Mother Delivers Baby, Develops Heart Disease
UC San Diego Sulpizio Cardiovascular Center among first in region to implant cardiac device
Three weeks after delivering her first child, Amanda began to suffer from extreme fatigue, headaches, a tight chest and stomach pain. An initial diagnosis of pneumonia changed for the worse: Amanda was experiencing heart failure. The 28-year-old’s life was at risk. She was quickly transferred to UC San Diego Sulpizio Cardiovascular Center (SCVC) where a multidisciplinary team implanted a novel cardiac device under her skin, leaving the heart untouched, to prevent sudden cardiac arrest.
“When Amanda first arrived at SCVC, she was in critical condition. It became clear within 24 hours that she needed emergency surgery or she would not survive,” said Eric Adler, MD, director of cardiac transplant and mechanical circulatory support at UC San Diego Health System.
The new mother was diagnosed with peripartum cardiomyopathy, a rare disorder in which a woman develops heart disease within the final month of pregnancy or within five months after delivery. Adler adds that one in 2,000 women suffers from the condition, the cause is not exactly known and it can be hard to correctly diagnosis.
“I knew I had to fight for my daughter,” said Amanda. “I am not a quitter and always strive for success. I wasn’t going to let heart failure beat me.”
Fractures and broken bones are no fun and the worst are those that require surgical screws. Sure, it’s a chance for some twisted braggadocio – “I’ve got precision-machined, surgical-grade titanium inside me!” – but these injuries are almost always very serious, painful and long-to- heal. The screws may be essential to holding things together in the right places during the healing process, but they present particular problems of their own.
To wit: They eventually must be removed, requiring more surgery and leaving behind a hole in bone that also must heal.
Much better would be a surgical screw strong enough to do its job and then go away. In a recent Nature Communications paper, scientists described just such a candidate. The screws are made of silk fibers. In experiments with rats, the screws successfully pinned bones together for eight weeks but behaved more like bone than metal. They are less stiff (reducing stress problems with surrounding bone), less sensitive to temperature changes, produce minimal inflammatory response and promote bone healing as they biodegrade.
The silk screws aren’t the first on the market. There are already screws made from polylactic acid, which is derived from corn starch, tapioca root and sugarcane. In 2010, a German company debuted a biodegradable screw made of polylactic acid and hydroxylapatite, a naturally occurring mineral that is also a primary component of natural bone and used in prosthetic devices. These screws are hollow to further encourage bone growth into them and reportedly completely disappear in two years.
And there is fracture putty, which in some cases could theoretically do away with screws altogether. It’s an experimental compound being developed by DARPA that is packed in and around compound bone fractures, where it quickly hardens to provide loadbearing capabilities while the bone heals. The putty is resorbed as the bone regenerates and grows into it.
Pregnancy and alcohol consumption in the Ukraine
Alcohol consumption during pregnancy is broadly considered to be a pointless health risk for both mother and unborn child. According to the Centers for Disease Control, there are no established safe levels of alcohol use during pregnancy. Drinking during pregnancy has been linked to fetal alcohol spectrum disorders (FASD) – a wide range of physical and mental disabilities, plus lasting emotional and behavioral problems.
In a 2012 CDC study, just under 8 percent of pregnant women (1 in 13) reported consuming alcohol within the past 30 days (compared to 51.5 percent of non-pregnant women). For binge drinking (six drinks on one occasion), the percentages were 1.4 percent and 15 percent, respectively.
These are numbers that experts and advocates alike say should be reduced in the U.S. The problem is even more daunting elsewhere.
In a recent paper published in the journal Alcoholism: Clinical and Experimental Research, Christina Chambers, MPH, PhD, and Wladimir Wertelecki, MD, both in the UC San Diego School of Medicine’s Department of Pediatrics, report that alcohol consumption among pregnant women in the Ukraine is alarmingly high.
The study, which included nearly 12,000 pregnant women in two regions of the Ukraine, found that among regular alcohol consumers, more than half (54.8 percent) of the women surveyed drank some alcohol in the month surrounding conception and 12.9 percent reported drinking three or more drinks on at least one occasion during the early months of pregnancy.
Consumption rates declined only slightly at mid-pregnancy. Nearly half of the women in the study (46.3 percent) reported consuming some alcohol in the most recent month of pregnancy and 9.2 percent said they drank at least three servings of alcohol at a sitting.
“What this tells us is that the women in the study did not avoid alcohol entirely during their pregnancy, and substantial numbers drank at risky levels,” said Chambers.
“The findings of both these studies suggest there is a need and opportunity for prevention in both in the Ukraine and the United States. It is so important that we continue to raise awareness of FASD and educate all women of reproductive age that prenatal alcohol can be harmful to the developing baby.”
The Ukraine survey was conducted in collaboration with Omni-Net for Children, a not-for-profit international non-governmental organization in the Ukraine involved in birth defects prevention. The study was part of an ongoing research effort funded by the National Institutes of Health, the National Institute of Alcoholism and Alcohol Abuse and the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, which promotes research on the mechanisms and prevention of FASD.
Anti-psychotic Medications Offer New Hope in the Battle Against Glioblastoma -
Researchers at the University of California, San Diego School of Medicine have discovered that FDA-approved anti-psychotic drugs possess tumor-killing activity against the most aggressive form of primary brain cancer, glioblastoma. The finding was published in this week’s online edition of Oncotarget.
The team of scientists, led by principal investigator, Clark C. Chen, MD, PhD, vice-chairman, UC San Diego, School of Medicine, division of neurosurgery, used a technology platform called shRNA to test how each gene in the human genome contributed to glioblastoma growth. The discovery that led to the shRNA technology won the Nobel Prize in Physiology/Medicine in 2006.
“ShRNAs are invaluable tools in the study of what genes do. They function like molecular erasers,” said Chen. “We can design these ‘erasers’ against every gene in the human genome. These shRNAs can then be packaged into viruses and introduced into cancer cells. If a gene is required for glioblastoma growth and the shRNA erases the function of that gene, then the cancer cell will either stop growing or die.”
Chen said that one surprising finding is that many genes required for glioblastoma growth are also required for dopamine receptor function. Dopamine is a small molecule that is released by nerve cells and binds to the dopamine receptor in surrounding nerve cells, enabling cell communication.
Abnormal dopamine regulation is associated with Parkinson’s disease, schizophrenia, and Attention Deficit Hyperactivity Disorder. Because of the importance of dopamine in these diseases, drugs have been developed to neutralize the effect of dopamine, called dopamine antagonists.
Following clues unveiled by their shRNA study, Chen and his team tested the effects of dopamine antagonists against glioblastoma and found that these drugs exert significant anti-tumor effects both in cultured cells and mouse models. These effects are synergistic when combined with other anti-glioblastoma drugs in terms of halting tumor growth.
“The anti-glioblastoma effects of these drugs are completely unexpected and were only uncovered because we carried out an unbiased genetic screen,” said Chen.
“On the clinical front, the finding is important for two reasons,” said Bob Carter, MD, PhD, chairman of UC San Diego, School of Medicine, division of neurosurgery. “First, these drugs are already FDA-cleared for human use in the treatment of other diseases, so it is possible these drugs may be re-purposed for glioblastoma treatment, thereby bypassing years of pre-clinical testing. Second, these drugs have been shown to cross the blood-brain barrier, a barrier that prevents more than 90 percent of drugs from entry into the brain.”
Chen is now working with the UC San Diego Moores Cancer Center Neuro-Oncology team to translate his findings into a clinical trial.
A protest rally following a fatal gang rape in 2012. Image courtesy of New York Magazine.
The rape crisis in India
In a letter published online in the journal Lancet, Anita Raj, PhD, director of the Center on Gender Equity and Health at UC San Diego, looks at recent statistics about rape in India and asks what they mean.
The data, she says, suggest that while the prevalence of sexual violence in India is among the lowest in the world at 8.5 percent, it translates to roughly 27.5 million female victims.
Just 1 percent of these victims, she said, report the crime to police.
Low reporting rates may be due in part to the fact marriage rape is not a crime in India, according to Raj, and most sexual violence in India occurs in marriage. Adolescent wives are most vulnerable, accounting for 24 percent of rape cases but only 9 percent of the total female population.
In the essay below, Raj elaborates upon the crisis confronting all Indians, and suggests some remedies.
In recent months, the international media has been rife with reports of gang rape in India, from a female Danish tourist in Delhi reportedly targeted after asking for directions to a village council-ordered attack upon a 20-year-old woman in West Bengal, allegedly raped as punishment for her relationship with a man outside her tribe.
These reports follow numerous other accounts of gang rape in India, all following the notorious and fatal 2012 gang rape of a young female physiotherapy student who was simply trying to take a bus home from the movies in Delhi. While hardly unique to India, the issue of rape in that country appears to be escalating in incidence and brutality.
The prevalence of non-partner rape is actually reported to be lower in India than in many other parts of the world, including the United States and North America, according to the World Health Organization. But crime data suggest the incidence of rape is growing in India and has been for some years, this growth may be attributed to both in actual numbers and in increased willingness of victims to report the crime.
A review of media reports over the past year suggests that rape, most notably gang rape, is a rising concern in India, particularly among unmarried adolescent and young adult females.
Unfortunately, crime data from India do not provide gang rape-specific data, limiting the ability to derive insights. Gang rapes are typically a fraction of all rape cases in the United States, where such data is collected: 10 percent of all sexual assaults involve multiple perpetrators, according to the U.S. Bureau of Justice statistics.
The preponderance of media-identified gang rape cases in India suggests this percentage may be higher there, at least in terms of non-partner rapes, though again, hard data is scant.
Nonetheless, gang rape speaks to a broad social acceptability of organized brutal and public acts of male-perpetrated sexual violence against women and girls. Without immediate, robust and ongoing intervention, the women and girls of India remain doomed to live fearfully in a country and society that sanctions brutality.
Kawasaki Disease and Pregnant Women -
UC San Diego researchers say risks are manageable, provided doctors recognize them
In the first study of its type, researchers at the University of California, San Diego School of Medicine have looked at the health threat to pregnant women with a history of Kawasaki disease (KD), concluding that the risks are low with informed management and care.
The findings are published in the March 6, 2014 online edition of the British Journal of Obstetrics and Gynaecology.
KD is a childhood condition affecting the coronary arteries. It is the most common cause of acquired heart disease in children. First recognized in Japan following World War II, KD diagnoses are rising among children in Asia, the United States and Western Europe. Predictive models estimate that by 2020 one in every 1,600 American adults will be affected by KD.
“A growing number of women with a history of KD are reaching child-bearing age, but there is little information available to guide their obstetrical care,” said study author Jane C. Burns, MD, professor and director of the Kawasaki Disease Research Center at UC San Diego and Rady Children’s Hospital-San Diego. “By and large, KD is virtually unknown among working obstetricians.”
KD is currently diagnosed by a constellation of clinical signs, with supporting lab tests that indicate high levels of inflammation. These signs include abrupt onset of high fever, accompanied by four of five criteria, among them: widespread rash, cracked and fissured lips, “strawberry tongue,” bloodshot eyes, lymph node enlargement and red, swollen hands and feet.
Without treatment, 25 percent of children with KD develop coronary artery aneurysms – balloon-like bulges of heart vessels – that may eventually result in heart attacks, congestive heart failure or sudden death. The condition can be treated with a high-dose of intravenous immunoglobulin and aspirin, reducing the risk of aneurysms to 5 percent. The long-term risk for adults with a history of KD in childhood is not known.
Senior study author John Gordon, MD, and colleagues conducted the first KD study of non-Japanese patients, and the first to explore the health risks to women with a history of KD and their offspring. They found that the health risks for mothers with no KD-related coronary artery damage were similar to the general population. For women with aneurysms, the risks were low with appropriate management and care.
“The main message is positive,” said Burns. “Women who have had KD can successfully deliver to term without complications. C-sections are not necessarily indicated if they have aneurysms, they can labor normally, if their overall cardiovascular status is OK.”
There is a genetic component to KD. The study found that two of the 21 children born to the 10 women with a history of KD also developed the disease. “There is clearly an increased risk in offspring,” said Burns, “but the (study) numbers are small so we cannot really calculate a risk until there is a larger population of KD adults who have had children.”
Vitamin D crystals, image courtesy of the NIH Office of Dietary Supplements
Vitamin D Increases Breast Cancer Patient Survival
Breast cancer patients with high levels of vitamin D in their blood are twice as likely to survive the disease as women with low levels of this nutrient, report University of California, San Diego School of Medicine researchers in the March issue of Anticancer Research.
In previous studies, Cedric F. Garland, DrPH, professor in the Department of Family and Preventive Medicine, showed that low vitamin D levels were linked to a high risk of premenopausal breast cancer. That finding, he said, prompted him to question the relationship between 25-hydroxyvitamin D — a metabolite produced by the body from the ingestion of vitamin D — and breast cancer survival rates.
Garland and colleagues performed a statistical analysis of five studies of 25-hydroxyvitamin D obtained at the time of patient diagnosis and their follow-up for an average of nine years. Combined, the studies included 4,443 breast cancer patients.
“Vitamin D metabolites increase communication between cells by switching on a protein that blocks aggressive cell division,” said Garland. “As long as vitamin D receptors are present tumor growth is prevented and kept from expanding its blood supply. Vitamin D receptors are not lost until a tumor is very advanced. This is the reason for better survival in patients whose vitamin D blood levels are high.”
Women in the high serum group had an average level of 30 nanograms per milliliter (ng/ml) of 25-hydroxyvitamin D in their blood. The low group averaged 17 ng/ml. The average level in patients with breast cancer in the United States is 17 ng/ml.
“The study has implications for including vitamin D as an adjuvant to conventional breast cancer therapy,” said co-author Heather Hofflich, DO, UC San Diego associate professor in the Department of Medicine.
Open wide, as in “ooooooh!”
Scientists have discovered the DNA of millions of microbes trapped in the calcified plaque of four medieval skeletons, which may give clues to what our ancestors ate and the diseases they fought, according to news reports.
Plaque is a biofilm, usually pale yellow that naturally accumulates on teeth. It’s created by multitudinous oral bacteria attempting to attach themselves to the smooth surfaces of your teeth. When you don’t brush well or regularly visit your dentist, it builds up. It’s the stuff scraped away by dental hygienists using whirring grinders and tiny, terrifying stainless steel tools.
In the days of yore, dental hygiene was far less rigorous, of course. Plaque built up on folk’s teeth, layer upon hardening layer, until it completely covered them and was often thicker than the tooth itself.
So brush often and well – and don’t forget to thoroughly rinse off your toothbrush when you’re done. The image above is a single toothbrush bristle covered with microscopic mouth detritus.
In First Moments of Infection, a Division and a Decision
UC San Diego scientists explain how and when T cells become effector or memory lymphocytes
Using technologies and computational modeling that trace the destiny of single cells, researchers at the University of California, San Diego School of Medicine describe for the first time the earliest stages of fate determination among white blood cells called T lymphocytes, providing new insights that may help drug developers create more effective, longer-lasting vaccines against microbial pathogens or cancer.
The findings are published in the March 2, 2014 online issue of Nature Immunology.
Naïve T lymphocytes patrol the front lines of the human body’s defense against infection, circulating in blood and tissues, searching for invasive microbes and other foreign antigens. They’re called “naïve” because they have not yet encountered an invader. When they do, these T cells activate and divide, giving rise to two types of daughter cells: “effector lymphocytes” responsible for immediate host defense and “memory lymphocytes” that provide long-term protection from similar infections.
“Researchers have been trying for a very long time to understand when and how T lymphocytes give rise to effector and memory cells during an infection,” said John T. Chang, MD, assistant professor in the Department of Medicine and the study’s co-principal investigator, along with Gene W. Yeo, PhD, assistant professor in the Department of Cellular and Molecular Medicine and Institute for Genomic Medicine.
Photo: T lymphocyte, courtesy of the National Institute of Allergy and Infectious Diseases.
Uterine fibroids are noncancerous growths of smooth muscle tissue in the uterus and extremely common. One in four women will experience them, typically in their child-bearing years. They aren’t life-threatening, but they can be enormously debilitating, causing heavy menstrual bleeding, pelvic pain, bladder problems and more.
There are treatments – drugs that release or block specific hormones and various types of surgery. The only current, 100 percent effective remedy for fibroids is a hysterectomy, which involves removing the uterus and results in sterilization. Of the estimated 600,000 hysterectomies performed annually in the United States, about 250,000 are due to fibroids.
In recent years, researchers have explored other approaches, including radiofrequency ablation in which MRI-directed sound waves are targeted at the fibroids, heating them and destroying fibroid cells. In time, the body reabsorbs the dead cells and the fibroids shrink.
We asked Shira Varon, MD, assistant clinical professor in the Department of Reproductive Medicine at the UC San Diego School of Medicine, to talk about new uterine fibroid treatments. Varon and colleagues are currently enrolling participants in a clinical trial of a new outpatient fibroid treatment.
Question: What causes fibroids? How does a woman know she has them?
Answer: Fibroids are the most common pelvic tumor in women and arise secondary to both genetic and hormonal factors. Women should suspect fibroids if they have symptoms of heavy or abnormal periods or pelvic pain or pressure.
Q: What are the shortcomings of currently available treatments?
A: Currently available surgical therapies, especially for women who still desire fertility, are limited to myomectomy (surgical removal of fibroids), which is usually performed via an open surgical procedure. Less commonly, if the patient is a candidate based on the location and size of her fibroids and skill of the surgeon, a myomectomy can be performed with a minimally invasive surgical procedure.
Q: Does radiofrequency ablation hurt?
A: RF ablation, or RFA, is a minimally invasive laparoscopic procedure that has a similar recovery and pain profile to a laparoscopic tubal ligation.
Q: What’s known about the long-term effects of RF? Once a woman has had fibroids, is she likely to get them again?
A: We are currently studying long-tern effects of RFA. The data that we have has followed patients for two years after having the procedure. It appears to be very safe without harm to the surrounding uterus. Whether or not a woman gets fibroids again depends upon her age at the time of the procedure, genetic factors and hormonal factors.