Prostate Cancer: Androgen Deprivation Therapy May Be Harmful For Some Men

David R. Ziehr B.S., MD Candidate Harvard Medical SchoolMedicalResearch.com Interview with:
David R. Ziehr B.S., MD Candidate
Harvard Medical School

Medical Research: What is the background for this study? What are the main findings?

Response: Androgen deprivation therapy (ADT), commonly achieved with gonadotropin-releasing hormone agonists or antagonists, is a mainstay of prostate cancer therapy. While randomized controlled trials demonstrate that ADT improves survival among men with unfavorable risk prostate cancer, retrospective studies have suggested that some men with comorbid illnesses such as heart disease may not derive a benefit from—or may even be harmed by—ADT. However, the nature of this harm has not been characterized. We studied over 5000 men with prostate cancer who were treated with brachytherapy (implanted radioactive seeds) with or without ADT. We analyzed the men based on pre-treatment cardiac comorbidity and examined the association between ADT and death from cardiac causes. We found that among men with congestive heart failure or a past myocardial infarction (MI), Androgen deprivation therapy was associated with a three-times greater risk of death from heart disease. However, Androgen deprivation therapy was not associated with greater risk of cardiac mortality in men without heart disease or with a risk factor for heart disease, such as diabetes, hypertension or hyperlipidemia.
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Screening Chemotherapies for Effectiveness On Cultures Of Breast Cancer Biopsy Cells

Melissa Skala, Ph.D. Assistant Professor of Biomedical Engineering Assistant Professor of Cancer Biology Vanderbilt University Nashville, TN 372MedicalResearch Interview with:
Melissa Skala, Ph.D.
Assistant Professor of Biomedical Engineering
Assistant Professor of Cancer Biology
Vanderbilt University Nashville, TN 37235

Medical Research: What is the background for this study? What are the main findings?

Dr. Skala: We developed a new metabolic imaging technique that is highly sensitive to tumor cell response to anti-cancer drug treatment. We coupled this imaging technique with new, three-dimensional cultures that can be grown from breast tumor biopsies. Together, our data indicate that this approach could be used to perform rapid, low-cost, and accurate drug screens for individualized treatment of cancer patients.
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Study Identifies Potential Target In Huntington’s Disease Pathway

Srinivasa Subramaniam, Ph.D., Assistant Professor Department of Neuroscience The Scripps Research Institute Jupiter, Florida 33458MedicalResearch.com Interview with:
Srinivasa Subramaniam,
Ph.D., Assistant Professor
Department of Neuroscience
The Scripps Research Institute Jupiter, Florida 33458

 

Medical Research: What is the background for this study? What are the main findings?

Dr.  Subramaniam: Huntington’s disease (HD) is a genetic disorder occurs due to a mutation in a protein called huntingtin (mHtt), which affects 5-10 people per 100000 populations worldwide. Our research revolves around the question— why mutant huntingtin despite its ubiquitous expression through out the body selectively affects brain regions such as striatum, a region that regulates voluntary movement. We now found that mHtt activates a protein kinase complex, mammalian target of rapamycin complex 1 (mTORC1), which is required for normal functions such as translation of genes into proteins and also organelle recycling. We found the mTORC1 activation is so robust and sustained in the striatum that lead to the severe motor disabilities and premature death of HD mice. Our study indicates a functional relationship between huntingtin and mTOR the developmentally important genes with implication in Huntington’s disease pathogenesis.

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Is Pretreatment With Platelet Inhibitors Beneficial or Harmful For Acute Coronary Syndrome?

MedicalResearch.com Interview with:
Anne Bellemain-Appaix
Service de Cardiologie-La Fontonne Hospital, Antibes, France and

Gilles Montalescot Professor of  Cardiology
Institut de CardiologiePitié-Salpêtrière Hospital
Université Paris 6, France
ACTION Study Group, Paris, France

Medical Research: What is the background for this study?

Response: Pretreatment with P2Y12 inhibitors for Non-ST-Elevation Acute Coronary Syndrome (NSTE-ACS) patients, although advised in current guidelines, has been recently questioned in term of benefit/risk ratio (no ischemic benefit and increase in major bleeding). We wanted to answer this question by giving enough power to results in a complete meta-analysis of studies comparing P2Y12 inhibitors pretreatment (defined as its administration before the coronary angiogram) to no pretreatment in NSTE-ACS. Continue reading

Does Milk Increase Bone Fractures?

MedicalResearch.com Interview with: Professor Karl Michaëlsson Professor in Medical Epidemiology, Senior Consultant in Orthopaedic Surgery Uppsala Clinical Research Institute
MedicalResearch.com Interview with:
Professor Karl Michaëlsson
Professor in Medical Epidemiology, Senior Consultant in Orthopaedic Surgery
Uppsala Clinical Research Institute

Medical Research: What are the main findings of the study?

Prof. Michaëlsson: A high milk intake is recommended for the prevention of osteoporotic fractures but milk is also the major dietary source of galactose intake. The addition of galactose by injection or in the diet is an established animal model of aging by induction of oxidative stress and inflammation. Previous research results regarding the importance of milk intake for the prevention of fractures and the influence on mortality rates are conflicting. High milk intake was in our study associated with higher mortality in one cohort of women and in another cohort of men, and with higher fracture incidence in women. In subsamples of two additional cohorts, one in males and one in females, a positive association was seen between milk intake and both urine 8-iso-PGF (a biomarker of oxidative stress) and serum interleukin 6 (a main inflammatory biomarker).

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Reliability of East German Pharmaceutical Investigations Questioned

MedicalResearch.com Interview with: Dr. med. Rainer Erices Institut für Geschichte und Ethik der MedizinMedicalResearch.com Interview with:
Dr. med. Rainer Erices
Institut für Geschichte und Ethik der Medizin

Medical Research: What are the main findings of the study?

Dr. Erices: The study presents the results of a first systematic investigation of clinical drug trials carried out by Western pharmaceutical firms in Eastern Germany in the 1980s. The scientific investigation of the East German Health system has only just started. The study shows that in that period of time, around 220 clinical trials were carried out. We now know how many patients took part and what remuneration the GDR received. It continues to be difficult to evaluate these tests. Despite intensive research efforts in different archives, we have been unable to find documentation on how detailed (and systematically) patients were informed about the trial they were taking part in. The responsible institutions repeatedly advised testers to stick to the law during the clinical trials. The law required that these trials should only be carried out on patients which had given their informed consent and had decided to participate voluntarily. However, so far there is no convincing proof that these legal requests were met.

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Community Interventions Improved Blood Pressure Control In Diverse Populations

Kevin L Thomas, MD Assistant Professor of Medicine Division of Clinical Cardiac Electrophysiology Duke Clinical Research InstituteMedicalResearch.com Interview with:
Kevin L Thomas, MD
Assistant Professor of Medicine
Division of Clinical Cardiac Electrophysiology
Duke Clinical Research Institute

 

Medical Research: What are the main findings of the study?

Dr. Thomas: The number of participants with controlled blood pressure (readings of less than 140/90) increased by 12 percent in the six months between the first and last readings. Mean systolic blood pressure for the population decrease by 4.7mmHg. The number of participants who had high blood pressure in the range of 140-149/90-99 decreased systolic blood pressure by a mean of  8.8mmHg and those with readings in the higher range of 150/100 or above decreased systolic blood pressure by 23.7percent. The study concluded that a program that followed this type of approach was associated with improved blood pressures across a diverse  high-risk community.”
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Gut Bacteria Linked To Heart Failure and Mortality Risk

Professor of Medicine, Cleveland Clinic Lerner College of Medicine at CWRU Director, Cardiomyopathy Program, Kaufman Center for Heart Failure Research Director, Section of Heart Failure and Cardiac Transplantation Medicine Heart and Vascular Institute, Cleveland Clinic Cleveland, OH 44195MedicalResearch.com Interview with:
W. H. Wilson Tang, MD FACC FAHA

Professor of Medicine,
Cleveland Clinic Lerner College of Medicine at CWRU
Director, Cardiomyopathy Program, Kaufman Center for Heart Failure
Research Director, Section of Heart Failure and Cardiac Transplantation Medicine
Heart and Vascular Institute, Cleveland Clinic Cleveland, OH 44195

Medical Research: What are the main findings of the study?

Dr. Tang: A chemical byproduct of gut bacteria-dependent digestion, TMAO (trimethylamine N-oxide), was previously shown to contribute to heart disease development. In this study, blood levels of TMAO for the first time are linked to heart failure development and mortality risk.
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Leftover US Hospital Supplies Can Have Lifesaving Impact Overseas

MedicalResearch.com Interview with:
Eric Wan BS and Miceile Barrett BS

Johns Hopkins University School of Medicine
Baltimore, MD

Medical Research: What is the background for this study? What are the main findings?

Answer: Access to surgery is limited in resource-poor settings and low-and-middle income countries (LMICs) due to a lack of human and material resources. In contrast, academic hospitals in high-income countries often generate significant amounts of unused and clean medical supplies that cannot be re-used in the operating rooms of high-income countries. Programs such as Supporting Hospitals Abroad with Resources and Equipment (SHARE) provide an avenue for recovery of these supplies and donation to resource-poor hospitals in LMICs. From data collected from SHARE supplies donated by Johns Hopkins, we found that the nationwide impact for these programs to be $15.4 million among US academic hospitals, which accounts for only 19 categories of commonly recovered supplies. When we tracked our donated supplies to hospitals in Ecuador serving the poor, we found that the cost-effectiveness of these donations was US $2.14 per disability-adjusted life-year prevented.
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Snoring During Twenties May Be Predictive of Sleep Apnea in Forties

MedicalResearch.com Interview with:
Dr. Swati Gulati, MD Internal Medicine
John H. Stroger Hospital of Cook County
Chicago, IL

Medical Research: What are the main findings of the study?

Dr. Gulati: We conducted an observational study by providing questionnaire about the onset and progression of sleep apnea symptoms to patients seen in our sleep clinic for CPAP set up. In our cohort, mean age at the onset of snoring was 28 years and the mean age at diagnosis was 52 years. There was a lag of almost 23 years between the onset of snoring and the diagnosis of sleep apnea. The snoring started in mid twenties (Phase I) and patients noticed poor concentration and headaches in mid thirties (Phase II). Later, patients developed cardiopulmonary symptoms in mid forties to the time of diagnosis (Phase III).

The evolution of simple snoring into apneic episodes occurred around 40 years of age after which there was a rapid progression of disease marked by development of Excessive daytime sleepiness (EDS), dyspnea and morning headaches. We also found that patients who had started snoring earlier or at a very young age had a more severe disease as documented by apnea-hypopnea index (AHI).

In the literature, most of the natural history studies have looked at the progression of sleep apnea after diagnosis with a shorter follow up period ranging from 6 to 10 years.   Through our study, we have aimed to determine the natural history of disease progression from simple snoring until the time of diagnosis.

Medical Research: What was most surprising about the results?

Dr. Gulati: We were surprised to find out that the symptoms of snoring started in the mid twenties and progressed over 2 decades before diagnosis. It was also surprising that the duration of snoring and change in weight were better predictors of obstructive sleep apnea (OSA)  severity than the patient characteristics at the time of diagnosis, such as age and BMI. In our study, weight gain per year was the strongest predictor of severity of sleep apnea and it made the BMI at the time of diagnosis insignificant. Surprisingly, we found no association between gender and AHI.

Medical Research: What should clinicians and patients take away from your report?

Dr. Gulati: Based on our study, snoring in these patients starts at an early age and not necessarily in the middle age. Evolution of simple snoring into sleep apnea and symptomatic manifestations takes at least a decade on average.

Significant symptoms of sleep apnea were ignored for at least 20 years by the patients or their physicians. This should provide ample time opportunity for physicians to screen patients for sleep disordered breathing. Timely screening and diagnosis of obstructive sleep apnea will lead to early initiation of treatment and will slow its progression.

 

Medical Research: What recommendations you have for future research as a result of this study?

Dr. Gulati: Since our study population consisted of patients with severe OSA, these findings should be tested on a sample of patient that includes mild to moderate OSA. Randomized controlled trials should be done to see if screening for snoring in young adults and initiation of early treatment can prevent the development of OSA and associated mortality.

 

CHEST abstract:

Progression of Symptoms of Obstructive Sleep Apnea  and Their Association With Its Severity at Diagnosis?
Swati Gulati; Aiman Tulaimat
Chest. 2014;146(4_MeetingAbstracts):946A. doi:10.1378/chest.1992430

 

 

 

 

“Bad Cholesterol” LDL-C Linked to Aortic Valve Disease

George Thanassoulis, MD MSc FRCP(C) Director, Preventive and Genomic Cardiology FRQ-S Clinician-Scientist/Chercheur-Boursier Clinicien Assistant Professor of Medicine, McGill University McGill University Health Center Montreal, QCMedicalResearch.com Interview with:
George Thanassoulis, MD MSc FRCP(C)

Director, Preventive and Genomic Cardiology
FRQ-S Clinician-Scientist/Chercheur-Boursier Clinicien
Assistant Professor of Medicine, McGill University
McGill University Health Center Montreal, QC

Medical Research: What is the background for this study? What are the main findings?

Dr. Thanassoulis: Although LDL-C (i.e. bad cholesterol) has been linked with aortic valve disease in several prior reports, randomized trials to lower cholesterol in aortic valve disease were not effective suggesting that cholesterol may not be important in valve disease.

To address this, we performed a Mendelian randomization study, that showed that a genetic predisposition to LDL-C, was associated with both calcium deposits on the aortic valve and aortic stenosis (I.e. Valve narrowing).  These results can be viewed as the effect of a life-long increase in LDL-C on the incidence of aortic valve disease and suggest that increases in LDL-C cause aortic stenosis.   Continue reading

Men With Sleep Disorders Have Greater Risk of Alzheimer’s Disease

Christian Benedict PhD Associate Professor of Neuroscience Uppsala University Dept. of NeuroscienceMedicalResearch.com Interview with:
Christian Benedict PhD
Associate Professor of Neuroscience
Uppsala University Dept. of Neuroscience

 

Medical Research: What is the background for this study?

Answer: Our study involved ~1500 men who were followed from 1970 to 2010. All participants were 50 years old at the start of study.

Medical Research: What are the main findings?

Answer: Men with reports of sleep disturbances had a 50%-higher risk to develop Alzheimer’s disease during the 40-year follow-up period, than men without reports of sleep disturbances.
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How To Quickly Disseminate Best Practices To Doctors

Luís A. Nunes Amaral PhD HHMI Early Career Scientist Professor of Chemical & Biological Eng. Professor of Medicine Howard Hughes Medical Institute Northwestern University, Evanston, IllinoisMedicalResearch.com Interview with:
Luís A. Nunes Amaral PhD
HHMI Early Career Scientist
Professor of Chemical & Biological Eng.
Professor of Medicine
Howard Hughes Medical Institute
Northwestern University, Evanston, Illinois

Medical Research: What is the background for this study? What are the main findings?

Dr. Amaral: There is a well known difficulty in promoting the rapid adoption of best practices by physicians.  Because of their work load and because of the inability to figure out when some result is a true advance or just hype, doctors tend to stick to what they believe works. Unfortunately, as a 15 year old Institute of Medicine study shows, this lack of adoption of best practices costs society hundreds of thousands of lives a year in the US alone.

The typical process for informing doctors of what best practices are (such as continual medical education and other broadcasting approaches) do not work well. We believe that a weakness of typical approaches is that they have a one talking to the many style, and they are out of a medical practice context.  Our hypothesis was that by seeding a few doctors with desired knowledge, one could have spread of the adoption through one-on-one contacts between physicians in the context of treating patients.  We found that this approach has the potential to be very effective.
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Age-Related Macular Degeneration: If One Eye Has It, The Other Eye More Likely To Develop It As Well

Ronald Klein, MD, MPH, Professor Department of Ophthalmology and Visual Sciences University of Wisconsin School of Medicine and Public Health Madison WIMedicalResearch.com Interview with:
Ronald Klein, MD, MPH, Professor
Department of Ophthalmology and Visual Sciences
University of Wisconsin School of Medicine and Public Health
Madison WI

Medical Research: What are the main findings of the study? 

Dr. Klein: We found that more severe age-related macular degeneration (AMD) in 1 eye was associated with increased incidence of age-related macular degeneration [levels 1-2: hazard ratio [HR], 4.90 [95%CI, 4.26-5.63] and accelerated progression [levels 2-3: HR, 2.09 [95%CI, 1.42-3.06]; levels 3-4: HR, 2.38 [95%CI, 1.74-3.25] and incidence of late age-related macular degeneration [levels 4-5: HR, 2.46 [95%CI, 1.65-3.66] in its fellow eye. Less severe AMD in 1 eye was associated with less progression of AMD in its fellow eye. We estimated that 51% of participants who develop any age-related macular degeneration maintained age-related macular degeneration severity states within 1 step of each other between eyes and 90% of participants stay within 2 steps.
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Cocoa Flavenols May Improve Age-Related Memory Decline

Scott A. Small, MD Boris and Rose Katz Professor of Neurology Division of Aging and Dementia Director, Alzheimer's Disease Research Center Taub Institute for Research on Alzheimer's Disease and the Aging Brain Department of Neurology, Columbia University New York, New YorkMedicalResearch.com Interview with:
Scott A. Small, MD
Boris and Rose Katz Professor of Neurology
Division of Aging and Dementia
Director, Alzheimer’s Disease Research Center
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain Department of Neurology, Columbia University New York, NY

Medical Research: What is the background for this study?

Dr. Small: Previous work, including from my lab, had shown that changes in a specific part of the brain—the dentate gyrus—are associated with age-related memory decline. Until now, however, the evidence in humans showed only a correlational link, not a causal one. To see if the dentate gyrus is the source of age-related memory decline in humans, we tested whether compounds called cocoa flavanols can improve the function of this brain region and improve memory. Flavanols extracted from cocoa beans had previously been found to improve neuronal connections in the dentate gyrus of mice.
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International Societies Urge Expedited Ebola Vaccine Development

Prof. Clive Maurice Gray   Division of Immunology, Institute of Infectious Diseases and Molecular Medicine,National Health Laboratory Services University of Cape Town, Cape Town, South AfricaMedicalResearch.com Interview with:
Prof. Clive Maurice Gray  
Division of Immunology, Institute of Infectious Diseases and Molecular Medicine,National Health Laboratory Services
University of Cape Town, Cape Town, South Africa

Medical Research: What is the background for this report? What are the main findings?

Prof. Gray: This report is a response on behalf to the International Union of Immunology Societies (IUIS) and is designed to focus a message from the global immunology community to those who are making vaccines and therapies implementing clinical trials and very importantly on Governments and funding bodies. Time is not our side and that vaccine efforts need to be expedited and that production of therapeutics needs to be ramped up. Due to the fact that many people in West Africa are dying, we wish to convey a strong message that to curb this outbreak, therapies and especially vaccines must be rolled out as soon as possible.

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Does Long Term Viagra Improve Heart Disease?

Dr. Andrea M. Isidori, MD, PhD Consultant - Assistant Professor of Endocrinology Department of Experimental Medicine Medical Pathophysiology Sapienza University of RomeMedicalResearch.com Interview with:
Dr. Andrea M. Isidori, MD, PhD
Consultant – Assistant Professor of Endocrinology
Department of Experimental Medicine
Medical Pathophysiology
Sapienza University of Rome

Medical Research: What is the background for this study? What are the main findings?

Dr. Isidori : Our meta-analytic research originated to clarify some controversies emerging from the available human studies. We wanted to analyze if chronic PDE5i administration was cardioprotective and safe, and, if so, where the benefits were mainly seen: cardiac muscle, peripheral vessels, or both. In the last sixteen years pre-clinical and clinical research into the extra-urological effects of PDE5i has expanded dramatically, revealing previously unsuspected indications for these drugs. Several animal studies have shown that PDE5i attenuates cardiac remodeling, with an anti-hypertrophic and anti-fibrotic effect, and protects the heart against different types of injury. Some small clinical trials have demonstrated that chronic PDE5 inhibition improves cardiac performance and geometry in various clinical conditions, including heart failure, myocardial infarction and diabetic cardiomyopathy.

We showed that continuous administration of Viagra improves cardiac performance (increase of ejection fraction and cardiac index) and has an anti-remodeling effect (decrease of left ventricular mass and increase of end diastolic volume) without a major impact on vascular parameters (blood pressure and vascular resistance) suggesting that it does indeed have a direct effect on the heart. The novelty of this meta-analysis is the identification of subgroups of patients that may benefit more from PDE5i: patients with cardiac hypertrophy and heart failure. Our study is the first to show in a large patient cohort that chronic PDE5i administration improves cardiac output and decreases heart rate. This could result in longer survival, increased exercise tolerance and a better quality of life. Surprisingly, the magnitude of effects was similar to that seen with the drugs currently used to treat these clinical conditions, and was obtained in a relatively brief period (3 to 12 months). Most strikingly, we found that PDE5is are among the very few drugs that are able to improve diastolic relaxation, thus helping the correct refilling of the ventricle after each contraction, a nearly unique feature in drugs used in cardiology, and with incredible potential for future development in the prevention of heart failure. We also demonstrated their high tolerability and safety in a population that included elderly patients with various stages of cardiac disease and numerous comorbidities who were taking multiple pharmacological treatments. This setting resembles what we normally see in real life, supporting that daily administration is safe and involves no increase in the risk of adverse events compared to on-demand use.
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Simple Nucleic Acid Biomarker May Enhance Bedside Diagnosis

Dr. Adam Woolley PhD Department of Chemistry and Biochemistry Brigham Young UniversityMedicalResearch.com Interview with:
Dr. Adam Woolley PhD
Department of Chemistry and Biochemistry
Brigham Young University

Medical Research: What is the background for this study? What are the main findings?

Dr. Woolley: High-performance biomarker analysis methods are usually complex and expensive. In contrast, simple and inexpensive biomarker detection methods
typically have low performance.

Our study demonstrates a simple nucleic acid measurement system that
requires no detection instrumentation. Nucleic acid mimics of microRNA were
quantified with sequence specificity down to 10 pg/mL levels.
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Traumatic Brain Injury Raises Dementia Risk in Elderly

Raquel C. Gardner, MD, Research Fellow San Francisco VA Medical Center Clinical Instructor Memory and Aging Center, Department of Neurology University of California, San FranciscoMedicalResearch.com Interview with:
Raquel C. Gardner, MD, Research Fellow
San Francisco VA Medical Center
Clinical Instructor
Memory and Aging Center, Department of Neurology
University of California, San Francisco

Medical Research: What are the main findings of the study?

Dr. Gardner: We found that people who experience a  traumatic brain injury (TBI )when they are 55 or older have a 26% higher chance of getting dementia over the next 5 to 7 years compared to people who experience bodily trauma.

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