Thursday, 14 December 2017

Huntington



Is there a more terrible disease than Huntington disease? Huntington is a neurodegenerative disorder with an incidence of 1 in 20,000 and is inherited as an autosomal dominant. An autosomal dominant condition ensures that if you carry a single mutant gene you inevitably develop the condition- a mutant gene which is passed onto 50% of your offspring. Huntington disease strikes in the prime years of life (30-40) and slowly destroys your motor and cognitive powers resulting in death, typically 15 to 20 years after developing initial symptoms. Consequently, due to the disease's late onset,  you are likely to pass it on to your children before you develop symptoms yourself. 

The culprit is a mutation affecting a gene which manufactures the huntingtin protein. Although the exact biological function of this protein is not fully known, it is likely that it plays a critical role in nerve function and development. The mutant protein undergoes an altered configuration causing chains of protein aggregates. The aberrant 'strings' of protein accumulate within the brain where they progressively destroy nerve tissue. Whole families are ravaged and destroyed by the disease. If you carry the mutant gene you linger under a death sentence without reprieve. It is no wonder that the suicide rate amongst Huntington families is high. 

Imagine being in your 20s watching your mother, or father, falter and decline both physically and mentally and knowing there is no hope of recovery; and that you have a 1 in 2 chance of being affected yourself. Genetic testing is available, however, some potential sufferers choose not to be tested. For those who choose diagnostic testing, a positive result is a hard psychological burden to bear, although reactions differ depending on temperament and circumstance. Even those testing negative are not spared as they must reconcile their good fortune with the knowledge that their siblings may not have faired so well. 

The only treatment to date has been palliative; no more than keeping the patient as comfortable as is possible until demise. However, recent research at University College London has focussed on a drug which blocks the formation of the aberrant protein and initial trials on Huntington patients have been very encouraging. The drug is injected into the spinal cord and interacts with messenger RNA from the damaged gene. This messenger RNA would then go on to direct the formation of the mutant protein. However, in the presence of the experimental drug the RNA molecule is rendered non-functional and therefore the damaged protein can no longer be manufactured. During the first human trial, it was demonstrated that the levels of the abnormal protein were substantially reduced.  

Is this a cure? Probably not. A reduction in the protein would have to be correlated with an improvement in the clinical condition. This will take further trials and many years work. Current work has been undertaken on patients already showing symptoms of the disease. Long term work will be necessary to see if the disease can be stabilised and even reversed. Perhaps the most enticing and exciting prospect will be to treat asymptomatic carriers of Huntington to see if the disease can be prevented from developing later in life. 

The use of drugs to target gene expression in combating genetic disease is not a new approach and has found a particular application in cancer. It is hoped that a similar approach can be adapted to treat other neurodegenerative conditions where a build up of protein is responsible for brain cell death. Alzheimer is one such condition where the deposit of protein plaques result in neural tissue destruction. 

The next wave of genetic research will herald a ‘golden age’ for disease treatment. Unlike many neurodevelopmental conditions, most autosomal disorders manifest at birth. The key, therefore, is to implement drug intervention in the womb, ideally early in embryo development. The goal will be to modify gene expression to prevent or ameliorate the condition. The rub, of course, is that sophisticated genetic therapy will not come cheap and therefore as a society, we may face the real dilemma of withholding effective treatment because of prohibitive cost. Tis indeed a brave new world.   

Just a comment: Astute readers will have noticed that I have not used the possessive apostrophe for Huntington disease. It is no longer considered correct form to refer to the disease as Huntington's disease (Huntington's chorea is right out). In the same way, Down's syndrome is rendered Down syndrome. As for the old tag, 'Mongol', this is deemed totally unacceptable in any polite medical lexicon.



Saturday, 9 December 2017

Bloody Christmas Songs

Tis nearly the time of year when goodwill and serene tranquillity overfloweth and everyone is full of good cheer and eggnog. Engaging, quaint and ragged urchins gather to sing carols in pitch-perfect harmony. The snow lays crisp and deep and Jack Frost nibbles at deliciously exposed, pink and plump nether regions…….

And then we have the obligatory Christmas song release. How could we endure the season without ‘Snoopy’s Christmas song’ or the dulcet tones of Cliff Richard as he belts out ‘Mistletoe and Wine’.  A time when every crooner, past and present, hits the music scene with a Christmas song, hoping to catch the mug punter with deep pockets and nostalgia in their hearts. Although there have been a few memorable Christmas inspired tunes, the majority are just hastily cobbled together crap replete with banal predictable lyrics allied with ridiculous and hackneyed, sentimental tunes of sick, syrupy mulch. For every Bing Crosby's 'White Christmas' there are 1,000 forgettable melodies. Do you recall the engaging: ‘Santa Claus Has Got the Aids This Year’ by the late lamented, Tiny Tim? Of course, you don’t- the whole effort was a pathetic attempt to cash in on the weirdly eccentric and pathetic, Tiny Tim.

So in the gentle spirit of Christmas, I would like to nominate my top five piss awful Christmas refrains. I’m quite aware that the selection is in some way arbitrary and prone to my own bizarre brand of subjective taste. In fact, there are so many bad Christmas songs that compiling a worthwhile list is virtually impossible. A music nerd, in 2014, scoured the song catalogues and came up with 914,047 tracks of Christmas themed songs. I’m sure the current inventory is in excess of a million and the vast majority will be complete and utter dross.      

5. Dominick the Donkey by Lou Monte




The lyrics to this particularly annoying song are pure unadulterated crap accompanied by a tune that will stick in your head turning your brain into spaghetti. Moma Mia!

4. This Christmas (I'll burn it to the ground)




The only saving grace of this cacophony is that it panders to my sick proclivity for 'burning stuff' and underlying nihilism. Other than that it is utter and absolute shite. At least you won't carry this tune in your head once the 'music' stops. Although to be fair I couldn't listen to this all the way to the end.

3. Mistletoe and Wine by Cliff Richard  




This list must contain at least one of Harry Webb's Christmas warbles. Our Cliff has knocked out 17 festive songs in his long career. Once touted as Britain's answer to Elvis Presley back in the 50s and early 60s he quickly morphed into the saccharine 'Peter Pan' of pop. Grandmas loved him and everyone else detested his smug self-righteous persona. I'm starting to digress. My own particular nemesis is 'Mistletoe and Wine'. A sticky sweet tune backed with trite lyrics. A mismatch of pagan 'Mid-Winter Festival' with supposed Christian sentiment.

2. Wonderful Christmas Time by Paul McCartney



I must confess, I’m not a fan of Paul McCartney’s post-Beatles work. And let’s be honest, ‘Wings’ were piss poor. Do you think Paul employed his wife  in the band because she was an  exceptional musician? Tis a wonder he didn’t put his dog on bongos. My particular nip of venom is reserved for the simpering sweet bubble-gum number, ‘Wonderful Christmas Time’. Here is a judicious selection of the insipid caramel lyrics:  “The party’s on, the feeling’s here that only comes, this time of year”. Perhaps I’m being a tad unfair to the man who wrote ‘Yesterday’, but the jarring muzak quality of the melody has me reaching for the petrol and matches. 

At last, we come to my personal choice for worst Christmas song. Many are called, but only one is chosen.

an
1. Do they know its Christmas


This may be a controversial choice. Those amongst you may aver that there are worse jingles out there jangling with discord on the harmonic waves. And of course, you would be right. Tis all a matter of criteria and I confess that I have not applied any stringent or consistent filter process. This list comprises those wretched songs which grate and gnaw at my very fibre. After masticating fully they spit the remnants on a bright white canvas. A pristine canvas despoiled and left sullied with ochre blotches of doom…..

Some will rave that the sentiment behind the enterprise was laudable and helped to raise money for Africa’s starving, seething masses. But when has sending gelt to Africa done any good? Most likely the aid will end up in the sticky fingers of the local War Lord/Chief/local corrupt government officials/Despot. And when has largesse ever been a sustainable manner to provide a stable economic base for a country? Surely this is a job for the elected government to address?

The original line up contained the ‘scourge of god’, Bob Geldof and Bono and a hastily thrown together line of, musicians of the time. The lyrics are predictably nauseating and reek of paternalism - what more needs to be said?        

To calm the fever in my blood I have added the following.  The heaving breast is stilled once more.


Tuesday, 28 November 2017

HORROR SCOPE



I pride my self on my rational tendencies. Isn’t this life complex enough without the consideration of supernatural realms and beings? I reserve much derision for diviners and sooth sayers. They generalise and vaguely report ‘information’ which is mundane and so common place that it could apply to anyone.

Horoscopes are particularly useless. Looking into the future based on the alignment of celestial bodies is clearly ludicrous and should have no role in a world dominated by the scientific paradigm.  
Imagine my surprise when I espied the following horoscope relating to my birth sign, Pisces, in the local rag.    

Today will be the last day of your life unless you continue living. Later in the month (if you are not dead) a horde of locusts will eat your veggie patch. Look out for low flying clouds.

Yours fates are controlled by a contrived conjunction of the planets, Uranus and Mars. Consequently, there is likely chance that you will be abducted by fierce Zenomorphs and suffer a ruthless and severe anal probing. Beware of aliens bearing surgical callipers.

The auspices look good. However, there is a strong possibility that your kneecaps will move independently but not beyond the limits of normal articulation and tendon protraction.

Mars is in the ascendancy and later in the month expect to be confronted by a host of barbarian marauders who will pillage the land make off with your chattels and render you speechless with a good, sound buggering. Your lucky colour is red, tinged with brown.

Considering the way your month is shaping up I recommend purchasing lots of the comforting salve, ‘Anal Soothe’ and perhaps one of those rubber ring thingys, you know the ones with the whole in the middle.

Due to your unfortunate and repeated sodomising you will be constrained to wear a ‘man sized’ nappy due to slack anal sphincter control. In the morning, don’t be alarmed if you see a critter doing a lazy backstroke in the moist detritus of your fetid waste.

I see money, lots of it, but none in your bank account. Your son will move back home after he breaks up with Locisha. I see bare fridges and the strange and inexplicable disappearance of all your beer.

Your lucky number is zero..

Arse, big sore, arrrrrrrsssssseeeeee 


Sunday, 26 November 2017

Mugumbo Ousted?


Enoch Mugumbo

Big fat, arse
Shock breaking news as the leader, Enoch Mugumbo, of the impoverished state, Mumbojumbo land, formerly Tiptonia, has been ousted in a military backed coup. Mugumbo has remained in office since gaining independence from Dudley North in 1980. During his tenure, thousands of Tiptonians have fallen into disused coal mines or committed suicide by repeatedly slicing themselves up with machetes.

Democracy, but not as we know it
Allegations of electoral fraud have been rampant over Mugumbo's 37 year tenure. Mugumbo's 'Darky Party' have consistently obtained over 120% of the electoral vote. Suspicions were raised when in 1990 Mugumbo's 'Darky Party' secured the election the day before the poll.

Ferrets
In 1980, Mugumbo seized the white-owned ferret farms. His intention, he said, was to redistribute the land between the rural poor. Instead, he gave the farms to his cronies with the last name of Mugumbo. Predictably, his lazy and mostly dozy supporters had no idea how to run a ferret farm and this once profitable enterprise collapsed into a pile of detritus and ferret shit. Inflation became rampant and the once stable. 'Mumbojumbo dollar' spiralled into a cycle of impending doom.

The king is dead, long live the queen
The final straw came in the guise of his much younger wife, Mrs Mugumbo. At 106, Mr Mugumbo wanted a seamless transition of power to his wife. Even the dimmest of his countrymen could see that the Dictatorship was to become a family business. But of course, this how the 'West Midlands' has always been run without the white folk. The military forces backed by the opposition party under the tutelage of Mr Ipod Mugumbo-Mugumbo (no relation), ousted the ailing president and forced him into retirement. Colonel Teapot Despot-Mugumbo seized power and was expected to return the 'democratic process' over to the opposition leader Mr Ipod Mugumbo-Mugumbo, however, in a press conference today the wily Colonel expressed the view that the initial stabilisation period was likely to last 100 years. In the interim, the Colonel will form a government composed of lackeys and family members. From now on the Colonel will be addressed as all highest god above all other gods etc, etc, etc.

Don't give a shit cos da got no oil or gold
The international community has expressed relief in public. But in private realise, tis business as usual. As for Mr Mugumbo, unlike his impoverished populace, he can live in opulence in a grand house while people starve. Perhaps, one day, when his bodyguard is out carousing and raping, a sound citizen will come out the bush and shoot him. Although, in fairness, tis likely the final 'report' will come from someone close, like the people he trusts the most, his bodyguard- unless the grim reaper takes him first.  


Colonel Despot-Mugumbo


Thursday, 23 November 2017

Bugger Christmas!



Tis nearly Christmas- ho, fucking, ho. The town mall is already displaying Christmas decorations and snot-nosed kids can sit on Santa’s calloused knee. Houses are adorned with Christmas lights and signs on lawns exhort/exclaim: ‘Santa Please Stop Here’.

Rampant, blatant commercialism is mainly to blame. Companies are keen to capitalise on the ‘Christmas Spirit’ and entice mug punters into their stores in order to offload large amounts of cheap plastic crap. To extend the time available for fleecing the sheep is paramount to corporate thinking.

And don’t get me going on about Christmas parties. Every year our department organises a Yuletide get together. Tis the time of year when the restaurants/pubs and social arenas hike up their prices to cash in on the good times. This year the lab, as one said: Bugger it. We are as mad as hell and won’t take it anymore”. Actually, I said, "ARSE", but I would say that, wouldn’t I?  So, we have decided to move the festivities to someone’s humble abode. As I have a rather large, well-appointed house, it has become incumbent upon my radiant and well-favoured head to provide the venue. The party will operate on the ‘bring a plate principle’. This is an endearing Kiwi custom where everyone comes to the party with a plate of food. The usual party fair will arrive; salads; pastry dainties and such like. Of course, everyone will bring an inordinate amount of booze. I’ll also provide the punch. The revenue free ethanol, which is used in our legitimate laboratory business, will mysteriously materialise in a rather large glass bowl together with cranberry juice and assorted floaty bits. Don’t worry, I’ll keep Shagger in his cage so we won't end up with ‘ferret chunks’ adulterating the concoction. I’ll also make sure that I don’t pick up the methanol by mistake; can’t have a repeat of my birthday party where several of the staff ended up in the Emergency Department.   

I’ve been asked about the Christmas decorations which will adorn the expansive ‘blue room’. Gasps of horror ensued when I pointed out that the party is on the 25th November, a full month before Christmas and consequently, there will be no festive festoons. Tis bad enough that the party has to occur in November due to various logistic vagaries.      

I’m sure everyone will have a great time. Counter to what most folk think scientists are an absolute hoot when lubricated with sufficient alcohol. I’m sure we will play, ‘Find Flaxen’s Underpants’, again. Last time I stuck them to the ceiling. Actually, I didn’t have to actively attach the underpants. They seemed happy to stay stuck on the ceiling due to a mysterious adhesive force.  Inevitably, later in the evening, I’ll end up pinching the arse of some young, nubile and attractive Research Assistant. Next day will be spent in the ‘dog box’ and I'll have to endure a lecture from the missus concerning appropriate behaviour and etiquette in these sort of circumstances. "Do you realise that the young lady in question is 7 years younger than your daughter"?  I, of course, will adroitly counter, in mitigation: "I was, very, very, drunk".   




Don't click the link

Tuesday, 21 November 2017

More Jolly Japes with Health & Safety

Keith Lard. Health & Safety Guru
As my gentle reader is no doubt aware, I am blessed with the designation: ‘Health & Safety Officer’. I confess that I’m not the best man for the job as I’m often spotted in the lab area with my lab coat inside out. However, as no bugger wants to take on the onerous task, the department gets the health and safety officer, it deserves. I have been likened to a cruise ship physician- ‘one step away from a malpractice suit’.

One of my tasks is to ensure that staff complete the annual ‘Health and Safety Questionnaire’: a series of 20 questions on the riveting topic of health and safety. During the 11 years of my tenure, the questions have not changed. At a meeting 7 years ago I pointed this out and suggested that the whole exercise was a complete waste of time. O horror of horrors. I had spoken ill about ‘Health and Safety’ and the health and safety gods were muchly (not a real word) displeased. I settled for a compromise. Every year I would formulate new questions to ensure that the exercise was not completely pointless. The gods who take note of this sort of thing were appeased and the palpable tension in the meeting dispersed like a dispersy thing.  

Since that fateful meeting, I have been diligently revising the questionnaire format. I also check everyone’s answers to make sure they are 100% correct. I reckon that at least half of the questionnaires (12) are error infested and therefore I’m obliged to return the erroneous forms to the errant staff members for correction. I did this as I was under the impression that someone in the Occupational Health Department actually scrutinised the forms for error. In fact, we had been informed that if the questionnaires contained errors they would be returned for revision. I had a sneaking suspicion that the whole affair was a paper exercise only and that no one actually checked the forms. In the spirit of quality control, I decided to send the questionnaires ‘unedited’. I had a quick glance through the submissions to confirm that they were error prone as usual. I did a similar thing last year and mentioned the whole sorry episode in a previous post entitled, ‘Health & Safety’. This year I thought I would perform a ‘Gold Audit’ and being of a mischievous twist of mind, I also decided to submit a questionnaire from a fictitious staff member, with the implausible name: Shagger ‘The Ferret’ Mugumbo. As Shagger does not have opposable thumbs he found it difficult to hold a pen and therefore his answers were dictated and loving transcribed by your genial and rather fetching, host.

Shagger is not a particularly smart ferret and his answers skirted along the lines: “I like shitting in corners; Fuck with me and I’ll bite your nose off; polystyrene makes my poo stringy”. All the answers had a ferret inspired theme. With trepidation, I submitted Shagger’s contribution with all the other questionnaires.

I awaited the dreaded email: “Dr Saxon, On review of this year’s Health and Safety questionnaire submissions, I noticed that you have acquired a new staff member to wit:- Shagger ‘The Ferret’ Mugumbo. Said staff member has not attended the obligatory Health & Safety induction day. Please contact Occupational Health to arrange attendance”.   

Instead, I received the following in bright bold type:

“Thank-you for your 100% compliance. The outstanding quality of your department's response has been noted and you have been selected and recommended for commendation”. ARSE.

As I recall, I received the exact same email last year. As for the commendation thingy; tis a complete mystery to me as nothing subsequently happened last year when I received this email and I suspect that my exemplary achievement will go unrecognised, again. At least I expected to be called upon the stage at a prestigious corporate event and handed a gold embossed plaque from our exalted CEO. A standing ovation would ensue and someone suitably primed, no doubt by higher management would shout at the top of their voice: “Surely, he is more god than man”.

Could it possibly be that the higher management folk are blowing smoke up my pert and impeccably coiffured, arse? (arse, big pert arse)-  perhaps.   

At the forthcoming Health and Safety meeting, I will take great pleasure in informing senior management about the sorry episode concerning Shagger’s valuable contribution to ‘Health and Safety’. I’m sure they will all be agog. Mayhap they will give him a commendation? 




Saturday, 18 November 2017

Full of meaty goodness

Should have brought salt and pepper and not myrrh
Some stories insinuate and invite derision. Greggs, the pie manufacturer, has produced an advent calendar presumably to promote their fancy pastry inspired comestibles. One of the panels depicts the classic nativity scene with one striking difference. Three wise men are clustered adoringly around the crib containing a delicious looking and steaming sausage roll. Traditionalists have rightly pointed out that the general interpretation of the nativity does not involve fancy pastry and the sausage roll should be substituted with the baby Jesus.

Fair enough, you say, our Saviour should not be Savioury. And it is hard to pay homage and devotion to an oversized sausie roll. Predictably, the usual suspects were outraged and protested vehemently. One religious fruit 'n' nut stated: "it obscures the real meaning of Christmas and may confuse people concerning the true message". Yea, or course we are all mentally deficient and can't distinguish between the baby Jesus and a pastry.

Sadly Greggs issued the following apology:  "We're really sorry to have caused any offence, this was never our intention."  However, the pastry chain has refused to take the advent calendar off the market and it will be available in all good stores from Monday. I'm certain with all the furore surrounding the event/advent the calendar will be a great success and fly off the shelves like 'hot sausie rolls'.


Clearly, some folk make a career of getting offended. My advice: Fuck off and attend to your own business and if they right eye offends thee then stop watching the news. Arse.