Medicine posts

August 2, 2010
08:00 AM
720 views

Pushing towards acknowledging sex differences in physiology and treatment efficacy

It is no surprise to many people that men and women are sometimes more susceptible to certain diseases than the other. By virtue of having differing anatomy, physiology, and gender expectations, we are going to be prone to different types of diseases, injuries, syndromes, and whatever-you-call-its. That being said, the majority of pathologies affect both men and women relatively equally. Despite that fact, rarely do clinical trials explore the difference in response to treatments based on sex. In 2008, Phyllis Greenberger wrote a letter to Science, Flaunting the Feminine Side of Research Studies, lamenting the fact that more studies didn't explore the effect of sex as a variable on treatment efficacy. To appropriately evaluate the success of women's representation in clinical trials, we must focus on the inclusion of women (and men) in studies of conditions that affect both sexes. Discussions of raw counts of overall research participation and inclusion of single-sex studies hide the fact that women's inclusion still lags in some key areas [...] Moreover, studies that include similar numbers of men and women rarely analyze or report the results by sex. This hampers our ability to understand the differences between men and women and to use this knowledge to improve health care outcomes.In response to this letter, Dr. Isis wrote a really excellent blog post detailing the complications involved in including women in cardiovascular clinical trials. Does Dr. Isis limit her research model because she secretly hates women (especially those hotter than her) and does not want to cure them? No, but she appreciates that the effects of estrogen on vascular function are hugely complex and temporally based. This stuff is so complex that people spend their careers studying it and there are all sorts of fancy books devoted to the topic. In the human studies Dr. Isis has been/is involved with, we have to be careful to study women in the context of their menstrual cycle. [...] I could not agree more with Ms. Greenberger that the inclusion of women in clinical research is vital to the understanding of our unique physiology and I applaud her for reminding us of this public health disparity. However, except in phase III or IV clinical trials where sample sizes may be sufficiently huge to allow for the inclusion of secondary endpoints and the splitting of populations for secondary analyses without devastating one's statistical power, splitting the populations of smaller, mechanistic studies can result in meaningless findings.There's no easy answer to this problem, especially in systems where the cycling of estrogen may be a confounding factor in treatment efficacy. Sex is not the only variable here, but also the levels of sex endocrines circulating through the system, which is dependent on each individual woman's place in her cycle at the time of treatment. Still, something has to be done, because not taking these variables into account can lead to a misleading conclusion about treatment efficacy.In Differences in Efficacy and Safety of Pharmaceutical Treatments between Men and Women: An Umbrella Review, published this month in PLoS ONE, Gartlehner et al. explored drug class reviews by the Drug Effectiveness Review Project to "determine whether clinically relevant differences in efficacy and safety exist between men and women when treated with commonly prescribed medications."[T]he exact differences between men and women at the genetic, cellular, or functional levels of the body are largely unknown. [...] Although differences in risks for and prognoses of several diseases have been well documented,, sex-based differences in responses to pharmaceutical treatments and accompanying risks of adverse events are less clear. Variations in absorption, distribution, metabolism, and excretion of pharmaceuticals between men and women have been investigated and demonstrated for various drugs. [...] The majority of these findings indicate differences on physiological, pharmacodynamic, or pharmacokinetic outcomes and are mostly attributed to hormonal fluctuations. Whether such findings translate into clinically relevant differences in efficacy and safety of pharmacological treatments remains undetermined.Unsurprisingly, they could only find studies that explored the effect of sex on treatment efficacy on 23% of the medications listed in the drug class reviews. Of that subsection, most of the medications had no significant difference in treatment efficacy between men and women. One difference they did find was that women respond less favorably than men to a relatively new class of antiemetics (5-HT3 antagonists) used to treat nausea in chemotherapy patients.During chemotherapy, serotonin is released by certain epithelial cells in the digestive tract. This serotonin goes back to the brain and stimulates the vagus nerve, which feeds to the medullary vomiting center. The medullary vomiting center is pretty cool, it's this little corner of your brain with the sole purpose of deciding whether or not you should be vomiting at any given time. The serotonin released in response to chemotherapy says to your brain, "Hey, you need to vomit now," and then you do. These 5-HT3 antagonists block the receptor for serotonin, so the message isn't received by the medullary vomiting center, and you get to keep your breakfast. (Interestingly, these drugs don't seem to work in response to motion sickness, just chemical stimulation.)Unfortunately for women, there's pretty clear evidence that men are more likely to see a positive result from these antiemetics than women:(Click to enlarge)58% of men, compared to 45% of women, responded favorably to prophylactic treatment with this class of antiemetics prior to chemotherapy. The mechanism underlying why this happens is unknown, but this is clear evidence that even in systems that don't directly involve endocrine cycling, men and women can still display different responses to treatments. The authors also found that women are more likely to experience adverse effects from statin medications, and that men are more likely to experience sexual dysfunction from second-generation antidepressants than women. Bear in mind that these findings are based on less than 1/4th of the drug classes reviewed by the Drug Effectiveness Review Project, because the vast majority of studies didn't even consider sex differences as a variable in treatment efficacy! Incorporating the effect of sex and endocrine cycling can be problematic for an investigator, as Dr. Isis describes in her post linked above, but even still she realizes the importance of doing it anyway whenever possible. At the end of the day, men and women are different, physiologically speaking, and clinical trials that do not attempt to address this fact somewhere along the line of treatment development are doing us all a disservice.Greenberger, P. (2008). Flaunting the Feminine Side of Research Studies Science, 322 (5906), 1325-1326 DOI: 10.1126/science.322.5906.1325b... Read more »

Greenberger, P. (2008) Flaunting the Feminine Side of Research Studies. Science, 322(5906), 1325-1326. DOI: 10.1126/science.322.5906.1325b

Gartlehner, G., Chapman, A., Strobelberger, M., & Thaler, K. (2010) Differences in Efficacy and Safety of Pharmaceutical Treatments between Men and Women: An Umbrella Review. PLoS ONE, 5(7). DOI: 10.1371/journal.pone.0011895

August 1, 2010
06:04 PM
900 views

Man as "Monkeys Wearing Pants": Why Humans Make Poor Money Choices

by William Yates, M.D. in Brain Posts

I don't read many economic blogs but one I do follow is Barry Rithholtz's The Big Picture. Barry acknowledges the limitations of human decision making and knowledge. His economic approach is a refreshing humbleness. He has stated that we need to remember that man is not far removed from our primate ancestors---we are basically "monkeys wearing pants". Understanding this, his investment approach is to know that all decisions may be influenced by bias of our monkey-based brain.This last week he posted a TED talk from Dr. Laurie Santo, a Yale University primate researcher. She basicly re-interates some of Rithholtz's claims based on her work with primates. Her primate lab has developed a way to see how monkeys make value decisions that involve money. The presentation is 19 minutes long. If you don't have time to view, I have posted by notes here:Notes on Laurie Santos' TED talk: A Monkey Economy As Irrational As OursTwo important observations about homo sapiens:1. Homo sapiens is really smart (and vain)2. We can be incredibly dumb and make dumb mistakes decisions and systems promoting environmental deterioration decisions and systems leading to global financial market collapseThe errors we make are predictable and persistentThis may be due to one of two reasons:Our environments are designed badly and we just need to redesign the environmentOur minds are designed badly--a more concerning, less manageable situation.Stantos' lab uses the brown capuchin monkeys species-New World primatesA question the have addressed is: "How can we get monkeys to simulate money-making decisions?"Monkeys are taught to use tokens to buy pieces of foodMonkeys are placed in a money marketplaceGiven wallet of tokensProvided choice at what to buyQualitatively and quantitatively the monkeys make decisions matching with the human marketplaceMonkeys did not saveMonkeys steal tokens from other monkeys and humansMonkeys show two decison-making biases Relativity--risk taking is not symmetrical Loss Aversion-we are less likely to risk if loss is involved than if gain is involvedHowever, this loss aversion bias actually at times increases risk for a bad outcomes, i.eHolding on to stock lossesFailure to take lower price on home you ownSo human decision-making biases may be part of our evolutionary developmentIf an evolutionary bias, they may be very difficult to overcome.The good news is that we can recognize our limitations, accept them and try to design an environment that reduces their effectComment: I wonder if in the example given, if risk aversion to loss relates to prioritizing choices that limit risk of starvation. If this is a basic strategy, a monkey would choose an option where two grapes are guaranteed and a chance of one grape (and starvation risk) is avoided. It is concerning that there may some other types of decisions we make might also be rooted in core evolutionary biases. Here, I thinking about choices to go to war and choices to stay in wars despite evidence of failure to make progress.Link to Dr. Santos' LabSantos LR, & Hughes KD (2009). Economic cognition in humans and animals: the search for core mechanisms. Current opinion in neurobiology, 19 (1), 63-6 PMID: 19541475... Read more »

Santos LR, & Hughes KD. (2009) Economic cognition in humans and animals: the search for core mechanisms. Current opinion in neurobiology, 19(1), 63-6. PMID: 19541475

July 31, 2010
10:44 AM
734 views

Feel like I-dosing?

by Henkjan Honing in Music Matters

A few months ago my facebook friends in the US started mentioning it. Only a few weeks later it appeared in the news in Europe, generating a lot of noise in Belgium last week when I-dosing or ‘binaural beats’ were condemned as a form of narcotics.The phenomenon of ‘binaural beats’ was first described in 1839 by Heinrich Wilhelm Dove. It is the sensation of hearing interference beats when two slightly different frequencies are played separately to each ear. The rate of the ‘perceived’ beats were claimed to modulate ones brain waves. However, little or no evidence has been brought forward since then. The few studies that seriously studied the effect could not support this claim (e.g., Owens et al., 1998), except that that it might have some effect on attention and arousal. Quite understandable, if you listen to one of the examples (see link).The recent media attention for this phenomenon seems to be successfully bootstrapped by a new company selling mp3’s with titles like ‘Quick Hit Simulations’ describing their product with statements like ‘binaural beats will synchronize your brainwaves and help you achieve a quick hitting simulated drug simulation.’ Prices around twenty dollar. This one's for free :-)Owens, J. et al. (1998). Binaural Auditory Beats Affect Vigilance Performance and Mood. Physiology & Behavior, 63 (2), 249-252. DOI: 10.1016/S0031-9384(97)00436-8.... Read more »

Owens, J. (1998) Binaural Auditory Beats Affect Vigilance Performance and Mood. Physiology , 63(2), 249-252. DOI: 10.1016/S0031-9384(97)00436-8

July 30, 2010
11:26 AM
872 views

Somatic Mutations in Four Human Cancers

by Daniel Koboldt in Massgenomics

In a letter to Nature this week, a group from Genentech presents an elegant analysis of 2,576 somatic mutations across 441 tumors comprised of breast, lung, ovarian, and prostate cancer types and subtypes. Using something called “mismatch repair detection” (MRD) technology, the authors surveyed 1,507 candidate genes spanning some 4 megabases of sequence, largely comprised [...]... Read more »

Kan Z, Jaiswal BS, Stinson J, Janakiraman V, Bhatt D, Stern HM, Yue P, Haverty PM, Bourgon R, Zheng J.... (2010) Diverse somatic mutation patterns and pathway alterations in human cancers. Nature. PMID: 20668451

July 30, 2010
09:07 AM
880 views

Donating Eggs from an Anoxic Brain Injury Patient?

by Brian McMichael, MD in Pallimed: a Hospice & Palliative Medicine Blog

focused on an ethical dilemma at end-of-life. It got coverage in the mainstream media as well, about a women who collapsed on an airplane with a pulmonary embolism, had severe anoxic brain injury, and the family requested her oocytes be harvested.... Read more »

Greer DM, Styer AK, Toth TL, Kindregan CP, & Romero JM. (2010) Case records of the Massachusetts General Hospital. Case 21-2010. A request for retrieval of oocytes from a 36-year-old woman with anoxic brain injury. The New England journal of medicine, 363(3), 276-83. PMID: 20647203

July 30, 2010
12:41 AM
777 views

Friday Weird Science: HEY GUYS, I’M SO DRUNK RIGHT NOW!!!!

by Scicurious in Neurotic Physiology

You know how it is when you’re in college (or high school). You’ve got that one kid (and yes, it has at some point been you) who’s never had a drink before, and they go to a party. You have a few drinks, they have a few drinks, and pretty soon, even though they have [...]... Read more »

Upile, T., Sipaul, F., Jerjes, W., Singh, S., Nouraei, S., El Maaytah, M., Andrews, P., Graham, J., Hopper, C., & Wright, A. (2007) The acute effects of alcohol on auditory thresholds. BMC Ear, Nose and Throat Disorders, 7(1), 4. DOI: 10.1186/1472-6815-7-4

July 29, 2010
03:00 PM
866 views

Making Sense of Sense

by Lorimer Moseley in BodyInMind

The roads less travelled – four paths to get from touch to the body I am studying medicine and as part of our course we do an Independent Learning project. I am doing mine in the Body in Mind research group here at NeuRA. My first task is to review a key paper in the [...]... Read more »

Serino A, & Haggard P. (2010) Touch and the body. Neuroscience and biobehavioral reviews, 34(2), 224-36. PMID: 19376156

July 29, 2010
01:12 PM
705 views

Global vs Local Cognitive Style in Autism: Central Coherence

by William Yates, M.D. in Brain Posts

The cognitive style known as central coherence is receiving increased attention across a variety of clinical neuroscience disorders. I had not been familiar with this concept of central coherence. Essentially, central coherence describes a style of thinking on a spectrum. On one end of the spectrum, you have individuals who tend to think globally or using a gestalt perspective. The big picture is seen rather than paying attention to details. The other end of spectrum includes individuals who are detail-oriented. Their perspective bias is to focus on details.Being on either extreme of the spectrum can produces problems. Very high central coherence can lead to problems with missing important details that need attention or action. Those with very low or weak central coherence can be detail bound, losing sight of important global interpretations of the situation or environment. The imaging correlates of coherence are being explored. Higher central coherence appears to involve increased right and left brain activation with problem-solving. Weak central coherence has been accompanied by less bilateral activation with tasks.Children and adults with autism spectrum appear to have weak central coherence and are overly focussed on details to the expense of a global perspective. This could explain typical autistic behaviors such as valuing sameness, attending to parts of objects and persistence in behaviors related to details.Rhonda Booth and Francesa Happe from the Social, Genetic and Developmental Psychiatry Centre at the Institute of Psychiatry in London have published a study of central coherence in children with autism, ADHD and controls.There study involved a simple sentence completion task. The example provided is--Complete this sentence "Hunting with a knife and". Child with weak central coherence typically finish this sentence with "fork". Normals tend to expand on a global response like "catch a bear". The authors tested a ten question Sentence Completion Task with the following findings:Completion scores (central coherence) increased with age--children younger than 13 had lower completion scoresMost (but not all) children with autism showed weak central coherence on the task (more local error responses)Children with ADHD did not differ from controls on the taskInhibition difficulties did not increase the weak coherence local response ratesThe authors conclude "the Sentence Completion Task appears to be a simple and easy-to-administer test capable of tapping local processing bias, or weak coherence, in a range of populations". You will likely be hearing more about the neuropsychological concept of coherence in a variety of studies across the clinical neuroscience disorders.Photo of Electrical Power Line Fire Courtesy of Yates PhotographyBooth, R., & Happé, F. (2010). “Hunting with a knife and … fork”: Examining central coherence in autism, attention deficit/hyperactivity disorder, and typical development with a linguistic task Journal of Experimental Child Psychology DOI: 10.1016/j.jecp.2010.06.003Lee PS, Foss-Feig J, Henderson JG, Kenworthy LE, Gilotty L, Gaillard WD, & Vaidya CJ (2007). Atypical neural substrates of Embedded Figures Task performance in children with Autism Spectrum Disorder. NeuroImage, 38 (1), 184-93 PMID: 17707658... Read more »

Booth, R., & Happé, F. (2010) “Hunting with a knife and … fork”: Examining central coherence in autism, attention deficit/hyperactivity disorder, and typical development with a linguistic task. Journal of Experimental Child Psychology. DOI: 10.1016/j.jecp.2010.06.003

Lee PS, Foss-Feig J, Henderson JG, Kenworthy LE, Gilotty L, Gaillard WD, & Vaidya CJ. (2007) Atypical neural substrates of Embedded Figures Task performance in children with Autism Spectrum Disorder. NeuroImage, 38(1), 184-93. PMID: 17707658

July 29, 2010
07:28 AM
936 views

Dendreon's sipuleucel-T data from the IMPACT trial shows no surprises

by Sally Church in Pharma Strategy Blog

Yesterday was a travel day but thanks to gippy wifi and a packed day, I didn't have the opportunity to post about some interesting articles on prostate cancer published in the NEJM, which I read and digested on the train...... Read more »

Kantoff, P., Higano, C., Shore, N., Berger, E., Small, E., Penson, D., Redfern, C., Ferrari, A., Dreicer, R., Sims, R.... (2010) Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer. New England Journal of Medicine, 363(5), 411-422. DOI: 10.1056/NEJMoa1001294

Longo, D. (2010) New Therapies for Castration-Resistant Prostate Cancer. New England Journal of Medicine, 363(5), 479-481. DOI: 10.1056/NEJMe1006300

July 28, 2010
02:46 PM
685 views

Models for the evolution of bacterial resistance

by Lab Rat in Lab Rat

I wrote about Quorum Sensing recently, the ability of bacteria to communicate with each other via small molecules which they can both excrete and sense. A lot of the research done on quorum sensing aims to find ways to block the system, as it is one of the main communication methods used to switch on virulence genes, and other genes which make the bacteria more infectious, and more likely to cause harm.Blocking quorum sensing would not in theory kill the bacteria, but it would give more time for the bodies immune system to recognize and destroy the bacteria. This is starting to be a more common approach in the design of anti-microbials, and in virus vaccines. A slower and less virulent form of both virus's and bacteria can sometimes be dealt with easily enough by the body's own immune system as it has more time to respond to the invading challenge.There is also an evolutionary reason for the effectiveness of quorum sensing disruption over conventional antibiotics. Antibiotics kill off any bacteria that aren't resistant, creating a highly competitive growth environment with a large selection bias against non-resistant bacteria. Disrupting the quorum sensing system on the other hand should mean that the bacteria are still growing in a non-selecting environment, right up to the point where the body's defense system kills them off. There is less evolutionary pressure on them to develop resistance.A paper in PLoS (reference below) looked at developing a method for how (and whether) resistance towards quorum sensing disruption might occur. They chose to base their model on the effects of altering the genes involved in quorum sensing, rather than other methods for quorum sensing disruption, such as blocking or destroying the little molecules used for signalling and one of the first things they found was that there are a large number of variations in these genes, despite the fact that many of the actual signalling molecules are fairly similar.Lots of gene variation means bad news for gene-based disruption as there is potential for the bacteria to share these genes among themselves, and thus potentially end up with a combination that renders the gene-blocking anti-bacterial invalid. And swopping genes is one of the things bacteria do best. Figure above shows two bacteria connecting together via a long thread-like molecule called a 'pilus'. The genes do not actually travel through the pilus, but the pilus pulls both bacteria close together allowing the gene (in the form of a plasmid) to be passed between them.Another thing that was examined was the effect of quorum sensing disruption on fitness. The idea that resistance to quorum sensing (which will henceforth be called QS as I can't be bothered to keep typing it out) will take more time to develop is based heavily on the idea that tampering with the QS does not affect the general health of the bacteria. Sure it prevents bacteria from communicating, but each individual bacteria is no less likely to thrive, and therefore there is less selection pressure.However almost all of these experiments (certainly those in academic labs) have been done in conditions of nice safe uber-rich bacterial growth media. Even slightly shaken bacteria may thrive fine on nutrient rich agar. Inside an actual living organism though (the normal living place of pathogenic bacteria) disrupting the QS system has major implications. Not just in the fact that non QS-able organisms are often outcompeted by other bacteria, but also because some QS-controlled proteins seem (under certain conditions) to be vital for bacterial growth. If disruption of QS is leading to bacterial death then this puts a massive evolutionary pressure on bacteria to evolve resistance, similar to the pressure to evolve antibiotic resistance.Interestingly (if slightly off topic) it is vaguely suggested that the necessity of QS for growth might help to prevent 'cheaters' within a bacterial population; bacteria that take up all the benefits of it's QS-ing neighbors (i.e biofilm formation, increased virulence etc) without having to expend energy into the QS system.In view of this data it looks as if, despite it's undoubtable advantages as an antimicrobial, QS-disrupting systems will inevitably succumb to bacterial resistance. In the presence of a selective pressure favoring it resistance will always develop. There is no golden bullet for antibacterial strategies, just a lot of little silver bullets that eventually loose their power.So as not to end this on a depressing note, it is worth mentioning that the fact that there is a lot of research going into alternative (i.e not antibiotics) antimicrobials is encouraging. Phage therapy and QS disruption will probably never replace antibiotic therapy, but it is worth having as many different strategies as possible to deal with the threat of bacterial infection.---Defoirdt T, Boon N, & Bossier P (2010). Can bacteria evolve resistance to quorum sensing disruption? PLoS pathogens, 6 (7) PMID: 20628566---Follow me on Twitter!... Read more »

Defoirdt T, Boon N, & Bossier P. (2010) Can bacteria evolve resistance to quorum sensing disruption?. PLoS pathogens, 6(7). PMID: 20628566

July 28, 2010
12:32 PM
1,141 views

Paleo Diet and Diabetes: Improved Cardiovascular Risk Factors

by Steve Parker, M.D. in Diabetic Mediterranean Diet Blog

Compared to a standard diabetic diet, a Paleolithic diet improves cardiovascular risk factors in type 2 diabetics, according to investigators at Lund University in Sweden. Researchers compared the effects of a Paleo and a modern diabetic diet in 13 type 2 diabetic adults (10 men) with average hemoglobin A1c’s of 6.6% (under good control, then). Most [...]... Read more »

Jönsson, T., Granfeldt, Y., Ahrén, B., Branell, U., Pålsson, G., Hansson, A., Söderström, M., & Lindeberg, S. (2009) Beneficial effects of a Paleolithic diet on cardiovascular risk factors in type 2 diabetes: a randomized cross-over pilot study. Cardiovascular Diabetology, 8(1), 35. DOI: 10.1186/1475-2840-8-35

July 28, 2010
08:15 AM
981 views

Mothers and Fathers with Alcoholism and Their Children

by William Yates, M.D. in Brain Posts

Being a child of a parent with alcoholism significantly increases your risk for alcoholism as well as other mental disorders. This risk is most likely moderated by a complex interaction between genetic factors and environmental effects.Clinicians typically classify family (and parental) history of alcoholism as being present or absent. But the family history of alcoholism is more complex than that. One issue that has received limited attention is the specific parent-child gender effects. Simply put, children of alcoholic parents can be one of six possible relationships:son with alcoholic fatherson with alcoholic motherson with both parents with alcoholismdaughter with alcoholic fatherdaughter with alcoholic motherdaughter with both parents with alcoholismMorgan and colleagues at Yale University have recently published some data on parent-child gender effects. They examined prevalence rates for alcoholism and mental disorders in men and women who had a father or mother with alcoholism. Data for this study came from the U.S. National Epidemiologic Survey of Alcohol and Related Conditions (NESARC). This data set is large with over 40,000 in the survey.Approximately 20% of the sample reported a paternal history of alcoholism while abut 5% reported a maternal history of alcoholism.A parental history of alcoholism typically increased for almost every mental disorder studied. The odds ratio of a substance use disorder increased about two to three times. Mood and anxiety disorder odds ratios typically increased by 1.5 to 2 indicating about a 50 to 100% increase in risk.For specific parent-child gender dyads, the studies main findings included:Female children with mothers with alcoholism generally experienced the most adult psychopathologyRates of mania were particularly high in female children of mothers with alcoholism and male children of fathers with alcoholismRates of alcohol abuse were particularly high for female children of fathers or mothers with alcoholismRates of nicotine dependence were particularly high for female children of mothers with alcoholismRates of panic disorder were particularly high for male children of alcoholic mothersThe authors note that a limitation of the study was an inability to adjust for psychiatric comorbidity in the parents. Parents with alcoholism are likely to have a higher rate of mood and anxiety disorders than parents without alcoholism.This study was unable to look at the effects of parental alcoholism in both parents. It is likely such a family history would have an even greater risk of offspring psychopathology.This study will alert clinicians that a positive parental history of alcoholism is only a starting point for exploring risk of psychopathology. Clinicians should pay specific attention to the parent gender and to the offspring gender in a comprehensive assessment.Despite these findings, it is likely that many with a parental history of alcoholism will grow up to productive lives and not have significant impairment or significant psychological problems. Insufficient attention has been paid to the role of resilience in modifying genetic and environmental risks associated with a parental history of alcoholism.Photo of Horse Racing Painting Courtesy of Yates PhotographyMorgan PT, Desai RA, & Potenza MN (2010). Gender-Related Influences of Parental Alcoholism on the Prevalence of Psychiatric Illnesses: Analysis of the National Epidemiologic Survey on Alcohol and Related Conditions. Alcoholism, clinical and experimental research PMID: 20645936... Read more »

Morgan PT, Desai RA, & Potenza MN. (2010) Gender-Related Influences of Parental Alcoholism on the Prevalence of Psychiatric Illnesses: Analysis of the National Epidemiologic Survey on Alcohol and Related Conditions. Alcoholism, clinical and experimental research. PMID: 20645936

July 28, 2010
02:30 AM
1,851 views

How do doctors cope?

by Dr Shock in Dr Shock MD PhD

Often I will tell my residents that if you can’t take care of yourself how do you expect to take care of your patients. Or in another way: the only difference between God and a doctor is that God knows he’s not a doctor. These sound like cliches but there is some truth in them. [...]

Related posts:Attachment Theory and Poorly Performing Doctors
Doctors reactions to memorable patients deaths’
Have mercy on the NHS Doctors
... Read more »

Jane B Lemaire, & Jean E Wallace. (2010) Not all coping strategies are created equal: a mixed methods study exploring physicians' self reported coping strategies. BMC Health Services Research. info:/10.1186/1472-6963-10-208

July 27, 2010
03:00 PM
1,065 views

When showing it doesn’t work doesn’t work

by Lorimer Moseley in BodyInMind

I went to Melbourne on the weekend. To break the time-honoured Moseley tradition of not working on weekends requires some convincing and I was convinced by the nature of the crowd – truly interdisciplinary – and the proximity of venue – a mere 1000 km away. I went to two talks, so I could get [...]... Read more »

Buchbinder, R., Osborne, R., Ebeling, P., Wark, J., Mitchell, P., Wriedt, C., Graves, S., Staples, M., & Murphy, B. (2009) A Randomized Trial of Vertebroplasty for Painful Osteoporotic Vertebral Fractures. New England Journal of Medicine, 361(6), 557-568. DOI: 10.1056/NEJMoa0900429

Bruce A. Levy. (2010) Is Early Reconstruction Necessary for All Anterior Cruciate Ligament Tears?. New England Journal of Medicine , 386-388. info:other/

July 27, 2010
11:00 AM
525 views

LOW BACK PAIN: Can low back pain be treated with hope?

by Paul Ingraham in SaveYourself

My short answer is: yes, and I call it “the confidence cure” (see The Mind Game In Low Back Pain). But it’s a deliciously complex subject. Steve Kamper writing for Body in Mind raises a number of good questions:

… just pump up the expectation volume and you get extra bang for your treatment buck. But what if the expectation effect is all you are getting?

A nice little read for therapists.

Steve Kamper for Body In Mind: What did you expect? Hands-up who thinks a patient’s expectations influence how well they do in treatment?

... Read more »

[1] Tilburt JC, Emanuel EJ, Kaptchuk TJ, Curlin FA, & Miller FG. (2008) Prescribing "placebo treatments": results of national survey of US internists and rheumatologists. BMJ (Clinical research ed.). PMID: 18948346

[2] Amanzio M, Pollo A, Maggi G, & Benedetti F. (2001) Response variability to analgesics: a role for non-specific activation of endogenous opioids. Pain, 90(3), 205-15. PMID: 11207392

[3] Machado LA, Kamper SJ, Herbert RD, Maher CG, & McAuley JH. (2009) Analgesic effects of treatments for non-specific low back pain: a meta-analysis of placebo-controlled randomized trials. Rheumatology (Oxford, England), 48(5), 520-7. PMID: 19109315

[6] Nunn, R. (2009) It's time to put the placebo out of our misery. BMJ, 338(apr20 2). DOI: 10.1136/bmj.b1568

July 27, 2010
10:19 AM
1,210 views

Bowel cancer cells forget which way is ‘up’

by Cancer Research UK in Cancer Research UK - Science Update

The cells in our bodies are highly organised – from our lungs to our liver, every cell knows its place and its job, helping to keep us healthy. But cancer cells don’t obey the rules – they ignore the body’s regulations and grow out of control. Now research from Dr Inke Nathke and her team [...]... Read more »

Quyn, A., Appleton, P., Carey, F., Steele, R., Barker, N., Clevers, H., Ridgway, R., Sansom, O., & Näthke, I. (2010) Spindle Orientation Bias in Gut Epithelial Stem Cell Compartments Is Lost in Precancerous Tissue. Cell Stem Cell, 6(2), 175-181. DOI: 10.1016/j.stem.2009.12.007

July 27, 2010
10:01 AM
1,508 views

Abnormal Circulating Cells in Lung Cancer Patients: Possible New Technique for Identification

by Sally Church in Pharma Strategy Blog

A while back I wrote about how circulating tumour cells (CTC's) see here and here, can be used as a potential new surrogate measure for prostate cancer, so it was with great interest that I read an excellent article (free...... Read more »

Katz, R., He, W., Khanna, A., Fernandez, R., Zaidi, T., Krebs, M., Caraway, N., Zhang, H., Jiang, F., Spitz, M.... (2010) Genetically Abnormal Circulating Cells in Lung Cancer Patients: An Antigen-Independent Fluorescence In situ Hybridization-Based Case-Control Study. Clinical Cancer Research, 16(15), 3976-3987. DOI: 10.1158/1078-0432.CCR-09-3358

July 27, 2010
07:00 AM
747 views

Caloric restriction as a treatment for malignant brain tumors

by EcoPhysioMichelle in C6-H12-O6 (old)

Caloric restriction (CR), which is significantly limiting the intake of food, has been known to increase lifespan and have a reducing effect on non-invasive tumors. CR limits blood glucose levels and forces the body to dip into its fat reserves for energy. These fat deposits are broken down into ketones, which provide an alternate source of fuel for the electron transport chain in the mitochondria. [...]... Read more »

Shelton, L., Huysentruyt, L., Mukherjee, P., & Seyfried, T. (2010) Calorie restriction as an anti-invasive therapy for malignant brain cancer in the VM mouse. ASN NEURO, 2(3), 171-177. DOI: 10.1042/AN20100002

July 26, 2010
05:17 PM
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Why People Believe Weird Things

by William Yates, M.D. in Brain Posts

Michael Schermer, the publisher of Skeptic magazine recently presented at TED looking at why humans tend to be open to self-deception. Some appear to be more vulnerable. He proposes this vulnerability is related to the brain's role in pattern recognition and detecting meaningful signal against a back drop of noise.I've linked to the TED video here and it is about 19 minutes. It is pretty entertaining along with being informative. If you don't want to view the video, I've summarized my notes from the talk here: The brain is a Belief engine: pattern seeking primates thrive on association learning Beliefs can be false and result in making poor decisionsThe brain's wiring contributes to risk in belief in strange and paranormal ideasThe brain prioritizes patternicity--the tendency to find meaningful patterns in both meaningful and meaningless noise.But beliefs are open to type I (false positive) and Type II errors (false negative). Patternicity can break down when cost of a type I error is less than the cost of making a type II error.Thd efault position is to assume all patterns are real and importantAnterior cingulate cortex in the brain modulates pattern recognitionPattern seeking increases when you feel out of controlPeople who have high belief in the paranormal more likely to find meaningless patternsRight brain hemisphere is more pattern effectiveDopamine increases pattern recognitionAntipsychotics reduce patternicity. Psychosis is false pattern recognition.Dopamine increases signal to noise ratios. Facial recognition is highlighted in the brain and is a human pattern biasFusiform gyrus in the brain is a key area for facial recognitionAgenticity: Tendency to infuse patterns with meaning, intention, and agency, often invisible beings and from the top down. Responsible for belief in aliens, supernatural and religious beliefs Temporal lobe stimulation produces euphoric out of body experience. The power of expectation and power of belief strongly influence or pattern perception.Krummenacher and colleagues from Switzerland have recently published a study of dopamine, paranormal belief and detecting meaningful stimuli.They examined a group of believers with paranormal experiences and a group of skeptics. L-dopa administration made skeptics less conservative in their decision making but made believers more conservative. They suggest that paranormal ideation is "an important personality dimension and needs to be assessed in investigations on the detection of signals in noise".The tendency to have a bias toward paranormal and suspicious ideas is noted in the description of schizotypal personality disorder. I would agree that this is a domain and personality characteristic that probably does not receive enough attention. Krummenacher P, Mohr C, Haker H, & Brugger P (2010). Dopamine, paranormal belief, and the detection of meaningful stimuli. Journal of cognitive neuroscience, 22 (8), 1670-81 PMID: 19642883... Read more »

Krummenacher P, Mohr C, Haker H, & Brugger P. (2010) Dopamine, paranormal belief, and the detection of meaningful stimuli. Journal of cognitive neuroscience, 22(8), 1670-81. PMID: 19642883

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