MedicalResearch.com Interview with:
Dr. Jonathan L. Silverberg MD PhD MPH
Assistant Professor in Dermatology, Medical Social Sciences and Preventive Medicine
Northwestern University, Chicago, Illinois
Medical Research: What is the background for this study?
Dr. Silverberg: Previous studies found associations between obesity and atopic dermatitis (AD). However, little was known about the association between AD and metabolic risk factors, such as central obesity and high blood pressure.
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MedicalResearch.com Interview with:
Dr. Glenn I. Fishman MD
Professor; William Goldring Professor of Medicine
Vice Chair Research Dept of Medicine
Director of the Leon H. Charney Division of Cardiology
NYU Langone
Medical Research: What is the background for this study? What are the main findings?Dr. Fishman: Sudden cardiac arrest (SCA) due to life-threatening ventricular arrhythmias is one of the leading causes of death in the US. Conditions that predispose to SCA can be acquired, as in atherosclerotic coronary artery disease, or inherited in the form of mutated cardiac ion channels, i.e. ion channelopathies. Mutations in the SCN5A cardiac sodium channel gene have been linked to progressive cardiac conduction disorders as well as atrial and ventricular arrhythmias. Understanding the mechanistic basis for lethal arrhythmias in cardiac sodium channelopathy patients has been limited in part due to the lack of adequate model systems that replicate human physiology. To address this limitation, we have developed the first genetically modified porcine model of an inherited channelopathy. A mutation in the SCN5A gene first identified in a child with the arrhythmic condition Brugada syndrome was introduced into the pig genome. Mutant pig hearts displayed conduction abnormalities and ventricular fibrillation bearing striking resemblance to the human condition.(more…)
MedicalResearch.com Interview with:
Bradley T. Lang, PhD
Researcher, Jerry Silver Lab
Department of Neurosciences
Case Western Reserve University School of Medicine
Medical Research: What is the background for this study? What are the main findings?
Dr. Lang: In the late 1980’s, Jerry Silver, PhD, discovered the presence of chondroitin sulfate proteoglycans in the developing nervous system, which form barriers to prevent aberrant growth. He has been building on this finding for more than 30 years, attempting to understand why the adult spinal cord is incapable of regenerating, or why axons don’t grow where they don’t. He has found that the glial scar, which surrounds the site of neural trauma, is incredibly rich in proteoglycans, which prevent regeneration in the spinal cord. In 2009 we collaborated with a group at Harvard to discover the very first receptor for chondroitin sulfate proteoglycans, protein tyrosine phosphatase-sigma, or PTPsigma.
Medical Research: What are the main findings?Dr. Lang: The findings in this paper are twofold. We first describe a novel mechanism of regeneration failure, where regenerating axons become stabilized within a gradient of chondroitin sulfate proteoglycan, completely preventing motility. This finding helps explain why axons persist in the vicinity of the glial scar after injury indefinitely, with little to no regeneration potential—they are simply embedded within the scar. We were able to model this interaction in a petri dish to screen for drugs that were capable of promoting motility.
The second finding in the manuscript is the discovery and characterization of a novel peptide therapeutic that binds to the receptor for chondroitin sulfate proteoglycans and releases inhibition. Most importantly, this drug was given systemically, similar to a daily insulin injection, avoiding complications due to direct nervous system infusion/injection. After several weeks of treatment (which began 1 day after injury), rats with severe spinal cord injury regained coordinated locomotion, bladder control, and/or balance. In total, 21/26 treated animals regained some function. (more…)
MedicalResearch.com Interview with:
Elizabeth A. Thomas, Ph.D.
Associate Professor
Department of Molecular and Cellular Neuroscience
The Scripps Research Institute
Medical Research: What is the background for this study? What are the main findings?
Response: Increasing evidence has demonstrated that epigenetic factors can profoundly influence gene expression, and in turn, influence resistance or susceptibility to disease. Epigenetic drugs, such as histone deacetylase (HDAC) inhibitors, are finding their way into clinical practice, and are being proposed for therapeutic use in several neurological disorders. Our previous studies have shown that selective HDAC inhibitors can cause beneficial effects in mouse models of Huntington’s disease, improving symptoms, and reducing severity of the disease. Our current studies show that one such compound can alter DNA methylation, an epigenetic mark that can be inherited, leading to changes in gene expression that are seen in the parent mouse exposed directly to the drug, as well as in offspring from the drug-treated male mice. Concurrent with these changes, we observed that offspring from drug-treated males shown improved disease symptoms, showing a delay in disease onset and a reduction of motor and cognitive symptoms that included improved performance in tests of balance, speed and memory.
These finding have significant implications for human health as they enforce the concept that ancestral drug exposure may be a major molecular factor that can affect disease outcome in a subsequent generation. One exciting aspect of our study is that the parental drug treatment made the offspring better, not worse, like other compounds known to cause transgenerational effects.
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MedicalResearch.com Interview with:
Ron B. Mitchell, MD
Professor of Otolaryngology and Pediatrics
William Beckner Distinguished Chair in Otolaryngology
Chief of Pediatric Otolaryngology
UT Southwestern and Children's Medical Center Dallas
ENT Clinic Dallas, TX 75207
Medical Research: What is the background for this study? What are the main findings?
Dr. Mitchell: The “gold standard” for the diagnosis of and quantification of obstructive sleep apnea (OSA) is polysomnography (PSG or a ‘sleep study’). However, the majorities of T&A procedures are done without PSG and are based on a clinical diagnosis. This is because PSG is expensive, requires overnight observation and is often unavailable. It is important to diagnose and quantify OSA as it allows for surgical planning and predicts the need and type of treatment after surgery.
We used data from the Childhood Adenotonsillectomy (CHAT) study; a large multicenter
trial (RCT), to look at the ability of clinical parameters to predict the severity of obstructive sleep apnea in children scheduled for a T&A.
The main findings of the study are that certain clinical parameters such as obesity and African American race as well as high scores on certain validated questionnaires (such as the pediatric sleep questionnaire- PSQ) are associated, but cannot predict OSA severity. PSG remains the only way to measure objectively the severity of OSA.
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MedicalResearch.com Interview with:
Rania Mekary, MS, Ph.D.
Harvard School of Public Health
Nutrition Department
Boston, Ma 02115
Medical Research: What is the background for this study? What are the main findings?
Dr. Mekar: Findings on weight training and waist circumference (WC) change have been controversial. Moreover, a lot of people focus on aerobic and only aerobic workout... They are not to be blamed because aerobic workout (e.g. jogging) relies mostly on fat as a source of energy while anaerobic workout (e.g. resistance) relies mostly on carbohydrates. Our study, however, showed that resistance training over the long-term was the most inversely associated with waistline change (aka abdominal fat), even more than aerobic exercise. We also justified physiologically why it is the case... It has to do with the greater Excess Post-exercise Oxygen Consumption (EPOC) as compared with aerobic training and also to the muscle adaptation and its increase in mitochondria which leads to more lipid oxidation upon engaging in anaerobic workout over the long-term. (more…)
MedicalResearch.com Interview with:
Giovanni Filardo, PhD, MPH
Director of Epidemiology, Baylor Scott & White Health, Dallas, TX
The Bradley Family Endowed Chair in Cardiovascular...
MedicalResearch.com Interview with:
David Gerberry PhD
Assistant Professor
Department of Mathematics and Computer Science
Xavier University, Cincinnati, Ohio
Medical Research: What is the background for this study? What are the main findings?Response: In an attempt to control the spread of HIV, governments in sub-Saharan Africa are considering providing antiretroviral drugs to people who do not have the virus but are at risk for becoming infected. Such drugs are known as pre-exposure prophylaxis, or PrEP. Given the cost of PrEP, an important question is how to maximize the impact of interventions given a fixed level of prevention resources.
A common strategy is to target resources to the individuals that are at the highest risk for infection. This group of people is often referred to as the "core group" and can be thought of as sex workers, clients of sex workers and other individuals that are at very high risk for infection. While targeting this core group is ideal and would result in the most cost-effectiveness interventions, being able to identify these individuals is difficult in practice and they are often unwilling to participate in the intervention; take pre-exposure prophylaxis or change their behavior for example. From a mathematical perspective it is also very difficult to quantify their increased level of risk. For example, is a sex worker at 5 times, 25 times, 100 times or 1000 times the risk for HIV infection? Without this quantification, it is impossible to estimate the cost-effectiveness of a targeted strategy.
In our work, we build an intervention strategy based on geographical targeting. This takes advantage of the fact that HIV incidence is much higher in certain geographical locations than others. Therefore, individuals in these areas are at increased risk for HIV infection. Most importantly, such an intervention is feasible because reliable data exists across much of sub-Saharan Africa for the severity of the HIV epidemic in different regions. To illustrate our ideas we used mathematical modeling to consider resource allocation in South Africa and found that targeting the provinces with highest HIV incidence would prevent 40% more infections than a plan that ignored geographic variation while using the same amount of resources.
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MedicalResearch.com Interview with:
Florentina E. Sileanu BS
Center for Critical Care Nephrology and Clinical Research, Investigation, and Systems Modeling of Acute Illness Center
Departments of Critical Care Medicine and Department of Biostatistics,
University of Pittsburgh Graduate School of Public Health and
Dr. John A. Kellum, MD, MCCM
Professor of Medicine, Bioengineering and Clinical & Translational Science
Vice Chair for Research Center for Critical Care Nephrology,
University of Pittsburgh School of Medicine
Pittsburgh, PA
Medical Research: What is the background for this study? What are the main findings?
Response: Acute Kidney Injury (AKI) affects millions of Americans each year resulting in increased short and long-term complications including need for dialysis and death. Many trials recruiting subjects at risk for AKI have focused on those with other (e.g. cardiovascular and respiratory) organ failures because these patients are at highest for AKI. However, patients without these conditions might not be at low-risk for AKI. We explored whether Acute Kidney Injury occurring as a single organ failure or occurring before other organ failures would be associated with the same outcomes as in sicker patients. Using a large, academic medical center database, with records from July 2000 through October 2008, we identified a "low-risk" cohort as patients without cardiovascular and respiratory organ failures defined as not receiving vasopressor support or mechanical ventilation within the first 24 hours of ICU admission. We were able to show that low-risk patients have a substantial likelihood of developing AKI and that the relative impact on mortality of AKI is actually greater for low-risk patients (OR, 2.99; 95% 2.62-3.41) than for high-risk patients (OR, 1.19; 95% 1.09-1.3).
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MedicalResearch.com Interview with:
Ying Xu
Assistant Professor, Ph.D.
Department of Civil, Architectural and Environmental Engineering
University of Texas, Austin
Medical Research: What is the background for this study? What are the main findings?
Response: Phthalates have been widely used as plasticizers to enhance the flexibility of polyvinyl chloride (PVC) products. They are ubiquitous and persistent indoor pollutants and may result in profound and irreversible changes in the development of human reproductive tract.
In this study, we found that the emissions of phthalates and phthalate alternatives increase significantly with increasing temperature. We developed an emission model and validated the model via chamber experiments. Further analysis showed that, in infant sleep microenvironments, an increase in the temperature of mattress can cause a significant increase in emission of phthalates from the mattress cover and make the concentration in breathing zone about four times higher than that in the room, resulting in potentially high exposure. In residential homes, an increase in the temperature from 25 to 35 ºC can elevate the gas-phase concentration of phthalates by more than a factor of 10, but the total airborne concentration may not increase that much for less volatile compounds.
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MedicalResearch.com Interview with:
Carolyn J. Crandall, MD, MS
Professor of Medicine
David Geffen School of Medicine
UCLA Medicine/GIM
Los Angeles, California 90024
Medical Research: What is the background for this study? What are the main findings?
Dr. Crandall: In a large group of postmenopausal women aged 50-79, we found that women who reporting having hot flashes at baseline had increased risk of hip fracture during the subsequent 8 years of observation, nearly double the risk compared with women who did not have hot flashes at baseline.(more…)
MedicalResearch.com Interview with: Brian I. Labow, MD
Director, Adolescent Breast Clinic
Assistant in Surgery Assistant Professor of Surgery
Harvard Medical School Primary
Medical Research: What is the background for this study? What are the main findings?
Dr. Labow: This study is part of our larger Adolescent Breast Disorder Study, in which we examine the impact of several breast disorders on adolescent girls and boys and measure the effect of treatment. In this present study we have found breast asymmetry, defined as having at least 1 cup size difference between breasts, can have a significant impact on the psychological wellbeing of adolescent girls. Validated surveys were given to adolescent girls with breast asymmetry, macromastia (enlarged breasts), and healthy unaffected girls between the ages of 12-21 to assess a wide array of health domains. Girls with breast asymmetry had noted deficits in psychological wellbeing and self-esteem when compared to healthy girls of the same age. These impairments were similar to those of girls with macromastia, a condition known to have significant negative mental health effects. Interestingly, these negative psychological outcomes did not vary by patient’s age or severity of breast asymmetry. Older and younger adolescents were negatively impacted similarly, as were those with lesser and greater degrees of breast asymmetry.
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MedicalResearch.com Interview with:
Daniel Irimia, M.D., Ph.D.
Assistant Professor
Division of Surgery, Science & Bioengineering
Massachusetts General Hospital and Harvard Medical School
Associate Director, BioMEMS Resource Center
Boston, MA 02129
Medical Research: What is the background for this study? What are the main findings?
Response: Sepsis is affecting more than half of the patients with major burn injuries (20 percent of body surface) and is the leading cause of death among these patients. Sepsis is also a significant complication for other critically ill patients. More than one million Americans are affected and it has been estimated that approximately 30% of these people die, despite significant advances in life support and antibiotics. Early diagnosis is essential, and it has been calculated that every 6 hours of delay in a sepsis diagnosis decreases the chances of survival by 10 percent.
We have found that the motility of the white blood cells called neutrophils, inside a microfluidic device, is significantly altered two to three days before sepsis develops. (more…)
MedicalResearch.com Interview with:
Martina Sanlorenzo, MD
Department of Dermatology
Mount Zion Cancer Research Center
University of California, San Francisco
Medical Research: What is the background for this study?
Dr. Sanlorenzo: We recently performed a meta-analysis and found an increased risk of melanoma in pilots and cabin crew. One of the possible occupational hazards responsible for this risk is UV radiation.
Medical Research: What are the main findings?Dr. Sanlorenzo: We performed UV measurements in airplane cockpits during flight and we found that windshields blocked UV-B but allowed UV-A transmission. We compared the UV-A dose in airplanes with the UV-A dose in tanning beds, whose use is a known risk factor for melanoma. Pilots flying for 56.6 minutes at 30,000 feet received the same amount of UV-A carcinogenic effective radiation of a 20-minute tanning beds session.
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MedicalResearch.com Interview with:
Uzma Samadani, MD. PhD. FACS.
Chief Neurosurgeon New York Harbor Health Care System
Co-Director Steven and Alexandra Cohen Veterans Center for PTSD and TBI
Assistant Professor Departments of Neurosurgery, Psychiatry and Physiology & Neuroscience
New York University School of Medicine New York , NY 10010
Medical Research: What is the background for this study? What are the main findings?
Dr. Samadani: Eye tracking has been used for 30 years to investigate where people look when they follow particular visual stimuli. Tracking has not, however, been previously used to assess underlying capacity for eye movement. We have developed a very unique eye tracking algorithm that assesses the capacity of the brain to move the eyes.
What we show in this paper is that with our eye tracking algorithm we can show
(1) normal people have eye movements that, within a particular range, have equal capacity for vertical and horizontal movement,
(2) people with specific weaknesses of the nerves that move the eyes up and down have decreased vertical capacity,
(3) people with weaknesses in the nerves that move the eyes to the side have decreased horizontal capacity,
(4) swelling in the brain can affect the function of these nerves and be detected on eye tracking,
(5) eye tracking may be useful as a potential biomarker for recovery from brain injury.
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MedicalResearch.com Interview with:
Reinier G.S. Meester, M.Sc
Department of Public Health,
ErasmusMC, Rotterdam, Netherlands
Medical Research: What is the background for this study? What are the main findings?
Response: Despite decreasing death rates from colorectal cancer over the past decades, it still ranks as the second leading cause of cancer deaths in the U.S. Screening for colorectal cancer is highly effective, but only 58% of the eligible population reported up-to-date with screening. This suggests that a substantial proportion of current colorectal cancer deaths in the U.S. are avoidable.
We found that approximately 60% (32,200 deaths) of current deaths from colorectal cancer may be due to not receiving screening.
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MedicalResearch.com Interview with: Dr. Ryan Hartmaier PhD
Postdoctoral Associate
Magee-Womens Research Institute (MWRI)
and the University of Pittsburgh Cancer Institute
Medical Research: What is the background for this study? What are the main findings?Response: The inhibition of signaling through the estrogen receptor is a major target in breast cancer therapy. However, within recurrent disease others have recently identified point mutations within the estrogen receptor as a mechanism of resistance to this therapy.
We undertook a comprehensive study of breast cancer progression by applying many next-generation sequencing technologies to a collection of paired primary-metastasis tissue samples from 6 patients. We placed special emphasis on the identification of structural variants (i.e. translocations, duplications, inversions, and deletions) acquired in metastatic breast cancer. In one patient with recurrent disease while on endocrine therapy, we identified a fusion gene between ESR1 (estrogen receptor alpha) and DAB2 (disabled-2). In vitro functional studies indicate that this fusion is constitutively active and hormone independent.
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MedicalResearch.com Interview with:
Fiona Larner, PhD Postdoctoral Research Associate
Department of Earth Sciences, University of Oxford, South Parks Road, Oxford, UK
Department of Earth Science & Engineering, Imperial College London, Exhibition Road, South Kensington, London, UK
Medical Research: What is the background for this study? What are the main findings?
Response: Zinc has been identified to have a role in breast tissue and breast cancer for over a decade. Zinc has several isotopes (different versions of zinc due to varying numbers of neutrons), which require slightly different amounts of energy to go through biological processes. By measuring the changes in the zinc isotopic signature, we can probe it's behaviour to a greater resolution to that currently available in medical institutions. We looked at the isotopic signatures in different tissues of healthy patients and those with breast cancer in order to understand the mechanisms involved in more detail and in search for a biomarker that uses these signatures to diagnose breast cancer.
We found that preferentially retains the lighter isotopes of zinc to a greater extent than healthy breast tissue. This means that the partnering heavy isotopes must be ejected from the cell, and may provide a biomarker for cancer in the future.
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MedicalResearch.com Interview with:
Leah M. Smith PhD
Department of Epidemiology, Biostatistics, and Occupational Health (Smith, Kaufman, Strumpf)
McGill University, Montréal, Quebec
Medical Research: What is the background for this study? What are the main findings?
Dr. Smith: The human papillomavirus (HPV) vaccine protects against types of HPV that cause cervical cancer and anogenital warts. The vaccine first became available in 2006. Since then, it has faced a great deal of controversy surrounding, in part, some of the unanswered questions about the real-world effects of the vaccine, especially on the young girls targeted for immunization. One issue that has received a great deal of public attention has been the concern that HPV vaccination might give girls a false sense of protection against all sexually transmitted infections that might lead them to be more sexually active than they would otherwise. As a result, some parents have been reluctant to have their daughters vaccinated. It is also reason why some religious groups have spoken out against the vaccine. This question is further important from a public health perspective because increases in risky sexual behaviour would inevitably also lead to increases in teen pregnancy and sexually transmitted infections (excluding anogenital warts), which would of course undermine the potential health benefits of the vaccine.
In this study, we directly addressed the question of whether HPV vaccination has led to increases in pregnancy and non-HPV-related sexually transmitted infections (both of which are proxies for risky sexual behaviour) among adolescent girls.
In our study of over 260,000 girls, we did not find any evidence that the HPV vaccine had a negative impact on these outcomes.
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MedicalResearch.com Interview with:
Dr. Matthew P. Goetz, MD
Associate Professor of Pncology
Mayo ClinicMedical Research: What is the background for this study? What are the main findings?
Dr. Goetz: There has been conflicting data with regard to the importance of metabolism as measured by CYP2D6 genetic variation. Two large “negative” studies were reported simultaneously in 2012 and these were referenced by guidelines that CYP2D6 should not be used to select hormonal therapy. Our findings demonstrated that these studies were flawed in part based on analytical validity issues. In short, the use of tumor tissue to derive CYP2D6 germline genotype leads to genotyping error in up to 45% of samples.
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MedicalResearch.com Interview with:
Atsushi Sorita, MD, MPH
Mayo Clinic, Division of Preventive Medicine
Rochester, MN 55905.
Medical Research: What is the background for this study? What are the main findings?Dr. Sorita: Prior studies have suggested that patients with heart attack who are admitted during off-hours (weekends, nights and holidays) have higher risk of death when compared with patients admitted during regular hours. In our study, we found that patients undergoing percutaneous coronary interventions for heart attack who were admitted during off-hours did not have higher mortality or readmission rates as compared with ones admitted during regular hours at a highly-integrated academic center in the United States.
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MedicalResearch.com Interview with:
Dr. Michael Yeaman Ph.D.
Professor of Medicine, Infectious Disease Specialist
Chief, Division of Molecular Medicine
David Geffen School of Medicine at UCLA
Los Angeles Biomedical Research Institute
Harbor-UCLA Medical CenterMedical Research: What is the background for this study? What are the main findings?Dr. Yeaman: In the U.S. and around the globe, skin and soft tissue infections caused by
methicillin-resistant Staphylococcus aureus (MRSA) continue to endanger the
health and lives of patients and otherwise healthy individuals. Treatment is
difficult because MRSA is resistant to many antibiotics, and the infections
can recur, placing family members and other close contacts at risk of
infection.
Infectious disease specialists at the Los Angeles Biomedical Research
Institute at Harbor-UCLA Medical Center (LA BioMed) tested a new
investigational vaccine, NDV-3, and found it holds new hope for preventing
or reducing the severity of infections caused by the "superbug" MRSA.
In the study, which was published Dec. 8 in the Proceedings of the National
Academy of Sciences USA, the researchers reported that NDV-3, employing the
recombinant protein Als3, can mobilize the immune system to fight off MRSA
skin infections in an experimental model. The researchers found the vaccine
works by enhancing molecular and cellular immune defenses of the skin in
response to MRSA and other S. aureus bacteria in disease models.
This is the first published study to demonstrate the effectiveness of a
cross-kingdom recombinant vaccine against MRSA skin infections. NDV-3 is
unique as it is the first vaccine to demonstrate it can be effective in
protecting against infections caused by both S. aureus and the fungus
Candida albicans. NDV-3 represents a novel approach to vaccine design that
pioneers an approach termed convergent immunity.
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MedicalResearch.com Interview with:
Dr James Gardiner
Reader in Molecular Physiology
Imperial College Hammersmith Campus
London 0NN
Medical Research: What is the background for this study? What are the main findings?Response: It is well known that glucose is a preferred food and is consumed in preference to other nutrients. Food intake is controlled by the brain in part this it is regulated by part of the brain called the hypothalamus. Glucokinase is an important component of glucose sensing and is expressed in the hypothalamus and specifically in the arcuate nucleus. A hypothalamic mechanism regulating glucose intake has not previously been identified.
Using a rodent model we demonstrated that increasing glucokinase activity in the arcuate nucleus increased food intake and body weight. If glucose was available as separately then glucose intake is increased but not weight. Decreasing glucokinase activity in the arcuate nucleus had the opposite effect, reducing glucose intake when it was available. Our results suggest that glucokinase controls glucose appetite and hence the amount of glucose consumed. This is the first time a mechanism controlling the intake of a specific nutrient has been described.(more…)
MedicalResearch.com Interview with:
Dr. Constantine A. Stratakis, M.D., D.Sc
National Institutes of Health, Clinical Research Center
Bethesda, MD 20892-1862
Medical Research: What is the background for this study? What are the main findings?
Dr. Stratakis: We have been working for years on the genetics of pituitary tumors in association with other conditions. A few years ago (attached), we studied for the first time a series of pediatric giants that we sequenced for then known genes. We found a few MEN1 and AIP mutations but all mutations were present in older kids with gigantism. This left out the youngest among the giants without any genetic defect. This was the first time I realized that I was dealing with a different disease. We started looking for additional genetic defects and when we found the Xq26 microduplications in 3 kindreds. We contacted the custodians of the largest series in the world - Dr. Beckers in Liege. He screened his cases, once we gave him the coordinates, and boom - it was there...
The most significant thing here is that this is a new disease really: the early pediatric gigantism is almost exclusively due to Xq26 microduplications unless it is part of a family with another syndrome (AIP, MEN1, Carney complex). If there is no family history and you are dealing with a toddler with gigantism, based in these data, there is a more than 80% chance of having an Xq26 defect. This is pretty amazing!
In addition, assuming that GPR101 is the responsible gene (which needs to be confirmed with additional studies) this identifies a new molecular pathway of increasing growth hormone secretion, most likely due to upregulation of GHRH - all of this needs to be confirmed in further human and animal studies.
The Xq26 genomic micro-arrangements (which contain the GPR101, but also 3 other genes) is the big news here...
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MedicalResearch.com Interview with:
M. Arfan Ikram, MD, PhD,and Ayesha Sajjad, MD
Department of Epidemiology
Erasmus University Medical Center, Rotterdam
Rotterdam, The NetherlandsMedical Research: What is the background for this study? What are the main findings?
Response: The occurrence of cognitive impairment and dementia after a stroke event are already known. Since these neuro-degenerative processes and stroke share vascular pathways in their pathogenesis such as small vessel disease, we aimed to study whether early cognitive impairment can be predictive of stroke onset in the elderly. We also hypothesized that a higher cognitive reserve (due to higher education attainment) may mask early symptoms of memory loss and thus put these older individuals at a higher risk of stroke. We found that self-reported subjective memory complaints as answered by a single question: “ Do you have memory complaints?” was highly predictive of stroke especially in older persons who were highly educated. In comparison, objective measures of cognitive impairment such as MMSE did not show any association with the risk of stroke.
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MedicalResearch.com Interview with:
Dr. Jane A. Mitchell
National Heart and Lung Institute
Imperial College, London, UKMedical Research: What is the background for this study? What are the main findings?Dr. Mitchell: Anti-inflammatory drugs (NSAIDs) work by inhibiting the enzyme COX-2. COX-2 selective anti-inflammatory drugs, like Vioxx, were introduced to reduce gastrointestinal side effects associated with these drugs. However, COX-2 inhibitors as well as most older NSAIDs are associated with increased risk of heart attacks although the precise mechanisms underlying these side effects are not completely understood.
The main findings of this study are:
1) COX-2 is highly expressed in the kidney where its genetic deletion leads to changes in more than 1000 genes.
2) Analysis of these genes revealed changes in 2-3 specific genes that regulate levels of ADMA, an endogenous inhibitor of the nitric oxide released by vessels, that can be reversed by giving more of the substrate for NO, L-arginine.
3) Further studies showed that ADMA was indeed increased in the plasma of mice where COX-2 gene was knocked out or in normal mice given a COX-2 inhibitor.
4) In mice where COX-2 was knocked out the release of nitric oxide from vessels was reduced and this could be reversed by supply L-arginine.
5) ADMA was also increased in human volunteers taking a COX-2 inhibitor
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MedicalResearch.com Interview with:
Dr. James Yu
Yale School of Medicine
Cancer Outcomes, Public Policy, and Effectiveness Research Center
Yale School of Medicine
Department of Therapeutic Radiology
New Haven, ConnecticutMedical Research: What is the background for this study? What are the main findings?Response: Hypo fractionated radiation has been shown to be safe and effective, and more convenient for women with early stage breast cancer after lumpectomy. It also has been identified by ASTRO as a practice that physicians can adopt to reduce healthcare expenses for patients and for society. We looked at the National Cancer Database, a database created by the American College of Surgeons for trends in the use of hypo fractionated radiation for breast cancer through 2011. We found that the use of hypofractionated radiation had increased to 22.8% in 2011. I found this remarkable as it predated the ASTRO choosing widely guidelines, and indicated to me that physicians were already thinking of ways of making treatment more convenient and affordable for patients and insurers.
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MedicalResearch.com Interview with:
Rachel Blitzblau, M.D., Ph.D.
Butler Harris Assistant Professor
Department of Radiation Oncology
Duke University Medical Center
Durham, NC 27710
Medical Research: What is the background for this study? What are the main findings?
Dr. Blitzblau: Radiation reduces the risk of loco-regional recurrence. Data from the CALGB 9343 study suggests that the local benefit from adjuvant radiation is less in older women with small, . The potential acute and late toxicities of radiotherapy, patient inconvenience and healthcare costs must be considered given the small clinical benefit associated with adjuvant radiotherapy in this patient group. We looked at rates of radiotherapy in women fitting the entry criteria of this trial before and after publication of 5 year results of the CALGB trial. We found an approximately 5% decrease in use of radiotherapy overall, and noted that there seemed to be a small but significant shift in the type of radiotherapy used for these patients. Less patients received standard whole breast radiotherapy, and more received a short course of treatment to just the tumor bed plus margin called accelerated partial breast irradiation. We concluded that the publication of the trial therefore had only a very small impact on practice patterns.
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MedicalResearch.com Interview with:
Ganesh Sivarajan, MD
Department of Urology
New York University Langone Medical Center
Medical Research: What is the background for this study? What are the main findings?Dr. Sivarajan: The surgical robot was designed to facilitate laparoscopic surgery. The surgeon sits at a console several feet away from the patient and is linked to a multi-armed robot which translates the surgeon’s movements from the console to surgical instruments inside the patient’s insufflated abdomen. The robot is equipped with a high resolution three dimensional camera which improves visualization over traditional open surgery and allows the manipulation of instruments in directions and angles which are difficult in traditional open surgery.
In light of these apparent advancements, the robot was rapidly adopted for use during radical prostatectomy. The outcomes data for men undergoing robotic versus open prostatectomy, however, have not demonstrated any clear advantage of robotic surgery, with some studies demonstrating benefit and other demonstrating harm. This fact coupled with the relatively high cost of the robot and its disposable equipment have led many to criticize robotic surgery and its rapid adoption.
Partial nephrectomy is a procedure performed for renal cancer in which just the malignant tumor is excised while the remaining healthy kidney is saved. It is increasingly considered to be preferable to the previous gold standard operation – radical nephrectomy or removal of the entire kidney largely secondary to the benefits accrued from preserving renal function. Despite actual changes in the treatment guideline recommending increased use of partial nephrectomy it remains vastly underutilized nationwide likely because of the technical challenges associated with its performance.
It has been suggested that the surgical robot facilitates the performance of partial nephrectomy, but this has not been definitively demonstrated in a model which controls for important variables as the effects of changing guidelines, secular trends supporting increased utilization over time and a variety of other hospital-level characteristics.
We sought to determine whether acquisition of the surgical robot was independently associated with increased utilization of partial nephrectomy – a guideline-supported procedure. If true, it would suggest that the acquisition of the surgical robot may have improved the quality of care of renal cell carcinoma patients.
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MedicalResearch.com Interview with:
Adeel A. Butt, MD, MS, FACP, FIDSA Vice Chair for Faculty Affairs
Department of Medicine Hamad Medical Corporation, Doha, Qatar
Adjunct Associate Professor of Medicine and Clinical and Translational Science
University of Pittsburgh School of Medicine
Medical Research: What is the background for this study? What are the main findings?
Dr. Butt: Precise rate of progression of liver disease in Hepatitis C (HCV) infection is unknown because the precise time of infection with HCV is seldom known. Knowledge of liver disease progression is critical to determine the optimal time for treatment.
We found that progression of liver disease starts early after acquiring HCV infection. This is more rapid than was previously thought. About 18% of HCV infected persons develop cirrhosis within 10 years of acquiring HCV infection, which is 3-fold higher than demographically similar HCV uninfected persons.
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MedicalResearch.com Interview with:
Dr. Jonathan L. Silverberg MD PhD MPH
Assistant Professor in Dermatology, Medical Social Sciences and Preventive Medicine
Northwestern University, Chicago, Illinois
Medical Research: What is the background for this study?
Dr. Silverberg: Previous studies found associations between obesity and atopic dermatitis (AD). However, little was known about the association between AD and metabolic risk factors, such as central obesity and high blood pressure.
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