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Medical News from Johns Hopkins
This is a service for doctors worldwide from Johns Hopkins International. To receive reports directly, please send e-mail to jhis@jhmi.edu or visit www.jhintl.net.
1. Gene Therapy Alternative to Calcium Channel Blockers Promising
2. Hopkins Study Offers Guidelines for Food Allergy Testing
3. New Surgical Technique Less Invasive Than Laparoscopy
4. Treatment Stops Side Effects of Thyroid Cancer Surgery
5. Hopkins Creates First Epigenetics Center
1. Gene Therapy Alternative to Calcium Channel Blockers Promising I
n animal studies, scientists at Johns Hopkins have developed what is believed to be the first successful gene therapy that mimics the action of calcium channel blockers, agents widely used in the treatment of heart diseases, including angina, arrhythmias, hypertension and enlarged heart.Their findings, published in the latest edition of Circulation Research, online July 8, may lead to a gene therapy alternative to calcium channel blockers and their sometimes severe side effects, but also further interest in gene therapies unique to one particular organ.
Using guinea pigs, the Hopkins team increased production of a key protein involved in heart conductivity, called G-protein Gem, by injecting into the animals' heart muscles a virus carrying the gene that codes for the protein. Increased levels of Gem decreased calcium current densities -- the chemical action of calcium channel blockers -- by 30 percent to 90 percent, when compared to a control group. When heart muscle was electrically stimulated to reproduce the effects of an irregular heartbeat, Gem infusion helped steady the heartbeat, returning it to a normal rhythm, just like calcium channel blockers do. No adverse side effects were observed.
"Calcium channel blockers are a valuable tool in combating arrhythmias and other forms of heart disease, but they can cause low blood pressure, heart block and constipation," said study lead author Eduardo Marbán, M.D., Ph.D., professor and chief of cardiology. "Our initial results with gene therapy are very promising."
2. Hopkins Study Offers Guidelines for Food Allergy Testing
A blood test that measures food-specific allergy antibodies can be used to help pediatric allergists with the difficult decision of when to reintroduce a food that a child has been allergic to, say researchers at Johns Hopkins. In their report, published in the July issue of The Journal of Allergy and Clinical Immunology, the researchers provide guidelines for using these antibody levels to determine which children should be offered an additional allergy test, known as an oral food challenge, in which the child eats small amounts of the food allergen to establish whether or not a food allergy really exists. Based on results of their investigation into how well IgE antibody levels could predict children's reactions on the oral food challenge test, the Hopkins team specifically recommends that challenge tests for milk, egg, and peanut be performed on children with at least a 50-50 chance of "passing."
This 50-50 challenge pass rate was most clear for milk, egg, and peanut and was associated with low levels (less than 2.0 kilounits of antibody per liter of blood) of food-specific IgE. "These findings make it clear that doing a blood test to measure IgE levels can accurately predict how a patient will fare during a food challenge, and we recommend its routine use in clinical practice to screen children with suspected allergies before a food challenge is performed," says Robert Wood, M.D., a pediatric allergist and the study's senior author. "By using our data as a guideline, physicians can better determine the appropriate time to try to reintroduce foods into an allergic child's diet," Wood adds. "An historical lack of such guidelines has led to considerable indecision in the appropriate timing of food challenges."
3. New Surgical Technique Less Invasive Than Laparoscopy
Laparoscopic surgeries have many advantages over traditional open surgery, including less pain, fewer complications and quicker recoveries. Now, scientists at Johns Hopkins have created a new surgical technique that in extensive animal studies is safe and may improve even further the benefit of minimally invasive surgery by leaving the abdominal wall intact. The new procedure, called flexible transgastric peritoneoscopy, or FTP, is performed by inserting a flexible mini-telescope, called an endoscope, and related surgical tools, through the mouth and into the stomach. After puncturing the stomach wall and the peritoneum, which also lines the inside of the abdominal and pelvic cavities -- the doctors can see and repair any of the abdominal organs, such as the intestines, liver, pancreas, gallbladder and uterus.
"FTP may dramatically change the way we practice surgery," said Anthony Kalloo, M.D., director of gastrointestinal endoscopy at Johns Hopkins and lead author of a report describing the new procedure in the July issue of Gastrointestinal Endoscopy. "The technique is less invasive than even laparoscopy because we don't have to cut through the skin and muscle of the abdomen, and it may prove a viable alternate to existing surgical procedures."
4. New Treatment Stops Side Effects of Thyroid Cancer Surgery
A new approach to therapy can avoid most of the debilitating effects of preparing for critical, postsurgical treatment for patients with thyroid cancer, according to an international study led by researchers from Johns Hopkins and the University of Pisa. Using a genetically engineered thyroid stimulating hormone (TSH) - called thyrotropin alfa, or rTSH - doctors destroyed the small amount of thyroid gland tissue that often remains after thyroidectomy, without the need to temporarily withhold thyroid hormone medication. This new approach also avoided the temporary but troubling symptoms flowing from the deficiency of thyroid hormone, such as fatigue, weight gain, chilliness, slowed thinking, depression, constipation and muscle cramps. The findings were presented at the annual meeting of The Endocrine Society in New Orleans, June 16-18.
"Recovery from thyroid cancer has been very difficult for patients because thyroid medication - to replace the thyroid hormone naturally produced by a healthy thyroid gland - has traditionally been withheld for four to six weeks after surgery so radioiodine could be used to identify and destroy glandular tissue that remained," said study co-lead investigator Paul Ladenson, M.D., chief of the Division of Endocrinology at Johns Hopkins.
5. Hopkins Creates First Epigenetics Center
With a $5 million, five-year federal grant, Johns Hopkins is establishing what is believed to be the first university-based research center devoted to studying epigenetics, an effort
that will set the stage for learning as much about our epigenetics as the Human Genome Project taught about the sequence of building blocks that make up our genes. Much as our genetic sequence is passed from parent to child, epigenetic "marks" that sit on our genes are also inherited. These "marks," usually small methyl groups, are attached to genes' backbones and convey information, such as identifying which parent the gene came from. The marks also normally turn genes on or off. But just as changes in genes' sequences can cause diseases such as cancer, gain or loss of epigenetic marks can, too, by improperly turning genes on or off.
"Epigenetics may be as important in certain conditions, or in contributing to the risk of developing certain conditions, as the genetic sequence is in other cases," says Andrew Feinberg, M.D., principal investigator of the epigenetics grant. Feinberg, who pioneered the study of epigenetics in cancer, will lead the new Center for the Epigenetics of Common Human Disease, which is funded by the National Human Genome Research Institute and the National Institute of Mental Health. Through the center's grant, Feinberg and his colleagues will first develop tools to create comprehensive information about epigenetics and then apply that information to the study of autism and bipolar disorder. The epigenetic information and technologies will also be available to researchersinvestigating other conditions.
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