Almond Holiday Chewies
Almond Chewies, delicious with coffee, tea, milk, anything. ©Joyce Hays, Target Health Inc.
Delicious, not too sweet, and easy to make.
1 (7-ounce) tube pure almond paste (not marzipan; 3/4 cup)
1 cup Splenda granulated, instead of regular sugar
Pinch of Kosher salt
2 large egg whites at room temperature for at least 30 minutes
Preheat oven to 3000F and place racks in the upper and lower thirds of your oven. Line two large sheet pans with parchment paper.
Pulsing paste, Splenda, salt ©Joyce Hays, Target Health Inc.
Pulse almond paste, sugar and salt in a food processor until broken up, then add egg whites and puree until smooth.
Space the chewies far apart, on the parchment ©Joyce Hays, Target Health Inc.
Going into the oven ©Joyce Hays, Target Health Inc.
Transfer batter to pastry bag fitted with a 3/8-inch tip and pipe 3/4-inch rounds (1/3 inch high) about 1-inch apart in pans. Dip a fingertip in water and gently tamp down any peaks. You need to leave a 1 inch space between these cookies, because suddenly, just before they’re done, they expand and puff up
Bake, rotating and switching position of pans halfway through (after 8 minutes), until golden and puffed, 15 to 18 minutes. The switch enables them to bake evenly.
Cooling the chewies ©Joyce Hays, Target Health Inc
Let these chewies cool in their pans. Once cool, they’re much easier to cleanly remove from the parchment.
I used these jams for filling. ©Joyce Hays, Target Health Inc.
You can make them into tiny sandwich cookies, spreading some jam (I used cherry, apricot, raspberry) between them, or ganache (3 ounces of semi-sweet chips melted with 1 to 2 tablespoons of cream). Then leave them to thicken a bit. You’ll get about twenty, if you sandwich them. The ganache is so easy to make, I would recommend this as one of your yummy fillings. Using granulated Splenda instead of sugar in the chewies, cuts the calories. Splenda is one of those sugar substitutes that works well in baking, or cooking at any temperature.
Chewies can be kept in an airtight container at room temperature for a day or two or frozen up to one month.
If you need to buy any of the following for this recipe, here’s where I got mine:
1. Food Processer, Wm-Sonoma, Amazon
2. Parchment paper for baking is at Food Emporium, Wm-Sonoma, Dean & Deluca
3. Pastry bag fitted with a variety of tips incl. 3/8-inch tip at Wm-Sonoma
4. Cookie sheets at Wm-Sonoma, Amazon
5. Tube of Almond paste at Dean & Deluca or Amazon
6. Granulated Splenda, from Fresh Direct, Amazon, just about anywhere
We’re starting our meal with glasses of icy Pino Grigio and hummus with warm pita, flat bread and raw veggie sticks. Yes, we keep on eating hummus as we never get tired of it. Next we’re having my baked zucchini sticks in marinara, with a simple turkey salad with dried cranberries, made from left-over turkey that we had last night.
Dessert is almond chewies and fresh blueberries. I served these almond chewies last night, but they disappeared rapidly, except for 4, so I made another batch.
Bon Appetit !
These amoebae eat human cells while they are still alive, and then move on. Terrifying.
It used to be thought that the parasite Entamoeba histolytica killed human cells with toxins and only ate them once they were dead–and that during its meals, it would eat cells by engulfing them whole, like other amoebas. But a new study shows that these parasites instead chomp on human cells while they are still alive, taking little bites until the cells die and then moving on. If people were completely rational, we would fear E. histolytica much more than something like sharks, since these tiny amoebae kill as many as 100,000 people every year (and sharks only kill about five to ten people worldwide annually).“This process of nibbling of cells went unrecognized by everyone in this field, including me, for over a hundred years,” study co-author and infectious disease specialist William Petri of the University of Virginia in Charlottesville told Science. The finding completely changes how scientists think of the parasites, and may lead to new treatments for pathogen, which lives in the gut and infects about 50 million around the world. In certain circumstances they can triggeramoebiasis, a potentially fatal diarrhoeal disease.
This habit of chewing bits of live cells in this way and moving on is remarkably strange, and basically unprecedented. “The ingestion of live cell material and the rejection of corpses illuminate a stark contrast to the established model of dead cell clearance in multicellular organisms,” the authors wrote in the study, published this week in Nature.
The scientists discovered the nibbling after introducing fluorescent material into amoebas and human cells, and observing them in a petri dish in the lab. “It was remarkable to see the amoebae were taking bites,” said microbiologist Katherine Ralston of the University of Virginia. The biting “resembled trogocytosis, a process in which immune cells extract bits of other immune cells, but was unique in that it occurred between a parasite and its host and ultimately caused cell death,” Science noted.
New gravity measurements determined Enceladus has a liquid water sea about as large as Lake Superior.
Buried under miles of ice, astronomers have detected a liquid water sea on one of Saturn’s moons, Enceladus. The sea is about the size of Lake Superior and it touches Enceladus’ silicate core… which means it could have minerals dissolved in it that are necessary for life. “It makes, in fact, the interior of Enceladus a very attractive potential place to look for life,” Jonathan Lunine, a Cornell University astronomer who worked on the study determining Enceladus has an ocean, said during a teleconference for reporters.
This extraterrestrial sea could also be the source of water for those funny jets Enceladus has geysering out of its south pole, but scientists don’t yet have data linking the two phenomena.
This new announcement comes from a team of Italian and U.S. scientists, who analyzed gravity data from the Cassini spacecraft. Cassini has been flying around Saturn for almost ten years now, passing close to the surfaces of Saturn’s moons and taking sexy photos of Saturn itself.
Scientists had previously suspected Enceladus may have an underground ocean. This latest study calculated the density of material in different parts of Enceladus after three gravity-measuring flybys. Those measurements revealed there’s something underneath Enceladus’ ice in the south that’s denser than the ice. Liquid water is the most likely explanation, says David Stevenson, a planetary scientist at the California Institute of Technology who also worked on the study.
Enceladus In this image, you can see the fissures on Enceladus’ southern region from which its jets of water vapor emerge. Image courtesy of NASA/JPL/Space Science Institute
Scientists weren’t always this excited about Enceladus, which is just one of Saturn’s more than 50 known moons. It’s small, with a diameter about one-seventh that of Earth’s moon’s. So at first, scientists thought it was likely inactive. Small objects like Enceladus cool quickly after they form, so they don’t have warm, active cores. They also don’t have enough gravity to hold an atmosphere. But in 2005, Cassini spotted plumes of ice erupting from Enceladus’ southern surface, revealing this little moon has more up its sleeve than anyone suspected.
The secret to little Enceladus’ activity is the strong tidal force it feels from Saturn’s gravitational pull. Its parent planet pulls Enceladus’ ice out of shape, creating friction and heat and melting ice into water. The liquid water then acts as a lubricant, encouraging more ice blocks to rub against each other and create more water. It’s even possible that the moon’s ice plumes come only from water created by flexing ice, not from the newly discovered under-ice sea. So far, scientists have no way of checking whether there’s any interior plumbing connecting the sea to the plumes.
Cassini’s immediate next plans are to make repeated flybys of the Saturnian moons Titan and Dione, which may also have underground oceans.
You can read about Enceladus’ underground sea in Iess, Stevenson, Lunine and their colleagues’ paper in the journal Science.
A chemical trigger regrows the thymus of a living mouse
Oh, to be a mouse. You’d have been cured of every conceivable cancer and now, you’d have something of a fountain of youth, too, at least for your thymus. A team of researchers has gotten immune-system organs called thymuses in mice to grow, The Economist reports. After the researchers’ treatment, the mice’s thymuses grew more than twice as large. The thymuses, which normally change in structure and become less efficient as animals age, also returned to a more youthful structure.
This is the first time anybody has been able to get a working organ in a mammal to rejuvenate itself, The Economist reports. It’s a step forward for this particular method organ regeneration. Of course, many labs have grown artificial organs in different ways. We’ve covered everything from a trachea, made from the patient’s own stem cells, to 3-D printed organs. Some of these, such as the trachea, have already been used in people.
In contrast, the thymus-growing method didn’t require any cells. Instead, it relied on a chemical trigger to make the thymuses grow. However, because the trigger only worked in mice that had been genetically engineered to be receptive to the trigger, the study is only a demonstration that getting organs to grow is possible. It will still take many years to figure out how exactly to trigger the similar growth in humans.
A team of three regenerative medicine researchers at the University of Edinburgh published the mouse-thymus work this month in the scientific journal Development.
Here are two rovers built to win the Google Lunar XPrize.
Next year, robots will land on the moon, competing for the Google Lunar XPrize. The contest offers $40 million in rewards, including a $20 million grand prize. Winning is fairly straightforward: Safely land a privately funded spacecraft, move it a third of a mile, and beam back HD-video “mooncasts.” Completing the challenge by December 31, 2015, however, is anything but easy. Organizers have already extended the deadline by a year, and of the 33 teams that initially registered, only 18 remain. Astrobotic, an offshoot of Carnegie Mellon University, survives as a leading contender. The group has finished a two-spacecraft design—Griffin, a car-size lander, and a surface explorer called Red Rover. It has also booked space aboard a rocket that’s scheduled to launch in October 2015. Here’s how Astrobotic plans to take home the prize.
GROSS WEIGHT: 1,150 lbs.
PAYLOAD CAPACITY: 600 lbs.
MAXIMUM POWER CONSUMPTION: 250 watts
DIMENSIONS: 6.5 ft. high by 9.8 ft. wide by 9.8 ft. long
WEIGHT: 220 lbs. (including payload)
SPEED: 20 feet per minute
POWER CONSUMPTION: 120 watts
1) REACH THE MOON
A SpaceX Falcon 9 rocket will send Astrobotic’s two-spacecraft stack on a trajectory toward the moon. From there, the four-legged aluminum lander, Griffin, will reach lunar orbit 4.5 days later.
2) LAND SOFTLY
Like an Apollo lander, Griffin will fire its main thruster to slow down and descend toward the moon. Four clusters of smaller thrusters, each fed by four spherical fuel tanks, will make minute course corrections to stick the landing.
3) GET MOVING
Once Griffin safely touches down, Red Rover will drop from the lander’s lower deck and begin its journey. Human drivers on Earth will steer it via joystick while monitoring 3-D camera footage. A passive rocker suspension system will keep all four wheels on the lunar surface at all times, allowing the craft to clamber over rocks and uneven terrain. Red Rover is also programmed to automatically avoid obstacles such as steep crater walls.
4) PHONE HOME
Red Rover will stream photos and video back to Griffin at five megabits per second (equivalent to cable Internet speeds), and Griffin will relay the data to Earth at a one-megabit-per-second clip (roughly as fast as DSL). Future rovers will talk directly to Earth to improve bandwidth—and shorten the laggy 10-second round-trip for packets of data.
EXTRA CREDIT CHALLENGES
Aside from $5 million for second place, teams can claim up to $4 million by completing the following technical challenges:
- Traveling 3.1 miles across the lunar surface (10 times farther than the grand-prize requirement)
- Surviving at least one lunar night, which lasts about 14 Earth days and during which temperatures dip to –260˚F
- Verifying the presence of water on the moon
What is the Clinical Trials Transformation Initiative?
Target Health is pleased to announce that it is now 6 years that it has been an active member of the Clinical Trials Transformation Initiative (CTTI).
CTTI was founded by the U.S. Food and Drug Administration (FDA) and Duke University as a public-private partnership whose mission is to identify and promote practices that will increase the quality and efficiency of clinical trials. CTTI now comprises more than 60 organizations from across the clinical trial enterprise. Members include representatives of government agencies (the FDA, Centers for Medicare and Medicaid Services, Office of Human Research Protections, National Institutes of Health, and other national and international governmental bodies), industry representatives (pharmaceutical, biotech, device, and clinical research organizations), patient advocacy groups, professional societies, investigator groups, academic institutions, and other interested parties.
Back in 2008 Glen Park, our Sr. Director of Clinical and Regulatory Affairs at Target Health suggested that we explore joining CTTI. After speaking with our good friend and colleague Judith Kramer, CTTI’s Founding Director, now retired, we joined immediately. CTTI has had, and continues to have, a profound impact on the way drugs, biologics and devices are tested in the US and around the world. Very tangible results are the most recent monitoring guidance and reflection papers from FDA and EMA, respectively. And yes, there is more to come.
This year, Dr. Jules Mitchel, President of Target Health was nominated to the Executive Committee as the representative of the Steering Committee. Decisions about the overall direction and strategy for CTTI are made by a 19-member Executive Committeethat is co-chaired by Dr. Robert Califf, Vice Chancellor for Clinical Research at Duke University, and CDR Melissa Robb, Associate Director for Regulatory Affairs, Office of Medical Policy, Center for Drug Evaluation and Research, U.S. Food and Drug Administration. The Executive Committee includes distinguished U.S. and international thought leaders in government, academia, industry, and patient advocacy who are experienced at envisioning and facilitating improvements in health care and medical research systems. This group ensures that CTTI informs and facilitates meaningful improvements to the design and conduct of clinical trials.
ON TARGET is the newsletter of Target Health Inc., a NYC-based contract research organization (eCRO), providing strategic planning, regulatory affairs, clinical research, data management, biostatistics, medical writing and software services, including the paperless clinical trial, to the pharmaceutical and device industries.
New York City on a sparkling but chilly day in February 2014
For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.
Joyce Hays, Founder and Chief Editor of On Target
Jules Mitchel, Editor
Hemophilia A, B, C
The word hemophilia comes from the Greek haima ?blood’ and philia ?love’.
Hemophilia refers to a group of inherited disorders that cause abnormal bleeding. The bleeding occurs because part of the blood — called 1) ___ – has too little of a protein that helps blood clot. Symptoms of hemophilia range from increased bleeding after trauma, injury, or surgery to sudden bleeding with no apparent cause. There are three types of hemophilia:
Hemophilia A — also called classic hemophilia — is most common and occurs in about 85% of people with hemophilia, while Hemophilia B — also called Christmas disease — is less common and occurs in about 15% of people with hemophilia.
Hemophilia A results from too little of a plasma protein called factor VIII, which helps blood clot. The greater the deficiency, the more severe the symptoms. Most people who have hemophilia A have moderate or severe symptoms.
1. Mild hemophilia: 5% to 25% of the normal factor VIII level
2. Moderate hemophilia: 1% to 5% of the normal factor VIII level
3. Severe hemophilia: Less than 1% of the normal factor VIII level
Hemophilia B results from too little of a plasma protein called factor IX, which helps blood clot. As in hemophilia A, hemophilia B can be mild, moderate, or severe. The greater the deficiency, the more severe the symptoms.
Hemophilia C is an autosomal genetic disorder (i.e. not X-linked) involving a lack of functional clotting Factor XI.
If there is no family history of hemophilia, an infant would not be tested for the condition. However, if there is a family history of hemophilia, specific tests can be done from an umbilical 2) ___ blood sample to see if a newborn infant has hemophilia. In fact, if the family desires, such testing can be done before a child is born. For moderate or severe hemophilia, doctors and caregivers usually don’t see any signs of the condition at birth or even for some time afterward. Symptoms in children may include:
1. Heavy bleeding in a male baby after circumcision
2. Excessive bruising or unusual bleeding during teething
3. Swollen, bruised joints or muscles when learning to walk
4. Frequent falls and bumps
For mild hemophilia, there may not be any noticeable symptoms until someone undergoes a dental procedure, which may result in heavy bleeding, or there may be no unusual bleeding unless there is an injury. There may also be bleeding inside 3) ___(internally), especially in the knees, ankles, and elbows. This bleeding can damage organs and tissues and may be life threatening.
Hemophilia usually is inherited. The disorder is passed from parents to children through genes. Hemophiliacs have little or no clotting factor. Clotting factor is a protein needed for normal blood clotting. There are several types of clotting factors. These proteins work with platelets (PLATE-lets) to help the blood clot. Platelets are small blood cell fragments that form in the bone marrow, a sponge-like tissue in the bones. Platelets play a major role in blood clotting. When blood vessels are injured, clotting factors help platelets stick together to plug cuts and breaks on the vessels and stop bleeding.
Hemophilia is rarely acquired, meaning it somehow develops during one’s lifetime. This can happen if one’s body forms antibodies (proteins) that attack the clotting factors in the 4) ___. The antibodies can prevent the clotting factors from working.
Hemophilia usually occurs in males (with rare exceptions). About 1 in 5,000 males are born with hemophilia each year. Hemophilia is a lifelong disease, but with proper treatment and self-care, most people with hemophilia can maintain an active, productive lifestyle. Signs and symptoms of spontaneous bleeding may include:
1. Many large or deep bruises
2. Joint pain and swelling caused by internal bleeding
3. Unexplained and excessive bleeding or bruising
4. Blood in the urine or stool
5. Prolonged bleeding from cuts or injuries or after surgery or tooth extraction
7. Nosebleeds without a known cause
8. Tightness in your joints
9. In infants, unexplained irritability
10. Unusual bleeding after immunizations
Emergency signs and symptoms of hemophilia may include:
1. Sudden pain, swelling, and warmth of large joints, such as knees, elbows, hips and shoulders, and of the muscles of arms and legs
2. Bleeding from an injury
3. Painful, lasting headache
4. Repeated vomiting
5. Extreme fatigue
6. Neck pain
7. Double vision
At first, because of limited mobility, a baby with hemophilia usually won’t have many problems related to hemophilia. But as your baby begins to move around, falling and bumping into things, superficial bruises may occur. This bleeding into soft tissue may become more frequent the more 5) ___ a child becomes. If one is pregnant or considering a pregnancy and have a family history of hemophilia, you may be referred to a medical genetics specialist or a specialist in bleeding disorders, who can help determine if you are a carrier of hemophilia. If one is a carrier, it’s possible to test the fetus during pregnancy to determine if it is affected by the disease.
Everyone has two sex chromosomes, one from each parent. Females inherit an X chromosome from their mother and an X chromosome from their father. Males inherit an X chromosome from their mother and a Y chromosome from their 6) ___.
The gene that causes hemophilia A or B is located on the X chromosome, so it can’t be passed from father to son. Hemophilia A or B almost always occurs in boys and is passed from mother to son through one of the mother’s genes. Most women who have the defective gene are simply carriers and exhibit no signs or symptoms of hemophilia. It’s also possible for hemophilia A or B to occur through spontaneous gene mutation. The gene that causes hemophilia C can be passed on to children by either parent. Hemophilia C can occur in both boys and girls.
For people with a family history of hemophilia, it’s possible to test the fetus during pregnancy to determine if it is affected by the disease. However, such testing poses some risk to the 7) ___. Analysis of a blood sample from either a child or an adult can show a deficiency of a clotting factor.
Treatment of mild hemophilia A may involve slow injection of the hormone desmopressin (DDAVP) into a vein to stimulate a release of more clotting factor to stop bleeding. Occasionally, desmopressin is given as a nasal medication. In moderate to severe hemophilia A or hemophilia B, bleeding may stop only after an infusion of clotting factor derived from donated human blood or from genetically engineered products called recombinant clotting factors. Repeated infusions may be needed if internal bleeding is serious.
Another class of drugs called antifibrinolytics is sometimes prescribed along with clotting factor replacement therapy. These medications help prevent clots from breaking down. If internal bleeding has damaged joints, physical 8) ___ can help them function better. Therapy can preserve their mobility and help prevent frozen or badly deformed joints. In cases where repeated bouts of internal bleeding has damaged or destroyed joints, an artificial joint may be needed.
Like most aspects of hemophilia, life expectancy varies with severity and adequate treatment. People with severe hemophilia who don’t receive adequate, modern treatment have greatly shortened life spans and often do not reach maturity. Prior to the 1960s when effective treatment became available, average life expectancy was only 11 years. By the 1980s the life span of the average hemophiliac receiving appropriate treatment was 50-60 years. Today with appropriate treatment, males with hemophilia typically have a near normal quality of life with an average lifespan approximately 10 years shorter than an unaffected male.
Since the 1980s the primary leading cause of death of people with severe hemophilia has shifted from hemorrhage to HIV/AIDS acquired through treatment with contaminated blood products. The second leading cause of death related to severe hemophilia complications is intracranial 9) ___ which today accounts for one third of all deaths of patients with hemophilia. Two other major causes of death include hepatitis infections causing cirrhosis and obstruction of air or blood flow due to soft tissue hemorrhage.
Severe cases of vitamin K deficiency can present similar symptoms to hemophilia. This is because vitamin K is necessary for the human body to produce several protein clotting factors. This vitamin deficiency is rare in adults and older children but is common in newborns. Infants are born with naturally low levels of vitamin K and do not yet have the symbiotic gut flora to properly synthesize their own vitamin K. Bleeding issues due to vitamin K deficiency in infants is known as hemorrhagic disease of the newborn, to avoid this complication newborns are routinely injected with vitamin K supplements.
Commercially produced factor concentrates such as Advate, a recombinant Factor VIII, come as a white powder in a vial which must be mixed with sterile water prior to intravenous injection.
Though there is no cure for hemophilia, it can be controlled with regular infusions of the deficient clotting factor, i.e. factor VIII in hemophilia A or factor IX in hemophilia B. Factor replacement can be either isolated from human blood serum, recombinant, or a combination of the two. Some hemophiliacs develop antibodies against the replacement factors given to them, so the amount of the factor has to be increased or non-human replacement products must be given, such as porcine factor VIII.
In early 2008, the US Food and Drug Administration (FDA) approved Xyntha (Wyeth) anti-hemophilic factor, genetically engineered from the genes of Chinese hamster ovary cells. Since 1993 recombinant factor products have been available and have been widely used. While recombinant clotting factor products offer higher purity and safety, they are, like concentrate, extremely expensive, and not generally available in the developing world. In many cases, factor products of any sort are difficult to obtain in developing countries.
In 2007, a clinical trial was published in the New England Journal of Medicine comparing on-demand treatment of boys (<30 months) with hemophilia A with prophylactic treatment (infusions of 25 IU/kg body weight of Factor VIII every other day) in respect to its effect on the prevention of joint-diseases. When the boys reached 6 years of age, 93% of those in the prophylaxis group and 55% of those in the episodic-therapy group had a normal index joint-structure on MRI. Prophylactic treatment, however, resulted in average costs of $300,000 per year. The author of an editorial published in the same issue of the NEJM supports the idea that prophylactic treatment not only is more effective than on demand treatment but also suggests that starting after the first serious joint-related hemorrhage may be more cost effective than waiting until the fixed age to begin. This study resulted in the first (October 2008) FDA approval to label any Factor VIII product to be used prophylactically. As a result, the factor product used in the study (Bayer’s Kogenate) is now labeled for use to prevent bleeds. Despite Kogenate only recently being approved for this use in the US, it and other factor products have been well studied and are often prescribed to treat Hemophilia prophylactically to prevent bleeds, especially joint bleeds.
On 10 December 2011, a team of British and American investigators reported the successful treatment of hemophilia B using gene therapy. The investigators inserted the F9 gene into an adeno-associated virus-8 vector, which has a propensity for the liver, where factor 9 is produced, and remains outside the chromosomes so as not to disrupt other genes. The transduced virus was infused intravenously. To prevent rejection, the patients were primed with steroids to suppress their immune response. In October 2013, the Royal Free London NHS Foundation Trust in London reported that after treating six people with hemophilia in early 2011 with the genetically modified adeno-associated virus, two years later all of the patients were still producing blood plasma clotting factor.
Anticoagulants such as Heparin and Warfarin are contraindicated for people with hemophilia as these can aggravate clotting difficulties. Also contraindicated are those drugs which have blood thinning side effects. For instance, medicines which contain aspirin, ibuprofen, or naproxen sodium should not be taken because they are well known to have the side effect of prolonged bleeding. Also contraindicated are activities with a high likelihood of trauma, such as motorcycling and skateboarding. Popular sports with very high rates of physical contact and injuries such as American football, hockey, boxing, wrestling, and rugby should be avoided by people with hemophilia. Other active sports like soccer, baseball, and basketball also have a high rate of injuries, but have overall less contact and should be undertaken cautiously and only in consultation with a 10) ___. Sources: Mayo Clinic; NIH.gov; WebMD.com; MedPageToday.com; Wikipedia
ANSWERS: 1) plasma; 2) cord; 3) body; 4) bloodstream; 5) active; 6) father; 7) fetus; 8) therapy; 9) hemorrhage; 10) doctor
John Conrad Otto MD; 1774-1844
John C. Otto, 1803: About seventy or eighty years ago, a woman by name of Smith, settled in the vicinity of Plymouth, New Hampshire, and transmitted the following idiosyncrasy to her descendants. It is one, she observed, to which her family is unfortunately subject, and had been the source not only of great solicitude, but frequently the cause of death. If the least scratch is made on the skin of some of them, as mortal a hemorrhagy will eventually ensue as if the largest wound is inflicted. So assured are the members of this family of the terrible consequences of the least wound, that they will not suffer themselves to be bled on any consideration, having lost a relation by not being able to stop the discharge occasioned by this operation.
The first medical professional to describe hemophilia was Abulcasis from Cordoba, Spain. In the 10th century he described families whose males died of bleeding after only minor traumas. While many other such descriptive and practical references to the disease appear throughout historical writings, scientific analysis did not begin until the start of the 19th century. In 1803, Dr. John Conrad Otto, a Philadelphian physician, wrote an account about a hemorrhagic disposition existing in certain families in which he called the affected males bleeders. He recognized that the disorder was hereditary and that it affected mostly males and was passed down by healthy females. His paper was the second paper to describe important characteristics of an X-linked genetic disorder (the first paper being a description of color blindness by John Dalton, of Manchester, England, who studied his own family). Otto was able to trace the disease back to a woman who settled near Plymouth in 1720. The idea that affected males could pass the trait onto their unaffected daughters was not described until 1813 when John Hay published an account in The New England Journal of Medicine.
Dr. John Dalton 1766-1844
In 1924, a Finnish doctor discovered a hereditary bleeding disorder similar to Hemophilia localized in a group of islands (called the Aland Islands) which are located to the southwest of Finland. This bleeding disorder is called Von Willebrand Disease.
The term hemophilia is derived from the term haemorrhaphilia which was used in a description of the condition written by Friedrich Hopff in 1828, while he was a student at the University of Zurich. In 1937, Patek and Taylor, two doctors from Harvard, discovered anti-hemophilic globulin. In 1947, Pavlosky, a doctor from Buenos Aires, found hemophilia A and hemophilia B to be separate diseases by doing a lab test. This test was done by transferring the blood of one hemophiliac to another hemophiliac. The fact that this corrected the clotting problem showed that there was more than one form of hemophilia.
HM Queen Victoria,1819-1901
Hemophilia has featured prominently in European royalty and thus is sometimes known as ?the royal disease’. Queen Victoria passed the mutation for Hemophilia B to her son Leopold and, through some of her daughters, to various royals across the continent, including the royal families of Spain, Germany, and Russia. In Russia, Tsarevich Alexei Nikolaevich, son of Nicholas II, was a descendant of Queen Victoria through his mother Empress Alexandra and suffered from hemophilia. It was claimed that Rasputin was successful at treating Tsarevich’s hemophilia. At the time, a common treatment administered by professional doctors was to use aspirin, which worsened rather than lessened the problem. It is believed that, by simply advising against the medical treatment, Rasputin could bring visible and significant improvement to the condition of Tsarevich. In Spain, Queen Victoria’s youngest daughter, Princess Beatrice, had a daughter Victoria Eugenie of Battenberg, who later became Queen of Spain. Two of her sons were hemophiliacs and both died from minor car accidents. Her eldest son, Prince Alfonso of Spain, Prince of Asturias, died at the age of 31 from internal bleeding after his car hit a telephone booth. Her youngest son, Infante Gonzalo, died at age 19 from abdominal bleeding following a minor car accident where he and his sister hit a wall while avoiding a cyclist. Neither appeared injured or sought immediate medical care and Gonzalo died two days later from internal bleeding.
Ryan White was an American hemophiliac who became infected with HIV/AIDS through contaminated blood products.
Prior to 1985, there were no laws enacted within the U.S. to screen blood. As a result, many hemophilia patients who received untested and unscreened clotting factor prior to 1992 were at an extreme risk for contracting HIV and hepatitis C via these blood products. It is estimated that more than 50% of the hemophilia population, i.e. over 10,000 people, contracted HIV from the tainted blood supply in the United States alone. As a direct result of the contamination of the blood supply in the late 1970s and early/mid-1980s with viruses such as hepatitis and HIV, new methods were developed in the production of clotting factor products. The initial response was to heat-treat (pasteurize) plasma-derived factor concentrate, followed by the development of monoclonal factor concentrates, which use a combination of heat treatment and affinity chromatography to inactivate any viral agents in the pooled plasma from which the factor concentrate is derived. The Lindsay Tribunal in Ireland investigated, among other things, the slow adoption of the new methods.
As reported last week, Biogen Idec on Monday March 31, 2014, received approval to market its hemophilia B treatment Alprolix in the United States. Biogen Idec, Inc. is an American biotechnology company specializing in drugs for neurological disorders, autoimmune disorders and cancer. The company was formed in 2003 by the merger of Cambridge, Massachusetts-based Biogen Inc. and San Diego, California-based IDEC Pharmaceuticals.
Hemophilia B, which reduces the ability for blood clotting, occurs in about one in 25,000 male births annually and affects about 4,000 females in the United States. The World Federation of Hemophilia global survey conducted in 2012 estimates that approximately 28,000 people are currently diagnosed with hemophilia B worldwide.
Obesity May Prime the Colon for Cancer
A large body of scientific literature says people who are obese are predisposed to a number of cancers, particularly colorectal cancer. According to a study in mice, published online in the journal Cell Metabolism (1 April 2014), obesity, rather than diet, causes changes in the colon that may lead to colorectal cancer. The finding bolsters the recommendation that calorie control and frequent exercise are not only key to a healthy lifestyle, but a strategy to lower the risk for colon cancer, the second leading cause of cancer-related death in the United States.
To better understand the processes behind this link, the authors fed two groups of mice a diet in which 60% of the calories came from lard. The first group of mice contained a human version of a gene called NAG-1, which has been shown to protect against colon cancer in other rodent studies. The second group lacked the NAG-1 gene. Results showed that the NAG-1 mice did not gain weight after eating the high-fat diet, while mice that lacked the NAG-1 gene grew plump. There was also another striking difference between the two groups of animals. The obese mice exhibited molecular signals in their gut that led to the progression of cancer, but the NAG-1 mice didn’t have those same indicators. The authors looked for molecular clues, by isolating cells from the colons of the mice and analyzing a group of proteins called histones. Histones package and organize DNA in a cell’s nucleus, and sometimes undergo a process known as acetylation, in which chemical tags bind to their surface. The pattern of acetylation varies depending on the chemical processes taking place in the cell.
The study showed that the acetylation patterns for the obese mice and the thin NAG-1 mice were drastically different. Patterns from the obese mice resembled those from mice with colorectal cancer. The additional weight they carried also seemed to activate more genes that are associated with colorectal cancer progression, suggesting the obese mice are predisposed to colon cancer. The key is to find out exactly how obesity prompts the body to develop colorectal cancer. The authors proposed that the likely candidates for triggering tumor growth in the colon are fat cells, but there are many more possibilities, but either way, finding these cellular switches may give rise to production of medications to keep people from getting colorectal cancer. The authors are optimistic the once the signaling pathways are identified and understand, treatments should follow.
Disorganized Cortical Patches Suggest Prenatal Origin of Autism
As the prenatal brain develops, neurons in the cortex differentiate into six layers. Each is composed of particular types of brain cells with specific patterns of connections.
According to an article published online in the New England Journal of Medicine (27 March 2014), the architecture of the autistic brain is speckled with patches of abnormal neurons, and this suggests that brain irregularities in children with autism can be traced back to prenatal development. The authors focused on genes that serve as cellular markers for each of the cortical layers as well as genes that are associated with autism.
Previously, Eric Courchesne, Ph.D. and Rich Stoner, Ph.D., of the Autism Center of Excellence at the University of California, San Diego joined colleagues from the Allen Institute for Brain Science to investigate the cellular architecture of the brain’s outermost structure, the cortex, in children with autism. Courchesne recently reported an overabundance of neurons in the prefrontal cortex of children with autism. For the current study, the authors analyzed gene expression in postmortem brain tissue from children with and without autism, all between 2 and 15 years of age.
The recent study found that the markers for several layers of the cortex were absent in 91% of the autistic case samples, as compared to 9% of control samples. Further, these signs of disorganization were not found all over the brain’s surface, but instead were localized in focal patches that were 5-7 millimeters (0.20-0.28 inches) in length and encompassed multiple cortical layers. These patches were found in the frontal and temporal lobes of the cortex-regions that mediate social, emotional, communication, and language functions. Considering that disturbances in these types of behaviors are hallmarks of autism, the authors concluded that the specific locations of the patches may underlie the expression and severity of various symptoms in a child with the disorder.
The patchy nature of the defects may also explain why early treatments can help young infants and toddlers with autism improve. According to the authors, since the faulty cell layering does not occur over the entire cortex, the developing brain may have a chance to rewire its connections by sidestepping the pathological patches and recruiting cells from neighboring brain regions to assume critical roles in social and communication functions.