Few residency programs teach new physicians about common errors, how to properly calculate dosages, and differences between prescribing for adults and children, Sharon Conroy, B.Pharm., of Derbyshire Children's Hospital and the University of Nottingham, and colleagues.
And even when training goes beyond a typical 30-minute to an hour presentation by a pharmacist, there are no validated tools to assess the individual's learning, they said.
Children's doses are calculated individually, leaving much room for error, they wrote. Additionally, children are particularly vulnerable to dosing mistakes.
Past studies have shown that graduating medical students or new doctors are not well prepared for prescribing for children. One study found that less than a third of final-year medical students were aware of drugs for anaphylaxis and chest infections.
In another, U.S. pediatric residents scored less than 70% on average when tested on prescribing and math skills and just 31% of British junior doctors answered all questions correctly on a prescribing test for which they had been provided references and calculators.
In 13 UK centers, training took the form of a presentation by specialist pharmacists, lasting between 30 and 60 minutes, eleven taught the completion of a drug chart, while seven discussed common prescribing errors. Ten centers provided trainees with an induction packet containing written information. One center provided a computer based prescribing course to teach trainees how to calculate drug doses correctly.
Only three centers tested prescribing competency, using workbooks, questions during lectures or formal testing. But there is no validated method of assessment, says Dr. Conroy.
Brain Building From Childhood Through The Teen Years
In 2004, brain imaging research uncovered new details about how young brains develop through the teen years. It is a story worth retelling for parents of newborns going through the incredible changes of the first years of live - and for the parents of teens struggling to catch a glimps into what is happening now.
Research confirms that during the teen years, the brain is ripe for learning new things. Scientists used to think there was a spurt of the production of gray matter, the tissue of the brain responsible for information processing, during the first eighteen months of life, and then a steady decline.
But in the late 1990s, brain scientist Jay Giedd discovered a second spurt of gray matter production just before puberty, followed by a period of "pruning" during the teenage years. "The second wave increases throughout childhood, peaks at about age eleven in girls and twelve in boys, and then in the teen years it prunes or thins down," Giedd explains. "The teen brain is particularly active in terms of the growth of connections and pruning back of those connections. It's a very tumultuous time in terms of the brain development story."
Giedd, chief of brain imaging at the National Institute of Mental Health (NIMH), and his colleagues at the NIMH and the University of California Los Angeles (UCLA), created a unique time-lapse 3D animation of the maturing brain by using magnetic resonance imaging (MRI) technology to scan the brains of thirteen healthy children and teenagers every two years for ten years.
They found that the first areas of the brain to mature, the extreme front and back, are those involved with the most basic functions, such as movement. The areas involved with spatial orientation and language are next, and the last to mature are the areas like the prefrontal cortex that are involved with more advanced "higher-order" functions like reasoning. "The brain grows in fits and starts, and different parts mature at different ages," says Giedd.
This look into actual brain development confirms that the teen years are the perfect time to give brains a workout. "We think that during the times when the brain is undergoing the big changes of growing new connections and then cutting them down is the time when practicing a new instrument or other concentrated focus might have a much greater impact than in much later years in life," Giedd says.
Arthur Toga, neuroscientist and head of the Laboratory of Neuro Imaging (LONI) at UCLA, oversaw the new brain animation, and says this research may also explain why learning seems much faster and easier when we're younger. "The brain is particularly plastic in these younger ages, because the circuitry is ready for tailoring," he says. "If you were to do a functional scan of somebody trying to play the piano for the first time, scanning them repeatedly as they took concentrated lessons over time, you would find the amount of brain that's necessary for that person to perform that piano concerto would become less as they become more proficient. The brain has the remarkable ability to capitalize on efficiency, to tune the appropriate circuitry. It may be that provides the necessary hardware to perform that task. The very same thing may be going on in maturation."
Contact Lenses With Circuits a Possible Platform for Superhuman Vision Movie characters from the Terminator to the Bionic Woman use bionic eyes to zoom in on far-off scenes, have useful facts pop into their field of view, or create virtual crosshairs. Off the screen, virtual displays have been proposed for more practical purposes -- visual aids to help vision-impaired people, holographic driving control panels and even as a way to surf the Web on the go.
The device to make this happen may be familiar. Engineers at the University of Washington have for the first time used manufacturing techniques at microscopic scales to combine a flexible, biologically safe contact lens with an imprinted electronic circuit and lights. "Looking through a completed lens, you would see what the display is generating superimposed on the world outside," said Babak Parviz, a UW assistant professor of electrical engineering. "This is a very small step toward that goal, but I think it's extremely promising." The results were presented today at the Institute of Electrical and Electronics Engineers' international conference on Micro Electro Mechanical Systems by Harvey Ho, a former graduate student of Parviz's now working at Sandia National Laboratories in Livermore, Calif. "People may find all sorts of applications for it that we have not thought about. Our goal is to demonstrate the basic technology and make sure it works and that it's safe," said Parviz, who heads a multi-disciplinary UW group that is developing electronics for contact lenses.
The prototype contact lens does not correct the wearer's vision, but the technique could be used on a corrective lens, Parviz said. And all the gadgetry won't obstruct a person's view.
"There is a large area outside of the transparent part of the eye that we can use for placing instrumentation," Parviz said. Future improvements will add wireless communication to and from the lens. The researchers hope to power the whole system using a combination of radio-frequency power and solar cells placed on the lens, Parviz said. A full-fledged display won't be available for a while, but a version that has a basic display with just a few pixels could be operational "fairly quickly," according to Parviz. Presented January 17-18, 2008 at the IEEE Conference, Tucson, Arizona, USA return to top of page
Human-Animal Embryos Get The Go-Ahead In The UK British scientists will try to create human-animal embryos for the first time after receiving the go-ahead from the government's fertility regulator on January 17, 2008. The Human Fertilisation and Embryology Authority said it had offered year-long licences to two teams of scientists that hope to use the embryos to study stem cells, the body's master cells that have the potential to form any tissue or organ.
The decision ends 12 months of delay during which the HFEA has sought to clarify whether the creation of embryos by fusing animal and human tissues is legal and scientifically justified. Leading scientists, including the government's former chief science adviser Sir David King, have given their backing to the research. Scientists at Newcastle University and King's College London want to create hybrid embryos by merging human cells with cow or rabbit eggs, in the hope of extracting valuable embryonic stem cells from them. The cells are expected to lead to revolutionary therapies for diseases such as Alzheimer's, Parkinson's and even spinal cord injuries.
Under existing laws, the embryos must be destroyed after 14 days when they are no bigger than a pinhead, and cannot be implanted into the womb. In a statement, the authority said its licensing committee had "determined that the applications satisfied all the requirements of the law".
Sir Richard Gardner, chairman of the Royal Society's stem cell working group, added: "This is the right decision by the HFEA and it will maintain the UK's position as an innovator and world leader in stem cell research." Published January 17, 2008 by the Human Fertilisation and Embryology Authority, UK return to top of page
Stem Cell Research Aims To Tackle Parkinson’s Disease
Scientists in Sweden are developing new ways to grow brain cells in the laboratory that could one day be used to treat patients with Parkinson’s disease, an international conference of biologists organised by the European Science Foundation (ESF) was told.
Professor Ernest Arenas of the Karolinska Institute in Stockholm presented his research to the EuroSTELLS “Stem Cell Niches” conference in Barcelona on January 11. Stem cell therapy holds the promise of treating disease by growing new tissues and organs from stem cells – ‘blank’ cells that have the potential to develop into fully mature or ‘differentiated’ cells. The EuroSTELLS is an ESF EURCORES programme, managed by the European Medical Research Councils (EMRC), that aims to develop a stem cell ‘toolbox’ by generating fundamental knowledge on stem cell biology.
Parkinson’s disease affects around three in a hundred of people aged over 65. The condition can cause muscles to become rigid and limbs to tremble uncontrollably. Parkinson’s disease results from the loss of a particular type of brain cell called dopaminergic (DA) neurons in the part of the brain called the substantia nigra.
Among the various approaches that are currently being discussed from an ethical perspective, is the possible approach of taking stem cells, growing them into new brain cells and transplanting these into the patient. “The idea is to start with stem cells and induce them to become neurons,” said Professor Arenas, whose research is carried out as part of a EuroSTELLS collaboration. “These could then be transplanted into the brain of the patient. Also, such cells could be ideal for developing and testing new drugs to treat brain disease.”
However, to create such cells that function efficiently and safely is a major challenge. Early efforts at growing DA neurons from embryonic stem cells produced cells which, when transplanted into animal models, had a tendency to form tumours or clumps, or die without an obvious reason.
Professor Arenas’s team studied the development of DA neurons in animals to determine the important biological molecules in the brain that were necessary for the cells to grow and function efficiently. The scientists identified one particular molecule that seemed to be key, a protein called Wnt5a. They showed that when this molecule, together with a second protein called noggin, was included in cultures of stem cells, far more DA neurons were produced than when these ingredients were not present Crucially the team also moved away from embryonic stem cells – which can be induced to grow into a wide variety of different cells. Instead they used neural stem cells – which are programmed to develop only into nerve cells.
When the researchers transplanted the cells into laboratory animals whose substantia nigra region of the brain was damaged, the results were promising. “We reversed almost completely the behavioural abnormalities, and neurons differentiated, survived and re-innervated the relevant part of the brain better” Professor Arenas said. “Furthermore we do not see the kind of proliferation of the cells that has occurred in the past and we get very little clustering when the cells are treated with Wnt5a. The cells are safer than embryonic stem cells and more efficient than fetal tissue.”
Dr. Rao, first became vice president for research at Carlsbad-based Invitrogen Corp., after leaving his position as section chief for stem cells at the National Institute for Aging, a division of the National Institutes of Health, when he resigned in 2005.
Rao said he left because President George Bush's ban on federal funding of new human embryonic stem cell lines made it impossible for him to do his research.
"I used to always argue that there was at least a decade lead in the U.S. versus other countries in terms of what is possible here - so it was a little bit of a surprise," Rao said.
"We never had a good model until we had embryonic stem cells," Rao said.
In April 2006, Rao joined Invitrogen to lead the company's new stem cell and regenerative medicine business. Invitrogen makes available more than 1,000 products used in both adult and embryonic stem cell research. Although the company is based in Carlsbad, it has laboratories in Frederick, Md.; Scotland, and India.
Rao said he was drawn to the Buck Institute by his longtime collaboration with Xianmin Zeng, who left the National Institutes of Health the same year Rao did to join the Buck Institute. Zeng, who has her own lab at Buck, will assist Rao with his work. Invitrogen has agreed that any discoveries Rao makes in his lab at the Buck Institute will belong to the institute.
In June 2007, the California Institute for Regenerative Medicine awarded the Buck Institute $4.1 million to establish a research center where scientists throughout the region can learn how to culture and use human embryonic stem cells.
Stemagen First to Create Cloned Human Embryos from Adult Cells Stemagen, a privately held embryonic stem cell research company, announced it has become the first in the world to create, and meticulously document, a cloned human embryo using somatic cell nuclear transfer (SCNT).
“No other scientific group has documented the cloning of an adult human cell, much less been able to grow it to the blastocyst stage, the stage at which it is the adult donor cell that is driving embryonic development, the stage that yields the cells (the inner cell mass) from which embryonic stem cell lines are made,” said Andrew French, Ph.D., lead author on the paper, who is Stemagen’s Chief Scientific Officer. Five blastocysts were developed from 25 donated mature oocytes. Three were confirmed to be clones based on DNA fingerprinting demonstrating the presence of the skin cell donor DNA in the blastocyst, while one was further confirmed to be a clone by an additional mitochondrial DNA (mtDNA) analysis which revealed the presence of oocyte donor mtDNA without any oocyte donor nuclear DNA. For technical reasons, the genetic material in the remaining two blastocysts did not amplify to the extent required for analysis, and so while it is likely they were clones, the evidence required to claim that with certainty was not present. Thus, in this study, cloned blastocysts were successfully created from approximately 10% of all mature donated oocytes, an unexpectedly high rate given past research in this field. The oocytes used in this study were donated by egg donors and intended parents undergoing egg donation cycles for reproductive purposes at the Reproductive Sciences Center in La Jolla, a leading fertility center specializing in egg donation and other advanced assisted reproductive technologies.
Stemagen and the Reproductive Sciences Center worked closely, over an extended period of time, with a leading independent Institutional Review Board (IRB) to develop procedures ensuring that all parties received comprehensive informed consent and that procedures were in place to protect their confidentiality in the process. All research procedures, including the culturing of the skin cells (fibroblasts) were performed under clinical laboratory conditions in close cooperation with the Assisted Reproductive Technologies (ART) Laboratory of the Reproductive Sciences Center, directed by Catharine Adams, Ph.D.
Stemagen CEO Samuel H. Wood, M.D., Ph.D., a co-author of the publication and a donor of the cells from which the embryos were cloned, points out that this research was exhaustively scrutinized by some of the world’s most respected scientists and underwent an exceptionally rigorous process of verification, “This achievement was so critical to our field, we felt we should spare no effort in the process of establishing the validity of our work.”
DNA fingerprinting is the scientifically accepted method for determining if an embryo is a true clone. According to French, “All samples were subjected to this type of analysis to determine their true genetic makeup.” For that, the company turned to Genesis Genetics, a recognized worldwide leader in the field of reproductive embryonic analysis. Published January 17, 2008 in the journal Stem Cells return to top of page
Tracking Leukemia's Starting Point Childhood leukemia starts silently, and how it begins is a perennial puzzle. Some leukemias have been tied to cancer "stem cells" that may drive the early stages of illness and possibly induce relapses. Researchers in the U.K., Italy, and Japan say they've discovered a stem cell for the most common form of childhood leukemia. Helping them were twin girls, one of whom has the disease and one of whom is healthy.
In about a quarter of childhood acute lymphoblastic leukemia (ALL) patients, the genetic alteration that puts cells on the road to cancer is the fusion of the genes TEL and AML1. Earlier studies of children with leukemia found that blood samples taken at birth had the fusion, suggesting that it occurs in utero. But the sequence of events leading to ALL, and whether "preleukemic" stem cells existed, wasn't known.
Tariq Enver, a stem cell biologist at the University of Oxford in the U.K., and his colleagues injected different combinations of TEL-AML1-positive leukemia cells from ALL patients into immunodeficient mice. Cells that, when injected in relatively small numbers, could self-renew and establish leukemia in an animal - and do the same when transplanted from that animal into a second - would be considered cancer stem cells. After several tries, the researchers found a subset of cells that qualified.
Were these cells present before leukemia struck? To find out, the team turned to young identical twin girls, Olivia and Isabella Murphy. Olivia had ALL, but the team was most interested in Isabella, who wasn't sick.
Because the twins had shared a placenta and a blood supply in utero, studying Isabella's blood could offer a snapshot of what Olivia's blood looked like before she got sick. In Isabella's blood, the researchers found a tiny number of preleukemic stem cells - about 0.002% of all cells drawn - and some of those had the TEL-AML1 gene fusion. These were the same type of cell that had established leukemia in the mice, although they lacked all the abnormal gene mutations of a true leukemic cell.
Still, the cells in Isabella didn't show up in other healthy children, suggesting they might be a first step on the road to leukemia but needed additional genetic mutations before disease became inevitable. Over 18 months of observation of Isabella, this cell population didn't progress to leukemia. The scientists theorize that the preleukemic stem cells had passed from one girl to the other in utero. Olivia had then sustained additional genetic hits and developed ALL.
The researchers report they recreated Isabella's preleukemic stem cells by inserting a TEL-AML1 fusion gene into cord blood stem cells with the same surface markers as those that were seen in Isabella. When these cells were injected into mice, the animals developed a form of preleukemia but didn't progress to cancer. "What does it take to get that to turn into leukemia?" asks Enver. No one knows the answer.
A preleukemic stem cell "had never really been identified," says Carol Stocking, a cancer biologist at the Heinrich Pette Institute in Hamburg, Germany, who's now convinced that it has. Still, there remains much controversy about cancer stem cells generally, including how important they'll be for treatment, says Charles Mullighan, a leukemia researcher at St. Jude Children's Research Hospital in Memphis, Tennessee.
But showing that this population of cells "persists over time [and is] not present in normal individuals ... is an important first step" in understanding how ALL starts, he says.
Toxoplasma Infection Increases Risk of Schizophrenia, Study Suggests
Findings from what is believed to be the largest comparison of blood samples collected from healthy individuals and people with schizophrenia suggest that infection with the common Toxoplasma gondii parasite, carried by cats and farm animals, may increase the risk of schizophrenia.
Most infections with toxoplasma occur early in life following exposure to the parasite in cat feces or undercooked beef or pork. Infections rarely cause symptoms, but the parasite remains in the body and can reactivate after lying dormant for years.
“Our findings reveal the strongest association we’ve seen yet between infection with this very common parasite and the subsequent development of schizophrenia,” says Robert Yolken, M. D., a neurovirologist at Hopkins Children’s who was among those conducting the analysis.
Previous studies have reported on the link between schizophrenia and the presence of toxoplasma antibodies, which are evidence of past infection, but this is the first study to show that infection with the parasite can precede the initial onset of symptoms and subsequent diagnosis with schizophrenia, Yolken says. Because the U.S. military routinely tests its active personnel for toxoplasma, among other infectious agents, and stores blood samples in a central repository, researchers were able to determine the time line between infection and a diagnosis of schizophrenia.
“Until now, the only thing we could say is that some people with schizophrenia also had been infected with toxoplasma at some point, but we couldn’t tease out which came first,” Yolken says. “With our current study, we were able to show that infection came first.”
While most people infected with toxoplasma never develop schizophrenia, the parasite may be a trigger in those genetically predisposed to the disorder, a classic example of how genes and environment come together in the development of disease, Yolken says..
In a groundbreaking study, Robert Sackstein, MD, PhD, and colleagues in the Department of Dermatology at the Biomedical Research Institute at Brigham and Women’s Hospital (BWH) harmlessly modified the surface of human mesenchymal stem cells (a type of adult stem cell that is the precursor of bone forming cells called osteoblasts), which directed the cells through the bloodstream into bone, where they matured into new bone cells. “Without genetically reprogramming a stem cell, which could cause adverse effects, we were able to navigate the cell to a predetermined location – a necessary first step towards achieving tissue regeneration,” said Sackstein, who is a bone marrow transplant physician at BWH and lead author of the research. “Stem cells must have a routing cue to traffic to where they’re needed, just like you need a zip code to deliver mail.” The Sackstein lab previously discovered the cell surface molecule HCELL, which is a homing receptor that seeks out the adhesion molecule E-selectin found on the lining of certain blood vessels.
Specifically, HCELL docks on E-selectin, allowing the cell to exit the blood and enter a target tissue. All prior attempts to intravenously inject mesenchymal stem cells to treat generalized bone diseases were doomed by the fact that the cells could not migrate to bone by simply being injected into the bloodstream.
Sackstein and colleagues chemically engineered the surface of human mesenchymal stem cells to express HCELL. Next, these cells were injected intravenously into mice, where they migrated to bone and made islands of human bone within the mouse bone. This occurred because blood vessels in bone continually express E-selectin, thereby recruiting the HCELL-bearing stem cells to that site.
Beyond its usefulness to treat generalized bone diseases, the researchers concluded that this gateway technology should enable adult stem cell delivery to any site of tissue injury because E-selectin is typically expressed on blood vessels within damaged tissue, including tissue injured by stroke or heart attack.
“We are cautiously optimistic that our approach has utility for every application of stem-cell based therapeutics and in particular, for treating osteoporosis,” said Sackstein. “Osteoporosis is the leading cause of disability world-wide among older adults. Half of all women and a quarter of men older than 50 will have bone fractures due to osteoporosis, so the next step for our research is to move towards clinical trials to use this strategy to treat and hopefully cure this and other generalized bone diseases.”
Mmmm … Bacteria When you eat a cup of yogurt, billions of bacteria make their way to your gut. Some researchers believe that these "probiotics" can be good for you, alleviating everything from bowel disease to allergies. Now, a team of researchers has shown that, at least in mice, supplementing food with a helping of "good" bacteria can cause profound metabolic changes, including some that may be linked to weight loss.
The human gut hosts 1000 species of microorganisms - more than a kilogram of cells in all. Recent studies indicate that this thriving ecosystem plays an important role in human health and may even contribute to obesity. Last year, Jeremy Nicholson, a biochemist at Imperial College London, and a team of researchers from Imperial College and the Nestlé Research Center in Lausanne, Switzerland, showed that replacing mouse gut microbes with human microbes caused widespread metabolic changes in the mice. Nevertheless, scientists remained skeptical that probiotics could have a similar effect, because probiotic foods add only a few billion foreign microbes to a native population of tens of trillions.
In the new study, Nicholson's group returned to the mice harboring human gut microbes. The researchers supplemented the animals' diets with a solution containing one of two species of Lactobacillus bacteria, which are present in yogurt and baby formula. Control mice were given saline solution as a supplement.
After 2 weeks, the team measured the metabolic profiles of the mice, analyzing feces, urine, plasma, intestinal contents, and liver tissue. The results, published in the 15 January issue of Molecular Systems Biology, show that although the composition of gut microbes changed only slightly in the three groups of mice, the animals' metabolic profiles - including various markers for blood cholesterol and amino acid levels in the liver - were profoundly different.
Of particular note, says Nicholson, was the effect of probiotics on bile acids, which help the small intestine absorb fat. Probiotics diminished the function of the acids, Nicholson notes, which may make it harder for the animals to absorb fat--and thus should keep them slim. As for how a relatively small number of foreign microbes could have such a dramatic effect, Nicholson believes it results from communication with the native bugs. "Gut bacteria talk to each other," he says, so despite their relatively modest numbers, "probiotics have a huge effect on what those other bugs do."
Although he cautions that the gut is simpler in the experimental mice than in humans, Glenn Gibson, a microbiologist at Reading University in the U.K., calls the work "very thorough" and says that it foretells an exciting and potentially revolutionary future in which microbial interventions can correct metabolic abnormalities. "We can't change human genetics," he notes, "but if we can alter metabolism with minor changes in gut bacteria, that's very exciting."
Dior is careful to word their online Flash demo of the XP line as "influenced" by stem cell technology, and not a result of using stem cells in their product.
However, they have liberally seeded the demo with scientific terms suggesting a connection between stem cells and the XP line. One marketer touts: "To help us achieve younger-looking skin in 2008, researchers at Dior's Innovation Centre used the latest technological advances to isolate the reconstructive properties of stem cells, the cells used to repair damaged skin, and use them to repair skin and remove wrinkles from the inside."
One of the properties of stem cells, however, is that they are living cells, dependent on continuous nourishment and part of a complicated bio-system [see article above]. No researcher to date keeps stem cells in a jar on the bathroom shelf ready for topical application. Perhaps DIOR can be applauded for popularizing a concept still unacceptable to some religious groups. But in no way are they using stem cells or stem cell technology in their cosmetics.
The method used for the achievement suggests the eventuality of realizing the long-standing dream of growing new heart tissue or even whole organs for transplant, reported Doris Taylor, Ph.D., of the University of Minnesota, and colleagues. In other studies, Dr. Taylor and colleagues said they had been able to repeat the process using pig hearts, which are equivalent in size and complexity to the human organ. However, the rat heart only operates at 2% of needed capacity to pump blood. "Going forward, our goal is to use a patient's stem cells to build a new heart," Dr. Taylor said in a statement.
The study was described as a "significant advance" by Wayne Morrison, M.D., of the Bernard O'Brien Institute of Microsurgery in Fitzroy, Australia. Dr. Morrison, who was not involved in the Minnesota study, led a team that last year reported growing beating heart muscle from adult stem cells inside a rat.
"They have demonstrated that they can create a heart that looks like a heart and is shaped like a heart and, most excitingly, that they can re-establish the blood vessels that were originally there," Dr. Morrison said in a statement.
But Dr. Morrison cautioned that the there's more work to be done before the process can be adapted for clinical use. "The next step is to see if this research can be transferred into living animals and can be upscaled beyond rats," he said. Dr. Morrison said one limitation of the process so far is that it requires an enormous number of cells for the re-seeding by stem cells of the vascular architecture (scaffold) created from a cadaver heart.
Gene Protects Newborns from Killer Respiratory Disease Yale School of Medicine researchers have isolated a gene that helps protect newborns from the most common respiratory cause of infant death in the United States - respiratory distress syndrome.
This gene, macrophage migration inhibitory factor (MIF), also helps fetal lungs develop, the researchers report this month in the Journal of Immunology.
The overt cause of respiratory distress syndrome is underdeveloped lungs—the more premature the newborns, the more likely they are to have a loss of lung volume caused by air space collapse and poorly developed capillaries. Infants with the syndrome often require mechanical ventilation within the first hours of life.
The Yale team wanted to pinpoint the molecular events leading to respiratory distress syndrome because, despite advances in treatment, survivors often develop chronic lung disease and are at higher risk of developing asthma.
“The finding is important because prematurity is not only the most common respiratory cause of infant mortality in the U.S., it also tends to be a more serious problem in inner city neighborhoods,” said Richard Bucala, M.D., professor of medicine and pathology, professor of epidemiology at Yale School of Public Health, and senior author of the study.
“Because relationships exist between the known human variants of MIF and the severity of other respiratory diseases such as asthma and cystic fibrosis, we are very interested to know whether MIF variants might be associated with a higher risk for developing respiratory distress syndrome or chronic lung disease in premature infants,” said Alia Bazzy-Asaad, chief of the pediatric pulmonary section at Yale School of Medicine and co-author of the study. “We hope to pursue this in future studies.”
During gestation, mothers acquire CD34+CD38+ cells from the fetus that persist for decades. In this study using mice, fetal T and B cells were looked for in the maternal thymus and bone marrow during and after gestation to see if these cells did in fact incorporate into the maternal system.
Kiarash Khosrotehrani and Michèle Leduc and team mated RAG–/–-deficient female mice to congenic wild-type mice (RAG+/+) and recovered fetal double-positive T cells (CD4+CD8+) with characteristic TCR and IL-7R expression patterns in the maternal thymus during the resulting pregnancies.
The scientists made similar observations in the thymus of mothers that had a normal immune response. The results suggest that during gestation mothers acquire fetal lymphoid undifferentiated cells that go on to develop into functional T cells. This fetal cell microchimerism (or persistence of low numbers of fetal cells in the mother after a pregnancy) may have a direct impact on maternal health.. Published January 15, 2008 in the Journal of Immunology return to top of page
The remarkable, though limited, recovery occurred in an 81-year-old man who received etanercept by perispinal injection into his neck, reported Edward L. Tobinick, M.D., of the Institute for Neurological Research, and Hyman Gross, M.D., of the University of Southern California.
The authors of the study believe "that excess TNF-alpha in Alzheimer's disease interferes with the synaptic regulatory functions of TNF-alpha. When TNF-alpha is in a normal physiologic range synaptic scaling is enabled, thereby preserving optimal functioning of the brain's neural network."
The report followed an open-label study Dr. Tobinick published in 2006, which involved 15 patients receiving the perispinal etanercept injections. Those patients showed improvements in cognitive performance lasting the full six months of the study.
Other Alzheimer's disease researchers were more skeptical. "The Alzheimer's field has plenty of open-label studies and case reports of improvement that have not panned out into new useful treatments," said Paul B. Rosenberg, M.D., of Johns Hopkins. Without confirmation in a controlled trial, "you shouldn't get too excited," he said. P. Murali Doraiswamy, M.D., of Duke, made a similar point. "Unless one does a controlled study, one can never get a good handle on efficacy and safety."
However, both researchers agreed that central nervous system inflammation and anti-cytokine therapies are "a promising area for study," as Dr. Doraiswamy put it. "It's not phony baloney," Dr. Rosenberg said. "This drug ought to be studied."
Study Suggests Genetic Connection Between Short Stature and Arthritis A common genetic variant linked to arthritis may also play a role in human height, a new study shows. The international study was co-led by the University of Michigan School of Public Health and published in the journal Nature Genetics. To arrive at their findings, researchers from the United States and Europe analyzed the genomes of more than 35,000 people. If there were average height differences for individuals with certain genetic variants, this indicated that something in that genomic region containing the variants likely influenced height. In this particular study, researchers initially examined the effects of more than 2 million genetic variants. The new variant accounts for less than 1 percent of the genetic basis of height, and is associated with an average difference in height of about 0.4 centimeters, or a little more than an eighth of an inch. The range went from 0.3 cm to 1.4 cm, depending on the population and whether an individual had one or two copies of the so-called taller version of the variant.
A variety of factors, including genetics, diet and prenatal environment, interact to determine how tall someone grows. It is currently thought that genetic factors are responsible for at least 80 percent of the variation in height among people.
The variants most strongly associated with height lie in a region of the human genome thought to influence expression of a gene for growth differentiation factor 5, called GDF5, which is a protein involved in the development of cartilage in the legs and other long bones.
Rare variants in the GDF5 gene have been associated with disorders of skeletal development, and more common variants recently have been tied to susceptibility to osteoarthritis of the hip and knees in Asian and European populations.
The study was conducted with a population of 2,650 children in the Mater-University Study of Pregnancy in Brisbane (Australia) in 1981. Maternal perception of offspring weight was reported when the children were 14 years old and at 5 or 14 years follow-up.
Forty percent of mothers of overweight children misclassified their child as normal or underweight, more so with boys than girls. Fifteen percent of mothers of normal weight children misclassified their child as underweight, again more so in boys than girls.
The sex of the child, child dissatisfaction, dieting and mom's own overweight were especially associated with misclassifing overweight children.
Overweight children already show signs of elevated blood pressure, cholesterol, triglycerides and insulin levels - and have a high risk for being overweight adults. Recent research showed that several of the major chronic diseases of adults including cardiovascular disease, hypertension and type 2 diabetes mellitus originate in early childhood.
However, to evaluate the benefits and harms of promoting increasing parental and child awareness of the child's weight status means understanding and educating parents to be aware of the obesity problem - through unbiased eyes. Published January, 2008 in the International Journal of Obesity return to top of page
While neonatal jaundice, a yellowing of the skin caused by a buildup of a blood product called bilirubin, is common in newborns and usually disappears on its own, it can progress to brain damage in a small fraction of cases.
The Children's Hospital researchers say that the predischarge bilirubin measurement, combined with the baby's gestational age, is the most accurate method for predicting whether the newborn is at risk. "The challenge facing every pediatrician who takes care of newborn babies is to identify those infants they send home that will develop a bilirubin level that could cause injury," said Ron Keren, M.D., M.P.H., a pediatrician at Children's Hospital and the lead author of the study. "We found that by measuring the bilirubin in every baby, and combining that information with the baby's gestational age, you could accurately predict which infants are at very high risk and which ones are at very low risk."
The authors caution that the study has a few limitations, including a small sample size. Some infants in the study were treated with phototherapy, high levels of colored light used to break down the bilirubin, before meeting the criteria. Finally, about half of the study participants were born to black mothers and the researchers' data indicates black infants are less prone to develop significant hyperbilirubinemia. “More research on risk-assessment strategies is needed to weigh the cost of implementing a universal program and its effectiveness for preventing severe hyperbilirubinemia against false test results, unnecessary testing and treatment, and delay in hospital discharge," said Keren.
Infants With Birthmarks Received Less Oxygen in Womb A hemangioma is a benign tumor of cells that line blood vessels, appearing during the first few weeks of life as a large birthmark or lesion. A new study reveals that a disturbance of oxygen depletion was found in placentas of babies who developed infantile hemangioma (IH).
Researchers reviewed placental samples from 26 pregnancies with babies who weighed less than 3.5 pounds, 13 consisting of newborns who developed IH after birth and 13 healthy preterm infants who did not have IH.
Only one of the infants without IH showed an abnormal placenta. The higher ratio of placental anomalies in babies with IH suggests that reduced oxygen to the placenta contributed to fetal stress, and that stress led to infantile hemangioma development. “Our results suggest that disturbed placental circulation is a factor underlying the development of hemangiomas in very low weight newborns and indicates that placental examination is essential for clarifying the physiologic changes leading to IH in babies with normal birth weight,” the authors conclude.
Children's Hospital and Health System Press Release January, 2008 return to top of page
Sometimes known as "Bubble Boy Disease," SCID is a genetic disorder that is fatal without early diagnosis and treatment. Babies diagnosed can be referred for potentially life-saving treatment.
The Wisconsin Department of Health and Family Services approved moving to phase two of the pilot screening program in which screening for SCID will be routine for all newborns in Wisconsin (estimated at 70,000 annually). The screening has been added to the current panel of 47 other tests that are given to newborns. "This complex disease can be cured with a bone marrow transplant if diagnosed early before serious infections develop. That is why the early detection and treatment of SCID through routine screening in newborns will save lives. The screening also will spare infants' repeated and prolonged hospitalizations and save millions of dollars in health care costs. We believe that the Wisconsin Newborn Screening Program will serve as a blueprint for newborn screening in other states, spurring testing to save the lives of infants throughout the nation," said Jack Routes, MD, medical director of Allergy and Clinical Immunology at Children's Hospital of Wisconsin.
SCID is the most lethal version of all primary immunodeficiency diseases. It often is called "Boy in the Bubble" after David Vetter a boy with SCID who died at age 12 after spending his life in a completely sterile environment, separate from all human touch, from the day he was born. SCID causes a defect in the white blood cells that helps protect the body from viruses, bacteria and fungi. Doctors know that SCID is the result of a mutation in one of at least 12 genes, and bone marrow transplants are presently the best treatment. The pilot study, which continues through 2010, will evaluate the effectiveness and outcomes of early testing for SCID. Once the pilot reaches completion, investigators hope for a rapid acceptance of the screening nationwide.
Children's Hospital and Health System Press Release January, 2008 return to top of page
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