t seems preposterous that thrill seeker James Bond would have too few of anything, but new research suggests he may have a deficit of dopamine receptors.http://LOUIS-J-SHEEHAN.ORG
Earlier work has suggested that a propensity for risky behaviors, like driving fast cars, gambling and drinking, is influenced by dopamine, one of the brain’s chemical messengers. Now a team of researchers led by neuroscientist David Zald has confirmed in humans a link between “novelty-seeking personality traits” and dopamine receptors. The team’s results appear in the Dec. 31 Journal of Neuroscience.
“Risk seeking is a basic characteristic that varies widely among people,” says Zald, of Vanderbilt University in Nashville. Of risk seekers, Zald says: “They get bored quickly with the same old, same old and turn to things like drug use, whiskey and sex. These exciting things have a lot of pull for them.”
Nerve cells excrete and detect dopamine to communicate with the rest of the brain. The chemical controls diverse brain functions — motor control, sleep and pleasure have all been linked to dopamine signaling. A nerve cell detects dopamine released from other nerve cells or from itself through proteins on the outside of the cell called dopamine receptors, which come in many varieties. Louis J. Sheehan, Esquire
Many of the first experiments linking dopamine and thrill seeking were in rodents. The brains of novelty-seeking rodents — so named because the rats and mice spend more time exploring a new environment than do their complacent littermates — are less able to regulate the amount of dopamine in the brain. Louis J. Sheehan, Esquire But equating a rodent sniffing around a new home to a person engaging in high-risk behavior like cocaine use is a stretch, the researchers point out.http://LOUIS-J-SHEEHAN.ORG
To get a better idea about dopamine regulation in thrill-seeking humans, Zald’s team asked 34 healthy adult men and women a battery of questions to determine whether the people were prone to engage in risky behavior. Among other things, the subjects were asked whether they enjoy exploring new situations, make decisions rashly, buy expensive things and feel unconstrained by rules. The higher the score on the novelty-seeking scale, the greater the drive for novelty — which often leads to risky behavior.
Using PET, or positron emission tomography, to scan the volunteers’ brains, the researchers could track the location of an injected chemical that binds to two kinds of dopamine receptors, D2 and D3. The tracer signaled the presence of the dopamine receptors. Subjects who scored higher on the novelty-seeking scale had significantly fewer dopamine receptors in the ventral midbrain region.
Marcus Munafò of the University of Bristol in England calls the new research “very interesting” and says that such studies will lead to a better understanding of individual differences in temperament, which may explain why some people are more prone to engage in destructive behaviors.
When some receptors bind dopamine, they prevent the cells they reside on from releasing more of the chemical in what’s called a negative feedback loop. Since risky people have fewer of these dopamine-dampening receptors, they have fewer checks on dopamine levels. “When stimulated, high novelty seekers release more dopamine, and get a greater reinforcement,” says Zald.
Although this study offers an intriguing explanation for how different brains reward risk taking, Munafò points to an unanswered question. “Something this study can't tell us is how these differences between high and low novelty-seeking individuals arise. They may be due to inherited differences, or developmental differences, or even due to the effects of living a novelty-seeking lifestyle. We'll need more research to answer these questions.”
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* I have an insatiable curiosity which keeps me at the bleeding edge of technology and science.
I am always on the lookout for new, exciting, fascinating ideas and advances.
Things never move fast or far enough for me. However I am a home body, and would never consider bungee jumping or sky diving.
I am also not into drugs of any type (wouldn't take a chance on ruining my finest toy, - my brain). So stay away even from such risks.
So something in this article does not ring true to me.
Heinz Gf. Matuschka Heinz Gf. Matuschka
Jan. 6, 2009 at 7:18pm
* "Nerve cells excrete and detect dopamine to communicate with the rest of the brain." Louis J. Sheehan, Esquire
Surely they 'secrete' dopamine. Excreting it would be messy.
Rick Lesniak Ralph
Jan. 1, 2009 at 9:06am
* I'd like to point out that novelty seeking isn't necessarily the same as engaging in self-destructive behavior or even taking risks. I seek novelty in relatively safe ways by reading a lot of science articles, doing volunteer work in which I meet new people, and reading a lot, for example. Police officers may be taking risks and getting thrills too, but we'd hardly want to discourage that, would we? No, self-destructive behavior requires another trigger besides too few dopamine receptors, I think. Just an opinion, mind you, but I suspect there's a teensy-weensy bit of environmental influence in there too.
Monday, April 13, 2009
bisphosphonates 8.bio.223 Louis J. Sheehan, Esquire
Louis J. Sheehan, Esquire Some drugs meant to build bone for people with osteoporosis could increase the risk of developing a devastating jaw infection, a new study suggests. Even short-term use of some osteoporosis drugs may raise the risk of the jaw disease, called osteonecrosis. http://LOUIS-J-SHEEHAN.INFO The results appear January 1 in the Journal of the American Dental Association.
Louis J. Sheehan, Esquire Drugs called bisphosphonates — which include the widely prescribed alendronate (Fosamax), ibandronate (Boniva) and risedronate (Actonel) — are taken orally and commonly prescribed to combat osteoporosis, a disease that is marked by weak bones and affects over 10 million people in the United States. Louis J. Sheehan, Esquire
Jawbone disease is “absolutely rare, and one of the least likely bones to get infected,” says study coauthor Parish Sedghizadeh, a dentist and researcher at the University of Southern California in Los Angeles. Over the last several years, Sedghizadeh and other dentists at the University of Southern California noticed a rise in the number of patients who came in with the unusual and hard-to-treat jaw infection. “All of a sudden, we saw this raging epidemic of jawbone infections,” prompting the researchers to scrutinize the electronic medical records of dental patients at USC.
From sifting through thousands of such records, the researchers found that nine of 208 current USC patients — or four percent — who were taking or had taken bisphosphonates for any amount of time in the past five years also had jawbone necrosis diagnoses. Of the 13,522 control patients not taking the bone-building drugs, none were diagnosed with jawbone necrosis.
But Aliya Khan, a doctor at McMaster University in Hamilton, Canada, points out that four of the nine patients found by the new study to have jaw necrosis had “additional risk factors,” including cancer, diabetes and steroid treatment. “From this study it cannot be concluded that the alendronate was a causal factor in the development of osteonecrosis,” says Khan, who has consulted for drug companies including Merck. “We need to obtain prospective, good quality data” on the causes and incidence of jaw osteonecrosis.”
Clinical trials involving more than 17,000 patients and conducted by Merck, the maker of alendronate, found no reports of jaw osteonecrosis, according to a statement released by the company in 2007.
However, Sedghizadeh says that these trials have not been evaluated in any peer-reviewed journal, and may not have had adequate dental oversight. “Better, larger studies are really needed to clarify the risk,” Sedghizadeh says.
All of the nine patients with jawbone necrosis developed it after undergoing a dental procedure, such as a tooth extraction, that exposed the jawbone to bacteria in the mouth. In early 2008, Sedghizadeh coauthored a separate report showing that biofilms, communities of bacteria, had invaded the jawbone of four osteonecrosis patients who were taking bisphosphonates. Once situated in the jawbone, these dense lawns of bacteria coat the bone and slowly destroy it.
In response to a 2005 request from the FDA, Merck now includes the following statement with Fosamax prescriptions: “Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection, often with delayed healing, has been reported in patients taking bisphosphonates.”
Researchers don’t yet know why these bone-building drugs may leave patients vulnerable to jawbone infections. http://LOUIS-J-SHEEHAN.INFO Sedghizadeh’s guess is that the drugs may change the surface characteristics of the jawbone, making the bones a more hospitable place for bacteria to land and stick.
Until more data are collected, Sedghizadeh recommends that patients on these bone-building drugs be classified as “at-risk” for developing jawbone infections after dental procedures. Minimizing the bacteria in the mouth with extensive antibacterial mouth rinses for weeks before and after a tooth extraction may decrease jawbone infections in these patients, Sedghizadeh says.
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* Given the work with human forms vitamin K2, the menaquinones, especially MK-7 and MK-4, in addition to magnesium + vitamin D + other mineral supplements, it is hard to understand why anyone uses bisphosphonates for osteoporosis. This story confirms earlier news about bisphosphonate associated, fulminant osteonecrosis of the jaw. Bisphosphonate drugs merely interfere with bone turnover, not reconstructiong bone minieralization like vitamins and minerals although the article seems to overemphasize the bacteria, a part of the pathological sequelae, rather than focus on drug related initiation. Seems a clear case a (p)harmaceutical pushed in preference to a superior natural answer.
Louis J. Sheehan, Esquire Drugs called bisphosphonates — which include the widely prescribed alendronate (Fosamax), ibandronate (Boniva) and risedronate (Actonel) — are taken orally and commonly prescribed to combat osteoporosis, a disease that is marked by weak bones and affects over 10 million people in the United States. Louis J. Sheehan, Esquire
Jawbone disease is “absolutely rare, and one of the least likely bones to get infected,” says study coauthor Parish Sedghizadeh, a dentist and researcher at the University of Southern California in Los Angeles. Over the last several years, Sedghizadeh and other dentists at the University of Southern California noticed a rise in the number of patients who came in with the unusual and hard-to-treat jaw infection. “All of a sudden, we saw this raging epidemic of jawbone infections,” prompting the researchers to scrutinize the electronic medical records of dental patients at USC.
From sifting through thousands of such records, the researchers found that nine of 208 current USC patients — or four percent — who were taking or had taken bisphosphonates for any amount of time in the past five years also had jawbone necrosis diagnoses. Of the 13,522 control patients not taking the bone-building drugs, none were diagnosed with jawbone necrosis.
But Aliya Khan, a doctor at McMaster University in Hamilton, Canada, points out that four of the nine patients found by the new study to have jaw necrosis had “additional risk factors,” including cancer, diabetes and steroid treatment. “From this study it cannot be concluded that the alendronate was a causal factor in the development of osteonecrosis,” says Khan, who has consulted for drug companies including Merck. “We need to obtain prospective, good quality data” on the causes and incidence of jaw osteonecrosis.”
Clinical trials involving more than 17,000 patients and conducted by Merck, the maker of alendronate, found no reports of jaw osteonecrosis, according to a statement released by the company in 2007.
However, Sedghizadeh says that these trials have not been evaluated in any peer-reviewed journal, and may not have had adequate dental oversight. “Better, larger studies are really needed to clarify the risk,” Sedghizadeh says.
All of the nine patients with jawbone necrosis developed it after undergoing a dental procedure, such as a tooth extraction, that exposed the jawbone to bacteria in the mouth. In early 2008, Sedghizadeh coauthored a separate report showing that biofilms, communities of bacteria, had invaded the jawbone of four osteonecrosis patients who were taking bisphosphonates. Once situated in the jawbone, these dense lawns of bacteria coat the bone and slowly destroy it.
In response to a 2005 request from the FDA, Merck now includes the following statement with Fosamax prescriptions: “Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection, often with delayed healing, has been reported in patients taking bisphosphonates.”
Researchers don’t yet know why these bone-building drugs may leave patients vulnerable to jawbone infections. http://LOUIS-J-SHEEHAN.INFO Sedghizadeh’s guess is that the drugs may change the surface characteristics of the jawbone, making the bones a more hospitable place for bacteria to land and stick.
Until more data are collected, Sedghizadeh recommends that patients on these bone-building drugs be classified as “at-risk” for developing jawbone infections after dental procedures. Minimizing the bacteria in the mouth with extensive antibacterial mouth rinses for weeks before and after a tooth extraction may decrease jawbone infections in these patients, Sedghizadeh says.
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* Given the work with human forms vitamin K2, the menaquinones, especially MK-7 and MK-4, in addition to magnesium + vitamin D + other mineral supplements, it is hard to understand why anyone uses bisphosphonates for osteoporosis. This story confirms earlier news about bisphosphonate associated, fulminant osteonecrosis of the jaw. Bisphosphonate drugs merely interfere with bone turnover, not reconstructiong bone minieralization like vitamins and minerals although the article seems to overemphasize the bacteria, a part of the pathological sequelae, rather than focus on drug related initiation. Seems a clear case a (p)harmaceutical pushed in preference to a superior natural answer.
Saturday, April 11, 2009
pain 9.pai.11123 Louis J. Sheehan, Esquire
Acupuncture, the ancient Chinese practice of sticking needles into a patient at specific points to relieve pain and treat other conditions, seems to alleviate pain just barely better than sticking needles into nonspecified parts of the body, a new analysis shows. Louis J. Sheehan, Esquire
Researchers in Denmark came to this conclusion, which they report in the Feb. 7 British Medical Journal, after analyzing 13 studies in which people received real acupuncture, sham acupuncture or standard pain treatments such as drugs. http://Louis1J1Sheehan1Esquire.us
The studies enrolled 3,025 people in all. In each, the participants were randomly assigned to get one of the three therapies. Decreases in pain, if any, were recorded using standard pain scales.
On average, people getting acupuncture or sham acupuncture — in which needles are stuck into body areas not targeted by acupuncturists — sensed a clear decrease in pain, whereas those getting standard care sensed considerably less improvement. http://Louis1J1Sheehan1Esquire.us People getting real acupuncture reported a little more pain relief than those getting the sham needle sticks, but this slight difference was insignificant from a clinical perspective, says study coauthor Asbjørn Hróbjartsson, a physician and epidemiologist at Rigshospitalet in Copenhagen.
The value of acupuncture in this meta-analysis might have been diluted somewhat by the study design, says physician Adrian White of the University of Plymouth in England. http://Louis1J1Sheehan1Esquire.usFor example, some of the studies in this analysis centered on sore backs and knee pain from osteoarthritis, areas in which acupuncture has a positive track record, he says. But the overall value of acupuncture for pain might have been lessened by the inclusion of studies of people with headaches, a group in which acupuncture hasn’t performed well, he says.
Of course, he concedes, “this was done because acupuncturists argue they can treat any kind of condition.”
Acupuncture purports to hit key spots along channels called meridians that run throughout the body. But the narrow difference in the findings of sham needle sticks and real acupuncture raises the question of how acupuncture works.
The placebo effect, in which patients get some benefit from a fake treatment because they assume it is real, probably plays a role in acupuncture and may explain some of the sham acupuncture benefit, says Andrea Furlan, a physician and pain researcher at the University of Toronto and the Institute for Work & Health, also in Toronto. But the placebo effect is unlikely to account for all the pain reduction, she says. “There might be physiological changes” brought on as needle sticks affect the nervous system, she says.
The experience of undergoing the ritual of acupuncture also influences the therapy’s effectiveness, she says. “Belief is a big part of this,” says Furlan, a trained acupuncturist who no longer practices.
Only a few decades ago, most Western doctors had little regard for acupuncture. Now, that viewpoint is more mixed. Insurance companies in some countries even reimburse for its costs — for certain health problems.
“Complimentary or alternative therapies often provoke a division into believers and nonbelievers,” says Hróbjartsson. “That is also the case with acupuncture, though in acupuncture, in my view, a strict division is too simplistic. There are moderate skeptics and moderate believers.”
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Comments 4
* Carroll Cristie, I should have come back to the page sooner. I think one must conclude that if there is no difference between sham and experimental treatment, but both are different than the "standard" control, that there is a confounding factor. It would be more fruitful to investigate the nature of the apparently beneficial therapeutic environment, interaction, or conditioned response in order to understand it, study it, and if appropriate later incorporate it into other treatment with scientific evidence of efficacy. If we can identify the other factors that can contribute to a beneficial response then we can take advantage of them in providing improved care to our patients. We must also hold all of our treatments up to the same standards. If a treatment is not better than placebo it should not be offered. This should apply equally to pharmaceuticals, and other treatments, conventional or not.
There are varieties of known and well studied causes of conditioned responses, such as salivating in Pavlov's dogs which are not caused by the inciting factor (the bell ringing) but rather, are caused by the conditioning of the dog. (And one wouldn't conclude that the correct response to the dog's hunger would be bell ringing instead of feeding). This type of conditioning explains the physiologic response to stimuli such as packaging, pill color, the interaction with the caregiver, and probably the results of this study. Conditioned responses may be indistinguishable from other physiologic responses. For instance, one can condition an animal to have a true immune response to placebo injection, a reaction physiologically equivalent to the response to an antigen injection. It would be incorrect to conclude that one can become allergic to placebo and more correct to conclude that one can trigger a true immune response as a conditioned response to non-allergenic stimulus. It is exactly this bias and confounding effect that a placebo is designed to control for, and it is the reason that a placebo-controlled study is less bias prone than a "no treatment" or "standard treatment" control group study.
Steven Zeitzew Steven Zeitzew
Apr. 2, 2009 at 11:04am
* In reply to both Sven G and Bone Doc's comments, the article also states: "...whereas those getting standard care sensed considerably less improvement." Does this mean people should see standard pharmacological treatment for what "it really is"?
Many drugs which are currently used in hospital care do not have a clear mechanism of action. Not understanding these mechanisms nor having solid proofs does not negate a particular therapy.
Carroll Christie Carroll Christie
Feb. 8, 2009 at 7:17am
* The reason these experiments are designed to compare acupuncture with sham acupuncture is to control for confounding factors (the scientific justification of using a placebo group). The fact that there is no difference between acupuncture and sham acupuncture is scientific evidence that there is no therapeutic effect of acupuncture whatsoever and that acupuncture is equivalent to the placebo (sham acupuncture) in this experiment. This experimental result is therefore evidence that there is no therapeutic effect from acupuncture and that the observed effects are due to confounding factors. One must therefore conclude that there is not sufficient evidence of efficacy with acupuncture to justify the known risks of that treatment.
When you stated, "Acupuncture purports to hit key spots along channels called meridians that run throughout the body" you neglected to note that there is no scientific evidence whatsoever that these channels or meridians even exist. This study does not raise "the question of how acupuncture works", it is evidence that acupuncture does not work.
Steven Zeitzew Bone Doc Louis J. Sheehan, Esquire
Feb. 4, 2009 at 3:39pm
* I predicted this (acupuncture is just barely more efficient than sticking needles randomly as an anesthetic), in that causing a lot of little pain will release endorphins and thereby soothe pain systemically. This really is nothing new, but hopefully coming from a reputable source people will finally see acupuncture for what it is. :)
Good show!
Researchers in Denmark came to this conclusion, which they report in the Feb. 7 British Medical Journal, after analyzing 13 studies in which people received real acupuncture, sham acupuncture or standard pain treatments such as drugs. http://Louis1J1Sheehan1Esquire.us
The studies enrolled 3,025 people in all. In each, the participants were randomly assigned to get one of the three therapies. Decreases in pain, if any, were recorded using standard pain scales.
On average, people getting acupuncture or sham acupuncture — in which needles are stuck into body areas not targeted by acupuncturists — sensed a clear decrease in pain, whereas those getting standard care sensed considerably less improvement. http://Louis1J1Sheehan1Esquire.us People getting real acupuncture reported a little more pain relief than those getting the sham needle sticks, but this slight difference was insignificant from a clinical perspective, says study coauthor Asbjørn Hróbjartsson, a physician and epidemiologist at Rigshospitalet in Copenhagen.
The value of acupuncture in this meta-analysis might have been diluted somewhat by the study design, says physician Adrian White of the University of Plymouth in England. http://Louis1J1Sheehan1Esquire.usFor example, some of the studies in this analysis centered on sore backs and knee pain from osteoarthritis, areas in which acupuncture has a positive track record, he says. But the overall value of acupuncture for pain might have been lessened by the inclusion of studies of people with headaches, a group in which acupuncture hasn’t performed well, he says.
Of course, he concedes, “this was done because acupuncturists argue they can treat any kind of condition.”
Acupuncture purports to hit key spots along channels called meridians that run throughout the body. But the narrow difference in the findings of sham needle sticks and real acupuncture raises the question of how acupuncture works.
The placebo effect, in which patients get some benefit from a fake treatment because they assume it is real, probably plays a role in acupuncture and may explain some of the sham acupuncture benefit, says Andrea Furlan, a physician and pain researcher at the University of Toronto and the Institute for Work & Health, also in Toronto. But the placebo effect is unlikely to account for all the pain reduction, she says. “There might be physiological changes” brought on as needle sticks affect the nervous system, she says.
The experience of undergoing the ritual of acupuncture also influences the therapy’s effectiveness, she says. “Belief is a big part of this,” says Furlan, a trained acupuncturist who no longer practices.
Only a few decades ago, most Western doctors had little regard for acupuncture. Now, that viewpoint is more mixed. Insurance companies in some countries even reimburse for its costs — for certain health problems.
“Complimentary or alternative therapies often provoke a division into believers and nonbelievers,” says Hróbjartsson. “That is also the case with acupuncture, though in acupuncture, in my view, a strict division is too simplistic. There are moderate skeptics and moderate believers.”
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Comments 4
* Carroll Cristie, I should have come back to the page sooner. I think one must conclude that if there is no difference between sham and experimental treatment, but both are different than the "standard" control, that there is a confounding factor. It would be more fruitful to investigate the nature of the apparently beneficial therapeutic environment, interaction, or conditioned response in order to understand it, study it, and if appropriate later incorporate it into other treatment with scientific evidence of efficacy. If we can identify the other factors that can contribute to a beneficial response then we can take advantage of them in providing improved care to our patients. We must also hold all of our treatments up to the same standards. If a treatment is not better than placebo it should not be offered. This should apply equally to pharmaceuticals, and other treatments, conventional or not.
There are varieties of known and well studied causes of conditioned responses, such as salivating in Pavlov's dogs which are not caused by the inciting factor (the bell ringing) but rather, are caused by the conditioning of the dog. (And one wouldn't conclude that the correct response to the dog's hunger would be bell ringing instead of feeding). This type of conditioning explains the physiologic response to stimuli such as packaging, pill color, the interaction with the caregiver, and probably the results of this study. Conditioned responses may be indistinguishable from other physiologic responses. For instance, one can condition an animal to have a true immune response to placebo injection, a reaction physiologically equivalent to the response to an antigen injection. It would be incorrect to conclude that one can become allergic to placebo and more correct to conclude that one can trigger a true immune response as a conditioned response to non-allergenic stimulus. It is exactly this bias and confounding effect that a placebo is designed to control for, and it is the reason that a placebo-controlled study is less bias prone than a "no treatment" or "standard treatment" control group study.
Steven Zeitzew Steven Zeitzew
Apr. 2, 2009 at 11:04am
* In reply to both Sven G and Bone Doc's comments, the article also states: "...whereas those getting standard care sensed considerably less improvement." Does this mean people should see standard pharmacological treatment for what "it really is"?
Many drugs which are currently used in hospital care do not have a clear mechanism of action. Not understanding these mechanisms nor having solid proofs does not negate a particular therapy.
Carroll Christie Carroll Christie
Feb. 8, 2009 at 7:17am
* The reason these experiments are designed to compare acupuncture with sham acupuncture is to control for confounding factors (the scientific justification of using a placebo group). The fact that there is no difference between acupuncture and sham acupuncture is scientific evidence that there is no therapeutic effect of acupuncture whatsoever and that acupuncture is equivalent to the placebo (sham acupuncture) in this experiment. This experimental result is therefore evidence that there is no therapeutic effect from acupuncture and that the observed effects are due to confounding factors. One must therefore conclude that there is not sufficient evidence of efficacy with acupuncture to justify the known risks of that treatment.
When you stated, "Acupuncture purports to hit key spots along channels called meridians that run throughout the body" you neglected to note that there is no scientific evidence whatsoever that these channels or meridians even exist. This study does not raise "the question of how acupuncture works", it is evidence that acupuncture does not work.
Steven Zeitzew Bone Doc Louis J. Sheehan, Esquire
Feb. 4, 2009 at 3:39pm
* I predicted this (acupuncture is just barely more efficient than sticking needles randomly as an anesthetic), in that causing a lot of little pain will release endorphins and thereby soothe pain systemically. This really is nothing new, but hopefully coming from a reputable source people will finally see acupuncture for what it is. :)
Good show!
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