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December 18, 2010
10:00 AM
4,384 views

Saturday Night Palsy

by James Byrne in Disease Prone

I would never have thought this was a real thing until I found references for it detailing a number of cases.
Saturday Night Palsy, also known as Radial Neuropathy, is caused by getting rip roaringly drunk and falling asleep in an unusual position such that the radial nerve is compressed. Most commonly this happens when the patient falls asleep with one arm over the back of a chair putting pressure on the radial nerve, which runs alongside the inside of the arm, by compressing the brachial plexus.... Read more »

Marchini C, Zambito Marsala S, Cavagna E, & Ferracci F. (2007) Saturday night brachial plexus palsy. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 28(5), 279-81. PMID: 17972044

Sathornsumetee S, & Morgenlander JC. (2006) Friday night palsy: an unusual case of brachial plexus neuropathy. Clinical neurology and neurosurgery, 108(2), 191-2. PMID: 16412841

June 3, 2011
07:22 PM
3,139 views

Treating the Bends

by James Byrne in Disease Prone

ResearchBlogging.org
Last week I wrote about the Bends, a medical problem based in an understanding of physics that results in bubbles of (primarily) nitrogen in your blood if you move from one atmospheric pressure to another to quickly, typically surfacing from depth while diving too fast.
The therapy is actually very simple – take the person back to the depth they were diving at to force the bubbles to resolve into the blood. This immediately solves of the symptoms of the condition but is a little impractical to drive the diver back to the beach and drag them underwater. So, instead, we fake it.... Read more »

Vann RD, Butler FK, Mitchell SJ, & Moon RE. (2011) Decompression illness. Lancet, 377(9760), 153-64. PMID: 21215883

Acott, CJ. (1999) Oxygen toxicity: A brief history of oxygen in diving. South Pacific Underwater Medicine Society Journal. info:/

Clark JM. (1974) The toxicity of oxygen. The American review of respiratory disease, 110(6 Pt 2), 40-50. PMID: 4613232

May 28, 2011
09:00 AM
1,139 views

Physics Medicine = The Bends

by James Byrne in Disease Prone

Arguably many diseases can be based in physics including heart disease, atherosclerosis and pretty much anything else to do with the pipes in your body but a disease known as ‘the bends’ or ‘decompression sickness’ invokes a bunch of physics laws and principles and then also requires a physics based treatment to deal with it.

... Read more »

Vann RD, Butler FK, Mitchell SJ, & Moon RE. (2011) Decompression illness. Lancet, 377(9760), 153-64. PMID: 21215883

February 18, 2011
10:11 PM
1,123 views

Third hand smoking - Can we ban this poison already?

by James Byrne in Disease Prone

I’m not going to write a post on why smoking is bad, it’s too obvious and if you don’t understand why then your probably never going to find this post anyway. I’m not even going to talk about second hand smoking, ie. blowing your death cloud at me on the street. Again it’s obvious why it’s bad and may even be worse than smoking the cigarette itself as second hand smokers don’t get the benefit of a filter. No, this post is about third hand smoking, a fun new way smokers can harm those around them long after they have butted out.

Yeah. That looks healthy.
I want to say here I don’t hate smokers, just smoking. That position will change however if you smoke near my food or drink or blow smoke directly at me. If you do that I’m going to nerd rage and you will take both barrels from someone who has spent the last decade in biomedical science. Just a warning…
The terms first, second and third hand smoke describe where the smoke came from. First hand smoke goes directly from the cigarette into the smokers lungs, second hand smoke comes from the exhaled smoke or smouldering end of a lit cigarette into a non-smoking persons lungs and third hand smoke is the contamination and subsequent consumption of items in an environment after the cigarette has been extinguished.
As the smoke dissipates and becomes invisible we tend to forget about it but cigarette smoke is full of fine particulate matter that then settles on everything in the local environment. Subsequent cigarettes layer particulate on top of previous layers and so a build up occurs. The smaller the area you smoke in the quicker the build up, for example the worse place seems to be the car.
Sleiman et al. (2010) looked at the formation of carcinogens on surfaces by looking at the interaction of nicotine and nitrous acid (found in the air) and found that if they left a cellulose pad in a smokers car to absorb third hand smoke and react with the air they could collect known carcinogens. In total they found 11 different carcinogens including, wait for it, polonium-210!!!

Even the cigarettes are sad.
Of course smokers also carry around third hand smoke on their skin and clothes so they too are also a walking, talking source of contamination.
The harm in third hand smoke is exaggerated in children, which of course is excellent. Children have higher respiration rates and so take in second hand smoke faster but also crawl around on the ground and put things in their mouths which are covered in third hand smoke residues. That’s not anecdotal either, children consume up to 20 times the amount of dust that adults do and when third hand smoke residue is present children get the brunt of the exposure.
At this stage no specific diseases have been linked to third hand smoke exposure but it is only a matter of time. In 2006 the US Surgeon General stated that there is no-risk free level of tobacco exposure and with more than 250 identified dangerous chemicals in each cigarette that’s a bit of an understatement. Prolonged second hand smoking is now associated with all sorts of respiratory conditions and cancers. Given that third hand smoking was only first described in 2010 it wont be long till we identify associated problems with cigarette residue exposure. Given the exposure to children is exaggerated many are tipping currently unexplained developmental impairment as a serious consequence of third hand smoking.
So how do we deal with third hand smoke? Easy actually. Beg, plead, cajole and support everyone you know to quit. Clean all your surfaces regularly, particularly around children and quit! Seriously, please quit.

This blog is a no smoking area.

ReferencesAvol EL, Gauderman WJ, Tan SM, London SJ, & Peters JM (2001). Respiratory effects of relocating to areas of differing air pollution levels. American journal of respiratory and critical care medicine, 164 (11), 2067-72 PMID: 11739136
Sleiman M, Gundel LA, Pankow JF, Jacob P 3rd, Singer BC, & Destaillats H (2010). Formation of carcinogens indoors by surface-mediated reactions of nicotine with nitrous acid, leading to potential thirdhand smoke hazards. Proceedings of the National Academy of Sciences of the United States of America, 107 (15), 6576-81 PMID: 20142504... Read more »

Avol EL, Gauderman WJ, Tan SM, London SJ, & Peters JM. (2001) Respiratory effects of relocating to areas of differing air pollution levels. American journal of respiratory and critical care medicine, 164(11), 2067-72. PMID: 11739136

Sleiman M, Gundel LA, Pankow JF, Jacob P 3rd, Singer BC, & Destaillats H. (2010) Formation of carcinogens indoors by surface-mediated reactions of nicotine with nitrous acid, leading to potential thirdhand smoke hazards. Proceedings of the National Academy of Sciences of the United States of America, 107(15), 6576-81. PMID: 20142504

January 21, 2011
06:13 PM
1,018 views

Halitosis - Your mouth smells like arse

by James Byrne in Disease Prone

Sometimes I'm going to write about rare cancers or blood diseases and sometimes I’m going to write about bad breath. That’s just the way I roll.

Halitosis literally means “condition of the breath” and has many causes and just as many home remedies. Original therapies (and by original I mean 1550 BC) like heavily herb infused wines didn’t remove the bad breath but like mints and other modern treatments they just attempted to cover the bad smell with something more pleasant.

Halitosis isn't limited to humans. Ever smelt a dogs mouth?
Halitosis can be divided into two distinct problems, transient halitosis (morning breath) and chronic halitosis. While the difference between these conditions is the time frame of affliction both have the same root cause. Sulphur.
A study by Suarez et al. looked at what caused the odour in people with morning breath and found that the unique smells produced by people were due to three sulphurous gases combining into a malodourous mixture. The gases, hydrogen sulphide (smell of rotting eggs), methanethiol (smell of rotting cabbage) and dimethylsulphide (which has a slight sweet smell), were present in varying quantities between participants giving them all bad morning breath.
The sulphurous gases are produced by bacterial build up in the mouth and in particular on the tongue. During the night your production of saliva drops significantly and with less saliva bacterial numbers increase dramatically. Saliva has a number of jobs in the mouth related to bacterial load but its three main roles are to acts as a tidal wave to wash bacteria out of the mouth, to inhibit bacterial growth using various chemical components and participate in the killing of bacteria by carrying parts of the immune system into the mouth. But less saliva equals more bacteria and consequently, bad breath.
Given this it wasn’t surprising that the treatments that Suarez et al. found good immediate treatments of halitosis (I say immediate because as saliva production increased the bad breath went away naturally) where mechanical scraping of the tongue. Specifically brushing of the teeth with toothpaste did nothing but brushing of the tongue with water was much more effective. Eating a dry bread roll was also very effective as it scraped across the tongue, removing bacteria.
The best treatment was a mouthwash of 5mL of 3% hydrogen peroxide – guess why. This treatment killed huge umbers of bacteria and immediately dropped the concentration of the sulphurous gases, which stayed low for hours afterwards.
While rare there are a few conditions that produce halitosis that has a non–oral origin but they are extraordinarily rare and halitosis is but one of a bevy of symptoms that the patient would possess.
Foetor hepaticus, or the ‘breath of the dead’, is seen in people with late stage liver failure. It is caused by the passage of thiols from the blood into the lung. These compounds are normally removed in the liver but as the liver shuts down thiols remain in the blood and can escape into the lungs. Apparently distinct from typical halitosis foetor hepaticus smells of sweet faeces.
Another condition, known as trimethylaminuria is also known as fish odour syndrome. People suffering from trimethylaminuria lack the metabolic enzyme Flavin containing monooxygenase 3 which breaks down trimethylamine to trimethylamine oxide. The result is that trimethylamine builds up in the blood and is removed in the urine, sweat and breath. Despite its name an odour of fish is rare and most sufferers just have an unusually strong and sometimes unpleasant odour.
So if you have halitosis, but don’t have late stage liver failure or metabolic disease, you can treat your bum breath with breakfast and mouthwash if you pedantic. So no excuse for blowing it in my face on the train from now on!

Reference Suarez FL, Furne JK, Springfield J, & Levitt MD (2000). Morning breath odor: influence of treatments on sulfur gases. Journal of dental research, 79 (10), 1773-7 PMID: 11077993... Read more »

Suarez FL, Furne JK, Springfield J, & Levitt MD. (2000) Morning breath odor: influence of treatments on sulfur gases. Journal of dental research, 79(10), 1773-7. PMID: 11077993

March 11, 2011
06:24 PM
955 views

Capsular Polysaccharide and Pneumococcal Disease

by James Byrne in Disease Prone

A paper came out as an ePublication ahead of print this week looking at the capsular polysaccharide of Streptococcus pneumoniae. Want to know how I know? I wrote it :)

Insert stock photo of pneumo. Check.

It seems a little wrong to blog my own paper but in reality more people will read this blog entry than will read the paper itself, and that’s fine. Its relevance is very narrow and the work very preliminary but really it’s the drive behind the work that is important. So lets talk about Streptococcus pneumoniae (aka the pneumococcus or simply pneumo) for a second to set the scene.

Pneumo is a big deal. It is responsible for roughly a million deaths in children under 5 around the world every year and is such a problem in the developing world its one of the bugs that Bill and Melinda Gates have taken a personal dislike to.

This data is taken striaght from the WHO website. The only modification is I have added Streptococcus pneumoniae as a separate bar. Deaths caused by pneumo make up approximately 2/3 of all lower respiratory infections. I colour coded the bars for some reason for another post, I cant remember the key... #badblogger

Despite being such a huge killer it’s actually a very common bacteria. Every single person on Earth probably has it right now, so in that respect it’s not a great killer but at the same time, it doesn’t want to be. If you kill the host you destroy your home and food source so pneumo is happily carried in populations without causing disease, for the most part.
I have spoken about pneumo like there is only one kind of pneumo but that’s as silly as saying there is only one kind of human. An important common characteristic is that the outside of each pneumo, similarly to humans, doesn’t always look the same. In humans, differences in skin colour, texture, etc allows us to tell people apart, for pneumo however it’s the chemical composition of a structure called the capsule which encases the entire bacterium.
This capsule has, roughly, 90 different common variations and the distributions of these variations (referred to as serotypes) change depending on geographical region, age and community.
The important thing about the capsule is its job. The bacterium uses the capsule to hide from the host immune system, which is what generally triggers an immune response, and so allows the bacteria to persist asymptomatically in the naso-pharynx.
But as I hinted before pneumo doesn’t always sit happily in the naso-pharynx…
Generally during some other infection the pneumo will descend into the lungs and cause pneumonia, from which the bacteria derives its name. Approximately 30% of pneumonia patients will develop bacteremia as the bacteria use the lung damage to gain access to the blood. Once in the blood the bacteria can move all around the body and cause all sorts of disease but importantly they can cause meningitis (inflammation of the meningies in the brain) and this occurs in approximately 30% of bacteraemic patients.
Pneumo relies on its capsule to hide from the immune system during pneumonia, bacteraemia and meningitis (collectively called the invasive pneumococcal disease of IPD’s), but what if you take the capsule away? It turns out the immune system can ‘see’ the bacteria very easily without its capsule and so un-encapsulated bacteria can sit in the naso-pharynx but if they try to cause trouble the immune system can knock them out very easily.
This is where my work comes in.
Now it’s true that we can treat pneumo with antibiotics and we have two vaccines against pneumo but its still a massive problem. Something in the order of 60% of all clinical isolates show some level of antibiotic resistance with up to 10% showing resistance to 4 or more common antibiotics. The vaccines we have are also of limited use as one doesn’t work in children, where most of the disease occurs and the other doesn’t have enough ‘serotype coverage’ to be effective throughout the entire world.
To compensate for this my lab looks at alternative vaccines and that protective capsule layer. My work has really been to investigate how the biosynthesis of this layer is regulated and look for potential to break the regulation and in doing so prevent capsule formation and the invasive potential of the pneumococcus.
The regulation of capsule biosynthesis is achieved through a dynamic phosphorylation cycle that essentially acts like a switch.

This model was developed by my supervisor based on extensive mutagenesis work.

This is the current working model of the regulation. On the left we have the capsule being synthesised. The details are a little much for here but ‘C’ is a protein embedded in the membrane, it interacts with ‘D’, a tyrosine kinase. A tyrosine kinase is an enzyme that adds a chemical group called a phosphate to something else. In this system it actually adds that group to itself and when it does it forces itself to change shape. This altered shape in ‘D’ (represented on the right of the diagram) is thought to either change ‘C’s’ shape as well or the change is simply relayed through ‘C’ to the outside of the cell and production of capsule stops. Instead when ‘D’ is phosphorylated any complete capsule is stuck to the cell wall. As this process is not a one way switch we need to return to the left of the diagram and this is achieved due to the activity of ‘B’ which is able to remove phosphate groups from ‘D’.
For what was published in the paper we (or rather I) performed some mutagenesis on ‘C’ that resulted in it not being able to relay the change in shape of ‘D’. This resulted in switches jammed on to the left or the right but incapable of changing.
Importantly other mutants that have been constructed with an inability to switch capsule biosynthesis properly are unable to cause disease. Our hope however is to reach a point where we know enough about this system that instead of relying on a mutation in ‘C’ to give us a switching defect we might be able to design a drug or inhibitor that blocks ‘C’ activity in vivo. But that’s 5 – 10 years away.
I think I’ll just write this and my other experiments up into my thesis, then worry about the rest of the work that needs doing…

References... Read more »

Byrne JP, Morona JK, Paton JC, & Morona R. (2011) Identification of Streptococcus pneumoniae Cps2C Residues that Affect Capsular Polysaccharide Polymerisation, Cell Wall Ligation and Cps2D phosphorylation. Journal of bacteriology. PMID: 21378192

Morona JK, Miller DC, Morona R, & Paton JC. (2004) The effect that mutations in the conserved capsular polysaccharide biosynthesis genes cpsA, cpsB, and cpsD have on virulence of Streptococcus pneumoniae. The Journal of infectious diseases, 189(10), 1905-13. PMID: 15122528

April 2, 2011
07:58 PM
928 views

Exploding Head Syndrome - No pun required

by James Byrne in Disease Prone

This is an old post from my previous blog. Recently it has been seeing a lot of activity so I thought I'd play around with it a bit and re-post it here. Enjoy :)

Sometimes when searching for disease to write about a wonderful thing happens. The clouds part, cherubs descend, angels play intricate harp-based musical compositions, and a beam of light illuminates the link to a wonderful disease. This happened to me the other day, and now, without further ado, let me introduce you to Exploding Head Syndrome. Best. Disease. Name. Ever.

Acute Exploding Head Syndrome sufferer (screenshot from the 1981 movie Scanners)

Okay so heads don’t actually explode but sufferers seem to experience a simulated explosion in the form of an incredibly loud noise coming from inside their own head. This sound can take many forms from ringing and screaming to, of course, explosions. One patient even described the preceding whistle of dropping bombs, the explosion of shells, and then complete silence, similar to an experience she endured as a child during the Blitz in London.
Exploding Head Syndrome is related to equally terrifying syndromes called ‘ice-pick headache’ and ‘needle in the eye syndrome’ but each of those have a pain component where Exploding Head Syndrome doesn’t (I can’t help capitalising Exploding Head Syndrome, it just feels like it should carry capitals).
The syndrome itself is described as “harmless but frightening” for sufferers. I guess the sensation that your head is about to explode isn’t pleasant but frightening doesn’t seem to be enough of a word to describe the torment.
Just to up the scare factor of this syndrome it seems to be associated with sleep. In a case study published in the British Medical Journal a woman described her attacks as…:“Being wakened by a sudden bang in the head, as if my head was bursting with a flash of light over both fields of vision, after which I would be dazed for a split second" [and then would] "Come round, terrified, my heart thumping. There was no pain, just a frightening sense of explosion.”Wow.
So what’s happening? Nobody has any idea. It isn’t auditory because deaf sufferers have been reported. It’s not linked to random nerve firing (often reflected in a condition called myoclonic jerks). It’s not linked to epilepsy. It’s not linked to migraines.
So we can’t understand what causes it, we have no idea what’s happening, we can’t say what might trigger it, it doesn’t seem to correlate with any associated conditions, apart from sleep – there’s only one thing missing here. Can we cure it? Of course not, what are you, stoopid?
There have been some reports that sedatives help but also, confusingly, apparently so do stimulants. Anti-depressants apparently help but not in all cases. The best bet for treatment seems to be to let it go away on its own. Many recorded cases had an acute onset where every night’s sleep was disrupted at least once and over a month to years the attacks became less frequent until they appeared to stop altogether.
I guess sufferers can take heart that if nothing else, being diagnosed with an Exploding Head makes for pretty interesting dinner party conversation!

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Listerine - Insensitive to Exploding Head Syndrome sufferers since 1914
Chakravarty, A. (2008). Exploding head syndrome: report of two new cases Cephalalgia, 28 (4), 399-400 DOI: 10.1111/j.1468-2982.2007.01522.x
Evans RW, & Pearce JM (2001). Exploding head syndrome. Headache, 41 (6), 602-3 PMID: 11437900
Kallweit U, Khatami R, & Bassetti CL (2008). Exploding head syndrome--more than "snapping of the brain"? Sleep medicine, 9 (5) PMID: 17709298
Pearce JM (1989). Clinical features of the exploding head syndrome. Journal of neurology, neurosurgery, and psychiatry, 52 (7), 907-10 PMID: 2769286... Read more »

Chakravarty, A. (2008) Exploding head syndrome: report of two new cases. Cephalalgia, 28(4), 399-400. DOI: 10.1111/j.1468-2982.2007.01522.x

Evans RW, & Pearce JM. (2001) Exploding head syndrome. Headache, 41(6), 602-3. PMID: 11437900

Kallweit U, Khatami R, & Bassetti CL. (2008) Exploding head syndrome--more than "snapping of the brain"?. Sleep medicine, 9(5), 589. PMID: 17709298

Pearce JM. (1989) Clinical features of the exploding head syndrome. Journal of neurology, neurosurgery, and psychiatry, 52(7), 907-10. PMID: 2769286

December 10, 2010
05:46 PM
897 views

Mucous Cancer - The mess of Pseudomyxoma peritonei

by James Byrne in Disease Prone

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This post is very important to me for two reasons. First of it’s my very first proper post at my new home here at Disease Prone. Secondly it is a post I have been in the process of putting together for a while after it was suggested to me by my lovely wife, a nurse whose insights in to disease and treatment I hope to include as regularly as possible. I hope you enjoy it and all future posts as much as I enjoy writing them. Peace out.
The last time I wrote about cancer it was for the Scientific American regarding how bacteria can be used as treatments so really it wasn’t even cancer I was talking about but when I was told about this doosey of a cancer I couldn’t help but write about it. This is significant for me as I am a bacteriologist who has spent a long time trying to avoid cancer (developing or writing about it), too many signalling pathways (imagine trying to memorise dozens of images like this), ick.

Pseudomyxoma peritonei is a relatively rare cancer that literally is translated to mean “false mucinous tumor of the peritoneum”. The tumour is unusual because it’s of a very specific cell type resulting in an overproduction and accumulation of mucous in the abdominal cavity, also known as the peritoneum.

I love using old Gray's Anatomy pictures. Click to embiggen but essentially the peritoneum is the blue bit.

Although controversial it is currently believed that these cancers start in the appendix and over time the small internal cavity fills with proliferating tumour cells and they mucous they are producing until the organ becomes occluded. Once occluded the appendix will fill up like a fleshy mucous balloon (‘distends’ in medical speak) and eventually will explode (again, ‘rupture’ for the medicos out there) leaking the appendix’s contents into the abdominal cavity. But the tumour isn’t dead so the production of mucous continues slowly leaking more and more mucous.
I say the origin is ‘controversial’ because it is very hard to work out for this type of cancer. Ordinarily when you are diagnosed with cancer the doctor finds the biggest tumour, points to the middle of it and says it started right here. With disseminated cancers like those in Pseudomyxoma peritonei there is no tumour (hence the false part of its name) and you only realise you have it when your insides start to fill up with mucous.
Treating these cancers, as you can imagine is quite difficult. First you have to detect it. As the tumour is slow growing, and doesn’t form a solid tumour it is very hard to detect pathology early enough to prevent rupturing of the appendix and release of muck into the abdominal cavity. However, early detection allows for the removal of the appendix and with a bit of luck all the cancerous tissue with it.
If you don’t find it early consider yourself booked in for cytoreductive surgery also known as debulking. This kind of surgery involves opening you up and removing as much mucous as possible from the peritoneal cavity and removing organs that have been exposed to the mucous + cancerous cell mix. Generally this means patients will have the organs at the bottom of the abdomen removed including ovaries, uterus, bladder, parts of the small intestine, appendix, and parts of the liver.
Then you hope and wish that works.

That dotted line across the middle is referring to the "transpyloric plane", essentially everything under it is removed in during cytoreductive surgery.
Alongside cytoreductive surgery you normally have your peritoneal cavity filled with good old chemotherapeutics.
Even if you survive all that it is very difficult to determine if the cancer is all gone for the same reasons it was hard to detect to begin with so patients look forward to a life of hospital waiting rooms as the current practice is to perform tests every 3 months to monitor for changes.
Commonly all of these techniques are now rolled into one operation called a Sugarbaker procedure. This procedure starts with complete cytoreductive tumour removal followed by surgical chemotherapeutic administration and removal of the right hemicolon, spleen, gallbladder, greater omentum and lesser omentum, uterus and ovaries in women and rectum in some cases then further work strips the peritoneum from the pelvis and diaphragm before removal of the tumour from the surface of the liver. Yeah, this operation takes about 10 hours and at the end you’re empty. That must be such a weird feeling.
Until my wife told me about this disease I had no idea such a cancer existed. Slow growing rare cancers rarely make it to public knowledge but they are really important. Pseudomyxoma peritonei does not kill many people per year as it is so rare but even after treatment the long term survival rates are only 40% or so, if you get it your in trouble.
Of all the cancers I’d like to never have (all of them) this one comes somewhere near the top of the list. As well as being deadly and impossible to treat with any confidence there’s a bunch of mucous and it’s the image of a burst appendix leaking dribbling mucous that I can’t shake.
Luckily, treatments are improving and survival rates are defiantly on the increase. One French study found th... Read more »

Hinson FL, & Ambrose NS. (1998) Pseudomyxoma peritonei. The British journal of surgery, 85(10), 1332-9. PMID: 9782010

Sherer DM, Abulafia O, & Eliakim R. (2001) Pseudomyxoma peritonei: a review of current literature. Gynecologic and obstetric investigation, 51(2), 73-80. PMID: 11223697

Brueggen C, Baird G, & Meisheid A. (2007) Pseudomyxoma peritonei syndrome of appendiceal origin: an overview. Clinical journal of oncology nursing, 11(4), 525-32. PMID: 17723965

Glehen O, Gilly FN, Boutitie F, Bereder JM, Quenet F, Sideris L, Mansvelt B, Lorimier G, Msika S, & Elias D. (2010) Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy: A multi-institutional study of 1290 patients. Cancer, 116(24), 5608-18. PMID: 20737573

January 25, 2011
06:51 PM
892 views

The Australia Antigen

by James Byrne in Disease Prone

I feel a little left out some times on the internet as many (but certainly not all) of my bloggy friends are English or American. So, just to fill you in, the 26th of January is Australia Day and it commemorates the landing of our first fleet in 1788 and the planting of the British flag in what was then known as New Holland and is now known as Sydney Cove, New South Wales, Australia. Most people celebrate the day with a public holiday, a beer or two, a barbi and the TripleJ Hottest 100.

We will get back to the Australiana theme in a moment but I want to take it down a notch first by talking about Hepatitis B virus.
Hepatitis diseases are not limited to those induce by viruses. In fact hepatitis just means inflammation of the liver from hepat(o)- for liver and –it is meaning inflammation of. This has led to the common misconception that the Hepatitis viruses (A, B, C, D, E) are related to each other, they’re not, but they do all cause liver inflammation. In fact according to the Balitmore Classification of viruses they fall in completely different families. Furthermore the run of letters, which also suggest relatedness, simply describe the order in which the viruses were identified.

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The Baltimore Classification describes the lifecycle of all viruses based on their genome structure. Protein is produced based on the mRNA sequence so that’s why all lines flow back to mRNA.

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While all are problematic in their own way for this post we are interested only in Hepatitis B virus (HBV), arguably the biggest problem in the (not) family of hepatitis inducing viruses.
How big a problem is HBV? Well, approximately 2 billion people worldwide are infected, greater than 350 million people are in the chronic phase of infection and its estimated that a quarter of these people will die of liver cancer or other complications directly caused by HBV.
Like many viruses encased in a membrane (a so called enveloped virus), HBV requires body liquid exchanges to transmit from person to person but is not necessarily picky as to which liquid and transmission has been observed by blood exchange, sexual contact and even maternal-foetal exchange across the placenta.
HBV disease is very well characterised and follows a fairly generalised route. Following transmission the viruses work their way into the blood stream and eventually find their way into the liver where they can attach and enter liver cells. Once inside the cells the virus and its components are very stable and viral replication kicks in resulting in huge numbers of virus being produced and seeking out new liver cells. This infection stage can last up to 6 months with almost no symptoms beyond generalised flu-like symptoms or a touch of jaundice.
Following initial viral replication there are three outcomes are possible. Best case scenario, you mount an early, strong and effective immune response that removes all the virus from your system. Worst case scenario #1 (short term), you develop a form of acute hepatitis called fulminant hepatitis which is caused by your immune system reacting too strongly and liquifiying your liver in an attempt to remove the virus resulting in a quick death. Worst case scenario #2 (long term), your immune response is slow or weak and the virus persists resulting in a chronic infection. An interesting little side note here is that if you are a child your chances of developing chronic hepatitis B skyrocket to 95% compared to the 5% chance to adults and at this stage we really don’t understand why.
So your either fine, dead or a time bomb and chronic sufferers can look forward to a life of medications attempting to prevent death. Having said that some chronic HBV patients go on and live lives free of complication or further symptoms but most end up with either a passive or active form of liver destruction depending on whether you show any symptoms or not respectively.
The destruction of the liver is immune mediated which mean the virus doesn’t actually kill liver cells but its presence activates the immune system inducing it to kill any cell with virus. As the liver can regrow your left with constant cell death and constant cell renewal but it all comes at a cost, scars. Scars in tissues are called scar tissue (duh) or more accurately fibroma. Fibromas are a problem as they impair organ function and when you develop too many the organ starts to die as blood cannot flow to all parts of the liver or promotes the liver to overcompensate and regenerate faster leading to cancer – hepatocellular carcinoma.

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Pic courtesy of my good friend Thomas Tu from the wonderful blog Disease of the Week. In unvaccinated hosts this is the pathway through HBV infection.

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So what can we do about HBV? Currently your best option is vaccination. Its pretty cheap (for me it was any way), very safe and really effective. As well as being the best option, its kind of the only option as all the anti-viral drugs currently available do not ‘cure’ the virus, they can only act to freeze or pause it. When you stop the drugs the virus un-pauses. As I will most definitely talk about at a later date vaccines are ... Read more »

Blumberg, B. (1984) Landmark article Feb 15, 1965: A "new" antigen in leukemia sera. By Baruch S. Blumberg, Harvey J. Alter, and Sam Visnich. JAMA: The Journal of the American Medical Association, 252(2), 252-257. DOI: 10.1001/jama.252.2.252

Lee WM. (1997) Hepatitis B virus infection. The New England journal of medicine, 337(24), 1733-45. PMID: 9392700

April 8, 2011
10:45 PM
877 views

Yes We C(r)an(berry)!

by James Byrne in Disease Prone

That title is awful I know but I'm tired. Cut me some slack :) I ran into a something that I have heard about before but assumed was rubbish and never really looked into it properly. A friend of mine insisted it was the case so I looked it up and I have to say, I was a little surprised.

So this is what cranberries look like. I never knew.
Cranberry juice is apparently very good at prevent urinary tract infection, particularly in women. There have been a few studies approaching it from different angles but, disappointingly, the studies all use different types of cranberry product, different doses and dosing techniques but despite all this the message seems to be pretty clear. Cranberries prevent urinary tract infections kicking in.
Before we can consider how this occurs its important to define what we are talking about. Urinary tract infections or UTIs are generally caused by a strain of Escherichia coli called Uropathogenic E. coli (UPEC) and it gets there by moving from the colon…ew. For this reason men rarely have to worry about them while they can be a chronic problem for women around the world, however the insertion of urinary catheters is a major risk factor for both genders. Clinical symptoms include burning sensation during urination and cloudy urine but these are only really evident once the bacteria have ascended the urethra into the bladder causing urethritis and cystitis respectively. If you want to feel real pain however let the little bastards work their way into your kidneys where kidney infection (or pyelonephritis) results in the above symptoms plus back pain and fever and the possibility of systemic spread.
So the first step in the infective process is generally stable colonisation of the colon. This step is often overlooked but without a source of UPEC it’s hard to get a proper infection going. The next step is invasion of the vaginal microbiota. Not an insignificant task since the vaginal niche is normally fully occupied by lactobacilli and other innocuous strains. Only once this has occurred can the UPEC ascend the urethra.

Having ascended the urethra the UPEC are not in the free and clear because the bladder and urethra have a formidable barrier to infection, the waterfall of flushing, cleansing urine that washes away all in its path. To overcome this UPEC have developed powerful adhesins, proteins used adherence of the bacterium to a surface and in this case specifically to the urinary epithelial tissue.
Adhesins are found in most pathogenic bacterial species but the array and strength of the UPEC adhesins is staggering. Among the most important adhesins produced by the UPEC are the pili. Pili are hair-like structures on the bacterial surface that are often capped with sticky (in the molecular sense) ends that facilitate adhesion. Importantly for UPEC possessing three different sticky caps (S, P and Type 1 pili) increases the chances of binding.
The S pili tend to be more important for adhesion outside of the gentio-urinary tract and so may play a part in systemic spread. In the urine however these pili bind the mannose filled protein uromodulin. Because of this S pili are called mannose sensitive pili and its thought that the ability to bind uromodulin, the most abundant protein in urine, possibly results in bacterial clumping and this allows a better opportunity for the P and Type 1 pili to do their thing. These two pili are responsible for the binding in the urethra and bladder.
Initially the Type 1 pili bind mannose sugars on the surface of the bladder cells allowing the bacteria to get some traction on the bladder/urethra walls before the P pili bind to a different sugar group to cement the interaction. The ability of P pili to bind non-mannose sugars has earned them the alternative title mannose resistant pili whereas type 1 pili are grouped with the mannose sensitive S pili.

The pili are the hairy bits on the picture of E. coli. The paper this pic is from is referenced at the bottom.
Once adhered to the host surface the UPEC can invade the epithelial cells but the bladder’s defence against this is to kick those invaded cells into the urine. A good defence strategy but it may contribute to tissue damage in the urinary tract when infections are recurrent. Also it seems some bacteria can prevent this expulsion of the cell they have invaded and in doing so remain as a reservoir of infection out of the way of the immune system and most antibiotic treatments.
Invasion does not always occur and instead some UPEC strains are able to release toxins directly onto the host epithelial surface due to the close interaction between bacterium and host. These toxins, as well as one of my boss’s favourite little molecules lipopolysaccharide (LPS) cause the inflammation that goes with the UTI.
So that’s the UTI side of things but where does Cranberry juice come into this story?
Cranberries (Vaccinium macrocarpon if you don’t mind) together with blueberries and Concord grapes constitute the only native fruit species to the US and Canada. Bet you didn’t know that, or maybe you did but I didn’t. In any case often the best way to work out what the native flora is capable of you have to look back to the indigenous peoples and, surprise surprise, Native Americans have known about and utilised the medicinal properties of cranberries for many years. Commonly used in different preparations to treat blood disorders, stomach issues, liver trouble and fevers.
By the 1880’s people were trying to work out what was doing what with cranberries and some German researchers found benzoic acid in cranberries. Then as now it was known to be a potent antiseptic and was included in a number of medicines and topical anti-bacteria treatments. This observation set researchers down the wrong path from the get go as the real power of cranberries lies in other activities of other compounds.
Continuing research into the antibacterial properties of cranberries found the benzoic acid was converted to hippuric acid, another antibacterial agent that also has a role in acidifying the urine. Everyone thought they were onto a winner. A powerful antibacterial compound excreted in the urine because you ate some cranberries. This is open and closed right? Well…

Could I be any clearer... Read more »

Raz, R., Chazan, B., & Dan, M. (2004) Cranberry Juice and Urinary Tract Infection. Clinical Infectious Diseases, 38(10), 1413-1419. DOI: 10.1086/386328

Gross, L. (2006) Bacterial Fimbriae Designed to Stay with the Flow. PLoS Biology, 4(9). DOI: 10.1371/journal.pbio.0040314

BODEL PT, COTRAN R, & KASS EH. (1959) Cranberry juice and the antibacterial action of hippuric acid. The Journal of laboratory and clinical medicine, 881-8. PMID: 13801916

Sobota AE. (1984) Inhibition of bacterial adherence by cranberry juice: potential use for the treatment of urinary tract infections. The Journal of urology, 131(5), 1013-6. PMID: 6368872

December 22, 2010
05:41 PM
859 views

(Merry) Christmas Disease

by James Byrne in Disease Prone

So I was feeling a little lazy and thought I should find a disease related to Christmas, that way it’d be topical and I’d look like a genius. Well maybe not a genius, as all I did was type “Christmas” and “disease” into google and it returned “Christmas disease”. Don’t worry though, the disease itself is pretty cool!

Contrary to popular belief Christmas disease is not limited to public drunkenness

Unfortunately for me my attempt at topical blogging reveals that Christmas disease is not named after the holiday but instead after Mr Stephen Christmas, a British migrant who immigrated to Canada, who was diagnosed at the age of 2 in 1949 with haemophilia. On a return visit to England in 1952 Stephen was again hospitalised and a sample of his blood was sent away to the Oxford Haemophilia Centre where it was determined by Rosemary Biggs and R.G. McFarlane that Mr. Christmas did not have a normal case of haemophilia, he had something that had never been described before.
Haemophilia is best described as a blood clotting disease. All haemophilia cases are genetic and are inherited from your parents and although there are many types the risk is that any blood vessel breakage could result in 'bleeding out' as suffers are unable to clot or coagulate normally so the blood keeps spilling.
The proteins responsible for allowing the blood to clot are called 'Factors' and there are 3 that are particularly important yet unhelpfully named as Factor VIII, IX and XI.

Oh noes I'm bleeding through my skin! Seriously can anyone see where the actual cut is?
Haemophilia C is caused by a genetic mutation that produces a non-functional Factor XI, a.k.a. plasma thromboplastin antecedent. The gene for Factor XI is carried on chromosome 4, which makes it a recessive autosomal disease. All that means is that there is an equal chance for both males and females to get it and for the full blown disease you need to inherit dodgy copies of the gene from both parents but an intermediate form of the disease can still occur if you receive only one dodgy copy. For this reason it is super rare making up about 1% of all haemophilia cases but in small groups where children are encouraged to marry and have children with others from inside the same group, say for example Ashkenazi Jews where C type Haemophilia affects 8% of the population, the proportyion of type C haemophilia cases goes up.
The genetic mutation for types A and B haemophilia are located on the X chromosome so are classified as X-linked disorders rather than an autosomal disorder like type C. This means the disease is more common, and often more serious, in males. The reason for this disparity is that males only have one X chromosome (remember males are XY at their sex chromosomes) while females have two X’s. One dodgy copy of a gene in an X chromosome in males = disease whereas females can in most cases accommodate one dodgy copy and still be fine.
Type A is the most common form of haemophilia accounting for 80% of all cases and is caused by a mutation destroying the activity of Factor VIII, a.k.a. anti-haemophilic factor. Factor VIII forms a complex with other clotting factors in the presence of high calcium concentration that result in a clotting cascade. For those of you with a bit of biology background you will know that Ca is not present in high concentrations anywhere in the body (except the bone) because it is biologically active and so its presence is a potent signal. Nerves use Ca during signalling, immune cells can follow a Ca gradient and other cells use it to talk to each other. Anyway when the concentration that is free in the blood goes up it indicates blood vessel damage and initiates the clotting cascade through activation of Factor VIII.
Finally we work our way back to Stephen Christmas. When the scientists at the Oxford Haemophilia Centre looked they found levels of Factor VIII was fine (at this stage type C hadn't been discovered so Factor XI wasn't analysed) but Stephen was lacking Factor IX. This type of Haemophilia was classed type B.
Type B haemophilia is X-linked and here the mutation breaks Factor IX, a.k.a. Christmas Factor, that acts as a serine protease. The activity of Factor IX is controlled by either XI or VIII as either can cut Factor IX in half which converts it from an inactive to active form. The cut or cleaved form of Factor IX also requires high Ca to function and in the right conditions will promote coagulation. Stephen Christmas’ condition was treated using transfusions of normal blood which contained normal Factor IX allowing him to clot normally but repeated transfusions in the early 60’s and 70’s resulted in him eventually contracting Human Immuno-deficiency Virus (HIV) which later developed into Auto Immune-deficiency Syndrome (AIDS) which he succumbed to in 1993.
Following the detection of HIV in Stephen’s body he became an active worker and proponent for screen of donated blood to increase the safety of transfusions, which was eventually adopted by 1985.

Stephen Christmas was kept alive by transfusions and I implore you to give blood too. Click here for your closest Australian donation centre and just Google for other countries. Best. Gift. Ever.
While Stephen Christmas’ life may have been afflicted by a horrible disease his gift was to help bring in an era of change that has undoubtedly saved millions of lives by screening donor blood for harmful elements, including HIV Hepatitis B and C viruses amongst many others.
Fun facts!!!Type B haemophilia is the form that ran/runs in both the British and Russian royal families!Christmas Disease is cause for a deficiency in functional Factor IX resulting in an inability to clot. Over production of Factor IX can be just as bad though and has in fact been linked to conditions such as deep vein thrombosis which are characterised by inappropriate and unnecessary clotting.
And with that I say have a great holiday period for those of you who are celebrating one ... Read more »

Rogaev EI, Grigorenko AP, Faskhutdinova G, Kittler EL, & Moliaka YK. (2009) Genotype analysis identifies the cause of the "royal disease". Science (New York, N.Y.), 326(5954), 817. PMID: 19815722

BIGGS R, DOUGLAS AS, MACFARLANE RG, DACIE JV, PITNEY WR, & MERSKEY. (1952) Christmas disease: a condition previously mistaken for haemophilia. British medical journal, 2(4799), 1378-82. PMID: 12997790

June 24, 2011
07:25 PM
855 views

No door? No problem. T. cruzi uses the window to cause Chagas Disease

by James Byrne in Disease Prone

For invasive pathogens the only way to survive, and consequently make you sick, is to get inside your cells. This is a rough exercise as you have an immune system working everywhere in the body to prevent this and the cell to be invaded is none too happy with the idea either so invasive pathogens must use tricks.... Read more »

Jermy A. (2011) Parasitology: Adding insult to injury. Nature reviews. Microbiology, 9(7), 484. PMID: 21625249

Andrade LO, & Andrews NW. (2005) The Trypanosoma cruzi-host-cell interplay: location, invasion, retention. Nature reviews. Microbiology, 3(10), 819-23. PMID: 16175174

Fernandes MC, Cortez M, Flannery AR, Tam C, Mortara RA, & Andrews NW. (2011) Trypanosoma cruzi subverts the sphingomyelinase-mediated plasma membrane repair pathway for cell invasion. The Journal of experimental medicine, 208(5), 909-21. PMID: 21536739

January 7, 2011
07:02 PM
838 views

Jumping Frenchmen of Maine Syndrome

by James Byrne in Disease Prone

Well I’m back! I’m not going to pretend like you missed me but I hope your glad to see another post out of me. I did a bit of writing during my time off to build up a bit of a backlog so hopefully I can keep posting regularly for a while. Anyway, without any further ado…
Jumping Frenchmen of Maine Syndrome
Best. Disease. Name. Ever.
This disease was first observed in 1878 by the neurologist Dr. George Miller Beard, a guy I will definitely talk about again, in French-Canadians, lumberjacks and presumably some French-Canadian lumberjacks living in northern Maine. So that explains the “Frenchman” and “Maine” parts but lets look at what makes this a “Jumping Syndrome”.

This is the famous jumping Frenchman Patrick de Gayardon. He has nothing to do with this story. Left Right.

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This syndrome is due to an exaggerated startle reflex resulting in uncontrolled jumps commonly but can also manifest as spasms throughout the body. The startle reflex is very important and forms part of the ‘fight or flight response’ normally.
Essentially a startle (which by definition has an auditory component) has three major neurological routes in the brain that have a number of effects. First, the auditory nerve fibres stimulate the cochlear root neurons (CRN) that form the first part of the central nervous systems auditory processing. Following this stimulation the CRN’s stimulate the nucleus reticularis pontis caudalis cells (PnC) located in the Pons (part of the brainstem). Finally the input into the Pons results in stimulation of motor neurons, particularly to the head and neck and the spinal cord. This results in the jerking response aimed at orientating you to the source of the startle while also priming your body for a response.

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Left shows brain side on with exposed brain stem and pons are highlighted while right shows the dorsal view of the brain stem (dorsal means back, think about the location of the dorsal fin on a dolphin) with the CRN highlighted.
One thing that I think is important to point out is how fast this all is. The time taken from the detection of the stimulus to the first muscles to react (in your jaw) is roughly 14 milliseconds! The last muscles to react (unsurprisingly in your feet and legs) receive stimulation after only 400 milliseconds!
Jumping seemed to not be the only unusual response in the Jumping Frenchman. Some exhibited echolalia (one of my favourite words and albums) or echopraxia. Others yelled, spasmed or hit out and another observation was made that confused matters further. Some jumpers would inexplicably follow commands given alongside their stimulus including one man who was startled whilst being given an order to throw causing him to launch the knife in his hand across the room. This was observed to be repeatable and the sufferer was ordered to throw a bunch of objects including a pipe he had just finished packing.
Researchers have looked for something in this community to explain this unusual stimulus response. This isolated community exhibits all the hallmarks of a population that might result in mutations that could develop and persist. Lending credence to this possibility were Beard’s original observations that the jumpers were confined to family groups but so far no genetic analysis has show a causal link to the condition.
These studies have suggested a different cause. In particular the work of the Saint-Hilaire’s which involved videotape evidence of a number of sufferers seems to suggest the response is psychological, not neurological, and may have been brought on by positive re-enforcement of this unusual behaviour in the small community.
Whatever the cause the disease still has a funny name. Almost feels like it should have been a Monty Python sketch if you ask me.

References
Saint-Hilaire MH, Saint-Hilaire JM, & Granger L (1986). Jumping Frenchmen of Maine. Neurology, 36 (9), 1269-71 PMID: 3528919
Saint-Hilaire, M., & Saint-Hilaire, J. (2001). Jumping Frenchmen of Maine Movement Disorders, 16 (3), 530-530 DOI: 10.1002/mds.1080
... Read more »

Saint-Hilaire MH, Saint-Hilaire JM, & Granger L. (1986) Jumping Frenchmen of Maine. Neurology, 36(9), 1269-71. PMID: 3528919

Saint-Hilaire, M., & Saint-Hilaire, J. (2001) Jumping Frenchmen of Maine. Movement Disorders, 16(3), 530-530. DOI: 10.1002/mds.1080

Howard R, & Ford R. (1992) From the jumping Frenchmen of Maine to post-traumatic stress disorder: the startle response in neuropsychiatry. Psychological medicine, 22(3), 695-707. PMID: 1410093

June 18, 2011
12:00 AM
818 views

Anti-cancer Fungi

by James Byrne in Disease Prone

Mycology, the study of fungi, is an often-overlooked member of the microbiology family. Having said that there are plenty of dedicated mycologists out there doing all sorts of cool stuff and plenty more fungal species doing all sorts of weird and wonderful things.... Read more »

King-Fai Cheng, & Ping-Chung Leung. (2008) General review of polysaccharopeptides (PSP) from C. versicolor: Pharmacological and clinical studies. Cancer Therapy. info:/

Luk SU, Lee TK, Liu J, Lee DT, Chiu YT, Ma S, Ng IO, Wong YC, Chan FL, & Ling MT. (2011) Correction: Chemopreventive Effect of PSP Through Targeting of Prostate Cancer Stem Cell-Like Population. PloS one, 6(6). PMID: 21674070

February 4, 2011
06:14 PM
777 views

Flooding and disease

by James Byrne in Disease Prone

I’m not sure what the coverage has been like overseas but most of the east coast of Australia has been hit pretty hard. First there were biggest floods Australia has seen for a VERY long time that started in Queensland and continue to affect the east cost of Australia. Then, instead of letting Queensland off the hook for a few weeks nature hit the coast with a cyclone THE SIZE OF THE U.S.A. that might move so far inland that it could dump rain into my state, which is a desert, halfway across our island continent.

A map showing Tropical Cyclone Yasi superimposed over the USA / news.com.au
While all of this was occurring I was thinking about what kind of diseases we can expect in flood damaged towns. Luckily, nothing has surfaced and this has been attributed to the integrity of the water supply being maintained (against all odds it should be added) but it could have been so much worse.
Floods can potentially increase the transmission of water and vector transmissible diseases. A vector transmissible disease is the fancy way of saying an infection that spreads between humans but requires an intermediate host, a vector. Malaria is a vector transmissible disease due to the requirement of mosquitoes for example.
Rates of diarrhoea (including cholera and dysentery), respiratory infections, hepatitis A and E, typhoid fever, leptospirosis, and diseases borne by insects are often seen to increase in flood affected areas. However it has also been observed that the increased rates are often small unless water supplies are contaminated or significant portions of the population are displaced causing crowding in the remaining safe areas.
Of particular importance during floods is leptospirosis. This disease (known by lots of names with my personal fav being Rat Catcher’s Yellows) is caused by a spirochaete (kind of bacteria) called leptospira that is commonly found in rodent urine. In floods rodent populations explode and of course rodent urine gets mixed into the water. The leptospira can then catch a free ride to your insides though open wounds (plenty in a crisis) or directly onto your airways or gastrointestinal system. Once there the disease goes through two phases, the first of which is annoyingly general flu-like symptoms but the second phase, separated by a brief period without symptoms, sees the development of meningitis, jaundice and renal failure.
Vector transmissible diseases are generally only a problem if flood waters become still. The initial flow of water will generally wash away any established breeding sites for insects like mosquitoes but after the flow water tends to pool and with lots of water comes lots of mosquitoes. Malaria is always the concern with flooding but previous major floods have resulted in outbreaks of dengue and West Nile Fever so it very difficult to predict what will happen. Luckily, it seems that despite all the extra water its actually the change in human behaviour (sleeping outside, temporary break in disease control and overcrowding of disaster centres) that is the major issues. This is lucky because changes in human behaviour can always be modified with experience of disaster situations.
The final concern many have about disease spread during disasters and particularly flooding is the danger posed by corpses. The Queensland floods took many lives and there were concerns that these individual tragedies could result in the spread of disease. Corpses actually pose very little threat as most agents in a body will die very soon after the host itself with the notable exception of HIV which can persist for up to a week. The major problem is if death occurred due to cholera or haemorrhagic fever both of which were not reported in the Queensland floods.

Flood-waters even got into the CBD
The Queensland floods and the continued devastation of Australia’s east coast (there have been reports of a monsoon in Victoria now as well) have been traumatic but it could have been much worse. The water supply staying safe for the majority of the crisis has undoubtedly saved thousands of lives and so while our hearts must go out to all those effected our thanks should go to the volunteers who helped in any way they could, including those charged with protecting the precious water supply and the medical staff who protected a state during a phenomenal crisis.
References
WHO: Flooding and communicable diseases fact sheet
Ohl, C. (2000). Flooding and human health BMJ, 321 (7270), 1167-1168 DOI: 10.1136/bmj.321.7270.1167
Howard MJ, Brillman JC, & Burkle FM Jr (1996). Infectious disease emergencies in disasters. Emergency medicine clinics of North America, 14 (2), 413-28 PMID: 8635416... Read more »

Ohl, C. (2000) Flooding and human health. BMJ, 321(7270), 1167-1168. DOI: 10.1136/bmj.321.7270.1167

Howard MJ, Brillman JC, & Burkle FM Jr. (1996) Infectious disease emergencies in disasters. Emergency medicine clinics of North America, 14(2), 413-28. PMID: 8635416

December 14, 2010
06:19 PM
666 views

Sickles, blood disease and the Greek god Priapus

by James Byrne in Disease Prone

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I saw the Carnal Carnival was coming up and this month’s theme is Blood. Blood disease, that shouldn’t be too hard I thought.So I started thinking about blood diseases and remembered a disease I learnt about in undergraduate genetics classes called Sickle Cell Anaemia.Sickle Cell Anaemia (SCA) is a very well characterised blood disease that changes the shape of red blood cells from the characteristic bi-concave disc (or doughnut shape as I usually explain to the undergrads I teach now) to an unusual crescent or ‘sickle’ shape.

I'm not saying SCA is associated with communism but it's a pretty big coincidence they both involve sickles if you ask me <pics:http://commons.wikimedia.org/wiki/File:Sicklecells4.jpg and http://commons.wikimedia.org/wiki/File:Hammer_and_sickle.svg>
The disease is caused by a recessive mutation in the haemoglobin gene that results in the unusual blood cell shape but also restricts the amount of oxygen that can be carried around. As a result, people who suffer from SCA find normal tasks exhausting and have a significantly reduced lifespan, down to about 42 in males and 48 in females respectively.One of the major complications arising from your blood cells not being quite the right shape is that they get stuck moving through blood vessels. Patients also have very unusual blood chemistry because feedback systems that monitor the ‘quality’ of the blood identify low oxygen levels in the blood and compensate by increasing production of red blood cells to fix the problem. Of course the blood cells are impaired so it takes more mutated blood cells to carry around the required oxygen than it would normal cells. What you are left with is viscous blood with a higher than normal cell count that has a tendency to clot.This can cause all sorts of problems, including blood vessel and organ damage. Generally painless, this disease is characterised by bouts of clots and tissue failure.It was discussed in my undergraduate genetics classes because it has been suggested that SCA may be a selectable adaption to ENABLE survival. It turns out that the places that show the highest levels of SCA are tropical and sub-tropical locations and sub-Saharan Africa, pretty much anywhere you find malaria in high numbers.As it turns out malaria requires normal shaped blood cells to reproduce. The mutation to the haemoglobin gene does limit the ability of the red blood cells to carry oxygen but this is preferential to dying from malaria. Interestingly the disease is worse when the haemoglobin gene you inherit from both parents is mutated but these people do not get malaria. If one parent has a wild-type or ‘normal’ copy of the haemoglobin gene then some children will receive both a mutated and a normal copy. These individuals produce both normal and mutated red blood cells and so are still susceptible to malaria but less so when compared to people with two ‘normal’ copies of the haemoglobin gene.

For those that are interested these are called Punnett squares and describe all the possible matings. SCA is the mutant haemoglobin, WT is the normal haemoglobin. Homozygous essentially means two of the same (i.e. homozygous SCA means two copies of the mutant gene). Heterozygous essentially means different two that are different (i.e. heterozygous SCA means one WT copy and one mutant copy)
SCA is a very interesting disease and deserves a serious discussion but when researching it I came across something I did not expect. ASPEN Syndrome. Association of Sickle cell disease, Priapism, Exchange transfusion, and Neurological events, is a mouthful of a syndrome.In order to understand what is happening we have to remember some of the consequences of SCA, in particular increased blood viscosity and a tendency to clot.Ever heard of the Greek god Priapus?Nice ‘member’ he’s got there huh. In medical terms that’s a Priapism.Its been estimated that up to 89% of men with SCA have suffered from ‘prolonged penile erection’ that can be intermittent or in some cases last many hours at a time. It seems that the increased viscosity and tendency to clot causes the flow of blood into the penis to pool. Females are not excluded and female priapism affects the clitoris, often it is referred to as clitorism.There are a few ways that a Priapism can be alleviated. In most people pseudoephedrine or other amphetamines can induce erectile dysfunction. If that doesn’t work then we move to treatment option two, aspiration of blood from the corpus cavernosum under local anaesthetic, a.k.a. big needle to drain blood straight out of the penis.

Cool! A LEGO syringe! <http://www.flickr.com/photos/seanmichaelragan/5224385684/sizes/l/>
For SCA patients these approaches would simply exaggerate the priapism ... Read more »

Mantadakis E, Ewalt DH, Cavender JD, Rogers ZR, & Buchanan GR. (2000) Outpatient penile aspiration and epinephrine irrigation for young patients with sickle cell anemia and prolonged priapism. Blood, 95(1), 78-82. PMID: 10607688

Swerdlow, P. (2006) Red Cell Exchange in Sickle Cell Disease. Hematology, 2006(1), 48-53. DOI: 10.1182/asheducation-2006.1.48

Claster, S. (2003) Managing sickle cell disease. BMJ, 327(7424), 1151-1155. DOI: 10.1136/bmj.327.7424.1151

Merritt AL, Haiman C, & Henderson SO. (2006) Myth: blood transfusion is effective for sickle cell anemia-associated priapism. CJEM : Canadian journal of emergency medical care , 8(2), 119-22. PMID: 17175874

September 14, 2011
06:05 PM
629 views

Peptidoglycan - The bacterial wonder wall

by James Byrne in Disease Prone

Quick, can you describe your grandparents? Staphylococcus aureus, or the Golden Staph, can and it is a single cell. If you couldn’t you should visit them more often. In any case, a very cool paper came out recently but before we can get there we need to begin by going backwards to explain a very important bacterial structure called peptidoglycan.... Read more »

Turner, R., Ratcliffe, E., Wheeler, R., Golestanian, R., Hobbs, J., & Foster, S. (2010) Peptidoglycan architecture can specify division planes in Staphylococcus aureus. Nature Communications, 1(3), 1-9. DOI: 10.1038/ncomms1025

van Heijenoort J. (2001) Formation of the glycan chains in the synthesis of bacterial peptidoglycan. Glycobiology, 11(3). PMID: 11320055

July 28, 2011
07:56 PM
579 views

Can’t fall asleep? You don’t want to read this then.

by James Byrne in Disease Prone

Unlike narcolepsy, which has been shown to have genetic and environmental triggers insomnia seems to have no genetic component. The closest thing to a genetic insomnia is the ominously named fatal familial insomnia, which my old friend Thomas wrote about here.

A diagnosis of insomnia relies on the way the following questions are answered, “Do you experience difficulty sleeping?” or “Do you have difficulty falling or staying asleep?” You answer yes to either of those and you have insomnia.... Read more »

Reiner PB, & Kamondi A. (1994) Mechanisms of antihistamine-induced sedation in the human brain: H1 receptor activation reduces a background leakage potassium current. Neuroscience, 59(3), 579-88. PMID: 8008209

Roth T, & Roehrs T. (2003) Insomnia: epidemiology, characteristics, and consequences. Clinical cornerstone, 5(3), 5-15. PMID: 14626537

Jacobs GD, Pace-Schott EF, Stickgold R, & Otto MW. (2004) Cognitive behavior therapy and pharmacotherapy for insomnia: a randomized controlled trial and direct comparison. Archives of internal medicine, 164(17), 1888-96. PMID: 15451764

July 17, 2010
12:03 AM
572 views

P. aeruginosa, Biofilms and Honey

by James Byrne in Disease Prone

A biofilm is generally described as a ‘synthesised environment housing a bacterial community on a surface’. This essentially means that organisms (not just bacteria) start to produce huge amount of ‘muck’ containing proteins, sugars and DNA and export it from the cell once bound to a ‘surface’. When it does this it generates its own little environmental niche and as that bacterial cell divides within the biofilm it can pool its resources allowing easier growth for the community as a whole. It also has other effects. Biofilms are largely resistant to disinfection and antibiotics as the bacteria can keep the actual environment at bay whilst happily existing in its own filth.... Read more »

Efem, S. (1988) Clinical observations on the wound healing properties of honey. British Journal of Surgery, 75(7), 679-681. DOI: 10.1002/bjs.1800750718

Bielecki, P., Glik, J., Kawecki, M., & Martins dos Santos, V. (2007) Towards understanding Pseudomonas aeruginosa burn wound infections by profiling gene expression. Biotechnology Letters, 30(5), 777-790. DOI: 10.1007/s10529-007-9620-2

PITTET, B., MONTANDON, D., & PITTET, D. (2005) Infection in breast implants. The Lancet Infectious Diseases, 5(2), 94-106. DOI: 10.1016/S1473-3099(05)01281-8

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