Alzheimer's - Dementia, Author Interviews, Blood Pressure - Hypertension, NIH / 03.02.2016

MedicalResearch.com Interview with: Dr. Juan M. Saavedra, MD and Dr. Abdel Elkahloun PhD Comparative genomics and Cancer Genetics Branch National Human Genome Research Institute, National Institutes of Health, Bethesda, MD MedicalResearch: What is the background for this study? What are the main findings? Response: Alzheimer’s disease is the most frequent age-related dementia, a progressing, devastating illness without effective treatment. By the time it is diagnosed, major and irreversible cell injury has already occurred. It is therefore imperative to identify therapeutic agents effective against early, pre-symptomatic injury mechanisms and risk factors increasing vulnerability the disease. We focused on a class of compounds blocking receptors for Angiotensin II, the Angiotensin Receptor Blockers (ARBs). These compounds are commonly used for the treatment of hypertension, a major risk factor for Alzheimer’s disease. We and others have found that in addition to their cardiovascular benefits, ARBs are strongly neuroprotective. The present study was designed to explore in depth the neuroprotective effects of one member of the ARB class, candesartan. To this effect we cultured neurons extracted from the rat brain. These neurons were exposed to high concentrations of glutamate, a recently identified early injury mechanism in Alzheimer’s disease. We found that candesartan prevented glutamate-induced neuronal injury. We conducted in-depth examination of our results by genome-wide expression profile analysis. We found that candesartan normalized glutamate-induced alterations in expression of hundreds of genes, including many involved in neuronal inflammation, cardiovascular disease, diabetes and alterations in amyloid metabolism a hallmark for Alzheimer’s disease. This was evidence of direct neuroprotective effects of relevance for this disorder. When we compared our results with published databases obtained from autopsy samples from Alzheimer’s disease patients, we found impressive correlations. The expression of more than 400 genes altered by glutamate and normalized by candesartan in our cultures was similarly changed in the Alzheimer’s databases. The conclusion was that our cell culture results represented alterations found in the human condition. Our observations provide novel evidence of neuroprotection from early mechanisms of injury in Alzheimer’s disease and support testing candesartan in controlled clinical studies including individuals at the early stages of the illness, to unequivocally demonstrate their therapeutic effect. (more…)
Author Interviews, NEJM, NIH, Opiods / 14.01.2016

For more on Opioids on MedicalResearch.com please click here. MedicalResearch.com Interview with: Wilson M. Compton, M.D., M.P.E. Deputy Director National Institute on Drug Abuse Medical Research: What is the background for this study? What are the main findings? Dr. Compton: Deaths related to opioids (from both prescription pain killers and street drugs, like heroin) have dramatically increased in the past 15 years.  How these different types of opioids are related to each other is important because the pain killers ultimately are derived from prescriptions written by health care providers and street drugs, like heroin, are from illegal sources.  The different types of opioids vary in there source but are quite similar in their effects in the brain.  Given the different sources, interventions to reduce availability vary across the two categories. There is also a concern that interventions to reduce the availability of prescription opioids may be encouraging people to switch to heroin.  That’s the main question addressed in this review. (more…)
Author Interviews, BMJ, Diabetes, NIH, OBGYNE / 13.01.2016

MedicalResearch.com Interview with: Cuilin Zhang MD, PhD Senior Investigator, Epidemiology Branch Division of Intramural Population Health Research NICHD/National Institutes of Health Rockville, MD 20852  Medical Research: What is the background for this study? What are the main findings? Dr. Zhang: Potatoes are the third most commonly consumed food crop in the world. In the United States, about 35% of women of reproductive age consume potatoes daily, accounting for 8% of daily total energy intake.  Gestational diabetes mellitus (GDM) is a common complication of pregnancy characterized by glucose intolerance with onset or first recognition during pregnancy. GDM is at the center of a vicious circle of 'diabetes begets diabetes' across generations. Potato foods are typically higher in glycemic index and glycemic load, but data are lacking regarding whether potato consumption is associated with the risk of Gestational diabetes mellitus. Medical Research: What is the background for this study? What are the main findings? Dr. Zhang: Women who eat more potatoes before pregnancy may have higher risk of gestational diabetes—the form of diabetes that occurs or first diagnosed during pregnancy—compared to women who consume fewer potatoes. Substituting potatoes with other vegetables, legumes or whole grains may help lower gestational diabetes risk. (more…)
AHA Journals, Author Interviews, Brigham & Women's - Harvard, NIH, Nutrition, Sugar, Weight Research / 12.01.2016

MedicalResearch.com Interview with: Dr. Caroline Fox, MD MPH National Heart, Lung, and Blood Institute Assistant Clinical Professor of Medicine Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Fox: There is evidence linking sugar sweetened beverages with obesity and type 2 diabetes. There is also evidence suggesting that specific adipose tissue depots may play a role in the pathogenesis of these diseases. We found that higher levels of sugar sweetened beverage (SSB) intake was associated with more visceral fat (fat in the stomach cavity) over 6 years. (more…)
Author Interviews, Genetic Research, Heart Disease, Neurological Disorders, NIH, Science / 05.12.2015

MedicalResearch.com Interview with: Jonathan Kaltman, MD Chief, Heart Development and Structural Diseases Branch Division of Cardiovascular Sciences National Heart, Lung, and Blood Institute Medical Research: What are the main findings? Dr. Kaltman:  Congenital heart disease (CHD) is the most common birth defect but the cause for most defects is unknown.  Surgery and clinical care of patients with congenital heart disease has improved survival but now we are learning that many patients have neurodevelopmental abnormalities, including learning disability and attention/behavioral issues. Medical Research:  What are the main findings?
  • Using exome sequencing we found that patients with  congenital heart disease have a substantial number of de novo mutations.  This finding is especially strong in patients with CHD and another structural birth defect and/or neurodevelopmental abnormalities.
  • Many of the genes identified are known to be expressed in both the heart and the brain, suggesting a single mutation may contribute to both congenital heart disease and neurodevelopmental abnormalities.
(more…)
Alcohol, Author Interviews, Gender Differences, NIH / 24.11.2015

MedicalResearch.com Interview with: Aaron White, PhD Senior Scientific Advisor to the Director Office of the Director National Institute on Alcohol Abuse and Alcoholism National Institutes of Health Bethesda, MD Medical Research: What is the background for this study? What are the main findings? Dr. White: Recent studies and anecdotal evidence suggest that alcohol use by women in the United States might be on the rise and that long-standing gender gaps in drinking and related consequences might be narrowing. Using data from the National Survey on Drug Use and Health, we found that differences in the drinking patterns of females and males ages 12+ narrowed between 2002 and 2012 for current drinking (drinking at least once in the last 30 days), number of drinking days per month, past year DSM-IV alcohol abuse, and past-year driving under the influence of alcohol. For instance, the percentage of women who drank in the previous 30 days rose from 44% to 48%, while for men the percentage decreased from 57% to 56%. Average drinking days per month increased for women from 6.8 to 7.3 days, but dropped for males from 9.9 to 9.5 days. Driving under the influence (DUI) declined for both, but less so for females (from 10.3% to 7.9%) than males (from 19.0% to 14.4%), thereby narrowing the gender gap for DUI. Analyses revealed additional changes within specific age groups in the population. (more…)
AACR, Author Interviews, NIH, Nutrition, Ovarian Cancer, Race/Ethnic Diversity / 13.11.2015

MedicalResearch.com Interview with: Bo (Bonnie) Qin, PhD Postdoctoral associate at Rutgers Cancer Institute of New Jersey Medical Research: What is the background for this study? What are the main findings? Response:  Ovarian cancer is among the top five causes of cancer death among women in the US. Compared to white women, African-American women tend to have a worse 5-year survival rate of ovarian cancer. It highlights a critical need for identifying preventive factors in African Americans, particularly through dietary modification, which is relatively low cost and low risk compared to medical treatments. We found that adherence to an overall healthy dietary pattern i.e. Alternate Healthy Eating Index (AHEI)-2010 may reduce ovarian cancer risk in African-American women, and particularly among postmenopausal women. Adherence to the current Dietary Guidelines for Americans i.e. Healthy Eating Index-2010, were also strongly associated with reduced risk of ovarian cancer among postmenopausal African-American women. (more…)
Author Interviews, Cancer Research, Endocrinology, Journal Clinical Oncology, Menopause, NIH / 07.11.2015

MedicalResearch.com Interview with: Elizabeth K. Cahoon, PhD Radiation Epidemiology Branch Division of Cancer Epidemiology and Genetics, National Cancer Institute National Institutes of Health Department of Health and Human Services Bethesda, MD Medical Research: What is the background for this study? What are the main findings? Dr. Cahoon: Although basal cell carcinoma (BCC) is the most common cancer in the United States, there is relatively little research on risk factors since few population-based cancer registries do not capture information on this malignancy. Sun exposure (in particular ultraviolet radiation) is the primary risk factor for basal cell carcinoma, but less is known about other factors that may affect this risk. A previous study found a relationship between menopausal hormone therapy (MHT) use and increased risk of BCC in a population of Danish women. In our study we looked to see if factors related to estrogen exposure from multiple sources was associated with basal cell carcinoma risk in a large, nationwide, prospective study. These included use of oral contraceptives or menopausal hormone therapy, but also reproductive factors (like age at menarche and menopause). We observed that women who experienced natural menopause later in life were more likely to develop basal cell carcinoma compared to women who had natural menopause at a younger age. In addition, women who reported using menopausal hormone therapy for one year or longer were more likely to develop basal cell carcinoma compared to women who did not report MHT use. Women who reported natural menopause and menopausal hormone therapy use for 10 or more years had the highest risk of basal cell carcinoma, compared to women with no menopausal hormone therapy use. (more…)
Author Interviews, Lifestyle & Health, NIH / 05.11.2015

MedicalResearch.com Interview with: Sarah K. Keadle, PhD, MPH Cancer Prevention Fellow Nutritional Epidemiology Branch Division of Cancer Epidemiology and Genetics National Cancer Institute   Medical Research: What is the background for this study? What are the main findings? Dr. Keadle: Television viewing is extremely prevalent in the U.S. Ninety-two percent of Americans have a television at home and watching TV consumes more than half of their available leisure time, potentially displacing more physical activities. Previous studies have reported a relationship between TV viewing and increased risk of death from the two most common causes of death in the U.S., cancer and heart disease. In our study, we followed more than 221,000 healthy Americans aged 50-71 years old for 14 years to look at this relationship. We confirmed the association with increased risk of death from cancer and heart disease. In addition, we found that TV viewing was associated with an increased risk of six other causes of death, including diabetes, influenza/pneumonia, Parkinson’s disease, and liver disease. Also, compared to individuals who watched less than one hour per day, those who watched 3-4 hours of TV per day were 15% more likely to die from any cause, and individuals who watched seven or more hours of TV per day were 47% more likely to die over the study period. (more…)
AHA Journals, Author Interviews, Dermatology, Heart Disease, NIH / 12.10.2015

Nehal Mehta, M.D., M.S.C.E., F.A.H.A. Lasker Clinical Research Scholar Section of Inflammation and Cardiometabolic Diseases NIHMedicalResearch.com Interview with: Nehal Mehta, M.D., M.S.C.E., F.A.H.A. Lasker Clinical Research Scholar Section of Inflammation and Cardiometabolic Diseases NIH Medical Research: What is the background for this study? What are the main findings? Dr. Mehta: Psoriasis increases cardiovascular disease (CVD), and this study shows for the first time that the amount of psoriasis on the skin is mirrored in the blood vessels by increasing blood vessel inflammation. Medical Research: What should clinicians and patients take away from your report? Dr. Mehta: Even one plaque may be too many if we are seeing a relationship between skin disease severity and vascular inflammation. (more…)
Author Interviews, NIH, OBGYNE, Pediatrics / 01.10.2015

Dr. Louis Germaine Buck Senior Investigator and Director of the Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) National Institutes of Health MedicalResearch.com Interview with: Dr. Germaine Louis Buck PhD Senior Investigator and Director of the Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) National Institutes of Health   Medical Research: What is the background for this study? What are the main findings? Dr. Germaine Buck: We wanted to develop intrauterine standards for ultrasound measured fetal growth, given that none currently exist for contemporary U.S. pregnant women.  Moreover, we wanted to determine if a single standard would be possible for monitoring all pregnant women, or if the standard needed to be tailored to pregnant women’s race/ethnicity.  This added step attempted to address the equivocal data about whether or not race/ethnicity is an important determinant of optimal fetal growth. Analyzing data from 1,737 low risk pregnant women with uncomplicated pregnancies who had 5 ultrasounds done at targeted times during pregnancy, we found significant differences in estimated fetal weight across the 4 maternal race/ethnic groups.  These differences were apparent beginning about 16 weeks gestation and continuing throughout pregnancy.  The differences in these curves were apparent when assessing infant’s birthweight, as well.  Overall, estimated fetal weights while women were pregnant were highest for White mothers followed by Hispanic, Asian, and Black mothers.  A 245 gram difference in estimated fetal weight was observed at 39 weeks gestation between pregnant White and Black women.  This pattern was then observed for measured birth weight, with highest birthweights for White then Hispanic, Asian, and Black infants. Other differences emerged by maternal race/ethnicity for individual fetal measurements:  longest bone (femur & humerus) lengths were observed for Black fetuses emerging at 10 weeks gestation, larger abdominal circumference for White fetuses emerging at 16 weeks gestation, larger head circumference for White fetuses emerging at 21 weeks gestation, and larger biparietal diameter for White fetuses emerging at 27 weeks gestation in comparison to other groups. The race/ethnic differences in fetal size were highly significant and across gestation.  If a single White standard was used for estimating fetal weight for non-White fetuses in pregnant women, between 5% and 15% of their fetuses would have been misclassified as being in the <5th percentile of estimated fetal weight. (more…)
Author Interviews, Breast Cancer, NIH, Weight Research / 31.08.2015

Dr. Alexandra White PhD in Epidemiology University of North Carolina at Chapel Hill Postdoctoral fellow National Institute of Environmental Health ScienceMedicalResearch.com Interview with: Dr. Alexandra White PhD in Epidemiology University of North Carolina at Chapel Hill Postdoctoral fellow National Institute of Environmental Health Science MedicalResearch: What is the background for this study? Dr. White: Many studies have shown that being overweight or obese is a risk factor for postmenopausal breast cancer. We know less about how obesity impacts breast cancer risk in premenopausal women. About a third of U.S. adults are obese, which is defined as having a body mass index (BMI) greater than 30. Similarly, the prevalence of abdominal obesity, measured by a person’s waist circumference, has increased by 10% in the last decade. In 2012, more than two-thirds of U.S. women had a waist circumference that indicated abdominal obesity. Abdominal obesity may be a better predictor than BMI for breast cancer risk and other chronic diseases, because it is related to insulin resistance and can reflect metabolically active fat stores. In order to understand how different types of obesity (overall vs. abdominal) influence breast cancer risk, we used information from >50,000 participants in the Sister Study. The Sister Study, led by scientists at the National Institute of Environmental Health Sciences, part of the National Institutes of Health investigates environmental and genetic risk factors for breast cancer. (more…)
Author Interviews, HIV, NIH, Pediatrics, Vaccine Studies / 15.08.2015

George K Siberry, MD, MPH, Medical Officer Maternal and Pediatric Infectious Disease (MPID) Branch Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda, MDMedicalResearch.com Interview with: George K Siberry, MD, MPH, Medical Officer Maternal and Pediatric Infectious Disease (MPID) Branch Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda, MD Medical Research: What is the background for this study? Dr. Siberry:  Vaccines may not work as reliably in children with HIV infection, especially when their HIV is not under effective treatment. Today, most children in the United States who were born with HIV infection are receiving effective HIV treatment and have reached school age or even young adulthood. However, many received their childhood vaccines before they got started on their HIV treatment (because modern HIV treatments weren’t available when they were very young or their HIV infection was diagnosed late). So we wanted to see if these older children still had immunity from the vaccines they received when they were much younger. Medical Research:  What are the main findings? Dr. Siberry: We looked specifically at whether older children with HIV since birth were protected against measles, mumps, and rubella, the three viral infections covered by the measles-mumps-rubella (or MMR) vaccine. We found that 1/3 up to almost 1/2 of these children were not protected against these viruses, even though nearly all of the children had received at least 2 MMR doses, as recommended. And even if their HIV was currently under excellent control.  When we analyzed factors that were linked to being protected, we found that one of the most important factors was whether you got your MMR vaccine doses after you got on good treatment for your HIV infection.  For instance, over 85% of children who had gotten at least 2 MMR vaccine doses after being on effective HIV treatment were protected against measles compared to less than half of those who didn’t get both of their MMR vaccine doses while on effective HIV treatment. (more…)
Author Interviews, NIH, Pain Research / 14.08.2015

Richard L. Nahin, Ph.D., M.P.H National Center for Complementary and Integrative Health National Institutes of Health, Bethesda, MarylandMedicalResearch.com Interview with: Richard L. Nahin, Ph.D., M.P.H National Center for Complementary and Integrative Health National Institutes of Health, Bethesda, Maryland Medical Research: What is the background for this study? Dr. Nahin: In 2011 the Institute of Medicine published a blueprint for transforming pain care in the United States.  In this report the IOM noted the lack of a comprehensive picture of pain’s prevalence and severity in the U.S., and especially noted that lack of data examining racial and ethnic groups. The current analysis of data from the 2012 National Health Interview survey is a step toward addressing these deficiencies.  Medical Research: What are the main findings? Dr. Nahin: The analyses found that an estimated 25.3 million adults (11.2 percent) had pain every day for the preceding 3 months. Nearly 40 million adults (17.6 percent) experience severe levels of pain.  Those with severe pain are also likely to have worse health status.  There were associations between pain severity and race, ethnicity, language preference, gender, and age. Women, older individuals, and non-Hispanics were more likely to report any pain, while Asians were less likely.  Minorities who did not choose to be interviewed in English are markedly less likely to report pain. (more…)
Author Interviews, Dermatology, JAMA, NIH, Pain Research / 07.08.2015

Edward W. Cowen, MD, MHSc Dermatology Branch, Center for Cancer Research National Cancer Institute Bethesda, MarylandMedicalResearch.com Interview with: Edward W. Cowen, MD, MHSc Dermatology Branch, Center for Cancer Research National Cancer Institute Bethesda, Maryland Medical Research: What is the background for this study? Dr. Cowen: Cutaneous leiomyomas are benign smooth muscle proliferations that are associated with pain that is typically not well-controlled by topical remedies or systemic pain medication. Hereditary leiomyomatosis and renal cell cancer is a rare syndrome in which patients may have dozens or even hundreds of these painful tumors. We sought to determine if botulinum toxin injected directly into leiomyomas may ameliorate discomfort and improve quality of life in patients who experience significant pain from cutaneous leiomyomas. Medical Research: What are the main findings? Dr. Cowen: In a double-blinded placebo-controlled study, we found that injection of botulinum toxin was associated with improved skin-related quality of life (p = 0.007) and decreased skin-specific pain (p = 0.048) on the Dermatology Life Quality Index. A trend for decreased pain (p = 0.06) by visual analog score was reported in the botulinum toxin treated group compared to the placebo group. (more…)
Author Interviews, Fertility, NIH / 29.07.2015

Carmen J. Williams, M.D., Ph.D. Principal Investigator National Institute of Environmental HealthMedicalResearch.com Interview with: Carmen J. Williams, M.D., Ph.D. Principal Investigator National Institute of Environmental Health Medical Research: What is the background for this study? Dr. Williams: G-protein coupled receptors are used by almost all cells to receive signals from the outside of the cell and transduce these signals into actions within the cell. There are hundreds of these receptors, but many of them link to a protein named Gq to transmit their signals to other cellular proteins. Gq is found in most cells, including eggs, and activating Gq protein is one way to artificially activate the egg to begin developing into an embryo, even though it is not the way sperm normally do this. In fact, if the egg is activated before the sperm arrives it prevents the sperm from binding and fusing with the egg, so fertilization cannot take place. As a result, we thought that a mechanism might be in place within eggs to prevent them from being activated prematurely by signals that could activate Gq by triggering G-protein coupled receptors. RGS2 was a good candidate for this function because it binds to Gq in a way that prevents Gq from transmitting signals to other cellular proteins. (more…)
Author Interviews, Cancer Research, NIH / 24.07.2015

Dr. Pam Marcus PhD Epidemiology and Genomics Research Program Division of Cancer Control and Population Sciences National Cancer Institute National Institutes of Health Bethesda, MD 20892MedicalResearch.com Interview with: Dr. Pam Marcus PhD Epidemiology and Genomics Research Program Division of Cancer Control and Population Sciences National Cancer Institute National Institutes of Health Bethesda, MD 20892 MedicalResearch: Why do we need to consider targeted cancer screening? Dr. Marcus: Cancer screening, the routine testing of asymptomatic individuals without a history of the disease of interest, is an important approach to cancer prevention and control. There is compelling evidence that screening for at least four cancers reduces disease-specific mortality, but population-based cancer screening also leads to unfavorable events. Only a minority of those screened will benefit, and many will have false-positive exams. Some screenees will experience undesirable sequelae, ranging from minor inconveniences to serious adverse events due to the exam itself or diagnostic evaluation. MedicalResearch: What is the goal of targeted cancer screening in average-risk individuals? Dr. Marcus: Targeted cancer screening attempts to segregate those who will benefit from screening from those who will not through use of information on disease risk. Average risk individuals are those not known to be at substantially elevated risk, including those without known inherited predisposition, without co-morbidities known to increase cancer risk, and without previous diagnosis of cancer or pre-cancer. The goal of targeted cancer screening in average risk individuals is to reduce the number of individuals who need to be screened while preserving the overarching benefit of reduced cancer-specific mortality in the general population. Targeted cancer screening is an example of precision medicine; visit http://www.nih.gov/precisionmedicine/goals.htm to learn more about the National Institute of Health’s Precision Initiative. (more…)
Author Interviews, Breast Cancer, Journal Clinical Oncology, NIH / 24.07.2015

Mitchell H. Gail, M.D., Ph.D. Senior Investigator Biostatistics Branch Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Rockville MD 20850-9780MedicalResearch.com Interview with: Mitchell H. Gail, M.D., Ph.D. Senior Investigator Biostatistics Branch Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Rockville MD 20850-9780 Medical Research: What is the background for this study? Dr. Gail: In the United States, breast cancer survival following diagnosis has been improving since the 1970s. We wanted to understand what might explain these shifts, to fully characterize the changes over time, and to explore whether tumor size and estrogen receptor status could help explain the  trends in age- and stage-specific breast cancer death rates after diagnosis. We evaluated survival from breast cancer from the date of diagnosis of all women diagnosed with invasive breast cancer in the US SEER Cancer Registries between 1973 and 2010. We excluded women with ductal or lobular carcinoma in situ.  We analyzed separate age groups (<50, 50-69, 70+ years) and SEER stage of disease (local, regional, distant). Medical Research: What are the main findings? Dr. Gail: Between 1973 and 2010, breast cancer death rates after diagnosis in the United States have fallen for each age group of women diagnosed with local or regional stage disease, not only in the first five years after diagnosis, but also thereafter.  For women under age 70, rates also fell for women with distant disease. Changes in tumor size or estrogen-receptor status do not explain much of the improvement among women under age 70 years, but do explain roughly half the improvement in 70+ year old women in the first five years after diagnosis. (more…)
Author Interviews, Cancer Research, JNCI, NIH, OBGYNE / 02.07.2015

MedicalResearch.com Interview with: Ashley S. Felix, PhD Bethesda, MD MedicalResearch: What is the background for this study? What are the main findings? Dr. Felix: Endometrial cancer prognosis is strongly affected by disease stage, or the extent of spread from the primary site. Endometrial cancers can spread via the lymph nodes, blood vessels, through the uterine wall, or through the fallopian tube into the peritoneal cavity. The last of these mechanisms is poorly understood, but appears to be a more common mode of spread for aggressive histologic subtypes of endometrial cancer. We hypothesized that women who previously underwent tubal ligation (TL) and later developed endometrial cancer would have lower stage disease, possibly by blocking passage of tumor cells along the fallopian tubes. Further, we hypothesized that TL would be associated with better prognosis, due to its relationship with lower stage. We found that women in our study who previously had tubal ligation were more likely to have lower stage endometrial cancer compared with women who did not report a previous tubal ligation. Specifically, tubal ligation was inversely associated with stage III and stage IV cancer across all subtypes of the disease, including aggressive histologic subtypes. Further, in statistical models of tubal ligation, tumor stage, and mortality, we observed no independent association with improved survival, suggesting that tubal ligation impacts mortality mainly through its effects on stage. (more…)
Author Interviews, Cancer Research, JAMA, NIH / 22.06.2015

MedicalResearch.com Interview with: Vinay Prasad, MD, MPH Medical Oncology Service, National Cancer Institute National Institutes of Health Bethesda, Maryland MedicalResearch: What is the background for this study? What are the main findings? Dr. Prasad: In medicine, there are two types of endpoints:  clinical endpoints and surrogate endpoints. Clinical endpoints, such as survival or quality of life, measure how a patient, feels, functions or lives.  In contrast, a surrogate endpoint is not a measure of patient benefit. Instead, it is merely hoped to correlate with one.  LDL levels are a surrogate for cardiovascular risk, for instance. Oncologists use and trust surrogate endpoints, such as response rate, progression free survival and disease free survival.  The majority of drug approvals and many guideline recommendations are based on improvements in surrogates.  Surrogates are assumed to correlate with overall survival, but we wanted to know if this was true, and under what circumstances. We reviewed all well done studies of surrogate-survival association.  We found that the majority--especially in the setting of metastatic disease--found a poor correlation between a surrogate and survival.  In fact, correlations were strong in only a handful of settings, such as adjuvant colorectal cancer.  Moreover, we found that correlations were always based on a subset of potentially informative literature, even when authors surveyed unpublished trials.  Missing data in these association studies raises the concern that correlations would be different if all data had been considered. Our overall conclusion was that most surrogate-survival correlations in oncology are based on weak evidence and are poor. (more…)
Author Interviews, Hepatitis - Liver Disease, NIH / 03.06.2015

Shyamasundaran Kottilil MBBS, PhD University of MarylandMedicalResearch.com Interview with: Shyamasundaran Kottilil MBBS, PhD Division of Infectious Diseases, Institute of Human Virology University of Maryland, Baltimore Laboratory of Immunoregulation National Institute of Allergy and Infectious Diseases National Institutes of Health, Bethesda, Maryland Medical Research: What is the background for this study? What are the main findings? Dr. Kottilil: During treatment with interferon-based therapies, hepatitis C viral load levels were clinically useful as on-therapy markers of treatment outcome. However, the standard-of-care for HCV treatment has recently evolved from interferon-based regimens to short-duration, all-oral, direct-acting antiviral (DAA) therapies. Therefore, it is important that we re-evaluate the utility of HCV viral loads during DAA regimens in guiding clinical decision-making. We found that Hepatitis C viral loads on treatment and at end of treatment were not predictive of treatment success versus relapse with DAA therapy. Contrary to our experience with interferon-containing regimens, low levels of quantifiable HCV RNA at end of treatment did not preclude treatment success. (more…)
Author Interviews, Heart Disease, NIH, Radiology / 03.06.2015

David A. Bluemke, MD, PhD, MsB, FAHA, FACR Director Radiology and Imaging Sciences Senior Investigator, National Institute of Biomedical Imaging and Bioengineering Adjunct Investigator, NLBI, NIDDKMedicalResearch.com Interview with: David A. Bluemke, MD, PhD, MsB, FAHA, FACR Director Radiology and Imaging Sciences Senior Investigator, National Institute of Biomedical Imaging and Bioengineering Adjunct Investigator,  NLBI, NIDDK Medical Research: What is the background for this study? What are the main findings? Dr. Bluemke: Most knowledge about the extent of coronary disease is from high risk patients who have coronary angiograms. Yet most individuals are symptomatic and have lower cardiovascular risk, and would not undergo a coronary angiogram. Coronary CT angiography can be used to evaluate the extent of plaque in low or moderate risk individuals. The most concerning type of plaque is "soft plaque", which can increase or rupture over time. Using coronary CT, all coronary plaque throughout the entire heart was measured. Importantly, the amount of soft plaque was uniquely associated with risk factors such as LDL, diabetes, and hypertension. (more…)
Author Interviews, Heart Disease, JACC, NIH, Race/Ethnic Diversity / 31.05.2015

Dr. Samson Y. Gebreab, Ph.D., M.Sc. Lead Study Author and Research Scientist National Human Genome Research Institute Bethesda, MarylandMedicalResearch.com Interview with: Dr. Samson Y. Gebreab, Ph.D., M.Sc. Lead Study Author and Research Scientist National Human Genome Research Institute Bethesda, Maryland Medical Research: What is the background for this study? Dr. Gebreab: It is well known that African Americans hold a commanding lead in cardiovascular disease (CVD) mortality and morbidity compared to whites and other ethnic groups.  Furthermore, the risk for developing CVD begins early in life and extends over a lifecourse.  Previous studies have indicated the influence of both childhood and adult socioeconomic status (SES) on CVD risk. However, the impact of lifecourse socioeconomic status (both childhood and adulthood) on CVD risk in African American population is not fully understood.  The purpose of our study was to investigate the associations of different measures of lifecourse socioeconomic status with cardiovascular disease risk in African Americans and whether the associations were modified by sex and/ or age after controlling for known cardiovascular disease risk factors.  We analyzed 10-year follow-up data of African American adults who were participating in Jackson Heart Study, Jackson, MS. Medical Research: What are the main findings? Dr. Gebreab: Our findings highlights that among those of lower socioeconomic status,  women and younger (<=50 years old)  African Americans are at increased risk of CVD, including heart disease and stroke compared to their counterparts of higher socioeconomic status groups.          African American women in the lowest socioeconomic status, had more than twice the risk of developing cardiovascular disease than those in the highest socioeconomic status group.          African Americans of 50 years and younger in the lowest socioeconomic status group had more than three times higher risk of experiencing a cardiovascular disease event than those in the highest socioeconomic status group. (more…)
Author Interviews, Nature, NIH / 13.05.2015

Humphrey Yao, Ph.D. Lead Researcher Reproductive and Developmental Biology Laboratory National Institute of Environmental Health Sciences (NIEHS) National Institutes of Health (NIH) Research Triangle Park, North CarolinaMedicalResearch.com Interview with: Humphrey Yao, Ph.D. Lead Researcher Reproductive and Developmental Biology Laboratory National Institute of Environmental Health Sciences (NIEHS) National Institutes of Health (NIH) Research Triangle Park, North Carolina Medical Research: What is the background for this study? What are the main findings? Dr. Yao: We wanted to understand how an organ forms, and what basic cell types were needed to form an organ. So, we used a mouse ovary model system to understand the process. The functional unit of the ovary is called the follicle, and it is made up of three types of cells — the maturing egg, granulosa cells, and theca cells. Scientists knew where the egg and the granulosa cells came from, but no one knew where theca cells came from. Theca cells are important, because they allow females to produce the hormones that sustain follicle growth. Researchers also lacked information about how the egg, granulosa cells, and theca cells talked to each other to promote growth and maintain a healthy ovary. We made two discoveries. First, we answered the long-standing question of theca cell origin by determining that they have two sources, both inside and outside of the ovary. We don’t yet know why theca cells have two sources. Second, we uncovered the molecular signaling system that the egg, granulosa cells, and theca cells use to communicate. We didn’t expect to find this three-way cellular crosstalk, but now that we know how they signal each other, I believe we are closer to understanding how an ovary develops and what happens when something goes wrong. Ovarian disorders, such as premature ovarian failure and polycystic ovarian syndrome, may start when cellular communication is altered or if the various cells fail to develop properly. (more…)
AACR, Author Interviews, Breast Cancer, NIH, Ovarian Cancer / 03.05.2015

Dr. Victoria L. Chiou, MD Medical Oncology Fellow Women’s Malignancies Branch National Cancer InstituteMedicalResearch.com interview with Dr. Victoria L. Chiou, MD Medical Oncology Fellow Women’s Malignancies Branch National Cancer Institute MedicalResearch: What is the background for this study? What are the main findings? Dr. Chiou: We studied the effects of different treatments in ovarian and breast cancer cell lines with and without BRCA1 mutation in the laboratory. Our discovery that olaparib pretreatment before carboplatin led to decreased carboplatin-induced DNA damage in tumor cells carrying BRCA1 mutation led us to a novel clinical question. We wanted to further understand whether there was an optimal way to deliver a combination of the new tablet formulation of olaparib with carboplatin chemotherapy in women with gynecologic and breast cancers. We launched our clinical trial to test this important question. Overall, we are pleased that the drug combination of olaparib and carboplatin chemotherapy can be given safely together, with preliminary activity in women with breast and ovarian cancer associated with germline BRCA mutations. We are excited to report the findings of this study, which is the first to report preclinical and clinical data on sequence specificity for this drug combination in this patient population. (more…)
Author Interviews, Cancer Research, Gastrointestinal Disease, Genetic Research, NIH / 30.04.2015

Dr. Steven Wank MDMedicalResearch.com Interview with: Dr. Stephen Wank MD Digestive Diseases Branch, NIDDK National Institutes of Health, Bethesda, Maryland MedicalResearch: What is the background for this study? Dr. Wank: Small intestinal carcinoids are rare and difficult to diagnose because symptoms may be absent or mistaken for more common diseases. Because carcinoids usually grow slowly over several years before spreading or causing symptoms, patients often seek medical attention late with advanced, incurable disease. However, when diagnosed at an early stage, carcinoid can be surgically cured. Presently, there are no long-term effective therapies for surgically non-resectable disease. Although carcinoids occur sporadically, there have been reports of family clusters (more than one blood relative with carcinoid). Hereditary small intestinal carcinoid has not been recognized as a disease and causative genetic factors have not been identified in either sporadic cases or families with multiple affected members. If small intestinal carcinoid occurs in families on a hereditary basis, we hypothesized that asymptomatic relatives in families with carcinoid are at a high risk of harboring an undiscovered tumor. To test this, we established a clinical research protocol at the National Institutes of Health in Bethesda, Maryland to screen asymptomatic relatives in families with at least two cases of small intestinal carcinoid in the hope of detecting their tumors at an early surgically curable stage. If successful in our endeavor, we would improve the outcome of the disease in these asymptomatic relatives and position ourselves to discover the genetic basis for their disease. Understanding the gene mutations causing small intestinal carcinoid would allow us to screen for the disease with a blood test, help us understand what causes the disease, and treat the disease with specific targeted therapies. (more…)
AACR, Author Interviews, Cancer Research, NIH, Vaccine Studies / 22.04.2015

Daniel C. Beachler, PhD, Postdoctoral fellow Infections and Immunoepidemiology Branch of the National Cancer Institute (NCI) MedicalResearch.com Interview with: Daniel C. Beachler, PhD Postdoctoral fellow Infections and Immunoepidemiology Branch of the National Cancer Institute (NCI) Medical Research: What is the background for this study? What are the main findings? Dr. Beachler: HPV is a common sexually transmitted infection. Individuals can acquire HPV infections in the epithelium of their cervical, anal and oral sites, and occasionally these infections lead to cancer. There are three prophylactic HPV vaccines on the market that can protect against HPV at these sites among those not been previously exposed to HPV. This study examined the effect of HPV vaccination of 18-25 year old women at all three anatomic sites. The combined multi-site HPV vaccine efficacy has not been reported previously. It was unknown whether the vaccine may protect non-infected sites against HPV infection or re-infection in women exposed to HPV prior to vaccination. We observed that the HPV vaccine provides the strongest protection at all three sites among women unexposed to HPV before vaccination. Additionally, we observed some protection at the non-infected sites in women who were previously infected with HPV. (more…)
Author Interviews, Biomarkers, Lancet, Lymphoma, NIH / 06.04.2015

MedicalResearch.com Interview with: Dr. Mark Roschewski, MD and Dr Wyndham H Wilson MD-PhD Lymphoma Therapeutics Section Lymphoid Malignancies Branch, Center for Cancer Research National Cancer Institute, National Institutes of Health Bethesda, MD 20892 Medical Research: What is the background for this study? What are the main findings? Response: Monitoring patients with diffuse large B-cell lymphoma (DLBCL) has relied on computed tomography (CT) scans which are imprecise, expensive and include radiation. We investigated the ability of a blood-based assay to monitor patients with DLBCL during and after their initial therapy. The assay we studied amplifies and quantifies small amounts of circulating tumor DNA from the patient’s blood. We showed that this assay effectively predicts which patients will relapse and identifies recurrence 3.5 months before CT scans. (more…)
Author Interviews, Exercise - Fitness, JAMA, NIH / 06.04.2015

MedicalResearch.com Interview with: Hannah Arem, MHS, PhD Division of Cancer Epidemiology and Genetics National Cancer Institute, Bethesda, MarylandMedicalResearch.com Interview with: Hannah Arem, MHS, PhD Division of Cancer Epidemiology and Genetics National Cancer Institute, Bethesda, Maryland Medical Research: What is the background for this study? Dr. Arem: The 2008 Physical Activity Guidelines for Americans recommend a minimum of 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity activity per week for “substantial” health benefit, and suggest “additional” benefit with more than double the exercise minimum. However, the guidelines note that there is a lack of evidence for an upper limit of health benefit. We set out to define the dose-response relationship between leisure-time physical activity and mortality and to determine the upper limit of benefit associated with higher levels of aerobic exercise. Medical Research: What are the main findings? Dr. Arem: We found that study participants who met the recommended minimum level of leisure-time physical activity derived most of the mortality benefit, with a 31% lower risk of death compared to inactive individuals. Study participants who engaged in three to five times the recommended minimum level of leisure-time physical activity had a marginally increased mortality benefit, with a 39% lower risk of death compared to inactive individuals. Three to five times the recommended minimum is equivalent to a weekly minimum of walking 7 hours or running 2 hours 15 minutes. (more…)