The value of pre-operative treatment with GnRH analogues in women with submucous fibroids: a double-blind, placebo-controlled randomized trial

BACKGROUND

Submucous fibroids are common benign tumours responsible for menorrhagia, subfertility and miscarriage. They can be readily removed by hysteroscopic transcervical resection of myoma (TCRM). To facilitate resection, pre-operative GnRH analogues have been suggested, but the value of this treatment is uncertain. Our aim was to assess the value of pre-operative GnRH analogues for the resection of submucous fibroids.

METHODS

This was a prospective, double-blind, placebo-controlled, randomized trial. Women found to have submucous fibroids on three-dimensional saline infusion sonohysterography (3D SIS) were randomized to receive GnRH or placebo. Following treatment patients underwent TCRM by a single operator blinded to the group allocation. Women were followed up 6 weeks after their operation to ascertain resolution of symptoms. The primary outcome measure of the study was completeness of fibroid resection. Secondary outcome measures included the duration of the TCRM, the fluid deficit recorded at TCRM, the resolution of symptoms post-operatively and the number of subsequent fibroid related operations.

RESULTS

Forty-seven women were randomized to GnRH or placebo. On the basis of intention-to-treat analysis, there was no significant difference in the number of complete fibroid resections between women who received GnRH analogues [14/24, 58.3% (95% CI 38.6–78.1)] and those who received placebo [16/23, 69.6% (50.8–88.4)] (RR 0.84, 95% CI 0.54–1.29; P = 0.43). Similarly there was no significant difference between the groups in any of the secondary outcome measures.

CONCLUSIONS

Our study does not support routine administration of GnRH analogues before transcervical resection of fibroid as we did not identify any benefit in such treatment.

Controlled-trials.com: ISRCTN06560767.

Up-regulation of apoptosis by gonadotrophin-releasing hormone agonist in cultures of endometrial cells from women with symptomatic myomas

BACKGROUND

The aim of the present study was to evaluate the effect of gonadotrophin-releasing hormone agonist (GnRH-a), which is widely used in the medical treatment of symptomatic myomas, on the rate of endometrial cell apoptosis in cultures from women with symptomatic myomas.

METHODS

The study included 36 women with symptomatic myomas without endometrial hyperplasia or endometrial carcinoma, and 22 controls. Endometrial biopsy specimens were obtained from all subjects. Levels of apoptosis were examined in epithelial endometrial cell cultures before and after incubation with GnRH-a (triptorelin). The percentage of apoptotic cells was evaluated using the terminal deoxynucleotidyl transferase-mediated d-UTP nick end labeling assay and flow cytometry was used to evaluate Annexin V levels.

RESULTS

Levels of spontaneous apoptosis were significantly lower in endometrial cultures from patients with symptomatic myomas than in those from control subjects (P < 0.01). Concentrations as low as 10–7 M GnRH-a enhanced apoptosis in endometrial cultures from patients with symptomatic myomas (3.48% ± 0.27% apoptotic cells in untreated samples and 25.45 ± 0.95% in cells treated with 10–7 M GnRH-a; P <0.01). The percentage of apoptotic cells also increased when cultures from control women were treated with GnRH-a (8.10 ± 0.18% in untreated samples and 15.29 ± 2.30% in treated samples; P <0.01). Levels of apoptosis were dependent on both dose of GnRH-a and time of treatment.

CONCLUSIONS

GnRH-a stimulates apoptosis in endometrial cells from patients with symptomatic myomas and this could, at least in part, account for the therapeutic action of GnRH-a.

Adnexal torsion: a predictive score for pre-operative diagnosis

BACKGROUND

Adnexal torsion (AT) is difficult to diagnose and requires immediate surgery. The aim of this study was to develop a simple score for assisting in the pre-operative diagnosis of AT in women with acute pelvic pain.

METHODS

Using data from a retrospective cohort of 142 patients with acute pelvic pain, we developed a score based on multiple logistic regression after a jackknife procedure. We validated the score in a prospective cohort of 35 women with acute pelvic pain.

RESULTS

Five criteria were independently associated with AT confirmed by surgery: unilateral lumbar or abdominal pain [adjusted odds ratio (aOR), 4.1; 95% confidence interval (95% CI), 1.2–14.0]; pain duration <8 h at first presentation (aOR, 8.0; 95% CI, 1.7–37.5), vomiting (aOR, 7.9; 95% CI, 2.3–27.0), absence of leucorrhoea and metrorrhagia (aOR, 12.6; 95% CI, 2.3–67.6) and ovarian cyst larger than 5 cm by ultrasonography (aOR, 10.6; 95% CI, 2.9–38.8). The torsion score was based on these five criteria. Low-risk and high-risk groups were derived from values of the score [probability of AT, 3.7% (95% CI, 0–7.8) and 69% (95% CI, 53–84), respectively]. Application of these criteria to the prospective cohort confirmed the diagnostic accuracy of the score [probability of AT, 0% (95% CI, 0–16) and 75% (95% CI, 26–100) in the low-risk and high-risk groups, respectively].

CONCLUSIONS

This easy-to-calculate score may prove useful for diagnosing AT in patients with acute pelvic pain seen at general or gynaecology emergency departments.

Investigating the Aging of Stem Cells

From the Korea Times: “Stem cells, or early-stage cells that retain the potential to turn into other specialized types of cells, are intriguing for their immense potential in treating a wide range of difficult diseases and conditions. And holding an important key to such innovations would be adult stem cells, which are taken from mature tissue, as they could theoretically be taken from patients, grown in culture and transplanted back into the patient without the fear of provoking an immune response. … The downside of adult stem cells, however, is that they age much faster than embryonic cells, which has limited their usefulness in transplants. … It has been presumed that the decreasing regenerative capacity of adult stem cells, which is linked to their aging, is a result of inborn genetic variations. But [researchers suggest] that the process isn’t dictated by heritable events, such as DNA damage, but rather determined by an ‘epigenetic’ regulation of gene expression. … There weren’t many studies on finding micro-RNAs related to the aging of cells and learn how they affect stem cells, but this area could be important in developing a way to have adult stem cells retain their normal ability for a longer time.”

View the Article Under Discussion: http://www.koreatimes.co.kr/www/news/tech/2010/08/133_71494.html

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

What We Know About Fat Tissue and Longevity

In a nutshell: “Adipose tissue accounts for approximately 20% (lean) to [more than] 50% (in extreme obesity) of body mass and is biologically active through its secretion of numerous peptides and release and storage of nutrients such as free fatty acids. Studies in rodents and humans have revealed that body fat distribution, including visceral fat (VF), subcutaneous (SC) fat and ectopic fat are critical for determining the risk posed by obesity. Specific depletion or expansion of the VF depot using genetic or surgical strategies in animal models has proven to have direct effects on metabolic characteristics and disease risk. In humans, there is compelling evidence that abdominal obesity most strongly predicts mortality risk, while in rats, surgical removal of VF improves mean and maximum life span. There is also growing evidence that fat deposition in ectopic depots such as skeletal muscle and liver can cause lipotoxicity and impair insulin action. Conversely, expansion of SC adipose tissue may confer protection from metabolic derangements by serving as a ‘metabolic sink’ to limit both systemic lipids and the accrual of visceral and ectopic fat. Treatments targeting the prevention of fat accrual in these harmful depots should be considered as a primary target for improving human health span and longevity.”

View the Article Under Discussion: http://www.ncbi.nlm.nih.gov/pubmed/20703052

Read More Longevity Meme Commentary: http://www.longevitymeme.org/news/

Medical Schools in US News College Rankings – eMaxHealth


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Medical Schools in US News College Rankings
eMaxHealth
In addition to the College, Harvard is comprised of 13 other schools and institutes, including the top-ranked Medical School. In 2009, total medical school ...
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Emory & Henry College tops local college rankingsTriCities.com
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For Women with Itchy Psoriasis Skin, Beer May be Culprit – CBS News


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For Women with Itchy Psoriasis Skin, Beer May be Culprit
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New research from Brigham and Women's Hospital and Harvard Medical School in Boston indicates that drinking beer can increase the risk of psoriasis by more ...
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What’s Truly at Stake in the Ground Zero Mosque Debate – Huffington Post (blog)


The Hindu
What's Truly at Stake in the Ground Zero Mosque Debate
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We do have religious freedom. I know the wounds are still very open, me myself included but you have to look at the big picture. You can't practice these ...
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all 3,715 news articles »

Enter the Trojans

In astronomy, a Trojan is an asteroid or moon that shares an orbit with a larger asteroid or moon, but does not collide with it.  The Trojan orbits within one of the Lagrangian points of stability ahead or behind the main body.

Usually the asteroids which accompany Jupiter around its orbit come to mind when you mention the Trojans.  The Jupiter asteroids were the first discovered, and are believed to be almost as numerous as those in the asteroid belt.  Since the Jupiter Trojans were discovered, scientist have found “Trojans” in the orbits of Mars, Neptune, and Saturn.

Discovered in Jupiter’s orbit in 1906 (588 Achilles was the first one), there have been 4,076 Jupiter Trojans found so far.  There are believed to be over a million Jupiter Trojans larger than 1 km in diameter.  As in the main asteroid belt, the Trojans form asteroid “families”.  Currently, most scientist believe the Trojans are “captured” Kuiper Belt Objects.  Sometimes the “capture” appears to imperfect.  The comet Shoemaker-Levy 9 is believed to have been one such imperfect capture.

Currently there are only four known Mars Trojans, and seven around Neptune.  There may be many more Trojans than those recorded so far; we’re just not in a position to see them yet.  Perhaps when New Horizons passes Neptune…

Martian Trojans, image by Andrew Buck, all rights reserved

There is some speculation that the Trojans are a source for new short-period comets and Centaurs.  Considering the four discovered around Mars, that puts them in our very near back yard.

I have it on good authority my voice makes its cable TV premiere tonight | The Loom

weeds440I have a strange job. A few weeks back I was wandering through the aisles of the local Walmart, searching for bug spray, when my phone rang. A very excited Robert Krulwich was calling. As I drifted past the potato chips and plasma-screen TVs, he declared to me with great excitement that I was going to be on the cable series Weeds.

Now, I’m pretty sure that if I had actually auditioned for the show, I would remember it. Or at least I could find some trace of the experience over on IMDB, searching for my name in the role of Pothead #8. So there I was at the store, getting totally lost trying to figure out what Krulwich was saying.

Gradually, the story emerged: a few months ago, I joined Krulwich and his partner in radio crime, Jad Abumrad to tape a couple segments for their fine show, RadioLab. In one of those segments, I describe the glories of parasites, focusing on one surgically fiendish wasp. Apparently the people at Weeds are RadioLab fans and sometimes work bits of it into their own show. And apparently, they are using my ramblings–at great length, I’m reliably informed–in the season premiere. What deeper meaning that Jad, Robert, and I could bring to their show, I can’t say–in part because I don’t have cable TV, so I’m not a regular viewer.

Suffice to say, it was a very long bug spray run. The new season airs tonight. If anyone sees it, fill me in! And if I can get my mitts on the clip, I’ll post it.

[Update: We've got it]


Fake Facebook “Dislike” Button Leads to More Dislike | Discoblog

facebookThey only wanted to show their disapproval. Friends eager to counterbalance all those Facebook “Likes” rushed to “Download the official DISLIKE button now” as received in a message. But, sadly, no dislike button was in store. Instead, installing the application provided users with several surveys and left their profiles vulnerable to spammer control. If there was ever a time to unleash their Dislike, this was it.

Yet, as Graham Cluley of the security firm Sophos told the BBC–mentioning a similar ploy that offered Facebookers the chance to see an anaconda vomiting up a hippo–such “survey scam” applications are nothing new:

“Anyone can write a Facebook app–these scams are constantly springing up.”

Perhaps Facebook should take note: Users were willing to sacrifice their security for the mere power to express negative feedback. Or, at least, the mere power to express negative feedback without typing.

Perhaps a compromise is in order? Unfortunately, a new Meh button application seems to need some tweaking. As in the Atlantic Wire:

Turns out, every time you click the “meh” button it registers your vote—allowing an individual user to “meh” something 10,000 times or more. That’s a lot of indifference.

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Astronomers Announce Priorities: Dark Energy, Exoplanets, Cosmic Origins | 80beats

LSSTThere is a lot of space to explore and a limited amount of money to spend. So every ten years the National Research Council’s “Decadal Survey“ recommends which astronomy and astrophysics projects should get first dibs. Last week, the committee released their recommendations for 2012 through 2021. The projects that got the thumbs-up from astronomers would tackle big tasks, like hunting for dark energy and seeking out new exoplanets.

Though funding agencies (like NASA, the National Science Foundation, and the Department of Energy), Congressional committees, and the scientific community often use the survey to select the observatories on which to focus attention and resources, some were skeptical about this report given the 2001 survey’s recommendations and results.

Although these reports have always been influential—policymakers like scientists to rank their needs—only two of the seven major projects that appeared on the wish list in the 2001 survey have been funded, leading astronomers to wonder if the exercise is as useful as they’d like it to be. Previous surveys have also been faulted for providing unrealistic cost estimates, as low as a fifth of what certain missions have ended up costing. As a result, there has been considerable pressure on the committee that authored [Friday's] report to prioritize projects more effectively and estimate costs better. [Science Insider]

This time, the committee hoped to avoid these budget underestimates by evaluating the financial and technical risk of each project.

“I think at the time of the previous decadal survey, people didn’t appreciate the importance of taking a second look at the cost of things and not just taking the word of the people submitting the projects,” says astronomer Claire Max of the University of California in Santa Cruz, a member of the final survey committee. This time around, the panel hired an outside expert to help estimate the funding and technical risk of each project. [Nature News]

Nature News outlines the survey’s funding recommendations for a wide range of projects, but two observatories–one in space and one on the ground–seem most promising to the committee, fitting with the survey’s major three priorities.

The committee highlighted three main areas of science, none of which should be too surprising to those who follow the field: Cosmic Dawn, New Worlds and the Physics of the Universe. Or, how did all of this get here, are there planets like Earth nearby, and what makes up the universe? Projects that are well suited to answer these questions, as well as technologically feasible, were given high recommendations. [Discovery News]

In Space

The survey recommends the most funding for the Wide Field Infrared Survey Telescope (WFIRST), a joint project between NASA and the Department of Energy, which has an estimated cost of $1.6 billion. After an expected launch in 2020, WFIRST will record light from distant supernova among other things, and hopefully provide insights into the universe’s expansion and dark energy. Committee members also believe the telescope may help in the hunt for exoplanets.

“WFIRST not only gets at all the dark energy [priorities], but it also has significant capability in exoplanet science and will do outstanding work in infrared survey science,” Michael Turner, a cosmologist at the University of Chicago and the Kavli Institute for Cosmological Physics told physicsworld.com. Turner, who served on the 23-member committee for the decadal survey, also notes that the survey did not reject the idea of a possible collaboration with the European Space Agency (ESA) to combine its planned Euclid dark-energy mission with WFIRST. [Physics World]

On the Ground

The survey also recommends support for the $463 million Large Synoptic Survey Telescope (pictured above). When completed, the telescope will survey the entire sky every week with a three-billion pixel digital camera to help researchers understand dark matter, dark energy, supernovae, near-Earth asteroids, and Kuiper belt objects.

In placing the LSST atop its priority list, the report highlighted the telescope’s technical readiness and its “compelling science case and capacity to address so many of the science goals of this survey,” including exploring the fundamental physical makeup of the universe by probing the nature of dark matter and dark energy. [Scientific American]

The DISCOVER blog Cosmic Variance has more on all this: 
The Next 10 Years of Astronomy explains what the Decadal Survey means to astronomers 
The Next Decade of US Space Astronomy
The Next Decade of US Ground Based Astronomy

Image: LSST Corporation


Genes and culture: OXTR gene influences social behaviour differently in Americans and Koreans | Not Exactly Rocket Science

Korean_american

There are great plays and bad ones, but the playwright’s actual text is only one aspect of a production. The very same words can take on radically different meanings depending on the whims of the director, the abilities of the actors and the setting of the stage. The same is true of our genes and our environments. In cases where genes affect our behaviour, the same stretch of DNA can lead to very different deeds, depending on individual circumstances. Just as a production defines a play, environments and cultures alter the effects of certain genes.

Heejung Kim from the University of California has discovered a great example of this effect by studying a gene called OXTR (or the ‘oxytocin receptor’, in full). The gene creates a docking station for a hormone called oxytocin, which is involved in all sorts of emotions and social behaviours, from trust to sexual arousal to empathy.

Kim looked at a specific version of the OXTR gene, whose carriers are allegedly more social and sensitive. But this link between gene and behaviour depends on culture; it exists among American people, who tend to look for support in troubled times, but not in Korean cultures, where such support is less socially acceptable. Culture sets the stage on which the OXTR gene expresses itself.

OXTR varies from person to person, and the DNA ‘letters’ at particular spots can affect the way we behave. According to previous studies, people with a ‘G’ at one specific site tend to be more sensitive parents, more empathetic and less lonely than those with an ‘A’. But most of these studies have been done with white, Western people who are hardly representative of the world at large – in fact, they’re positively W.E.I.R.D.

To looked outside this “thin and rather unusual slice of humanity”, Kim compared 134 Korean students with 140 American ones, all with comparable splits of age, gender and background. Using a questionnaire, she measured how stressed each volunteer was feeling at that point in their lives, and how they cope with stress. As with previous studies, Kim found that Koreans are less likely than Americans to turn to their social circle for support and they get less out of doing so; they are more concerned about burdening their friends and straining their relationships.

The OXTR gene exerts its influence against the background of these contrasting cultural conventions. Distressed Americans with one or more copies of the G version were more likely to seek emotional support from their friends, compared to those with two copies of the A version. But for the Koreans, the opposite was true – G carriers were less likely to look for support among their peers in times of need (although this particular trend was not statistically significant). In both cases, the G carriers were more sensitive to the social conventions of their own cultures. But the differences between these conventions led to different behaviour.

And in a further example of the influence of the environment, Kim only found this pattern among people who were experiencing a lot of stress. In the low stress group, she found that Americans were indeed more likely to seek emotional support than Koreans, but their OXTR gene had no bearing on their choices.

Of course, Koreans and Americans differ not just in their cultures, but in their genes (including many others beyond OXTR). To account for that, Kim also worked with a small group of 32 Korean-Americans who were born and raised in the US, but were genetically Korean. Kim found that the link between OXTR and emotional support among these volunteers was much closer to the culturally similar Americans than the genetically similar Koreans.

Richard Ebstein, who has worked on OXTR before, says, “Overall, I would say it’s a very interesting finding… These types of studies are needed to help us get a better understanding of how it’s not just nature or nurture but rather the interplay between the two that contributes to how we deal with the social environment.” However, he’s not convinced (and nor am I) that Kim looked at enough people, particularly in the extra experiment with the Korean-Americans. Ebstein wants to see them repeat the results in a much larger group.

Even so, Kim’s results are compelling. They’re also unusual in looking for an interaction between genes and culture. Many studies have looked at how nature and nurture work together but in most cases, the “nurture” bit involves something social that’s either harsh or kind, such as loving or abusive parenting. In one of the most famous examples, people with the ‘low-activity’ version of the MAOA gene tend to be more aggressive than those with the ‘high-activity’ one, but only if they’ve been abused or neglected as children. Kim’s study stands out because it looks as cultural conventions instead, and Ebstein says that it “provides an interesting new avenue for researching gene-environment interactions.”

Kim also hopes that her work will encourage more scientists to investigate the ways in which genes and culture evolve together. She notes that the G version of OXTR is more common among white Americans than Korea. It’s tantalisingly possible that American culture has come to emphasise social support partly because more people have genes that skew them towards social behaviour. So genes constrain culture, while culture creates the stage on which genes exact their influence.

Reference: PNAS http://dx.doi.org/10.1073/pnas.1010830107

More on genes and environment:

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Where writing is silent | Gene Expression

In my post on Empires of the Word I observed that quite often the written record is silent on many matters which only language or genes tell us must have occurred. The Indo-Aryan character of the dominant language on the island of Sri Lanka seems to be a geographical anomaly in the least, but perhaps most strange of all is the existence of a language and ethnic group of clear Southeast Asian provenance on the island of Madagascar. To my knowledge Arab, Persian and South Asian sources do not record the existence of a prominent Southeast Asian maritime diaspora which spanned the Indian ocean in the years before 1000 A.D., but we know that it did exist. A new paper on the genetics of the island of Comoros fleshes out another piece of the puzzle, Genetic diversity on the Comoros Islands shows early seafaring as major determinant of human biocultural evolution in the Western Indian Ocean:

The Comoros Islands are situated off the coast of East Africa, at the northern entrance of the channel of Mozambique. Contemporary Comoros society displays linguistic, cultural and religious features that are indicators of interactions between African, Middle Eastern and Southeast Asian (SEA) populations. Influences came from the north, brought by the Arab and Persian traders whose maritime routes extended to Madagascar by 700–900 AD. Influences also came from the Far East, with the long-distance colonisation by Austronesian seafarers that reached Madagascar 1500 years ago. Indeed, strong genetic evidence for a SEA, but not a Middle Eastern, contribution has been found on Madagascar, but no genetic trace of either migration has been shown to exist in mainland Africa. Studying genetic diversity on the Comoros Islands could therefore provide new insights into human movement in the Indian Ocean. Here, we describe Y chromosomal and mitochondrial genetic variation in 577 Comorian islanders. We have defined 28 Y chromosomal and 9 mitochondrial lineages. We show the Comoros population to be a genetic mosaic, the result of tripartite gene flow from Africa, the Middle East and Southeast Asia. A distinctive profile of African haplogroups, shared with Madagascar, may be characteristic of coastal sub-Saharan East Africa. Finally, the absence of any maternal contribution from Western Eurasia strongly implicates male-dominated trade and religion as the drivers of gene flow from the North. The Comoros provides a first view of the genetic makeup of coastal East Africa.

In the paper they note that ~6% of the Y chromosomal lineages were Southeast Asian, while ~15% of mtDNA lineages were. That indicates that the Southeast Asian presence on the Indian ocean was a case of folk migration, men, women and children on the move. The data from Madagascar indicate something similar, both male and female lineages show Southeast Asian imprint among the highland Malagasy (I don’t make much of the proportional difference because this is just one sample). In contrast, they show in this paper that there’s a substantial West Eurasian (probably Arab, Indian and Persian) Y chromosomal gene flow into the population of Comoros, but no West Eurasian mtDNA. So in this case you have a clear contrast with that of the Southeast Asian seafarers, the Muslim merchants who settled on the Comoros did not bring their children or womenfolk. It was not a folk migration, but a mercantile network. Because of the nature of the sources, and the cultural influence of the West Asians, we know of their presence from the historical record. In contrast, the arguably more substantial folk migration of Southeast Asian seafarers from Borneo is hidden in the text. They may have been of no concern or beneath mention from the perspective of the Muslim merchant princes, but the fact that they were no longer on the high seas by the time the Portuguese arrive may also indicate that they were driven off by the same Muslim merchant princes in the years after 1000. If the latter is the case the silence may be due to the inclination to forget an unpleasant rivalry.

All this goes to show that history’s reliance on text can mislead and obscure real dynamics. Even social and economic history which attempts to tunnel-down to the level of the populace is still heavily reliant on written records. In the case of seafarers it seems likely that even archaeologists would be unable to detect their movements because of the liminal nature of their settlements. The linguistic and cultural influences in Madagascar and in East Africa indicate a sojourn by Austronesians in that coast, but there is no physical or textual record. There is the “dark history” which we ignore because of current ideological preferences, and then there is the dark history which has fallen outside of our methodological window.

Dienekes has more on this paper.