New Gene Mutation Found to Cause Retinitis Pigmentosa in SW USA Hispanics

MedicalResearch.com Interview with:

Stephen P. Daiger, PhD TS Matney Professor of Environmental and Genetic Sciences Human Genetics Center, School of Public Health and Mary Farish Johnston Distinguished Chair of Ophthalmology Ruiz Dept. of Ophthalmology and Visual Science The Univ. of Texas HSC at Houston

Dr. Daiger

Stephen P. Daiger, PhD
Professor, Human Genetics Center
Thomas Stull Matney, Ph.D. Professor in Environmental and Genetic Sciences
Mary Farish Johnston Distinguished Chair in Ophthalmology
The University of Texas Health Science Center at Houston

 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Thanks for your questions about our research.  My research group and I have a long-term interest in finding genes and mutations causing inherited retinal diseases.  Our main focus is on retinitis pigmentosa (RP) and, more specifically, the autosomal dominant form of RP.

Inherited retinal diseases are progressive, degenerative diseases of the retina.  Onset can be very early in life, even at birth, or much later in life.  As the degeneration develops an affected person may first experienced limited loss of vision, progressing to severe loss of vision, ending, in many cases, in legal or complete blindness.  About 300,000 Americans are affected by inherited retinal disease and 50% of these have RP.  RP, like most hereditary conditions, can be inherited in an autosomal dominant, autosomal recessive or X-linked fashion.

One of the surprising, and in some sense, disturbing findings in studying  retinitis pigmentosa is that mutations in many different genes can cause this disease.  We now know that mutations in more than 80 genes can cause RP and thousands of different mutations have been found in these genes.  With next-generations sequencing it is possible to find the cause of RP in from 50% to 80% of cases, depending on the underlying mode of inheritance.For example, in our research we can find the disease-causing mutation in about 75% of families with autosomal dominant RP.  Needless to say, a primary aim of our research is to find the cause in the remaining 25%.

In looking for the cause of retinitis pigmentosa in the remaining 25%, that is, those in whom mutations were not detected by earlier methods, we found a potential dominant-acting mutation in the arrestin-1 gene (gene symbol “SAG”) using whole-genome sequencing.  Molecular modeling suggests this mutation is damaging.  This was unexpected because previously-reported mutations in this gene were associated with Oguchi disease, a recessive retinal disease with symptoms distinct from RP.  On further testing our cohort of patients with autosomal dominant RP, we found this mutation in nearly 4% of families.  Even more surprisingly, when we looked closely at the affected families, and worked with our collaborators to test other patients, we discovered that all of the families with the dominant-acting SAG mutation — 12 total — were of Hispanic origin.  By interviewing informative family members we learned that these families have their roots in the Southwestern United States.  Historically, the mutation may have arisen hundreds of years ago, consistent with genetic variation tracking with the mutation.

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Fixed-Dose Blood Pressure Medications Save Money In The Long Run

MedicalResearch.com Interview with:

Kalyani B. Sonawane, PhD Assistant Professor/ PhD Program Director Department of Health Services Research, Management and Policy College of Public Health and Health Professions University of Florida Gainesville, FL 32610

Dr. Sonawane

Kalyani B. Sonawane, PhD
Assistant Professor/ PhD Program Director
Department of Health Services Research, Management and Policy
College of Public Health and Health Professions
University of Florida
Gainesville, FL 32610

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Almost one-third of Americans have high blood pressure. Of those patients who are prescribed medication to control their blood pressure, about 30 percent have problems with side effects and nearly 50 percent will not have their blood pressure controlled within the first year of taking medication. In such scenarios, physicians have the option to either add a medication, such as fixed-dose combination, to the patient’s regimen or gradually increase a patient’s dose of their current drug to achieve blood pressure control; and gradually decrease the dose of their current drug or switch to a different drug to resolve side effects. Using healthcare claims data, we compared the economic impact of these alternative treatment modification strategies.

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Animal Study Suggests Lorcaserin (Belviq®) May be Useful to Reduce Opioid Intake

MedicalResearch.com Interview with:
Christina R. Merritt and Kathryn A. Cunningham
Center for Addiction Research
University of Texas Medical Branch
Galveston, TX 77555

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Opioid use disorder (OUD) is one of the top public health problems in the United States. Overdoses on prescription opioids, heroin and fentanyl accounted for 33,091 deaths in the U.S. in 2015 (https://www.cdc.gov/mmwr/volumes/65/wr/mm655051e1.htm); each day, 91 Americans die from an opioid overdose (https://www.cdc.gov/drugoverdose/epidemic/). The first-ever Surgeon General’s Report on Alcohol, Drugs and Health (https://addiction.surgeongeneral.gov/ ) observed that more people used prescription opioids than tobacco in 2015. Furthermore, individuals with OUD, the most problematic pattern of opioid abuse, often relapse, particularly in environments associated with past drug use, and new means to help maintain abstinence are needed.

Serotonin (5-hydroxytryptamine; 5-HT) function in the brain, particularly through its cognate 5-HT2C receptor, is an important regulator of the abuse liability of cocaine and other psychostimulants. Previous studies suggested that the weight loss medication and selective 5-HT2C receptor agonist lorcaserin (Belviq®) can curb cocaine- and nicotine-seeking in preclinical models, even when tested in tempting environments. We administered lorcaserin to rats who were trained to take the powerful painkiller oxycodone (OxyContin®), a prescription opioid currently approved for treatment of acute and chronic pain with characteristically high abuse potential. Lorcaserin suppressed oxycodone intake as well as the drug-seeking behaviors observed when rats were exposed to cues such as the lights and sounds previously associated with drug intake. Taken together, these findings highlights the therapeutic potential for lorcaserin to extend abstinence and enhance recovery from OUD.

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BRCA Testing Shifts From Cancer Patients to Unaffected Women

MedicalResearch.com Interview with:

Fangjian Guo, MD, PhD Department of Obstetrics and Gynecology Center for Interdisciplinary Research in Women’s Health University of Texas Medical Branch Galveston TX

Dr. Fangjian Guo

Fangjian Guo, MD, PhD
Department of Obstetrics and Gynecology
Center for Interdisciplinary Research in Women’s Health
University of Texas Medical Branch
Galveston TX

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: BRCA testing in patients diagnosed with early-onset breast or ovarian cancer can identify women with high-risk mutations, which can guide treatment. Women who learn they have a high-risk mutation may also want to inform family members that they may also carry a high-risk mutation.

Additionally, BRCA testing can be used to identify high-risk mutation carriers before they develop breast or ovarian cancer. Carriers can then manage their cancer risks with screening (MRI/mammogram), chemoprevention, or prophylactic surgery. Current guidelines recommend BRCA testing for individuals who are considered high-risk for breast or ovarian cancer based on personal or family history.  However, this practice fails to identify most BRCA mutation carriers. It is estimated that more than 90% of mutation carriers have not been identified. One of the issues is that many women who do get tested are actually low-risk and do not have any personal or family history of breast or ovarian cancer.

This study assessed how BRCA testing was used in the US health care system during the past decade. We found that in 2004 most of the tests (75.7%) were performed in patients who had been diagnosed with breast or ovarian cancer. Only 24.3% of tests were performed in unaffected women. However, since 2006, the proportion of BRCA tests performed in unaffected women has increased sharply, with over 60% of the tests performed in unaffected women in 2014.

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Mutliple Sclerosis: Ocrelizumab Lowers Rate of Disease Progression and Disability

MedicalResearch.com Interview with:

Jerry S. Wolinsky, MD Emeritus Professor in Neurology McGovern Medical School part of UTHealth | The University of Texas Health Science Center at Houston Houston’s Health University Department of Neurology Houston, Texas 77030

Dr. Jerry Wolinsky,

Jerry S. Wolinsky, MD
Emeritus Professor in Neurology
McGovern Medical School
The University of Texas Health Science Center at Houston
Houston’s Health University
Department of Neurology
Houston, Texas 77030

MedicalResearch.com: What is the background for this study?

Response: Multiple sclerosis (MS) clinically is a very heterogeneous disease. It presents in considerably different ways and has a very poorly predictable clinical course. In an attempt to better communicate between experts in the field, there have been multiple attempts to categorize “typical” courses of the disease. How we think about the disease is in part driven by these somewhat artificial categories that lump our patients into those with relapsing forms of the disease (relapsing remitting with or without accumulating clinical disability, and secondary progressive with accumulating disability eventually occurring even in the absence of apparent clinical episodes of the disease), and primary progressive MS, where patients are slowly or sometimes rather rapidly accumulating disability in the absence of prior clinical relapses.

However, the distinctions between multiple sclerosis patients are not always as clear as the definitions would suggest, and it is certain that patients with primary progressive multiple sclerosis sometimes have clinical relapses after years of never having had relapses, and show MRI evidence of having accumulated many lesions in the brain over the course of their disease. Until now, none of the drugs that have shown benefit for relapsing disease have been able to convincingly show clinical benefit for patients with primary progressive disease, and for that matter have shown variable results when attempted in patients categorized as having secondary progressive courses. While some of our currently approved drugs have shown hints of benefit when tried in major clinical trials in primary progressive MS, the results were not been robust enough to seek regulatory approval.

The Oratorio study design was based on lessons learned from prior trials in primary progressive and relapsing forms of MS, as well as the recognition that B cells might play an important role in the immunopathogenesis of disease based on a considerable amount of preclinical work and observations in patients with multiple sclerosis.

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Can Low Dose Oral Nicotine Have Beneficial Health Effects?

MedicalResearch.com Interview with:

U. H. Winzer-Serhan Ph.D. Associate Professor Department of Neuroscience and Experimental Therapeutics Texas A&M Health Science Center

Dr. Ursula H. Winzer-Serhan

Ursala. H. Winzer-Serhan Ph.D.
Associate Professor
Department of Neuroscience and Experimental Therapeutics
Texas A&M Health Science Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Nicotine is a plant alkaloid that is naturally occurring in the tobacco plant. Smoking delivers nicotine to the brain where it acts as a stimulant. Tobacco and electronic cigarette smoking delivers many other chemicals to the body, which are harmful and can cause cancer.

However, the drug nicotine by itself is relatively benign and poses few health risks for most people. Nicotine acts in the brain on nicotinic receptors, which are ion channels that are widely expressed in the brain. They play an important role in cognitive functions. Research with rodents and in humans has shown that nicotine can enhance learning and memory, and furthermore, can protect neurons during injuries and in the aging brain. With the increasingly older population, it becomes more and more important to delay cognitive decline in the elderly. Right now, there is no drug available that could delay aging of the brain.

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Almost 5 Million Unnecessary Pap Smears Done Annually In Women With Hysterectomy

MedicalResearch.com Interview with:

Fangjian Guo, MD, PhD Assistant Professor BIRCWH Scholar Department of Obstetrics & Gynecology Center for Interdisciplinary Research in Women’s Health The University of Texas Medical Branch

Dr. Fangjian Guo

Fangjian Guo, MD, PhD
Assistant Professor
BIRCWH Scholar
Department of Obstetrics & Gynecology
Center for Interdisciplinary Research in Women’s Health
The University of Texas Medical Branch

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: National guidelines consistently recommend against cervical cancer screening among women with a history of a total hysterectomy for a benign condition. These women are unlikely to develop high-grade cervical lesions. The goal of our study was to assess whether these guidelines are being followed. We examined the use of Pap testing among US adult women with a history of total hysterectomy for a benign condition and the roles of health care providers and patients in the initiation of Pap test use.

We found that in 2013, 32% of women who have had a hysterectomy received an unnecessary recommendation for cervical cancer screening from a health care provider in the past year; 22.1% of women with hysterectomy received unnecessary Pap testing. Although the majority of Pap tests were performed at a clinician’s recommendation, approximately one fourth were initiated by patients without clinician recommendations. According to standard 2010 US Census population figures, about 4.9 million unnecessary Pap tests are performed annually among women who have had a total hysterectomy for a benign condition. At approximately $30 per test, $150 million in direct medical costs could be saved annually if screening guidelines were followed for these women.

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Statin Users Have Lower Incidence of Uterine Fibroids

MedicalResearch.com Interview with:

Mostafa Borahay, MD, PhD, FACOG Assistant Professor Department of Obstetrics and Gynecology Galveston, TX

Dr. Mostafa Borahay

Mostafa Borahay, MD, PhD, FACOG
Assistant Professor
Department of Obstetrics and Gynecology
Galveston, TX

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Uterine fibroids are the commonest tumors of the female reproductive system. More than 50% of women are estimated to have uterine fibroids. In fact, 1 out of 4 women undergo a hysterectomy in the United States and half of these hysterectomies are due to fibroids.
Recently we demonstrated that statins, drugs used to fight high cholesterol, have anti-tumor effects on uterine fibroids as shown in cells and animal models.

In this current study, we examined the incidence of uterine fibroids and fibroid-associated symptoms in women taking statins for high cholesterol. We performed this using large national patient database.
We found that compared to non-users, statin users have lower incidence of uterine fibroids. Furthermore, they have less heavy bleeding, pelvic pain and other fibroid-associated symptoms. Also, they needed less surgeries to remove tumors (myomectomy).

MedicalResearch.com: What should readers take away from your report?

Response: Currently, we don’t have a successful, safe long term medical treatment for uterine fibroids. Surgeries, typically a hysterectomy, is commonly performed for fibroids. This study provide some evidence that a safe long term medical treatment can be available for treating these tumors. This provides hope for many women, especially those interested in preserving their childbearing potential.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: After finding strong evidence from cellular and animal experiments and using patient databases, our next step is clinical trials. We plan to start a clinical trial for statins in women with fibroids in the near future. The established safety of statins represents a huge advantage.

MedicalResearch.com: Is there anything else you would like to add?

Response: The successful work over the last few years stresses the huge benefits from and the critical need for a multidisciplinary teams in medical research. Our team included clinicians, basic scientists and biostatisticians and epidemiologists.

Also, there is a need for more funding for medical research. Scientific research to discover innovative treatments requires funding and therefore the National Institutes of Health (NIH) and other funding bodies have a large responsibility to fulfil.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Am J Obstet Gynecol. 2016 Jun 28. pii: S0002-9378(16)30381-7. doi: 10.1016/j.ajog.2016.06.036. [Epub ahead of print]
Statin Use and Uterine Fibroid Risk in Hyperlipidemia Patients: A Nested Case-Control Study.
Borahay MA1, Fang X2, Baillargeon JG2, Kilic GS3, Boehning DF4, Kuo YF2.

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

Could Methylene Blue Improve Memory in Patients With Cognitive Impairment?

MedicalResearch.com Interview with:

Timothy Q. Duong, Ph.D Stanley I. Glickman MD Professor of Ophthalmology, Radiology, and Physiology South Texas Veterans Health Care System, VA Southwest National Primate Research Center University of Texas Health Science Center San Antonio, Texas

Dr. Timothy Duong

Timothy Q. Duong, Ph.D
Stanley I. Glickman MD Professor of Ophthalmology, Radiology, and Physiology
South Texas Veterans Health Care System, VA Southwest National Primate Research Center
University of Texas Health Science Center
San Antonio, Texas

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: A single oral dose of methylene blue increased fMRI response in the bilateral insular cortex during a task that measured reaction time to a visual stimulus. The fMRI results also showed an increased response during short-term memory tasks involving the brain’s prefrontal cortex, which controls processing of memories. Methylene blue was also associated with a 7 percent increase in correct responses during memory retrieval. The findings suggest that methylene blue can regulate certain brain networks related to sustained attention and short-term memory after a single oral low dose.

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Requests for Abortions in South American Rise Dramatically Since Zika, Especially in Brazil

MedicalResearch.com Interview with:

Abigail R.A. Aiken, MD, MPH, PhD Assistant Professor LBJ School of Public Affairs University of Texas at Austin Austin, TX, 78713

Dr. Abigail Aiken

Abigail R.A. Aiken, MD, MPH, PhD
Assistant Professor
LBJ School of Public Affairs
University of Texas at Austin
Austin, TX, 78713

MedicalResearch.com: What is the background for this study?

Response: As Zika began to emerge as an epidemic in Latin America and its links with microcephaly began to be realized, we were aware that women in the region who were already pregnant or who would become pregnant would have a very limited set of reproductive options. Research and media attention about the possible biological effects of Zika in pregnancy began to appear rapidly. But much less attention was been paid to the impacts of Zika on women. We followed the responses of governments and health organizations and when they began to issue advisories warning women to avoid pregnancy, we knew it would be important to investigate the impacts of those advisories. A country-wide policy that is impossible to follow if you are pregnant or cannot avoid pregnancy is an unusual and important public issue. Accurate data on abortion are very difficult to obtain in Latin America because in most countries, abortion is highly restricted. We wanted to provide a window on the issue of how women were responding to the risks of Zika and its associated advisories, so we worked with Women on Web (WoW), an online non-profit telemedicine initiative that provides safe medical abortion to women in countries where safe, legal abortion is not universally available.

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