Sildenafil Use and Increased Risk of Inciden… [JAMA Intern Med. 2014] – PubMed – NCBI

JAMA Intern Med. 2014 Jun 1;174(6):964-70. doi: 10.1001/jamainternmed.2014.594.

Sildenafil Use and Increased Risk of Incident Melanoma in US Men: A Prospective Cohort Study.

Abstract

IMPORTANCE The RAS/RAF/mitogen-activated protein kinase and extracellular signal-regulated kinase (ERK) kinase/ERK cascade plays a crucial role in melanoma cell proliferation and survival. Sildenafil citrate (Viagra) is a phosphodiesterase (PDE) 5A inhibitor commonly used for erectile dysfunction. Recent studies have shown that BRAF activation down-regulates PDE5A levels, and low PDE5A expression by BRAF activation or sildenafil use increases the invasiveness of melanoma cells, which raises the possible adverse effect of sildenafil use on melanoma risk. OBJECTIVE To evaluate the association between sildenafil use and risk of incident melanoma among men in the United States. DESIGN, SETTING, AND PARTICIPANTS Our study is a prospective cohort study. In 2000, participants in the Health Professionals’ Follow-up Study were questioned regarding sildenafil use for erectile dysfunction. Participants who reported cancers at baseline were excluded. A total of 25 848 men remained in the analysis. MAIN OUTCOMES AND MEASURES The incidence of skin cancers, including melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC), was obtained in the self-reported questionnaires biennially. The diagnosis of melanoma and SCC was pathologically confirmed. RESULTS We identified 142 melanoma, 580 SCC, and 3030 BCC cases during follow-up (2000-2010). Recent sildenafil use at baseline was significantly associated with an increased risk of subsequent melanoma with a multivariate-adjusted hazard ratio (HR) of 1.84 (95% CI, 1.04-3.22). In contrast, we did not observe an increase in risk of SCC (HR, 0.84; 95% CI, 0.59-1.20) or BCC (1.08; 0.93-1.25) associated with sildenafil use. Moreover, erectile function itself was not associated with an altered risk of melanoma. Ever use of sildenafil was also associated with a higher risk of melanoma (HR, 1.92; 95% CI, 1.14-3.22). A secondary analysis excluding those reporting major chronic diseases at baseline did not appreciably change the findings; the HR of melanoma was 2.24 (95% CI, 1.05-4.78) for sildenafil use at baseline and 2.77 (1.32-5.85) for ever use. CONCLUSIONS AND RELEVANCE Sildenafil use may be associated with an increased risk of developing melanoma. Although this study is insufficient to alter clinical recommendations, we support a need for continued investigation of this association.

PMID:
24710960
[PubMed – in process]
Posted in Aging, Fifth Avenue Concierge Medicine, Forensic Neuropsychiatry, Health, keto, News | Tagged , |

New York Magazine Best Doctors Nomination

New York Magazine Best Doctors Nomination

Thank you for the votes!
http://nymag.com/nymag/toc/20140609

Maurice Preter MD Nominated To Castle Connolly / New York Magazine Best Doctors of New York 2014

Posted in keto, News |

Maurice Preter MD and Donald F. Klein, MD, DSc: Lifelong opioidergic vulnerability through early life separation: A recent extension of the false suffocation alarm theory of panic disorder.

Fresh off the [Epub] press. Of interest to some.

Keywords: Affective neuroscience; Childhood parental loss (CPL); Endogenous opioids; Panic disorder pathophysiology

From the conclusion:
“[…W]e objectively, experimentally showed a physiological link between endogenous opioid system deficiency and panic-like suffocation sensitivity in healthy adults. This is consonant with the expanded Suffocation-False Alarm Theory of panic suggesting an episodic functional endogenous opioid deficit (Preter and Klein, 1998). The specificity of the naloxone + lactate model of clinical panic should be tested using specific anti-panic components, possibly including opioidergic mixed agonist-antagonists such as buprenorphine. If specific, the naloxone + lactate effect in normal humans affords a screening method for testing putative anti-panic drugs which is currently not available. This could obviate the experimental treatment of panic disorder patients in drug development.
Our data also show for the first time that actual separations and losses during childhood, such parental death, parental separation or divorce (CPL), effect lifelong alterations in the physiological reactivity of the endogenous opioid system of healthy adults.
This result encourages epigenetic inquiry into the effects of CPL on endogenous opioid systems, and their role in resilience under extreme stress. In addition, a redefinition of what constitutes a (truly) healthy control in clinical research protocols may be called for.”

Neurosci Biobehav Rev. 2014 Apr 9. pii: S0149-7634(14)00082-7. doi:10.1016/j.neubiorev.2014.03.025.

 [Epub ahead of print]

Lifelong opioidergic vulnerability through early life separation: A recent extension of the false suffocation alarm theory of panic disorder.

Preter M1, Klein DF2.

Author information

1Corresponding Author. Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA. Electronic address: mp2285@columbia.edu.

2Phyllis Green and Randolph Cowen Institute for Pediatric Neuroscience, Department of Child and Adolescent Psychiatry, New York University Langone Medical Center 550 1(st) Ave, New York, NY 10016, USA. Electronic address: donaldk737@aol.com.

Abstract

The present paper is the edited version of our presentations at the “First World Symposium On Translational Models Of Panic Disorder”, in Vitoria, E.S., Brazil, on November 16-18, 2012. We also review relevant work that appeared after the conference. Suffocation-False Alarm Theory (Klein, 1993) postulates the existence of an evolved physiologic suffocation alarm system that monitors information about potential suffocation. Panic attacks maladaptively occur when the alarm is erroneously triggered. The expanded Suffocation-False Alarm Theory (Preter and Klein, 2008) hypothesizes that endogenous opioidergic dysregulation may underlie the respiratory pathophysiology and suffocation sensitivity in panic disorder. Opioidergic dysregulation increases sensitivity to CO2, separation distress and panic attacks. That sudden loss, bereavement and childhood separation anxiety are also antecedents of “spontaneous” panic requires an integrative explanation. Our work unveiling the lifelong endogenous opioid system impairing effects of childhood parental loss (CPL) and parental separation in non-ill, normal adults opens a new experimental, investigatory area.

Copyright © 2014. Published by Elsevier Ltd.

KEYWORDS:

Affective neuroscience, Childhood parental loss (CPL), Endogenous opioids, Panic disorder pathophysiology

PMID:

24726574

[PubMed – as supplied by publisher]

via Lifelong opioidergic vulnerability thr… [Neurosci Biobehav Rev. 2014] – PubMed – NCBI.

 

Posted in Affective Neuroscience, Aging, China, development, epigenetics, Events, Fifth Avenue Concierge Medicine, Forensic Neuropsychiatry, Health, keto, News, Psychiatry/Neurology | Tagged , , , , , , , , , , , , , |

Metabolic features of the cell danger response. [Mitochondrion. 2013] – PubMed – NCBI

This is a really exciting integrative paper on the (clinically and heuristically relevant) hot topic du jour: Inflammation.  I came across it when I was researching Tourette’s syndrome and inflammation – am seeing increasing numbers of patients without a good explanation for their symptom exacerbation, with respiratory disease and low Vitamin D levels.

Mitochondrion. 2013 Aug 24. pii: S1567-7249(13)00239-0. doi: 10.1016/j.mito.2013.08.006. [Epub ahead of print]

Metabolic features of the cell danger response.

Abstract

The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis. The resulting metabolic mismatch between available resources and functional capacity produces a cascade of changes in cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid dynamics, bioenergetics, carbon and sulfur resource allocation, protein folding and aggregation, vitamin availability, metal homeostasis, indole, pterin, 1-carbon and polyamine metabolism, and polymer formation. The first wave of danger signals consists of the release of metabolic intermediates like ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species (ROS), and is sustained by purinergic signaling. After the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatory and regenerative pathways is activated to reverse the CDR and to heal. When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results. Metabolic memory of past stress encounters is stored in the form of altered mitochondrial and cellular macromolecule content, resulting in an increase in functional reserve capacity through a process known as mitocellular hormesis. The systemic form of the CDR, and its magnified form, the purinergic life-threat response (PLTR), are under direct control by ancient pathways in the brain that are ultimately coordinated by centers in the brainstem. Chemosensory integration of whole body metabolism occurs in the brainstem and is a prerequisite for normal brain, motor, vestibular, sensory, social, and speech development. An understanding of the CDR permits us to reframe old concepts of pathogenesis for a broad array of chronic, developmental, autoimmune, and degenerative disorders. These disorders include autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), asthma, atopy, gluten and many other food and chemical sensitivity syndromes, emphysema, Tourette’s syndrome, bipolar disorder, schizophrenia, post-traumatic stress disorder (PTSD), chronic traumatic encephalopathy (CTE), traumatic brain injury (TBI), epilepsy, suicidal ideation, organ transplant biology, diabetes, kidney, liver, and heart disease, cancer, Alzheimer and Parkinson disease, and autoimmune disorders like lupus, rheumatoid arthritis, multiple sclerosis, and primary sclerosing cholangitis.

© 2013. Published by Elsevier B.V. All rights reserved.

KEYWORDS:

Inflammation, Innate immunity, Mitochondria, Oxidative shielding, Oxidative stress, Purinergic signaling

PMID:
23981537
[PubMed – as supplied by publisher]

via Metabolic features of the cell danger response. [Mitochondrion. 2013] – PubMed – NCBI.

Posted in Complementary - Alternative Medicine, dietary, epigenetics, Events, Fifth Avenue Concierge Medicine, Health, keto, new treatments, News, Psychiatry/Neurology, Uncategorized | Tagged , , , , |

The top online health services for consumers | VentureBeat | Health | by Christina Farr

The top online health services for consumers | VentureBeat | Health | by Christina Farr.

Digital health is booming. A number of web-based and mobile service companies are bringing transparency to health care.

Instead of selecting a doctor based on a friend’s recommendation, you can now peruse anonymous reviews. Rather than calling a doctor’s office and waiting on hold, you can book an appointment online. And instead of paying exorbitant fees for a procedure, you can compare prices at different hospitals.

But how many of these tools do patients actually use, and how useful are they?

To separate reality from hype, VentureBeat has decided to create a top 10 index of online consumer health service technologies. To be clear, we’re not looking at fitness gadgets. This list focuses on web-based medical information services, like WebMD and ZocDoc.

The qualities we’re looking for are fairly straightforward. Companies and services on the index should be the following:

  • Innovative
  • Providing real value to consumers
  • Bridging gaps between multiple platforms
  • Validated by the market (i.e., patients like it)

The goal for this research is to do what VentureBeat does best: Cutting through the hype to determine whether these technologies are providing any real value to consumers.

To kick things off, we’ve compiled this initial list. This is not the final index; rather, we want you, our readers, to take a look at these companies and give us your feedback. If you use them already, we’d love to know how you use them. If you use something different that you think should be on our index, we definitely want to know about that!

Take a look at our initial suggestions and complete the survey to help us build a definitive index. We’ll publish the official index — perhaps after dropping some of these initial companies and adding others you suggest.

This index will be an ongoing project for VentureBeat. As the market continues to evolve, companies will fade off the list if they prove less valuable, and new companies may rise up to take their places.

WebMD

WebMD is still the largest source of medical information on the Web, according to ComScore. The site provides health information about dozens of conditions and feedback from certified physicians. As it’s been around since 1996, it’s one of the most established med-tech companies. But the business model has suffered in recent years, which resulted in the Atlanta-based company laying off 14 percent of its workforce. WebMD is facing the heat from newcomers to the space, like HealthTap and Everyday Health. Have you used WebMD? Take the survey and tell us if you’d recommend it.

Everyday Health

Everyday Health is a digital media company that owns and operates websites to provide health and wellness information. The website provides advice and support, health tips, and recipes, and it attracts about 30 million unique visitors. It even has a television series that airs on ABC each weekend. The company has been around since 2002 and competes with WebMD. Have you used Everyday Health? Take the survey and tell us if you’d recommend it.

Castlight Health

Castlight Health claims to be a leader in health care transparency. If you work for a large corporation, you’ve probably heard of it. Employers foot the bill so you can access information about the cost and quality of care, including physicians and hospitals. You can also shop for procedures and/ or book doctor’s visits.

Castlight is currently sees use from employees at household name companies like Honeywell and Kraft, and it’s likely to see more customers sign up as the Affordable Care Act takes effect. Castlight has raised a massive $181 million in venture funding, making it a strong contender for an initial public offering. Have you used Castlight Health? Take the survey and tell us if you’d recommend it.

HealthTap

HealthTap is a Silicon Valley-based Q&A site for consumers to ask health-related questions, and receive answers from certified physicians.

The focus is on slick design and ease of use — it was founded by Stanford graduate Ron Gutnam. The company claims that thousands of certified physicians and medical experts have already signed up, and this week, the startup heard from its 10,000th user who said the site saved her life.  Have you used HealthTap? Take the survey and tell us if you’d recommend it.

Microsoft HealthVault

Google attempted to build a consumer health platform — and it failed. This demonstrated how challenging it is to engage with patients between doctor’s visits. Microsoft’s service, HealthVault, is still ongoing. It’s a website to store health and fitness data that caters to care providers and patients. It’s designed so that you can easily port information from devices, including smartwatches, fitness gadgets, and blood pressure monitors.

Once HealthVault has compiled all this data, the next step will be to provide insights you can actually use. Microsoft isn’t the only company working on this; virtually all the household name technology and health companies are building data analysis tools.

Have you used HealthVault? Take the survey and tell us if you’d recommend it.

Patient Fusion

Patient Fusion is the consumer-focused offering from electronic medical record startup Practice Fusion, which books doctor appointments and browse reviews. The site only launched in April, but it already claims to have over 2.5 million reviews of doctors from patients.

Patient Fusion competes with New York-based ZocDoc, which also books doctor appointments on the web. Have you used Patient Fusion? Take the survey and tell us if you’d recommend it.

ZocDoc

New York-based ZocDoc is a website for patients to book doctor’s appointments. You can search for a doctor by specialty, location, and your insurance plan. ZocDoc has been around for six years, and its founder is Cyrus Massoumi, an entrepreneur who couldn’t find a specialist to see to his burst ear drum.

Today, 4 million patients use it each month, and it services population centers that account for 40 percent of the U.S. population. Have you used ZocDoc? Take the survey and tell us if you’d recommend it.

iTriage

Health insurance giant Aetna recently acquired the parent company behind iTriage, a new mobile and web application to help patients take charge of their health. Aetna is positioning iTriage as its “patient engagement” platform, meaning that it provides useful information.

iTriange is best known for its free symptom checker — it’s an easy way to find out whether a creepy-looking rash warrants a doctor’s visit. You can also use iTriage to locate the nearest hospital and book an appointment. Have you used iTriage? Take the survey and tell us if you’d recommend it.

PatientsLikeMe

PatientsLikeMe is a community-focused site for people to connect with others who share genetic conditions and diseases. For people with chronic conditions, the site also offers a tracking function so you can see how your health fares over time. The company was started by MIT mechanical engineers Jamie and Ben Heywood after their brother was diagnosed with ALS and they couldn’t find much support online.

PatientsLikeMe is a relative newcomer, but it has raised over $34 million in venture capital, and it’s one to watch. Have you used PatientsLikeMe? Take the survey and tell us if you’d recommend it.

Caring.com

Caring.com is a website for caregivers to find information about how to support aging relatives. The site provides tips and advice for managing medication and a search engine for finding nearby care providers. More than 50 million people in the U.S. care for someone over the age of 50, so it’s a huge market opportunity.

The company launched in 2007 by Jim Scott and Steve Fram, who worked at BabyCenter for over seven years. The company subsequently raised over $23 million in financing. Have you used Caring.com? Take the survey and tell us if you’d recommend it.

 

Posted in Events, Fifth Avenue Concierge Medicine, Health, keto, News, Uncategorized | Tagged , |