor of biochemistry and microbiology at Rutgers University for four decades, his work led to the discovery of over twenty antibiotics (a word which he coined) and procedures that have led to the development of many others. The proceeds earned from the licensing of his patents funded a foundation for microbiological research, which established the Waksman Institute of Microbiology located on Rutgers University's Busch Campus in Piscataway, New Jersey (USA). In 1952 he was awarded the Nobel Prize in Physiology or Medicine in recognition "for his discovery of "streptomycin" the first antibiotic active against tuberculosis", despite the fact that this medicine was indeed discovered by Albert Schatz, one of Waksman's graduate investigators working under his direction.

In 2005 Selman Waksman was designated an ACS National Historical Chemical Landmark in recognition of his significance for isolating more than fifteen antibiotics, including streptomycin, which was the first effective treatment for tuberculosis

Receiver operating characteristic

In signal detection theory, a receiver operating characteristic (ROC), or simply ROC curve, is a graphical plot of the sensitivity, or true positives, vs. (1 − specificity), or false positives, for a binary classifier system as its discrimination threshold is varied. The ROC can also be represented equivalently by plotting the fraction of true positives (TPR = true positive rate) vs. the fraction of false positives (FPR = false positive rate). Also known as a Relative Operating Characteristic curve, because it is a comparison of two operating characteristics (TPR & FPR) as the criterion changes.

ROC analysis provides tools to select possibly optimal models and to discard suboptimal ones independently from (and prior to specifying) the cost context or the class distribution. ROC analysis is related in a direct and natural way to cost/benefit analysis of diagnostic decision making. The ROC curve was first used during World War II for the analysis of radar signals before it was employed in signal detection theory. Following the attack on Pearl Harbor in 1941, the United States army began new research to increase the prediction of correctly detected Japanese aircraft from their radar signals.

In the 1950s, ROC curves were employed in psychophysics to assess human (and occasionally non-human animal) detection of weak signals. In medicine, ROC analysis has been extensively used in the evaluation of diagnostic tests. ROC curves are also used extensively in epidemiology and medical research and are frequently mentioned in conjunction with evidence-based medicine. In radiology, ROC analysis is a common technique to evaluate new radiology techniques. In the social sciences, ROC analysis is often called the ROC Accuracy Ratio, a common technique for judging the accuracy of default probability models.

ROC curves also proved useful for the evaluation of machine learning techniques. The first application of ROC in machine learning was by Spackman who demonstrated the value of ROC curves in comparing and evaluating different classification algorithms

Razi

Muhammad ibn Zakariyā Rāzī (Mohammad-e Zakariā-ye Rāzi: Persian: محمد زکریای رازی), known as Rhazes or Rasis after medieval Latinists, (August 26, 865, Rayy— 925, Rayy) was a Persian  physician, alchemist and chemist, philosopher, and scholar. He is recognised as a polymathm and Biographies of Razi, based on his writings, describe him as “perhaps the greatest clinician of all times.” Numerous “firsts” in medical research, clinical care, and chemistry are attributed to him, including being the first to differentiate smallpox from measles, and the discovery of numerous compounds and chemicals including alcohol and kerosene, among others. Edward Granville Browne considers him as "probably the greatest and most original of all the physicians, and one of the most prolific as an author".

Although Rhazes (or Razi) was a Persian living in Iran, his work was published in both Persian and Arabic lanugages, as such was the case for most Persian scientists during this era. Such multi-lingual publications in Persia were analogous to the later usage of the Latin language for scientific publications in Europe in the following centuries.

Rhazes made fundamental and enduring contributions to the fields of medicine, alchemy, music, and philosophy, recorded in over 200 books and articles in various fields of science. He was well-versed in Persian, Greek and Indian medical knowledge and made numerous advances in medicine through own observations and discoveries.

Well educated in music, mathematics, philosophy, and metaphysics, he finally chose medicine as his professional field. As a physician, he was an early proponent of experimental medicine and is considered the father of pediatrics. He was also a pioneer of neurosurgery and ophthalmology. He was among the first to use Humoralism to distinguish one contagious disease from another. In particular, Razi was the first physician to distinguish smallpox and measles through his clinical characterization of the two diseases. And as an alchemist, Rhazes is known for his study of sulfuric acid and for his discovery of ethanol and its refinement to use in medicine. He became chief physician of Rayy and Baghdad hospitals. Razi Invented what today is known as rubbing alcohol.

Rhazes was a rationalist and very confident in the power of ratiocination; he was widely regarded by his contemporaries and biographers as liberal and free from any kind of prejudice and very bold and daring in expressing his ideas without a qualm.

He traveled extensively but mostly in Persia. As a teacher in medicine, he attracted students of all disciplines and was said to be compassionate and devoted to the service of his patients, whether rich or poor.

Egerton Yorrick Davis and Penis Captivus

The term penis captivus describes a relatively rare medical condition in which a woman's vaginal muscles uncontrollably spasm during intercourse, trapping her partner's penis inside her vagina. The only solution to such a problem is to administer muscle relaxants to the female in question, thereby alleviating the spasms and effecting a penile escape. Case studies of penis captivus have been documented in reputable medical literature. Really.

However, this condition does not actually exist.

In reality, penis captivus started out as an elaborate hoax perpetrated by a playful physician in the late 19th century. During this time period, sexology and the study of sexual dysfunction was just beginning to come into vogue with the work of pioneers like Richard von Krafft-Ebing and later, Havelock Ellis. Of particular interest was the condition known as vaginismus, in which the muscles of the vaginal wall uncontrollably contract, making sexual penetration either very painful or physically impossible. On December 4, 1884, the Philadelphia Medical News published a letter from an ex-Army physician named "Egerton Y. Davis" which purported to describe an actual case study of a rare form of vaginismus called penis captivus (or alternatively, de cohesione in coitu). Until this point, the condition had existed as a purely hypothetical situation.

Dr. Davis recounts an unusual house call he made late one night to the home of a well-to-do patient. When Davis arrived, the gentleman explained that his coachman required the doctor's services. Allegedly, the master of the house, whilst investigating strange noises coming from the servants' quarters, had inadvertently stumbled upon the coachman and the downstairs maid mid-coitus. The maid was so surprised at the interruption that her entire body, including her vagina, just locked up. As she was apparently a very small woman, these muscular contractions held the coachman's penis in place, and no amount of pushing or pulling could disengage the couple. After several abortive attempts to use ice and lubricant to solve the problem, the good doctor dosed the woman with chloroform to relax her muscles and free the hapless coachman.

Davis goes on to describe the coachman's penis as semi-erect and extremely swollen near the top of the shaft and the glans. He admits that he did not examine the maid's genitals or anus before attempting the extraction, but suggests that sudden contraction of both her anal sphincter and the muscles in her vaginal wall had constricted the flow of blood to and from her partner's member, causing his penis to become abnormally engorged near the top and creating a "lock and key" situation. The letter concludes by quoting the infamously raunchy line from Shakespeare's Othello, along with theorizing that the biblical story of Phinehas could be explained through the penis captivus phenomenon (With a single javelin thrust, Phinehas simultaneously killed a man and a woman who had engaged in the sinful act of whoredom).

A week before receiving the letter, the Philadelphia Medical News had published an article detailing several different forms of vaginismus and suggesting that penis captivus might be physiologically possible. Thus, the journal was eager to print Dr. Davis' case study as a followup to the previous article, and did not check the veracity of the letter before publication. This oversight is understandable, as it probably would have taken a week or two to confirm the case study (at the time, communication by telegraph was limited, and the telephone was still a new invention). However, the journal never bothered to check out Davis' story even after the letter was published (one would think that someone would have requested more information).

There are several aspects of the letter that make the case study rather questionable. By today's standards, it is anecdotal at best. There are few specific details about the patients, other than a brief mention that the maid probably weighed less than 90 pounds. Dr. Davis seems more concerned with making witty literary allusions than relaying pertinent medical information. Finally, the geography of the letter doesn't quite match up. When signing the letter, Egerton Y. Davis wrote "Ex U.S. Army" after his name, states in the body of the letter that his practice is located in England, and originally sent the piece to The Canada Medical and Surgical Journal, which then forwarded it to Philadelphia Medical News. Despite these inconsistencies, Dr. Davis' informal case study was held as incontrovertible proof of the existence of penis captivus for nearly a century. It was referenced in numerous urology and sexology textbooks and medical articles.

As it turns out, there was no such person as Egerton Y. Davis. The name was a pseudonym for Sir William Osler, who served on the editorial board for the Philadelphia Medical News. Generally speaking, Osler was a staunch believer in scientific research, which ironically led him to submit the fallacious case study. The article on vaginismus that had been published the previous week was written anonymously by fellow board member Theophilius Parvin. Osler felt that Parvin had inserted too much editorial commentary and neglected medical facts when writing the article. Therefore, he devised a little prank to play on his colleague. Osler wrote the letter from Davis, forged an accompanying letter from the editor of The Canada Medical and Surgical Journal, and had a friend mail both documents from Montreal in order to obtain a legitimate Canadian postmark. Osler figured that, after the false case study was published, surely someone would recognize it for what it was, greatly embarrassing Parvin (as he was the one who decided to publish the letter as a followup to his own article) and eliciting a hearty round of laughter from the rest of the journal's staff. Much to Osler's chagrin, the medical community bought into the idea of penis captivus hook, line and sinker.

Egerton Yorrick Davis was a known pseudonym (and somewhat of an alter ego) that Osler used on multiple occasions, a fact that is well documented in his biography The Life of Sir William Osler, written by Harvey Cushing and first published in 1925. Osler carried the secret of the penis captivus debacle to his grave (he passed away in 1919), and Cushing either didn't make the connection or chose to allow Osler's hoax to continue. It wasn't until the early 1970s that physicians, curious as to why there are no documented cases of penis captivus after the 1884 letter, dug into the matter and discovered the prank.

Nowadays, most members of the medical community discount the theory of penis captivus as implausible, if not impossible. Vaginismus is a physical manifestation of a psychological condition (usually because a woman has been sexually abused in her past), and invariably occurs before penetration, not during intercourse. A few physicians (who are in a distinct minority) believe that penis captivus may be possible, but if so, the condition would certainly cease to be a problem after the man loses his erection. To this day, Osler's prank continues to live on in the form of urban legend.

Interestingly, a phenomenon similar to penis captivus does occur in other species, namely canids (such as dogs and wolves). The males of these species have a penis with a particularly bulbous head compared to human males. Due to this bulbous structure, a mating male and female may remain locked together in the copulatory position for as long as 10-20 minutes after ejaculation. This is probably an evolutionary mechanism to prevent the female from immediately running off and mating with another male.

Read more at http://everything2.com/title/penis+captivus

Occam's razor vs Hickam's dictum

Pluralitas non est ponenda sine necessitate.

— William of Occam, 14th century

In the 14th century, William of Occam stated,“Plurality must not be posited without necessity.”

Hickam's dictum is a counterargument to the use of Occam's razor in the medical profession. The principle is commonly stated: "Patients can have as many diseases as they damn well please". The principle is attributed to John Hickam, MD. Hickam was a faculty member at Duke University in the 1950s, and was later chairman of medicine at Indiana University.

When discussing Occam's razor in contemporary medicine, doctors and philosophers of medicine speak of diagnostic parsimony. Diagnostic parsimony advocates that when diagnosing a given injury, ailment, illness, or disease a doctor should strive to look for the fewest possible causes that will account for all the symptoms. However, this principle has very important limits in medical practice. The actual process that occurs when diagnosing a patient is a continuous flow of hypothesis and testing of that hypothesis, then modifying the hypothesis, and so on. In the context of this method, the principle of Hickam's dictum asserts that at no stage should a particular diagnosis be excluded solely because it doesn't appear to fit the principle of Occam's razor. The principle of Occam's razor, or parsimony, does not demand that the diagnostician necessarily opt for the simplest explanation, but instead guides the medical practitioner to seek explanations, without unnecessary additional assumptions, which are capable of accounting for all relevant evidence.

A key reason for using Hickam's dictum as a limiting principle to that of Occam's razor is, it is often statistically more likely that a patient has several common diseases, rather than having a single rarer disease which explains their myriad symptoms. Another key reason is that, independently of statistical likelihood, some patients do in fact turn out to have multiple diseases. In such cases multiple categories of diagnosis may indeed have independent causes rather than a single source; i.e. may be due to separate events or combinations of events to which the patient may have been subjected or exposed. Thus Hickam's dictum provides physicians with a counterbalancing principle to the unfettered use of Occam's razor in diagnosis.

An example of the utility of Hickam's dictum is Saint's triad of hiatus hernia, gallbladder disease, and diverticulosis. C. F. M. Saint was a British surgeon. His triad has no known pathophysiological relationship, nullifying the usefulness of Occam's razor. Hickam's dictum is similar in principle to William of Chatham's anti razor

The Discovery of Insulin

The story of the discovery of insulin has been well chronicled beginning with a young physician, Frederick Banting, in London, Ontario, imagining that it might be possible to isolate the internal secretions of the pancreas by ligating the pancreatic ducts to induce atrophy of the acinar cells and thereby minimize contamination of the tissue extract with digestive enzymes. Banting presented his suggestion to J. J. R. Macleod, a distinguished physiologist at the University of Toronto who provided Banting with a laboratory for the summer and some dogs for the experiments. Macleod was initially skeptical, but eventually agreed to let Banting use his lab space while he was on vacation for the summer. He also supplied Banting with ten dogs to experiment on, and two medical students, Best and Clark Noble, to use as lab assistants, before leaving for Scotland. Since Banting only required one lab assistant, Best and Noble flipped a coin to see which would assist Banting for the first half of the summer. Best won the coin toss, and took the first shift as Banting's assistant. Loss of the coin toss may have proved unfortunate for Noble, given that Banting decided to keep Best for the entire summer (and eventually shared half his Nobel Prize money and a large part of the credit for the discovery of insulin with the winner of the toss)

During the summer of 1921, Banting and Best made remarkable progress, and by fall they had isolated material from pancreas extracts that dramatically prolonged the lives of dogs made diabetic by removal of the pancreas. In the winter of 1922, Banting and Best treated their first human patient, a young boy, who's life was saved by the treatment. This was a stunning accomplishment. Consider that from the start of the research in the summer of 1921 to treating a human patient successfully in the winter of 1922, the pace, especially by current standards for clinical treatments, was remarkable.

With that achievement, Macleod, who had been initially unenthusiastic about the work, assigned his entire laboratory to the insulin project. He also enlisted the Eli Lilly Company to aid in the large scale, commercial preparation of insulin although the University of Toronto received the patent for insulin production. By 1923, insulin was available in quantities adequate for relatively widespread treatment of diabetes. Although the success of the insulin project was remarkable, the rewards for the research workers were, it seems, quite controversial. The 1923 Noble Prize in Physiology or Medicine was awarded to Banting and Macleod. Apparently, Banting was annoyed at the omission of Best and gave him half of his share of the prize. There was also, perhaps, the feeling that Macleod had done little in the initial stages of the work and was an undeserving recipient. Macleod split his share of the Prize with J. B. Collip who had made contributions to the later stages of the work on insulin purification.

After the spectacular events of 1921–1923, the University of Toronto established the Banting and Best Department of Medical Research separate from the University. Banting accomplished little during the rest of his career and died in a plane crash in 1940. Best, however, had a long successful tenure at the University of Toronto working on insulin and subsequently other important topics including the importance of dietary choline and the development of heparin as an anticoagulant.

Read more at The Discovery of Insulin: the Work of Frederick Banting and Charles Best Robert D. Simoni, Robert L. Hill and Martha Vaughan /The Journal of Biological Chemistry,

Mona Lisa

The painting Mona Lisa in the Louvre, Paris, by Leonardo da Vinci (1503-1506), shows skin alterations at the inner end of the left upper eyelid similar to xanthelasma, and a swelling of the dorsum of the right hand suggestive of a subcutaneous lipoma. These findings in a 25-30 year old woman, who died at the age of 37, may be indicative of essential hyperlipidemia, a strong risk factor for ischemic heart disease in middle age.

Read 'Xanthelasma and lipoma in Leonardo da Vinci's Mona Lisa' by Dequeker J, Muls E, Leenders K in sr Med Assoc J. 2004 Aug;6(8):505-6.

An old woman with Pagets disease

A Grotesque Old Woman (or The Ugly Duchess) is perhaps the best-known of Quentin Matsys' works. It served as a basis for John Tenniel's depiction of the Duchess in Alice's Adventures in Wonderland. It is likely a depiction of a real person with Paget's disease, though it is sometimes said to be a metaphorical portrait of the Duchess Margarete of Tyrol-Görz, who was known as Maultasch, which, though literally translated "satchel mouth", was used to mean "ugly woman" or "whore" (because of her marital scandals).

Painting: A Grotesque Old Woman , Oil on wood, 64 x 45,5 cm, National Gallery, London.

Lymphadenopathy in a painting by Marinus Van Reymerswaele.

Does the moneychangers wife have a lymphoma? Or could it be scrofula?

Painting:The moneychanger and his wife, Prado museum

The three graces

Clinical features suggestive of hypermobility syndrome and a positive Trendelenburg sign are described in a painting "The Three Graces" (1638-1640) by Peter Paul Rubens, Prado, Madrid. The most obvious findings are scoliosis, positive Trendelenburg sign, and hyperextension of the metacarpal joints, hyperlordosis, and flat feet. The sitters, presumably Hélène Fourment (second wife of Rubens) and her sisters, support the hereditary familial aspect of hypermobility.

Read the full article at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1753831/

Polymyalgia rheumatica with temporal arteritis, as painted by Jan van Eyck in 1436

See Jan Van Eyck's work in the municipal museum of Bruges depicting the Holy Virgin with Canon Van der Paele (1436).Does the canon have temporal arteritis?
Yes, says Dr J. V. Dequeker.
In one hand he has his glasses, and in the other he is holding up his breviary
with difficulty. His hands are very fine looking, though wrinkled and stiff, as
occurs in rheumatism. Also note his prominet left temporal artery..

Access the free full text (Can Med Assoc J. 1981 June 15; 124(12): 1597–1598_ through pubmed central.

Auenbrugger and the wine barrels

Josef Leopold Auenbrugger or Leopold von Auenbrugg (b. November 19, 1722, Graz, Austria; died May 17, 1809), Austrian physician who invented percussion as a diagnostic technique. On the strength of this discovery, he is considered one of the founders of modern medicine.[citation needed]

Auenbrugger was a native of Graz in Styria, an Austrian province. His father, a hotel keeper, gave his son every opportunity for an excellent preliminary education in his native town and then sent him to Vienna to complete his studies at the university. Auenbrugger was graduated as a physician at the age of 22 and then entered the Spanish Military Hospital of Vienna, where he spent 10 years.

He found out that, by tapping lightly on the chest, one could assess the texture of underlying tissues and organs. This technique had its origins in testing the level of wine casks in the cellar of his father's hotel. With this method, he was able to plot outlines of the heart. It was the first time that a physician could relatively accurately and objectively determine an important sign of diseases. He published his findings in a booklet, but nobody paid much attention to it. The value of percussion in physical examination was later recognized by Jean-Nicolas Corvisart, who popularized it teaching it to his students in France, and by Josef Skoda in Vienna.

During his ten years of patient study, Auenbrugger confirmed his observations on the diagnostic value of percussion by comparison with post-mortem specimens, and besides made a number of experimental researches on dead bodies. He injected fluid into the pleural cavity, and showed that it was perfectly possible by percussion to tell exactly the limits of the fluid present, and thus to decide when and where efforts should be made for its removal.

His name is also associated with Auenbrugger's sign, a bulging of the epigastric region in the thorax, in cases of large effusions of the pericardium, the membrane which envelops the heart.

His later studies were devoted to tuberculosis. He pointed out how to detect cavities of the lungs, and how their location and size might be determined by percussion. He also recognized that information with regard to the contents of cavities in the lungs and conditions of lung tissue might be obtained by placing the hand on the chest and noting the vibration, or fremitus, produced by the voice and breath. These observations were published in a little book called Inventum Novum, the full English title being, "A New Discovery that Enables the Physician from the Percussion of the Human Thorax to Detect the Diseases Hidden Within the Chest". It is now considered one of the most important classics of medicine.

Like most medical discoveries, Auenbrugger's method of diagnosis at first met with indifference. Before his death, however, it had aroused the attention of French physician René Laennec, who, following up the ideas suggested by it, discovered auscultation.

Auenbrugger lived to a happy old age. He was especially noted for his cordial relations with the younger members of his profession and for his kindness to the poor and to these suffering from tuberculosis. He is sometimes said to have died in the typhus epidemic of 1798, but the burial register of the parish church in Vienna, of which he had been for half a century a faithful member, shows that he did not die until 1807.

Rene Laennec and the Stethoscope

When Rene Laennec was 5 years of age, his mother died of tuberculosis, and he was sent to live with an uncle who was a priest. At the end of the French revolution, 4 years later, Laennec was sent to live with another uncle, Dr Guillaume Laennec of Nantes, and remained with him until he was 19 years of age. Dr Laennec's was a pious Catholic household with a humanistic cultural environment that, of course, included an interest in medicine.

In 1800, Laennec left for Paris to seek medical education with Corvisart at La Charite Hospital. There he manifested an avidity for anatomy, pathology, clinical medicine, research, and writing papers. He received a degree in 1804, and continued with his mentor.


Laennec accepted an offer in 1816 from Necker Hospital to serve as physician. It was there that he invented the stethoscope. Laennec diligently followed patients with chest ailments from the bedside to the autopsy table, and correlated sounds heard with organ pathology found. He soon reached the conclusion that intrathoracic organs generated specific sounds with speaking, breathing, and coughing in health and in disease; and that these sounds could be conveyed to the ear with a stethoscope. Laennec developed an instinctive skill in the diagnosis of intrathoracic organ disease from sounds heard with the new instrument.

In 1819, Laennec published the results of his research, Traite de l'auscultation mediate et des maladies des poumons et des coeur. The following passage related how the stethoscope was invented and its usefulness: "In 1816, I was consulted by a young woman with symptoms of a diseased heart...percussion was of little avail on account ...of fatness. The application of the ear... inadmissible by the age and sex of the patient. I recollected a fact in acoustics ... the augmented sound conveyed through solid bodies....I rolled a quire of paper into a cylinder and applied one end to the heart and one end to the ear...and thereby perceived the action of the heart...more clear and distinct. I have been enabled to discover new signs of the diseases of the lungs, heart and pleura."

During all his life of 45 years, Laennec was thin and sickly looking, but this did not limit his practice, teaching, research, hospital responsibilities, and writing. Arduous work, however, finally took its toll on his health: "I know that I have risked my life, but the book I'm going to publish will be, I hope, useful enough to be of more value than the life of a man."

Laennec left for Brittany, his birthplace, recovered his health, and returned to Paris in 1822. He succeeded his deceased mentor at the College de France, was appointed professor of medicine at both Necker and La Charite, and was made a Knight of the Legion of Honor. Foreign students flocked to Paris to learn the new medicine and the use of precussion and the stethoscope. Some were Americans who returned home inspired to transform a stagnant medicine.

The second edition of Traite (1826) introduced a nomenclature of auscultatory sounds (rales, fremitus, egophony, pectoriloquy, bronchophony) heard in organ pathology that formerly was called "lung fever." Again arduous work severely taxed Laennec's health and strength. He returned to Brittany and died on August 13, 1826.

It was not until 1821 that The New England Journal of Medicine reported the invention of the stethoscope. In 1885, a professor of medicine in the United States stated, "He that hath ears to hear, let him use his ears and not a stethoscope"; and the founder of the American Heart Association, L. A. Connor (1866-1950) carried a silk handkerchief to place on the wall of the chest for ear auscultation. Nevertheless, this useful substitute for the ear quickly began winning converts.

The word stethoscope comes from the Greek words stethos meaning "chest", and skopos meaning "observer."

Read the original article, The inventor of the stethoscope: Rene Laennec - Journal of Family Practice, August, 1993 by Harry Bloch http://findarticles.com/p/articles/mi_m0689/is_n2_v37/ai_13248765/

Moniz and Lobotomy

António Caetano de Abreu Freire Egas Moniz (November 29, 1874 – December 13, 1955), known as Egas Moniz, was a Portuguese neurologist and the developer of cerebral angiography, best known for introducing the controversial psychosurgical procedure leucotomy (also known as lobotomy), for which be became the first Portuguese national to receive a Nobel Prize.

He wrote broadly on topics within and outside[citation needed] medicine, and also held several legislative and diplomatic posts in the Portuguese government.

Rosemary Kennedy, sister to John, Robert, and Edward Kennedy underwent a lobotomy at age 23, which left her permanently incapacitated. Her sister, Eunice Kennedy Shriver, founded the Special Olympics in her honor in 1968.

Byetta and Gila monster

Exenatide is a synthetic version of exendin-4, a hormone found in the saliva of the Gila monster. It displays biological properties similar to human glucagon-like peptide-1 (GLP-1), a regulator of glucose metabolism and insulin secretion. According to the package insert, exenatide enhances glucose-dependent insulin secretion by the pancreatic beta-cell, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying, although the mechanism of action is still under study. Exenatide is manufactured and marketed by Amylin Pharmaceuticals and Eli Lilly and Company.

The Pacific Yew and the Periwinkle

The chemotherapy drug paclitaxel (Taxol), used in breast, ovarian and lung cancer treatment, is derived from Taxus brevifolia, the Pacific Yew tree.

Vincristine (brand name, Oncovin), also known as leurocristine, is a vinca alkaloid from the Catharanthus roseus (Madagascar periwinkle), formerly Vinca rosea and hence its name. It is a mitotic inhibitor, and is used in cancer chemotherapy.

HeLa cells

The living cells of a woman who died of cervical cancer more than half a century ago could reveal how we might extend our own lifespans.

Secrets of immortality could be tantalisingly close. The woman in question is Henrietta Lacks, whose tragedy has allowed researchers around the world to better understand the links between cancer, when cells seem to be able to multiply indefinitely, and ageing, when they become senescent and lose the ability to divide.

The story of this research dates back to the winter of 1951 when the mother of five underwent a seemingly routine biopsy for a suspicious cervical mass. A portion went to the pathology lab for diagnosis but, unknown to the black 31-year-old, another was diverted for research by two investigators at Johns Hopkins University, Baltimore.

In a review in the journal Nature, Dr Toren Finkel of the National Heart Lung and Blood Institute, Bethesda, and Manuel Serrano and Maria Blasco in the Spanish National Cancer Research Centre, Madrid, conclude: "The small part that remained in the laboratory would forever change the course of science."

George Otto Gey and Martha Gey of Johns Hopkins had spent the better part of the preceding two decades attempting to find a human cell that could grow indefinitely in the lab. That search would end with the arrival of the biopsy sample taken from Lacks.

Although Lacks died eight months later, her fast-growing cells still multiply in vials of red liquid held by laboratories around the world. Known as 'HeLa' cells in her honour, there are probably more alive today than in her entire body when she lived and have conferred on her a kind of immortality. To researchers studying human ageing, they pose a fundamental question: If human tissue cells can live indefinitely, why not people?

Her cells help lead to a clearer understanding of the barriers that separate normal cells from their cancer counterparts, says Dr Finkel. "These same barriers now appear to be intimately connected to how and why we age. Perhaps Henrietta's final gift to us is the growing realisation that somewhere within the curse of the cancer cell's immortality there might also lie the secret of how we might understand and extend our own lifespan."

Researchers have been slowly stripping away the many secrets that endow cancer cells with the gift of immortality. One of the most promising lines of research is into telomeres, protective caps that form around chromosomes - bundles of genes - in cells. Every time the cell divides, the telomeres get a little shorter until the cell self-destructs. But cancer cells can rebuild them with an enzyme called telomerase.

On the day Lacks died, George Gey himself appeared on American TV to announce the dawn of a new era in medical research. For the first time, he explained, it was possible to grow human cells continuously in culture. Since then, her cells have become a standard laboratory tool for studying the effects of radiation, growing viruses and testing medications.

Initially, the cell line was said to be named after a "Helen Lane" or "Helen Larson", in order to preserve Lacks's anonymity.

They helped eradicate polio, flew in early space shuttle missions and sat in nuclear test sites around the world. They have been subject to genetic analysis, revealing the presence of a human papillomavirus now thought to cause the disease and that they probably have the same mutations as present half a century ago, helping to answer many scientific questions.

"Undoubtedly, none of these questions were contemplated on that day in October 1951 when Henrietta Lacks's body was laid to rest in an unmarked grave near her family's small tobacco farm," they write in Nature "Unbeknownst to those who gathered in that Virginia field-but as we now know-not all of Henrietta was buried that day."

The family was not asked for consent, a sad commentary on biomedical research in the 1950s, when it was not uncommon for doctors to conduct research on patients without their knowledge. Because Gey had called them HeLa cells, it was only years later that the family only discovered her strange legacy to modern science

Read more at http://www.telegraph.co.uk/science/science-news/3303912/How-Henriettas-cells-gave-us-new-hope.html

Another interesting read http://www.nytimes.com/2010/02/02/health/02seco.html?em A Lasting Gift to Medicine That Wasn’t Really a Gift by Denise Grady/ NY Times

Legionnaires' disease

Legionellosis refers to the two clinical syndromes caused by bacteria of the genus Legionella. Pontiac fever is an acute, febrile, self-limited illness that has been serologically linked to Legionella species, whereas Legionnaires' disease is the designation for pneumonia caused by these species. Legionnaires' disease was first recognized in 1976, when an outbreak of pneumonia took place at a hotel in Philadelphia during the American Legion Convention. The causative agent proved to be a newly discovered bacterium, Legionella pneumophila, that was isolated from lung specimens obtained from the victims at autopsy

Rx - The eye of Horus

There are several explanations for the symbol Rx.

The symbol Rx is derived from the major lines in the symbol of the Eye of Horus. Horus was an Egyptian god, the god of Nekhen, a village in Egypt, and god of the sky, of light, and of goodness. He was the son of Isis, the nature goddess, and Osiris, the god of the underworld. Osiris was murdered by his evil brother Seth, the god of darkness and evil. Horus sought to avenge his father's death by challenging his uncle Seth to a firght. Seth cut out Horus's eye, but Thoth, a god associated with wisdom and compassion, magically restored the eye. Horus did defeat Seth, finally. The eye of Horus consisted of the sun and the moon, and it was the moon eye that was damaged. This explained the phases of the moon-the waning of the moon was the eye being damaged and the waxing, the healing. The eye of Horus became a powerful symbol of healing in the eyes of the Egyptians. In Egyptian art, the eye of Horus strongly resembles the modern Rx of the physician. Horus's eye, also called he wadjet eye, became a symbol for health.

Anothet common explanation is that it comes from the Latin word recipi or recipere, which means "take" and is abbreviated as Rx. The symbol can also be traced to the sign of Jupiter, which was found on ancient prescriptions to appeal to the Roman god Jupiter.

St Anthony's Fire - Ergotism

Not in years had France seen such rain. Farmers slogged stolidly out to their fields to harvest the sodden crops, mill the grain and send it on its way. In little (pop. 4,400) Pont-Saint-Esprit, perched on a bluff along the River Rhone in southern France, the townspeople sat glumly in their bistros sipping wine, watching the swollen river slip past the medieval bridge which gives the town its name.

Then, without warning, pain and sudden death clutched Pont-Saint-Esprit. On a Saturday night three weeks ago, the town's doctors began getting calls from people complaining of heartburn, stomach cramps and fever chills. At first, they thought it was a mild epidemic of meat poisoning. But the calls kept flooding in. By Monday, 70 houses in the village had become tiny hospitals, with most of their families in bed. Then the doctors found their first clue: every one of the patients had eaten bread from the shop of Baker Roch Briand. All eight of Pont-Saint-Esprit's bakeries were ordered temporarily shut.

Red Flowers & Molten Lead. That night the first man died in convulsions. Later, two men who had seemed to be recovering dashed through the narrow streets shouting that enemies were after them. A small boy tried to throttle his mother. Gendarmes went from house to house, collecting pieces of the deadly bread to be sent to Marseille for analysis. Among the stricken, delirium rose: patients thrashed wildly on their beds, screaming that red flowers were blossoming from their bodies, that their heads had turned to molten lead. Pont-Saint-Esprit's hospital reported four attempts at suicide.

What was the mysterious madness? Pont-Saint-Esprit speculated that the village idiot had hexed Baker Briand's flour, that the flour had been packed in fertilizer sacks, that rats in the grain elevator had contaminated the flour. The police knew better. They had traced the flour back from Briand's bakeshop through the government-controlled flour depot to a mill near Poitiers, nearly 300 miles away.

The Parasite. Last week the word came back from the police laboratory:"We have identified a vegetable alkaloid having the toxic and biological characteristics of ergot, a cereal parasite." Pont-Saint-Esprit had been stricken by ergot poisoning, a medieval disease as old as its proud bridge, so old that it had almost been forgotten. Modern medicine knows about ergot, but has rarely seen it in the form of an epidemic disease.* It is a black fungus that grows on wet grain, contains chemicals that powerfully affect the blood vessels and the nervous system. Doctors often use ergot extracts to start contractions in the uterus in childbirth.

In the Middle Ages, growing uncontrolled in wet summers, ergot was no such helpful friend. The disease was called "St. Anthony's Fire," and raged periodically through Europe. Monastic chroniclers wrote of agonizing burning sensations, of feet and hands blackened like charcoal, of vomiting, convulsions and death. Whole villages were driven mad. That, in effect, was what had happened to Pont-Saint-Esprit in 1951.

By week's end, French police had found the miller who ground the ergot-laden rye and a man who acknowledged selling him the grain, charged them both with involuntary homicide. In Pont-Saint-Esprit, the toll of illness passed 200; four had died, 28 were still on the critical list. France considered itself lucky: all the contaminated grain seemed to have gone into that one bag of flour delivered to Baker Roch Briand


Read more: http://www.time.com/time/magazine/article/0,9171,815355-2,00.html#ixzz0bhDFMQL7

Anthony the Great (c 251–356), (different from St Antony of Padua) also known as Saint Anthony, Anthony the Abbot, Anthony of Egypt, Anthony of the Desert, Anthony the Anchorite, Abba Antonius (Ἀβᾶς Ἀντώνιος), and Father of All Monks, was a Christian saint from Egypt, a prominent leader among the Desert Fathers. He is celebrated in many churches on his feast days: 17 January in the Eastern Orthodox Church and Western churches; and Tobi 22, (January 30) in the Coptic Orthodox Church and the Coptic Catholic ChurchSt.
Anthony was a third century Egyptian ascetic, who lived an unblemished life in the desert near the Red Sea, fasting for long periods, which was probably the reason for the visions and temptations he is said to have experienced. He believed them to be the work of the devil, and resisted steadfastly. In his own lifetime, Anthony had no direct connection with ergotism, however his name was taken by an Order of Hospitallers, founded in France about 1100. The Hospitallers, wearing black robes embroidered with blue crosses, travelled widely across medieval Europe, ringing little bells to attract alms, and the hospitals they thus funded became pilgrimage centres for sufferers from ergotism.6 The Antonite monks were credited with many cures, and thus Anthony's name and life story became attached to the disease. What were said to be the saint's bones were sprinkled with holy water or wine, which was then drunk by the afflicted; however it seems more likely that cures were related to the Hospitallers providing a diet free from contaminated grain. Amputated limbs were frequently left at the sites of shrines to St Anthony as offerings of thanks and evidence of the saint's success

Read more in Lancet. 2002 May 18;359(9319):1768-70.St Anthony's fire and living ligatures: a short history of ergometrine.
De Costa C.

Wiki tells me that erysepelas and zoster are also some times called St Anthony's Fire

Image: temptation of St Anthony/ Dali