12 Nov Study Examines Link Between L-Carnitine and Atherosclerosis
Posted at 11:50h
in Author Interviews
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Dr. Bellamine[/caption]
MedicalResearch.com Interview with:
Aouatef Bellamine,
Medical Research: What is the background for this study? What are the main findings?
Dr. Bellamine: About two years ago, Robert Koeth and his colleagues (Nat Med. 2013 May;19(5):576-85) published a paper linking atherosclerosis and increased cardiac disease risks to Trimethylamine N-oxide (TMAO), a degradation product of dietary quaternary ammonium compounds such as L-Carnitine, Betaine and Choline. When these compounds are not completely absorbed into the intestine, bacterial gut metabolizes them to TMA (Trimethylamine) which is absorbed to the blood and further metabolized by the liver flavin-containing mono-oxygenases (FMOs) to TMAO. This is why some people use injectable l carnitine products.
Koeth’s observation was based on
- 1- clinical association between L-Carnitine levels increased incidence of major cardiac events,
- 2- on increased lesion formation in ApoE-/- mouse, a disease model used to study atherosclerosis.The conclusion was that TMAO promotes atherosclerosis. Although the association is established, the cause to effect cannot be clarified given the lack of dose response in this mouse model (a single dose has been used) and the small number of animals in the treatment group making the difference between treatments (3 out of 11 animals). In addition, TMAO has been described to play the role of a molecular chaperone, preventing the protein unfolding. TMAO is also found in fish where it plays an important role in maintaining a normal osmolality. Fish is reported otherwise to be a healthy food source and its consumption is not linked to atherosclerosis occurrence.
Dr. Lei Xu[/caption]
MedicalResearch.com Interview with:
Lei Xu, MD, PhD
Steele Laboratory of Tumor Biology
Radiation Oncology Department
Massachusetts General Hospital
Medical Research: What is the background for this study?
Dr. Lei Xu: Neurofibromatosis 2 is characterized by benign tumors that develop throughout the nervous system. The most common site of these tumors is the eighth cranial nerve, which carries hearing and balance information from the ears to the brain. Although these vestibular schwannomas grow slowly, they usually lead to a significant or total hearing loss by young adulthood or middle age. The tumors can also press on the brain stem, leading to headaches, difficulty swallowing and other serious neurologic symptoms. While the tumors can be surgically removed or destroyed with radiation treatment, both approaches can also damage hearing.
Several previous investigations had suggested that – unlike other benign tumors – vestibular schwannomas induce the formation of new blood vessels, as malignant tumors do. A 2009 New England Journal of Medicine study led by Scott Plotkin, MD, PhD, at Massachusetts General Hospital reported that treatment with the antiangiogenesis drug bevacizumab caused shrinkage of NF2-schwannomas in most of the treated patients and improved hearing in more than half. But the limitations of that approach – the fact that not all patients responded, that the hearing improvement was often transient and that some patients could not tolerate long-term bevacizumab treatment – indicated the need to better understand the mechanisms of anti-angiogenesis on the function of tumor-bearing nerves.
Dr. Thakar[/caption]
MedicalResearch.com Interview with:
Charuhas Thakar, MD
Director, Division of Nephrology and Hypertension Professor of Medicine
University of Cincinnati
Medical Research: What is the background for this study? What are the main findings?
"Diabetes is the major contributor to the growing burden of end-stage renal disease,” says Charuhas Thakar, MD, professor and director of the Division of Nephrology and Hypertension at the UC College of Medicine.
"Acute kidney injury is a common problem among diabetic patients who require admissions to hospitals. Approximately one-third of patients who develop AKI also have diabetes mellitus.”
Dr. Thakar along with a team of researchers have looked at a cohort of about 3,700 patients with Type 2 diabetes longitudinally followed for a five-year period to determine AKI’s impact.
AKI is a rapid loss of kidney function, which is common in hospitalized patients.
It has many causes that include low blood volume, exposure to substances or interventions harmful to the kidney and
obstruction of the urinary tract.
MedicalResearch.com Interview with:
Dr. Giuseppe Andò
University of Messina, Messina, Italy
Medical Research: What is the background for this study?
Dr. Andò: Patients’ preference for radial access for coronary angiography and percutaneous intervention is paralleled by an almost complete abolition of access-site bleeding. Given the deleterious impact of any clinically relevant bleeding event on short- and long-term outcomes, the use of radial access should translate into a reduction in net adverse events, especially in patients with high risk of bleeding such as those with an acute coronary syndrome. Nonetheless, studies conducted over the past decade by pioneers of 
MedicalResearch.com Interview with:
Dr. Wanpen Vongpatanasin MD
Program Director, Hypertension Fellowship Program
Professor of Internal Medicine
Director of the University of Texas Southwestern Hypertension Program
Medical Research: What is the background for this study? What are the main findings?
Dr. Vongpatanasin: Home blood pressure measurement may reveal very different number when compared to clinic blood pressure in hypertensive patients. This difference can manifest as white coat hypertension (White Coat Hypertension; elevated office blood pressure with normal ambulatory or home blood pressure), or masked hypertension (MH; elevated ambulatory or home BP with normal office blood pressure). Although numerous epidemiological studies from Europe and Asia have shown increased cardiovascular risks associated with White Coat Hypertension and masked hypertension, previous studies have not addressed cardiovascular outcomes associated with White Coat Hypertension and masked hypertension in the general population in the United States.
We found that participants in the Dallas Heart Study, a multiethnic populational-based study in the Dallas County, both White Coat Hypertension and MH are associated with increased aortic stiffness and markers of kidney damage when compared to the group with normal blood pressure both at home and in the clinic. Furthermore, both white coat hypertension and masked hypertension are associated with increased risk of cardiovascular events, including coronary heart disease, stroke, atrial fibrillation, heart failure, and cardiovascular death over a median follow-up period of 9 years.
Dr. Nagler[/caption]
MedicalResearch.com Interview with:
Arielle Nagler MD
Instructor, Department of Ronald O. Perelman Department of Dermatology
NYU Langone Medical Center
Medical Research: What are some of the best ways to keep our skin healthy?
Dr. Nagler: Sun protection is the single, most important step you can take to keep your skin healthy. Sun protection can help to prevent many of the signs of aging including wrinkles, changes in skin texture, and uneven pigmentation. Also sun protection has been shown to prevent certain types of skin cancer, which may save you from the distress and scarring of treatment. While we should all be careful in the sun, sun protection doesn’t mean that you have to avoid all outdoor activities and deprive yourself of outdoor fun. If you have any issues with your skin, or want more information, you might want to look into someone like this 
Dr. Manning[/caption]
MedicalResearch.com Interview with:
Shannon D. Manning, Ph.D., M.P.H.
Dept. of Microbiology and Molecular Genetics
Michigan State University
E. Lansing, MI 48824
Medical Research: What is the background for this study? What are the main findings?
Dr. Manning: Diarrheal disease is a leading cause of morbidity and mortality in children under the age of five and is commonly caused by many different bacterial pathogens.
We have observed that infection with four different bacterial pathogens (Salmonella, Shigella, Shiga toxin-producing E. coli, and Campylobacter) all induce the proliferation of a population of microbes, namely Escherichia, which are already present in the gut of healthy individuals.
Dr. McKay[/caption]
MedicalResearch.com Interview with:
Brian S. McKay, Ph.D
Associate Professor
Department of Ophthalmology and Vision Science
University of Arizona
Medical Research Building, Room 212
Tucson, AZ 85724
Medical Research: What is the background for this study?
Dr. McKay: AMD (age-related macular degeneration) is a disease that is race-related. White people get the disease and lose vision to AMD at much higher rate than Blacks or Hispanics.
Thus, while race is complex, pigmentation may protect from the disease. With this starting point, my laboratory went after the pigmentation pathway to determine how pigment may affect photoreceptor (the retinal cells that actually catch the light) survival. The pigmented cells in the back of the eye are the retinal pigment epithelial cells (RPE), the rest of the retina does not pigment, it is clear not brown. We discovered that when the RPE make pigment they turn on molecular pathways to foster photoreceptor survival. Next we discovered the ligand for a receptor on the RPE that was tied to governing photoreceptor survival and pigmentation. That ligand was L-DOPA.
Knowing that L-DOPA is given to many aging individuals (those at risk of AMD), we developed a team to ask whether those taking L-DOPA for movement disorders are protected from AMD.
Dr. McCabe[/caption]
MedicalResearch.com Interview with:
Edward R. B. McCabe, MD, PhD
Senior Vice President and Chief Medical Officer
Professor Adjunct of Pediatrics
Yale University School of Medicine
Distinguished Professor Emeritus, Department of Pediatrics & Inaugural Mattel Executive Endowed Chair of Pediatrics, UCLA School of Medicine
Inaugural Physician-in-Chief, Mattel Children's Hospital
Chief Medical Officer March of Dimes
Medical Research: What is the background for this study? What are the main findings?
Dr. McCabe: 
Dr. Barnes[/caption]
MedicalResearch.com Interview with:
Geoffrey Barnes, MD, MSc
Clinical Lecturer
Cardiovascular Medicine and Vascular Medicine
University of Michigan Health System
Medical Research: What is the background for this study?
Dr. Barnes: Although warfarin has been the primary anticoagulant used for stroke prevention in atrial fibrillation for over 60 years, four new direct oral anticoagulants (DOACs) have been introduced into the market since 2010. Dabigatran, which directly inhibits thrombin, was found to have better prevention of ischemic stroke and a significant reduction in hemorrhagic stroke (bleeding strokes) for patients with 
Dr. Molnar[/caption]
MedicalResearch.com Interview with:
Miklos Z Molnar, MD, PhD, FEBTM, FERA, FASN
Associate Professor of Medicine
Division of Nephrology, Department of Medicine
University of Tennessee Health Science Center
Memphis, TN, 38163
Medical Research: What is the background for this study? What are the main findings?
Dr. Molnar: We examine the association between presence of depression and all-cause mortality; incident Coronary Heart Disease (CHD) (new onset AMI, CABG or PCI), incident ischemic stroke, slopes of eGFR (OLS, <-5 vs ≥-5 ml/min/1.73m2/yr) in 933,211 diabetic (based on ICD9, medication and HbA1c ≥ 6.5%) US Veterans with eGFR ≥ 60 ml/min/1.73m2 at baseline. We adjusted for independent covariates, collected from VA databases, such as age, gender, race, BMI, marital status, income, service connection, comorbid conditions (ICD9), baseline eGFR, serum albumin.
Mean age was 64±11 years, 97% were male and 18% African-American. Depression was present in 340,806 (37%) patients at enrollment. During a median follow-up of 7.3 years, 180,343 patients (19%) developed Chronic Kidney Disease (CKD).AS (adjusted hazard ratio [aHR] and 95% confidence interval [CI]: 1.20 (1.19-1.21)). Similarly, depression was associated with 35% higher risk of incident stroke (aHR and 95% CI: 1.35 (1.32-1.39), 24% higher risk of incident CHD (aHR and 95% CI: 1.24 (1.22-1.27) and 25% higher risk of all cause mortality (aHR and 95% CI: 1.25 (1.24-1.26) during the follow-up.
Dr. Silverberg[/caption]
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? What are the main findings?
Dr. Silverberg: We previously showed that adults with eczema are more likely to smoke cigarettes, drink alcohol and have sedentary lifestyle. We wondered whether chronic eczema might negatively impact upon other health behaviors, such as seeking preventive care and vaccinations. On the other hand, previous studies from our group and others found that both children and adults with eczema have a number of comorbid medical and mental health conditions. One potential reason for this is detection bias from since eczema patients are “plugged into” the healthcare system because of their skin disease, which allows them to be diagnosed more frequently with other health problems.
We sought to understand the routine and preventive healthcare behaviors of children and adults with eczema. We found that adults with eczema were more likely to be vaccinated for tetanus, influenza, hepatitis A and B viruses, human papilloma virus and pneumonia. Moreover, they were more likely to undergo age-appropriate health screenings, such as blood pressure and cholesterol checks, but not cancer screening. Adults with eczema were more likely to interact with a variety of general doctors and specialists.
Similarly, 
Dr. Cooper[/caption]
MedicalResearch.com Interview with:
Lauren Cooper, MD
Fellow in Cardiovascular Diseases
Duke University Medical Center
Duke Clinical Research Institute
Medical Research: What is the background for this study? What are the main findings?
Dr. Cooper: Heart failure guidelines recommend routine monitoring of serum potassium and renal function in patients treated with a mineralocorticoid receptor antagonist (MRA). Specific monitoring recommendations include: within 2-3 days of initiation of the drug, again at 7 days, monthly for at least 3 months, then every 3 months thereafter. However, no large studies had evaluated compliance with these safety recommendations in routine clinical practice. Using Medicare claims data from 2011, we evaluated monitoring of serum creatinine and potassium levels among patients with heart failure initiated on an MRA.
After MRA initiation, rates of guideline-recommended laboratory monitoring of creatinine and potassium were low. Of 10,443 Medicare beneficiaries included in this study, 91.6% received pre-initiation testing; however, only 13.3% received appropriate testing in the first 10 days after drug initiation and 29.9% received appropriate testing in the first 3 months. Only 7.2% of patients received guideline-recommended laboratory monitoring both before and after MRA initiation. Chronic kidney disease was associated with a greater likelihood of appropriate testing (relative risk, 1.83; 95% CI, 1.58-2.13), as was concomitant diuretic use (relative risk, 1.78; 95% CI, 1.44-2.21).
MedicalResearch.com Interview with:
Dr. Priscilla Kaliopi Brastianos MD
Instructor, Medicine, Harvard Medical School
Assistant Physician in Medicine
Hematology/Oncology, Massachusetts General Hospital
Medical Research: What is the background for this study? What are the main findings?
Response: Craniopharyngiomas are rare brain tumors that can cause serious problems because of their location near critical structures in the brain, such as optic and other cranial nerves, the pituitary gland and the hypothalamus. Not only does the growing tumor compromise neurological and hormonal functions by impinging on these structures, but treatment by surgical removal or radiation therapy can produce the same symptoms by damaging adjacent tissues. In addition, since the tumor adheres to these nearby critical structures, complete removal is difficult, which can lead rapid recurrence. Medical therapies have not been effective for craniopharyngiomas, namely because we did not understand the molecular underpinnings of these tumors. Last year, we performed genomic characterization of craniopharyngiomas, with the goal to identify potential therapeutic targets. We were surprised to find that nearly all papillary craniopharyngiomas have BRAF mutations, which are the same mutations that have been found in 
