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Thu 31 Jul 2008 04:00 AM

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Research matters

News from the Harvard Medical School research community.

News from the Harvard Medical School research community.


Many infants and toddlers don't get enough vitamin D: Researchers call for supplements for breastfeeding infants and increased milk intake for toddlers

Many otherwise healthy infants and toddlers have inadequate vitamin D levels that may put future bone health at risk.

Many otherwise healthy infants and toddlers have inadequate vitamin D levels that may put future bone health at risk, finds a study from Children's Hospital Boston.

The major risk factor for infants was exclusive breastfeeding without vitamin D supplementation; for toddlers, it was inadequate milk consumption. Findings appear in the June issue of Archives of Pediatrics & Adolescent Medicine.

Led by Catherine Gordon, MD, MSc, Director of the Bone Health Program at Children's, the researchers studied 365 infants and toddlers who visited the hospital's general pediatric clinic for well-child exams at age 9 and 18 months, respectively.

Blood testing found that 40 percent of the children had vitamin D levels below the optimum considered good for bone health, and 12 percent were frankly deficient.

Of the deficient group, 13 children (32.5 percent) had evidence of bone loss, as assessed by computed radiography of the wrist and knee. Three children (7.5 percent) had bone changes consistent with rickets (a softening of the bones that can lead to fractures, stunted growth and deformities like curved spine and bowed legs), although only one of these children had signs of rickets on physical examination.

"We were struck by the number of children in our study with suboptimal vitamin D levels," says Gordon. "Vitamin D status is not routinely checked as part of routine care, and the majority of the children did not show signs of rickets or other evidence of a deficiency, so it is concerning that this problem would have otherwise gone undetected."

In infants, the major predictor of deficiency was exclusive breastfeeding without vitamin D supplements. Infants in this category were 10 times more likely to be vitamin D deficient than infants who were exclusively bottle-fed. (Breast milk does not contain vitamin D, whereas formula and cow's milk are fortified with the vitamin.) In toddlers, the major risk factor was inadequate milk consumption: blood vitamin D levels increased in close correlation with the number of cups per day of milk the child drank.

"As a pediatrician, I am pleased that breastfeeding has become more common among new mothers," says Gordon. "Of concern, however, is the rise in cases of rickets accompanying this trend. Our data suggest the importance of vitamin D supplementation for young children, and particularly breast-fed infants."

The authors were struck by the strength of the correlation between vitamin D deficiency and breastfeeding without supplementation, since only 8 percent of children in the study were exclusively breastfed.

Although the American Academy of Pediatrics and Institute of Medicine recommend that infants and children receive 200 IU daily of supplemental vitamin D, few breastfed infants in this study were receiving such supplementation.

Since both dark skin and sunscreen reduce absorption of the ultraviolet rays that help the body manufacture vitamin D, the researchers expected to find skin pigmentation, sunscreen use and time spent outdoors to be predictive of vitamin D deficiency.

However, their data revealed no significant correlation with these factors. They speculate that the layers of clothing babies are typically dressed in may prevent them from absorbing enough sunlight.

"We were surprised that neither skin pigmentation nor season significantly predicted vitamin D deficiency," Gordon says. "Our data suggest that unique risk factors for this problem can arise, ones that pediatric health care providers should be cognizant of in the care of young children."The infant and toddler years are the first crucial period for laying down bone. Once bone mass reaches its peak--by age 18--it can never increase. No one really knows what will happen when children with bone loss enter adulthood and old age, but Gordon fears they may be predisposed to osteoporosis.


MGH study confirms benefit of surgery for gastroesophageal reflux: Most patients report improved quality-of-life and satisfaction with procedure

Total plaque burden is considered the most important predictor of coronary events.

Despite the growing availability of prescription and over-the-counter medications for gastroesophageal reflux disease (GERD), surgical treatment remains a viable alternative for patients whose symptoms persist.

In the May 2008 Archives of Surgery, surgeons from Massachusetts General Hospital (MGH) report their survey of almost 200 patients who had laparoscopic antireflux surgery at the MGH over a 10-year period.

Specifically designed to assess GERD-related symptoms, the survey produced near-normal quality-of-life scores from most respondents, who also indicated considerable satisfaction with their long-term results.

"Our results indicate that, in appropriate selected patients, antireflux surgery is an excellent treatment alternative that provides very good results for patient quality of life," says David Rattner, MD, chief of General and Gastrointestinal Surgery at MGH and senior author of the report.

Many individuals experience gastroesophageal reflux - when acidic stomach contents rise into the lower esophagus, producing the burning sensation called heartburn. When those symptoms become chronic and occur more than twice a week, they are considered GERD.

In addition to persistent discomfort, GERD can lead to serious consequences, including bleeding of the esophageal lining and, in the most serious cases, esophageal cancer.

Lifestyle changes can reduce some GERD symptoms; and while many patients are helped by over-the-counter or prescription medications, symptoms persist for some individuals.

Surgery designed to rebuild and strengthen the muscular valve between the esophagus and the stomach offers an option for these patients and for those who would like to avoid lifetime medication use.

Rattner explains that some recent reports in the medical literature have questioned whether the long-term benefits of surgical repair outweigh the risks present in any sort of surgery.

Previous outcomes evaluations, which had inconsistent results, have used a survey designed to assess quality-of-life issues relevant to a number of disorders.

This new study uses the Gestroesophageal Reflux Disease - Health-Related Quality-of-Life Scale (GERD-HRQL), which focuses on GERD symptoms.

Copies of the GERD-HRQL survey were mailed to about 350 patients who had laparoscopic antireflux surgery at the MGH from 1997 to 2006.

Completed surveys were returned by 191 patients, who were responding an average of five years after surgery. Among patients whose procedure was their first antireflux operation, the average GERD-HRQL score was 5.71, similar to that of the normal population.

Scores on the GERD-HRQL can range from 0 to 45, with 0 indicating no GERD-related symptoms.

Patients whose procedure had been a reoperation had an average score of 14.25. Among first-procedure respondents, 71 percent indicated they were satisfied with their outcomes, and 88 percent responded that they would have the procedure again.While 43 percent of respondents reported taking some antireflux medications after their surgery, most of those patients had not had any testing to verify the recurrence of GERD.

"Some reports have claimed that resumption of antireflux medications indicates that surgery is a failure, but that isn't necessarily true," Rattner says.

"The symptoms of GERD are so non-specific, and patients may resume taking medications on their own. When patients who resume these drugs have been actually tested for the presence of reflux, most of them are shown not to have GERD."

Surgical treatment remains a viable alternative for patients whose (GERD) symptoms persist.

"Only 1.2 percent of survey respondents reported needing repeat surgery, which does not support others' assertions that about half these procedures fail," Rattner adds.

"Our results let us say that, when this surgery is performed by an expert surgical team at a high-volume center, the outcome for most patients is excellent."

Rattner is a professor of Surgery at Harvard Medical School. The study's co-authors are lead author Denise Gee, MD, MGH Department of Surgery, and Michael Andreoli, Boston University School of Medicine.

Prostate cancer treatment

Utilization and outcomes for minimally invasive prostate cancer treatment

Many patients perceive minimally invasive surgery as the better choice over open surgical procedures; however, up to this point, little data was available about utilization and outcomes of minimally invasive radial prostatectomy (MIRP) to treat prostate cancer compared with the older open radical prostatectomy approach.

Jim Hu, MD, MPH, and colleagues at Brigham and Women's Hospital (BWH) assessed surgical utilization and complications, lengths of hospital stay and cancer outcomes in over 2,700 men who underwent prostate cancer surgery and found that MIRP usage almost tripled between 2003 and 2005 - a striking finding since the procedure was introduced in the US in 2000.

Additionally, the researcher found although MIRP patients had less surgical complications and shorter hospital stays by almost three days, they were more likely to require additional cancer treatments after surgery compared to men undergoing open surgery.

These findings appear in the May 10, 2008, issue of the Journal of Clinical Oncology.

"In short time, MIRP has taken over as one of the most popular treatments for prostate cancer, but one cannot help but think this procedure was adopted by surgeons too quickly because cancer outcomes for MIRP patients overall were not as favorable as those who underwent open radical prostatectomy," said lead author Hu.

"However, the results of our national study differ from outcomes at high volume centers where cancer control for the open and minimally invasive approaches are very similar."

The researchers found that experienced or high volume MIRP surgeons were more likely to have favorable cancer outcomes compared to low-volume MIRP surgeons, suggesting that the rapid adoption of the procedure by eager surgeons, not the procedure itself, is a possible cause for worse long-term outcomes compared with open radical prostatectomy.

"There is a steep learning curve for MIRP and based on our research, I would tell patients deciding on a prostate cancer treatment to pay attention to the experience of their doctor and not be seduced by the smaller incisions and newer technologies offered by minimally invasive surgery," Hu added.


New method shown effective in detecting dangerous coronary plaque

A significant number of patients who suffer a heart attack never have any warning signs. For many of these individuals, the source of the problem is noncalcified plaque, a buildup of soft deposits embedded deep within the walls of the heart's arteries, undetectable by angiography or cardiac stress tests - and prone to rupture without warning.Now a new noninvasive method has shown success in detecting and measuring noncalcified plaque.

In a pilot clinical study led by investigators at Beth Israel Deaconess Medical Center (BIDMC), the technique -- voxel analysis used in conjunction with MDCTA (multi-detector computed tomography angiography) - was shown to be equally as effective as catheter coronary angiography in identifying patients at risk for heart disease.

Reported in the June 2008 issue of the American Journal of Roentgenology (AJR), the new findings may help doctors monitor the effects of medical treatment to reduce patients' risk of atherosclerosis and heart disease.

"The importance of quantifying plaque is critical because total plaque burden is considered the most important predictor of coronary events," explains the study's senior author Melvin Clouse, MD, PhD, Emeritus Chairman of the Department of Radiology and Director of Radiology Research at BIDMC and Deaconess Professor of Radiology at Harvard Medical School. "Furthermore, the rupture of soft noncalcified plaque has been implicated as the cause of heart attack."

Exercise stress testing and coronary angiography, the standard methods for diagnosing atherosclerosis and heart attack risk, both work by visualizing the lumen, the channel through which blood flows.

However, because the lumen also increases in size as plaque progresses, coronary artery disease may go undetected until late in the disease process. And, adds Clouse, "Because soft plaque buildup may not significantly narrow the lumen, conventional angiography and stress tests fail to provide a complete picture of plaque accumulation."

The investigators set out to evaluate a new method of plaque assessment using multidetector computed tomography angiography (MDCTA). Unlike coronary angiography, in which a catheter is threaded through the femoral artery and up into the heart, MDCTA is not invasive.

The CT scanning method, comprised of 64 separate scans, provides a detailed cross-sectional view of the blood vessel wall based on the amount and volume of blockage present. Its ability to differentiate plaque density makes it particularly useful in distinguishing between stable plaque and unstable plaque.

"The latest MDCT scanners have made it possible to detect noncalcified plaque," explains Clouse. "However, due to a number of technical and physiologic factors, accurate and reproducible measurements of this plaque was difficult and time-consuming. We, therefore, developed a new technique that would overcome these obstacles."

The researchers analyzed 41 normal and eight abnormal arterial cross sections with noncalcified plaque selected from 10 patients undergoing MDCTA for percentage of stenosis and plaque volume using a voxel analysis technique, in which density values are measured to identify the boundaries between epicardial fat and the outer arterial wall and between the inner wall and the lumen.

"Voxel analysis estimates the volume of plaque in a blood vessel based on a range of volumetric densities," explains Clouse. Within the selected volume, the number of voxels having a density within the range of plaque is established, from which the volume of plaque is then estimated. (In CT scans, voxel values are Hounsfield units, which give the opacity of material to X-rays.) The detailed measurements - nearly 2,300 in total - provided physicians with a detailed picture of the coronary arteries and surrounding areas.

"By plotting a voxel histogram across the arterial wall, we were able to measure the amount of plaque, as well as the narrowing of the artery," explains Clouse.

Importantly, he notes, the technique additionally defines the outer boundary of the adventitia, the connective tissue surrounding the artery. Though considered extraneous to the artery, the adventitia appears to play a critical role in the disease process.

"Using this new method, we hope to be able to be able to better assess the effects of medication treatment and lifestyle interventions in treating atherosclerosis," says Clouse, who as a member of a team of clinical investigators will study the effects of lifestyle intervention (diet, exercise and omega-3 fatty acid supplement) or salsalate medication compared to placebo on coronary artery calcification as assessed by MDCTA.

This article is provided courtesy of Partners Harvard Medical International.

Research Matters brings together selected research being conducted at Harvard Medical School's 18 affiliated institutions. For more information, visit the Harvard Medical School website at

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