Categotry Archives: Medicine

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The Polio Crusade

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Categories: Medicine

In the summer of 1950 fear gripped the residents of Wytheville, Virginia. Movie theaters shut down, baseball games were cancelled and panicky parents kept their children indoors — anything to keep them safe from an invisible invader. Outsiders sped t...

In the summer of 1950 fear gripped the residents of Wytheville, Virginia. Movie theaters shut down, baseball games were cancelled and panicky parents kept their children indoors — anything to keep them safe from an invisible invader. Outsiders sped t…
American Experience: The Polio Crusade
Airs Monday, April 12, 2010 at 9 p.m. on KPBS TV

Credit: March of Dimes

Above: Nurse and child with polio. This program is the story of the largest public health experiment in American history — the effort to eradicate polio, one of the 20th-century’s most dreaded diseases.
April 9, 2010
It was the largest public health experiment in American history – a crusade that eradicated polio, one of the 20th century’s most dreaded diseases. The polio epidemic terrified Americans for decades, affecting thousands of children, leaving many crippled, paralyzed or condemned to life in an iron lung.

Photo Gallery
In the mid-twentieth century, the National Foundation for Infantile Paralysis (predecessor to today’s March of Dimes) pioneered a new approach to philanthropy, raising money a dime at a time from millions of small donors. The nonprofit enlisted poster children, celebrities, presidents, and other partners in their high-profile campaigns. View the photos.
But on April 26, 1954, hope emerged. At the Franklin Sherman Elementary School in McLean, Virginia, six-year-old Randy Kerr stood at the head of a long line of children and waited patiently while a nurse gently rolled up his sleeve, then filled a syringe with a cherry-colored liquid containing the world’s first polio vaccine.

Developed just a few years earlier by virologist Jonas Salk, the polio vaccine had not yet been widely tested on humans. No one was certain it was safe or whether it could provide effective protection against the disease. In the coming weeks, nearly two million school children in 44 states received the shots. The Salk vaccine trials were the dramatic culmination of years of research and a multi-million dollar investment, made up in large part by public donations.

Based in part on David Oshinsky’s Pulitzer Prize-winning book, “Polio: An American Story,” “The Polio Crusade” chronicles a decades-long crusade, fueled by the bold leadership of a single philanthropy and its innovative public relations campaign, and features a bitter battle between two scientists and the breakthrough of a now-forgotten woman researcher.

The 20th-century effort to eradicate polio is chronicled. Included: lawyer Basil O’Connor (1892-1972), who developed the “March of Dimes” concept to help fund research; the competition between polio researchers Jonas Salk and Albert Sabin.

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Polio Virus

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Categories: Medicine

Early Polio History Polio (also known as poliomyelitis or infantile paralysis) is an illness caused by poliovirus. At one time, poliovirus infection occurred throughout the world. The history of polio begins with records from antiquity mentioning crip...

Smithsonian National Museum of American History
Quote. To initiate infection, the virus must first attach to its cell-surface receptor and then deliver its RNA to the appropriate cellular compartment. End Quote. -David Belnap, biochemist, 2000
Poliomyelitis is a viral disease. There are three types of poliovirus and many strains of each type. The virus enters through the mouth and multiplies in the throat and gastrointestinal tract, then moves into the bloodstream and is carried to the central nervous system where it replicates and destroys the motor neuron cells. Motor neurons control the muscles for swallowing, circulation, respiration, and the trunk, arms, and legs.

Human nerve cells have a protruding protein structure on their surface whose precise function is unknown. When poliovirus encounters the nerve cells, the protruding receptors attach to the virus particle, and infection begins. Once inside the cell, the virus hijacks the cell’s assembly process, and makes thousands of copies of itself in hours. The virus kills the cell and then spreads to infect other cells.

Factoids
bullet Many types of human cells have receptors that fit the poliovirus; no one knows why the virus favors motor neurons over other cells for replication.
bullet For every 200 or so virus particles that encounter a susceptible cell, only one will successfully enter and replicate.
bullet In tissue culture, poliovirus enters cells and replicates in six to eight hours, yielding 10,000 to 100,000 virus particles per cell.
bullet One way the human immune system protects itself is by producingantibodies that engage the protein covering of the poliovirus, preventing the virus from interacting with another cell.
bullet There are three types of poliovirus: 1, 2, and 3. Type 1 is the most virulent and common. Both the Salk and Sabin vaccines are “trivalent” that is, active against all three virus types. Type 2 poliovirus has not been detected anywhere in the world since 1999.
bullet A person who gets polio is immune to future infection from the virus type that caused the polio.
Illustration of the poliovirus attached to neuron receptors
Poliovirus bound to a neuron receptor Illustration courtesy of Link Studio
Photo of poliovirus bronze models next to microscopic images
Scientifically accurate bronze models (without patina) of the poliovirus created for the Smithsonian by Edgar Meyer, 2005.
These models are an adaptation of James Hogle’s image of the poliovirus and were specially cast in bronze for the exhibit. They are the first three dimensioanl representations of the poliovirus

Poliovirus Capsid Model and Scientific Art
Scientists use many types of models to visualize concepts about the real world. Environmentalists and climatologists make computer graphics models of the entire earth. In 1953, James Watson and Francis Crick used a brass model of DNA‘s structure—the so-called “double helix”—as a physical analog of genes. All models are partly right and partly wrong because they represent only a level of knowledge at a given time. This bronze model of the poliovirus was made by for the exhibition by biochemist/artist Edgar Meyer, based on the first three-dimensional images of poliovirus that virologist James Hogle at Harvard obtained from X-ray crystallography in 2000. While the model represents the surface relief at a very high resolution, the shell (capsid) in nature is more complex than artwork or X-ray crystallography can show.

A Vaccine to Prevent Polio
Scientists could make vaccines even before they completely understood how they functioned. Eventually researchers learned that vaccines work by fooling the body’s immune system into producing antibodies even though there is no disease. Jonas Salk and Albert Sabin used this knowledge to create two different kinds of polio vaccines.

Life Cycle of the Poliovirus Animation (popup window)
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Illustration of the life cyle of the poliovirus
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Life cycle of the poliovirus
Illustration courtesy NMAH

Photo of James Hogle
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James Hogle in his Harvard Medical School lab, 2000

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History of Asperger’s Disorder

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Categories: Medicine


By AMI KLIN, PH.D AND FRED R. VOLKMAR, M.D.

Asperger Syndrome (AS, also known as Asperger’s Disorder) is a severe developmental disorder characterized by major difficulties in social interaction, and restricted and unusual patterns of interest and behavior.

Autism is the most widely recognized pervasive developmental disorder (PDD). Other diagnostic concepts with features somewhat similar to autism have been less intensively studied, and their validity, apart from autism, is more controversial.

One of these conditions, termed Asperger syndrome (AS) was originally described by Hans Asperger, who provided an account of a number of cases whose clinical features resembled Kanner’s (1943) description of autism (e.g., problems with social interaction and communication, and circumscribed and idiosyncratic patterns of interest). However, Asperger’s description differed from Kanner’s in that speech was less commonly delayed, motor deficits were more common, the onset appeared to be somewhat later, and all the initial cases occurred only in boys. Asperger also suggested that similar problems could be observed in family members, particularly fathers.

This syndrome was essentially unknown in the English literature for many years. An influential review and series of case reports by Lorna Wing (1981) increased interest in the condition, and since then both the usage of the term in clinical practice and number of case reports and research studies have been steadily increasing. The commonly described clinical features of the syndrome include:

  1. paucity of empathy;
  2. naive, inappropriate, one-sided social interaction, little ability to form friendships and consequent social isolation;
  3. pedantic and monotonic speech;
  4. poor nonverbal communication;
  5. intense absorption in circumscribed topics such as the weather, facts about TV stations, railway tables or maps, which are learned in rote fashion and reflect poor understanding, conveying the impression of eccentricity; and
  6. clumsy and ill-coordinated movements and odd posture.

Although Asperger originally reported the condition only in boys, reports of girls with the syndrome have now appeared. Nevertheless, boys are significantly more likely to be affected. Although most children with the condition function in the normal range of intelligence, some have been reported to be mildly retarded. The apparent onset of the condition, or at least its recognition, is probably somewhat later than autism; this may reflect the more preserved language and cognitive abilities. It tends to be highly stable, and the higher intellectual skills observed suggest a better long-term outcome than is typically observed in autism.

Higher Functioning Autism or Asperger’s?

There are many similarities with autism without mental retardation (or “Higher Functioning Autism”), and the issue of whether Asperger syndrome and Higher Functioning Autism are different conditions is not resolved.

To some extent, the answer to this question depends on the way clinicians and researcher make use of this diagnostic concept, since until recently there was no “official” definition of Asperger syndrome. The lack of a consensual definition led to a great deal of confusion as researchers could not interpret other researchers’ findings, clinicians felt free to use the label based on their own interpretations or misinterpretations of what Asperger syndrome “really” meant, and parents were often faced with a diagnosis that nobody appeared to understand very well, and worse still, nobody appeared to know what to do about it.

School districts are often not aware of the condition, insurance carriers could not reimburse services provided on the basis of this “unofficial” diagnosis, and there was no published information providing parents and clinicians alike with guidelines on the meaning and implications of Asperger syndrome, including what should the diagnostic evaluation consist of and what forms of treatment and interventions were warranted.

Asperger’s Ascent to an Official Diagnosis

This situation has changed somewhat since Asperger syndrome was made “official” in DSM-IV (APA, 1994), following a large international field trial involving over a thousand children and adolescents with autism and related disorders (Volkmar et al., 1994). The field trials revealed some evidence justifying the inclusion of Asperger syndrome as a diagnostic category different from autism, under the overarching class of Pervasive Developmental Disorders. More importantly, it established a consensual definition for the disorder which should serve as the frame of reference for all those using the diagnosis. However, the problems are far from over. Despite some new research leads, knowledge on Asperger syndrome is still very limited. For example, we don’t really know how common it is, or the male/female ratio, or to what extent there may be genetic links increasing the likelihood of finding similar conditions in family members.

Clearly, the work on Asperger syndrome, in regard to scientific research as well as in regard to service provision, is only beginning. Parents are urged to use a great deal of caution and to adopt a critical approach toward information given to them. Ultimately, the diagnostic label – any label, does not summarize a person, and there is a need to consider the individual’s strengths and weaknesses, and to provide individualized intervention that will meet those (adequately assessed and monitored) needs. That notwithstanding, we are left with the question of what is the nature of this puzzling social learning disability, how many people does it affect, and what can we do to help those affected by it. The following guidelines summarize some of the information currently available on those questions.


This article by Ami Klin, Ph.D., and Fred R. Volkmar, M.D., Yale Child Study Center, New Haven, Connecticut and was originally published by the Learning Disabilities Association of America, June 1995. To learn more about Asperger’s Syndrome and Autism, please visit the Yale Developmental Disabilities Clinic website.

Scientifically Reviewed

 

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Banting and Best isolate insulin 1922

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Categories: Medicine

In 1920, Canadian surgeon Frederick Banting visited the University of Toronto to speak to the newly appointed head of the department of physiology, John J.R. Macleod. Macleod had studied glucose metabolism and diabetes, and Banting had a new idea on how to find not only the cause but a treatment for the so-called “sugar disease.”

Late in the nineteenth century, scientists had realized there was a connection between the pancreas and diabetes. The connection was further narrowed down to the islets of Langerhans, a part of the pancreas. From 1910 to 1920, Oscar Minkowski and others tried unsuccessfully to find and extract the active ingredient from the islets of Langerhans. While reading a paper on the subject in 1920, Banting had an inspiration. He realized that the pancreas’ digestive juice was destroying the islets of Langerhans hormone before it could be isolated. If he could stop the pancreas from working, but keep the islets of Langerhans going, he should be able to find the stuff! He presented this idea to Macleod, who at first scoffed at it. Banting badgered him until finally Macleod gave him lab space, 10 experimental dogs, and a medical student assistant.

In May, 1921, as Macleod took off for a holiday in his native Scotland, Banting and his assistant Charles Best began their experiments. By August they had the first conclusive results: when they gave the material extracted from the islets of Langerhans (called “insulin,” from the Latin for “island”) to diabetic dogs, their abnormally high blood sugars were lowered. Macleod, back from holiday, was still skeptical of the results and asked them to repeat the experiment several more times. They did, finding the results the same, but with problems due to the varying purity of their insulin extract.

Macleod assigned chemist James Bertram Collip to the group to help with the purification. Within six weeks, he felt confident enough of the insulin he had isolated to try it on a human for the first time: a 14-year-old boy dying of diabetes. The injection indeed lowered his blood sugar and cleared his urine of sugars and other signs of the disease. Banting and Best published the first paper on their discovery a month later, in February, 1922. In 1923, the Nobel Prize was awarded to Banting and Macleod for the discovery, and each shared their portion of the prize money with the other researchers on the project.

Ironically, Banting’s original idea wasn’t entirely correct. He and Best later found they could obtain insulin even from an intact pancreas. Improved technology for testing and detecting sugar in the blood and urine provided information that earlier researchers didn’t have, and this encouraged them to pursue a line of thinking that may have looked like a dead end to those working in the decades before them.

The discovery of insulin was one of the most revolutionary moments in medicine. Though it took some time to work out proper dosages and to develop manufacturing processes to make enough insulin of consistent strength and purity, the introduction of insulin seemed literally like a miracle. One year the disease was an automatic death sentence; the next, people — even children — had hopes of living full and productive lives even with the disease. Estimates show there are more than 15 million diabetics living today who would have died at an early age without insulin.

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