Is magnesium beneficial in treating Irukandji jellyfish stings?

http://www.youtube.com/watch?v=Ws5hImeonEA

3 out of 5 stars

Randomized trial of magnesium in the treatment of Irukandji syndrome. McCullagh N et al. Emerg Med Australas 2012;24:560-565.

Abstract

Irukandji Syndrome  is caused by stings from several jellyfish, primarily Carukia barnesiImportant symptoms include pain and cramping in trunk and extremities. In addition, catecholamine surge causes tachycardia and hypertension. Two deaths have been reported from intracranial hemorrhage associated with Irukandji Syndrome.

Because magnesium has been shown to decrease catecholamine release and receptor responsiveness, and based on anecdotal evidence from a handful of cases, magnesium has become in some venues recommended treatment of Irukandji Syndrome.

The primary goal of this randomized, double blind study from Cairns, Australia was to determine the effect of adding magnesium on total analgesic requirement in patients presenting with Irukandji Syndrome.Patients received standard treatment alone, with fentanyl bolus plus additional doses via a patient-contolled pump, with standard treatment plus magnesium. There were 17 patients in the placebo group and 22 in the magnesium group. The authors found no difference between the placebo and magnesium groups regarding mean total opiate dose (53 and 50 morphine equivalent doses, respectively) or mean length of stay (19 and 20.7 h).

They conclude that the study:

. . .did not demonstrate a benefit in the use of magnesium in the treatment of Irukandji syndrome. As such the current use of magnesium needs to be reconsidered until there is good evidence to support its use.

This study has many limitations, which the authors discuss in detail. The number of patients enrolled is extremely small. There is no evidence that the dose of magnesium used was optimal, or that the results would apply to other geographic areas where the variety of jellyfish causing Irukandji Syndrome may be different.Baseline patient characteristics — most importantly pain scores — were not measured or reported. To their credit, the authors discuss the limitations in detail. Unfortunately, because of the difficulties involved in doing these kind of studies, we probably will never know whether or not magnesium truly helps in these cases.

Dr. Jamie Seymour, a co-author of this study, is featured in the video above. and also in the one below. Both are about Irukandji Syndrome, and both are well worth watching.

http://www.youtube.com/watch?v=GK_Cl_54Qh8

A great discussion of Jack Barnes and his discovery of what caused Irukandi syndrome was posted by Chris Nickson at Life in the Fast Lane. To read it, click here.

Brain Freeeeeeeze (Marin IJ)



It’s popsicle-o-clock at the Ballard house and everyone is content… until a horrible shriek reverberates through the home. The perpetrator is three-year-old Holden and his tribal yell quickly morphs into a plaintative wail of “brain freeeeeeeeezzzzze.” In a moment, the pain (for all of us) recedes and our daughter, removing her hands from her ears, asks, “Dad, what causes ‘brain freeze?’” Until recently I would have answered: “Popsicles.” But now, thanks to new evidence, I can instead tell her, “vasodilatation of the anterior cerebral artery.”

This past April, Jorge Serrador of Harvard Medical School and colleagues reported the results of a small study suggesting an explanation for the bodily processes (physiology) involved with brain freeze (known in medicalese as sphenopalatine ganglioneuralgia.) Now, I know what you might be thinking – with autism unexplained and cancer uncured, aren’t there greater priorities for medical research than a painful yet benign experience like sphenopalatine ganglioneuralgia? And, you would be absolutely right. However, there is a bit more to it, and some have long posited that the physiology of brain freeze might be related to that of other (less temporary) conditions – such as post-traumatic and migraine headaches. In fact, prior studies have suggested that migraine sufferers are more likely than other folks to experience brain freeze. So, with that in mind, let’s get back to the research at hand.

Serrador and colleagues recruited thirteen healthy adults willing to suffer through brain freeze in the name of science (and I’m guessing there were other inducements as well). While researchers monitored the blood flow in their brains with transcranial Doppler (ultrasound), the volunteers sipped ice water through straws pressed against their upper palates. Then, they raised their hands to signal the freeze and thaw of brain freeze. Brain blood flow under these conditions was then compared with that of the same volunteers sipping warm water. The results of the study were presented at the Experimental Biology 2012 conference in San Diego and were notable in that the researchers observed that one particular artery, the anterior cerebral artery, dilated rapidly and flooded the brain with blood in conjunction with the freeze sensation. Soon after this vasodilatation occurred, the same vessel constricted (tightened) as the volunteers' pain receded. Now, remember, this was a small study and it’s results have yet to complete the rigorous peer review process associated with manuscript publication. Nonetheless, there do seem to be some important implications in these findings.

1)     Migraine headaches. These are thought to be caused by abnormal dilation of arteries in the brain, and many existing treatments attempt to modulate this process. These results then, support this concept and may lead to greater focus on migraine treatments that prevent dilation in the first place. And, for people with friends or family members with migraines, this study provides us with a way to relate to their pain. For some with migraines, the headache must certainly feel like one long brain freeze. Ouch.

2)     The suddenness of sensation matters. We’ve all heard about the frog that will jump out of a pot of boiling water but will stay in a tub slowly brought from ambient temperature to a boil. One of the aspects of brain freeze that makes it so uncomfortable is the rapidity and severity of its onset. This principle is worth keeping in mind for other situations. Take, for example, removing a bandage. The conventional wisdom is that pulling it off quickly is better, as it gets the pain over and done with. But some researchers, such as Dan Ariely, the author of the fascinating book Predictably Irrational, contend the opposite; the quicker the pain the more severe the pain, and thus the greater the overall discomfort. So perhaps very slowly removing a band-aid is actually more comfortable than yanking it right on off. That’s a topic to be exposed more thoroughly some other time.

3)     Now,I can turn Holden’s occasional freezathon into a spelling lesson for his sister. Ok, here we go, let’s try “sphenopalatine ganglioneuralgia.” S...P...H…

On Breast Cancer Risk (Marin IJ)




Establishing cause and effect is one of the trickiest aspects of medicine. So-called “causality” can be elusive, especially once you move beyond connect-the-dots type circumstances (exhibit A; Mom cuts finger with bagel knife = bleeding Mom.)

Here in Marin, we worry and wonder a lot about breast cancer. Why does a particular woman get breast cancer? How does another woman avoid it? These are difficult and often unanswerable questions. Unlike the knife and finger example, there are a litany of possible reasons why an individual might develop breast cancer. And, even if we expand the question to what increases the risk of breast cancer across a broad population, satisfactory answers are slippery. It is with this in mind that we should view the recent evidence regarding breast cancer in Marin County.

It is well documented that Marin has historically had an abnormally high rate of new breast cancer cases. In particular, data from the late 1990s demonstrate breast cancer rates some 15% higher than those found across the rest of the state. Multiple culprits – lifestyle, hormones, toxins, and genetics – have been proposed and studied, without the emergence of a single smoking gun.

A study recently published in the Journal of the American College of Surgeons has proposed yet another possible cause – genetic differences in Vitamin D receptors. The study, conducted by Dalessandri and colleagues, examined the DNA of 164 Caucasian women living in Marin and diagnosed with breast cancer between 1997-1999. They compared their genetic profiles with those of 174 breast-cancer-free matched controls and found that women at statistically high risk for breast cancer were 1.9 times more likely to have a specific difference (called a variant) in the gene which dictates how the body utilizes Vitamin D (the Vitamin D receptor). Vitamin D has received quite a bit of attention for its possible benefit in deterring certain types of cancers and animal models have demonstrated that it has a beneficial effect on breast cancer tumor growth. Thus, differences in how Vitamin D is processed by its receptors is a logical explanation for why certain women (in Marin and elsewhere) would be at higher risk for developing cancer.

But before you march out to determine your Vitamin D receptor profile, let’s put these findings in proper prospective. First of all, this was a small “pilot” study and should be considered preliminary evidence. Medical practice and investigation is ripe with prominent associations that have not borne out in larger studies; oat bran and heart disease, and (who can forget?) vaccines and autism, and on and on. In fact, there are more disproven associations in medicine than proven ones.

A much larger study of Marin Women (the “Marin Women’s Study” www.marinwomensstudy.org) with 14,000 participants is ongoing and analysis of their DNA samples (there are some 8500 available) should provide more robust data on Vitamin D receptor variants and genetic risk. Furthermore, the genetic data from Dalessandri’s study is from fifteen years ago – during a time when breast cancer rates were peaking – especially in Marin. While multi-factorial, we know that this peak was due, in part, to combined post-menopausal hormone (estrogen and progesterone) therapy – a known risk factor for developing breast cancer, and a treatment more common (at the time) in Marin than elsewhere in California. Thus, we must be careful to extrapolate the findings regarding breast cancer risk from a prior generation to today’s milieu. Finally, one must always be particularly fastidious when reviewing the results of studies that focus on a specific proprietary drug (remember Vioxx?) or test. While this study was funded by state, county and charitable sources, the results quite prominently affect the fortunes of genetic testing company InterGenetics Incorporated, which is marketing OncoVue® - a “genetic-base, breast cancer risk test.”  Thus, while interactions between genes and the environment is certainly a promising field, the jury on Vitamin-D receptors and breast cancer is most definitely still out.

Where then, does this leave us with breast cancer causality? Well remember, this is tricky – proving a clear-cut link between a dietary item, personal habit, or medical treatment and a disease process is fraught with the potential for mis-interpretation. Nonetheless, there are certainly some risk factors that we can confidently delineate. Some genetic risk is clearly proven – and a family history of breast cancer is a known red flag – especially if due to a known BRCA mutation. In terms of risky environmental exposures, an Institute of Medicine committee report released last year summarizes these quiet nicely as “hormone therapy that combines estrogen and progestin, exposure to ionizing radiation…excess weight among post-menopausal women and alcohol consumption.” Other environmental agents – chemicals such as bisphenol A (BPA) – have been implicated and are biologically plausible but at this time unproven. Mary Mockus, a surgeon at Kaiser-Permanente San Rafael and a member of the collaborative Marin Women’s Study team, thinks that the ‘toxic soup’ present in higher socioeconomic areas like Marin County is likely to play some role in the higher breast cancer rates, but that we are unlikely to ever identify one clear cut perpetrator. And, this then, fits quite well with what we know about causality in medicine.

Thus for Marin women, the best advice for preventing breast cancer is probably the best advice for preventing many diseases; sleep well, get regular exercise, know your family’s medical history and discuss individualized screening plans with your doctor…don’t smoke, avoid excesses of alcohol, drugs and ionizing radiation, and eat plenty of green leafy vegetables. And a healthy Vitamin D level (ask your doctor!) won’t hurt either.