Degenerative Scoliosis: a Q & A with neurosurgeon William Taylor
More than half of all adults over the age of 70 have degenerative scoliosis – a curving of the spine that may cause pain, numbness and postural changes that result in decreased height and the appearance of shrinking.
When conservative approaches like physical therapy, steroid injections or bracing do not produce satisfying results, surgery becomes a primary option. A new minimally invasive alternative called lateral lumbar interbody fusion permits certain patients to avoid the current, typical open surgery, and return to everyday activities more quickly.
We asked William Taylor, MD, a neurosurgeon at UC San Diego Health System, to explain the nature of degenerative scoliosis and how some patients can stand a taller, faster.
Q: What causes curvature of the spine as we age?
A: Curvature of the spine may be caused by a number of factors, including fractures, congenital defects and even prior back surgery. In adults, scoliosis is usually related to degenerative disc disease, living longer and conditions such as osteoporosis and osteoarthritis. Everyone’s spine has a slight natural “S” curve, but with degenerative scoliosis, the spine is tilted more than 10 degrees in one direction. Sometimes patients may be teased about getting shorter in older age, but in reality this is a serious health condition that can cause pain and distressing neurological symptoms, such as numbness or tingling in the legs or difficulty taking deep breaths.
Q: How does the new surgical option differ from the current standard of care?
A: This new approach, which emerged about one year ago as part of a broader, on-going progression toward minimally invasive surgery, allows correction of up to 30 degrees per spinal segment in a minimally invasive procedure under general anesthesia. I’m able to make a 3-inch incision on a person’s side near their rib cage. I can then pass instruments through the incision to rebuild the defective portion of the spine with a small permanent implant. I like this approach because I can avoid all of the major organs and structures, such as muscles and ligaments.
In contrast, the other option is a major surgery in which the spine is rebuilt with long incisions in both the front and the back of the patient’s body. With this approach, there is a greater likelihood of trauma, blood loss and complications.
Eligibility for either surgery depends on the severity of the scoliosis. Both are appropriate for different types of patients.
Q: Are there age constraints to these techniques?
A: Because lateral lumbar interbody fusion is designed to be less invasive, it is appropriate for patients of all ages. I have treated patients from the ages of 25 to 80. When the quality of the patient’s life has decreased or if curvature of the spine is so severe that it displaces the internal organs, causing cardiovascular or pulmonary dysfunction, it’s time to consider treatment.
Also in older adults, if the spine is curved so much that the person’s balance is unsettled, there may be an increased risk of falls and fractures. That presents other health risks. By using a less invasive approach, patients may experience decreased pain, a shorter hospital stay, and most important, a quicker return to what was once their normal way of life. Of course there are always risks involved with any surgery. These should be discussed at length with one’s doctor.
UC San Diego Receives Grand Challenges Explorations Grant For Groundbreaking Research in Global Health and Development
The University of California, San Diego School of Medicine announced today that it is a Grand Challenges Explorations winner, an initiative funded by the Bill & Melinda Gates Foundation. Greg G. Goldgof, a graduate student in UC San Diego’s Biomedical Sciences Graduate Program and the Medical Science Training Program will pursue an innovative global health and development research project, titled “Outsmarting Malaria: Developing next generation anti-malarials that prevent the evolution of drug resistance.”
Grand Challenges Explorations (GCE) funds individuals worldwide to explore ideas that can break the mold in how we solve persistent global health and development challenges. Goldgof’s project is one of over 50 Grand Challenges Explorations Round 10 grants announced today by the Bill & Melinda Gates Foundation.
To receive funding, Goldgof and other Grand Challenges Explorations Round 10 winners demonstrated in a two-page online application a bold idea in one of four critical global heath and development topic areas that included agriculture development, neglected tropical diseases and communications.
“I am very appreciative that the Bill & Melinda Gates Foundation has funded my proposal to develop a new technology for drug development to treat malaria,” said Goldgof. “This information will be used to prioritize drug candidates for clinical trials and to identify new malaria drug targets for future therapies.”
Escherichia coli bacteria, magnified 10,000 times
With hot days ahead, thoughts naturally turn to the cool blue of swimming pools. Alas, not everything floating in those crystalline waters these days turns out to be an inflatable toy. A new report from the Centers for Disease Control surveyed 161 heavily used pools in metro-Atlanta in 2012. They ranged from public pools to pools at private clubs and water parks.
The CDC researchers sampled the pools’ filters, looking at what they contained. Of the 161 tested pools, more than half – 93 or 58 percent – contained Escherichia coli, a bacterium that lives abundantly in the gut of humans and other warm-blooded animals.
For the most part, E. coli is harmless, but some strains are pathogenic and are culprits behind many contaminated food events and recalls. In this case, however, the presence of E. coli is particularly icky since the bacterium is a strong indicator that someone (plural?) didn’t quite make it out of the pool to the restroom.
Actually, the CDC puts an even ickier spin on it, as only science can: “Each person has an average of 0.14 grams of fecal material on their perianal surface that could rinse into the water,” the authors observed (metaphorically).
Public pools had the highest incidence at 70 percent, followed by water parks at 66 percent and private clubs at 49 percent.
On the plus side, the researchers didn’t find any evidence in the pool filters of O157:H7, the E. coli strain most associated with food contamination and illness.
While distinguished in its disgustingness, E. coli wasn’t the most abundant of the microbes found doing the backstroke next to swimmers. That claim fell appropriately to Pseudomonas aeruginosa, a bacterium that causes swimmer’s ear. It was found in 95 of the 161 filter samples, a 59 percent incidence.
The CDC scientists were quick to note their Atlanta survey can’t be generalized to pools everywhere, but they did say the rates of pool-related illnesses nationally have been rising. Part of the problem is pool maintenance, to be sure, but swimmers have to take some of the blame.
“Swimmers have the power and responsibility to decrease the risk for recreational water illnesses by practicing good hygiene,” they wrote, suggesting that people shower thoroughly before entering a pool, take regular restroom breaks followed by another quick shower rinse before re-entering a pool and if you’re suffering from a diarrheal ailment, best stick to lounging in the sun.
Just remember to use sunscreen.
Angelina Jolie and the oncogene
It’s not surprising that Angelina Jolie’s announcement that she had preventive double mastectomy is big news. You can read about it here, here, here and here – among myriad places.
The fact remains, though, that Jolie’s dilemma and decision is far from novel. It’s one faced by many women, almost all without the glare or notice of media.
With that in mind, we reprise a pair of Q&As posed to breast cancer experts at UC San Diego: Teresa Helsten, MD, assistant clinical professor in the School of Medicine’s Division of Hematology-Oncology at Moores Cancer Center and Sarah Blair, MD, associate professor of Surgery at Moores Cancer Center.
Question: Angelina Jolie opted for her surgery based on the fact she carried the BRCA1 oncogene, which reportedly boosted her risk of breast cancer to 87 percent. How can a woman know if she should be tested for this genetic mutation?
Helsten: Above all, any woman (or man, in the case of breast cancer) who is concerned about the possibility of carrying a genetic mutation for breast/ovarian cancer should consult with her physician. Physicians may provide counseling or refer patients to trained genetic counselors for evaluation.
Things that might make a woman think about her risks include the following:
Q: Once tested and the gene is present, what are a woman’s options?
Helsten: If a woman is found to carry a genetic mutation that increases her risks of breast and ovarian cancer, there are several things to think about:
What about screening for other family members? A trained genetic counselor or physician can counsel as to who should consider testing and how. When in doubt, other family members can discuss with their own physicians.
Does she want to do anything to reduce her risks of developing breast and ovarian cancer? If so, she will need to discuss carefully with her physician to help make the right decision for her as every case is unique. Options include increased surveillance (which doesn’t lower the risk of cancer, but increases chances of detection); taking risk-reducing medications (e.g., tamoxifen); and surgical removal of breasts and/or ovaries. For example, removal of both breasts by mastectomy reduces the risk of breast cancer by approximately 90-95 percent. These decisions can be very personal and very difficult, but the good news is that they almost never need to be made in a rush. It is worth taking the time to get informed in order to make a decision that is fits the individual.
Q: Does having the genetic mutation for breast cancer mean breast cancer is inevitable?
Helsten: No, cancer is not inevitable, but the risks are usually quite high. Depending on the specific mutations discovered, the lifetime risks of breast cancer for BRCA1/2 carriers are estimated to be 56-84 percent. For ovarian cancer, the lifetime risks are a bit lower. They are estimated to be 36-46 percent for BRCA1 and 10-27 percent for BRCA2 mutation carriers.
Q: Last year, comedian and actress Wanda Sykes underwent a double mastectomy for “stage zero breast cancer.” People are fairly familiar with stages I through IV, which denote the progressive size and spread of a tumor and its likely prognosis. What is stage 0 breast cancer?
Blair: When I counsel my patients, I show them a picture to demonstrate the difference. Basically these tumors start in the duct, which is a tube that drains milk when you breast feed. Tumors that are stage 0 are confined inside the duct and cannot spread outside to other parts of the body. However, if the tumor is left alone they can eventually break through the duct and become invasive. Early treatment prevents spread of the tumor.
Q: Was Sykes’ decision to have a radical mastectomy based on her family history of breast cancer typical for a stage 0 patient?
Blair: Most women are good candidates for breast conservation, which is removal of that area of the breast or lumpectomy plus radiation. I would also recommend the drug Tamoxifen for women with estrogen sensitive tumors. This drug treats the tumor itself and helps prevent future tumors. However, some women do not want to take Tamoxifen because of its side effects. For the average woman with stage 0 their lifetime risk of developing a second cancer in either breast is 20 percent. Some women with a strong family history of breast cancer, i.e. multiple relatives with breast cancer, may have a higher risk of a second cancer, particularly if they are diagnosed at a young age. These women may consider more aggressive surgical treatment to prevent future cancers. Typically, most women do not have radical surgery but those that do have much better cosmetic outcomes than in the past.
Q: Does a diagnosis of stage 0 mean that the cancer is 100 percent curable?
Blair: Unfortunately, nothing is 100 percent in medicine but there is a high likelihood of being cured. The chance of being cured depends on the size of the tumor and its appearance under the microscope or grade. In general the chance of being cured is greater than 90 percent.
Photo courtesy of AP
Scanning electron micrograph of color-enhanced colony of Streptococcus pneumoniae, which causes pneumonia. Image courtesy of Debbie Marshall, Wellcome Images
There’s not much argument these days that human breast milk is far superior to formula. Study after study in recent years has shown not only that it’s more nutritious than the manufactured stuff, but also that mom’s milk contains key ingredients that help newborns fend off a variety of infectious agents, illnesses and diseases, including HIV transmission from mother to child.
The case for mom just got stronger with a pair of new studies.
In the first, published in PLoS One by researchers at the University of Buffalo, scientists found that a protein complex in human breast milk protein – dubbed HAMLET, short for Human Alpha-lactalbumin Made LEthal to Tumor cells – may help reverse the antibiotic resistance of some bacteria that cause ailments like pneumonia and staph infections.
In petri dish and animal tests, HAMLET boosted bacterial sensitivity to multiple classes of antibiotics, including penicillin and erythromycin. It was so effective, in fact, that methicillin-resistant Staphylococcus aureus (MRSA) became vulnerable again to antibiotics it had previously disdained.
The Buffalo researchers said bacteria struggled to develop resistance to HAMLET, perishing in massive numbers even after generations of exposure. “Unlike synthetic drugs, HAMLET is a naturally occurring human milk protein-lipid complex, and so is not associated with the types of toxic side effects that we so frequently see with the high-powered antibiotics needed to kill drug-resistant organisms,” said study co-author Laura Marks.
In the second study, out of the University of Pittsburgh and published in PNAS, researchers found that the survival chances of premature babies measurably improved when they added a naturally occurring ingredient found in human breast milk to the preemies’ formula.
Babies born too early – generally before 36 weeks’ gestation – are typically fed formula because mother’s milk is not readily available. Sometimes, however, the premature infant quickly develops major gastrointestinal problems: The belly begins to bloat and x-rays reveal necrotizing enterocolitis (NEC), a condition in which intestinal tissue begins dying. In about half of these cases, the babies do not survive.
The Pittsburgh scientists noted that preemies who are breast-fed are more likely to survive NEC than preemies on a formula diet. They discovered that breast milk contains high levels of sodium nitrate, which is converted to nitrite by gut bacteria. The nitrite, in turn, is converted into vasodilator nitric oxide, a compound that helps keep blood vessels feeding intestinal tissues open and flowing.
“When we gave formula supplemented with sodium nitrate and nitrite analog to premature mice (models), we saw improved blood flow in the intestine, and NEC did not develop,” said study co-author Mark Gladwin.
Gladwin and colleagues are continuing their research to determine whether it is safe and feasible to add sodium nitrate, which as a food preservative has been linked to heart disease and cancer, to baby formula in order to prevent NEC.
Separated from its originating tumor and wandering in either the blood or lymphatic system, “circulating tumor cells” may become metastatic precursors to new tumors elsewhere in the body. In this scanning electron micrograph, a single CTC is trapped on a microchip. Image courtesy of Mehmet Toner and Daniel Haber, Massachusetts General Hospital/Cell.
Tumor-Activated Protein Promotes Cancer Spread
Researchers at the University of California, San Diego School of Medicine and UC San Diego Moores Cancer Center report that cancers physically alter cells in the lymphatic system – a network of vessels that transports and stores immune cells throughout the body – to promote the spread of disease, a process called metastasis.
The findings are published in this week’s online Early Edition of the Proceedings of the National Academy of Sciences.
Roughly 90 percent of all cancer deaths are due to metastasis – the disease spreading from the original tumor site to multiple, distant tissues and finally overwhelming the patient’s body. Lymph vessels are often the path of transmission, with circulating tumor cells lodging in the lymph nodes – organs distributed throughout the body that act as immune system garrisons and traps for pathogens and foreign particles.
The researchers, led by principal investigator Judith A. Varner, PhD, professor of medicine at UC San Diego Moores Cancer Center, found that a protein growth factor expressed by tumors called VEGF-C activates a receptor called integrin α4β1 on lymphatic vessels in lymph node tissues, making them more attractive and sticky to metastatic tumor cells.
“One of the most significant features of this work is that it highlights the way that tumors can have long-range effects on other parts of the body, which can then impact tumor metastasis or growth,” said Varner.
Varner said α4β1 could prove to be a valuable biomarker for measuring cancer risk, since increased levels of the activated protein in lymph tissues is an indirect indicator that an undetected tumor may be nearby.
She said whole-body imaging scans of the lymphatic network might identify problem areas relatively quickly and effectively. “The idea is that a radiolabeled or otherwise labeled anti-integrin α4β1 antibody could be injected into the lymphatic circulation, and it would only bind to and highlight the lymphatic vessels that have been activated by the presence of a tumor.”
Varner noted that α4β1 levels correlate with metastasis – the higher the level, the greater the chance of the cancer spreading. With additional research and clinical studies, doctors could refine treatment protocols so that patients at higher risk are treated appropriately, but patients at lower or no risk of metastasis are not over-treated.
The researchers noted in their studies that it is possible to suppress tumor metastasis by reducing growth factor levels or by blocking activation of the α4β1 receptor. Varner said an antibody to VEGF-R3 is currently in Phase 1 clinical trials. An approved humanized anti-α4β1 antibody is currently approved for the treatment of multiple sclerosis and Crohn’s disease. Varner said her lab at UC San Diego Moores Cancer Center is investigating the possibility of developing one for treating cancer.
Higher Child Marriage Rates Associated with Higher Maternal and Infant Mortality
Countries in which girls are commonly married before the age of 18 have significantly higher rates of maternal and infant mortality, report researchers in the current online issue of the journal Violence Against Women.
The study, by Anita Raj, PhD, a professor in the Department of Medicine in the University of California, San Diego School of Medicine and Ulrike Boehmer, PhD, an associate professor in the Boston University School of Public Health, is the first published ecological analysis of child marriage and maternal mortality. The study demonstrates that a 10 percent reduction in girl child marriage could be associated with at 70 percent reduction in a country’s maternal mortality rate.
“Our analyses accounted for development indicators and world region, and still documented that nations with higher rates of girl child marriage are significantly more likely to contend with higher rates of maternal and infant mortality and non-utilization of maternal health services,” said Raj.
“Though child marriage is not highly common in the United States,” said Raj, “these findings are meaningful because they hold true for adolescent pregnancy, regardless of marriage. Young age at childbirth increases risk for both maternal and infant mortality.”
Girl child marriage is defined as the marriage of girls age 17 and younger. Although the practice has generally declined in recent years, it remains relatively common in regions like South Asia and sub-Saharan Africa, where up to 70 percent of females in some countries are married as minors. Worldwide, the United Nations estimates more than 60 million women and girls are affected, and considers girl child marriage to be a health and human rights violation.
Nanoparticles of porous silicon, each 100 times smaller than a human hair, might be used as injectable microscopic reservoirs of therapeutic drugs. The surface of the particles can be coated with targeting molecules. Image courtesy of Chia-Chen Wu, UC San Diego.
DARPA, the U.S. Defense Advanced Research Projects Agency, has awarded $6 million to a multi-institutional team of researchers to develop nanotechnology therapies for the treatment of traumatic brain injury.
Led by Professor Michael J. Sailor, PhD, from the University of California San Diego, the project team seeks to use nanoparticles and similar approaches to deliver therapeutics to injured brains and reduce infections.
Ballistics injuries that penetrate the skull have amounted to 18 percent of battlefield wounds sustained by men and women who served in the campaigns in Iraq and Afghanistan, according to the most recent estimate from the Joint Theater Trauma Registry, a compilation of data collected during Operation Iraqi Freedom and Operation Enduring Freedom.
“A major contributor to the mortality associated with a penetrating brain injury is the elevated risk of intracranial infection,” said neurosurgeon Clark C. Chen, MD, PhD, of the UC San Diego Health System, noting that projectiles drive contaminated foreign materials into neural tissue.
Under normal conditions, the brain is protected from infection by a physiological system called the blood-brain barrier. “Unfortunately, those same natural defense mechanisms make it difficult to get antibiotics to the brain once an infection has taken hold,” said Chen. Watch a video and read the entire news release here.
A scanning electron micrograph of a human blastocyst (5 days after fertilization of the egg), revealing the inner cell mass that will become the embryo. Image courtesy of Yorgos Nikas, Wellcome Images
Life. Bits. Self.
The development of human life is an indisputable marvel of choreographed complexity: A single fertilized egg divides and multiplies, the resulting cells differentiating into the roughly 300 cell types required to build a human being.
Among the great and enduring questions of developmental biology is how exactly embryogenesis occurs. What process or plan directs differentiating cells to do what they do, to choose their pathways to becoming neurons, fat cells, hair cells or various hormone secreting cells?
In a paper published today in Cell, a multi-institutional team of scientists, including Bing Ren, PhD, head of the Laboratory of Gene Regulation at the Ludwig Institute for Cancer Research at UC San Diego and professor in the UCSD School of Medicine’s Department of Cellular and Cellular Medicine, describe how genes are turned on and off to direct early human development – and report novel genetic mechanisms that play key roles not just in normal development but perhaps in diseases like cancer as well.
Using large-scale genomics technologies, the researchers focused on two key processes in unprecedented detail. The first involves the tacking of methyl molecules to cytosine, one of the four DNA bases that comprise the genetic code; the second involves chemical modifications to proteins called histones, which provide the scaffolding used by winding DNA in cell nuclei.
Histone modification, the researchers found, is more commonly used to regulate genes in early embryonic development, switching them on and off as needed. “DNA methylation” tends to be used in the later stages of development when cells are increasingly locked into specific fates and functions.
“You can sort of glean the logic of animal development in this difference,” said Ren in a news release issued by the Ludwig Institute. “Histone methylation is relatively easy to reverse. But reversing DNA methylation is a complex process, one that requires more resources and is much more likely to result in potentially deleterious mutations.
“So it makes sense that histone methylation is largely used to silence master genes that may be needed at multiple points during development, while DNA methylation is mostly used to switch off genes at later stages, when cells have already been tailored to specific functions, and those genes are less likely to be needed again.”
The scientists also noted two other significant findings:
Ren said the work creates a new information resource for biomedical research, not just for better understanding of early human development, but also of the many diseases that trace their roots to our own.
CDC-Recommended Non-Profit Launches “MotherToBaby CA” In Time for Mother’s Day
Experts Provide Free Answers about Medications and More during Pregnancy and Breastfeeding
As Mother’s Day approaches, the University of California, San Diego School of Medicine announces MotherToBaby CA, the new name of its free, statewide counseling service that connects experts in the field of birth defects research with moms-to-be and the general public. MotherToBaby CA was formerly known as the California Teratogen Information Service (CTIS) Pregnancy Health Information Line and is housed at the Center for the Promotion of Maternal Health and Infant Development, a division of UC San Diego and Rady Children’s Hospital.
MotherToBaby CA is an affiliate of the international non-profit Organization of Teratology Information Specialists (OTIS), a prestigious professional society that supports and contributes to worldwide initiatives for teratology education and research. MotherToBaby affiliates and OTIS, which are suggested resources by many agencies including the Centers for Disease Control and Prevention (CDC), are dedicated to providing evidence-based information to mothers, health care professionals, and the general public about medications and other exposures during pregnancy and while breastfeeding.
“In addition to my primary health care provider, MotherToBaby experts offered me an added layer of support by giving me an individualized risk assessment,” said Pamela Salgado, a San Diego resident who called the service when she was thinking about getting pregnant. She had questions about the safety of a long-term medication she was taking and its potential risks during pregnancy. “Afterwards, I felt informed and empowered to make smart decisions about my health. Today, I have a healthy three-year-old boy.”
All North Americans can be connected with MotherToBaby experts toll free through its phone counseling service 866-626-6847 or online at MotherToBabyCA.org, where a private, online chat counseling service is also offered.