It was a Saturday, about tea-time in the quaint village of Athelstaneford, East Lothian. Mrs Alexandria Agutter sat in her cottage, enjoying the delights of the late-summer evening with a glass of gin and tonic. She listlessly sipped from the rather generous pick-me up, no doubt chewing over the happenings of the day. Blast! The taste was much too bitter to her liking. She stood up. And promptly crumpled to the floor in a dizzied heap. It had not been five minutes when a fiery pain gripped her parched throat and in her frenzied turn she watched the bleary room become draped in a gossamery silk. How Dame Agatha would approve. But this is no crime novel, on that fateful day, 24th August 1994, poor Mrs Agutter immortalised herself in the history books of forensic medicine; she was the victim of a revered toxin and a vintage one it was too. She had unwittingly imbibed a G&T laced with a classic poison of antiquity. A clue from the 21st century: do you recall the first Hunger Games film adaption? Those inviting purple-black berries or as Suzanne Collins coined them ‘Nightlock’; a portmanteau of hemlock and Deadly Nightshade. True to the laters’ real life appearance those onscreen fictional fruits played a recurring cameo role. Deadly Nightshade is a perennial shrub of the family Solanaceae and a relative of the humble potato (a member of the Solanus genus). It is a resident of our native woodland and may be found as far afield as Europe, Africa and Western Asia. The 18th century taxonomist, Carl Linnaeus gave the plant an intriguing name in his great Species Plantarum. The genus Atropa is aptly named after one of the three Greek Fates, Atropos. She is portrayed shearing the thread of a mortal’s life so determining the time and manner of its inevitable end. The Italian species name belladona (beautiful woman) refers to the striking mydriatic effect of the plant on the eye. The name pays homage to Pietro Andre Mattioli, a 16th century physician from Sienna, who was allegedly the first to describe the plant’s use among the Venetian glitterati - ladies of fashion favoured the seductive, doe-eyed look. Belladona is poisonous in its entirety. It was from the plant’s roots in 1831, the German apothecary Heinrich F. G. Mein isolated a white, odourless, crystalline powder: it was (surprise, surprise) atropine. Atropine is a chiral molecule. From its natural plant source it exists as a single stereoisomer L-atropine, which also happens to display a chiral potency 50-100 times that of its D-enantiomer. As with many other anaesthetic agents it is administered as a racemic mixture. How strange that atropine now sits among the anaesthetist’s armamentarium, its action as a competitive antimuscarinic to counter vagal stimulation belies its dark history. It was a favourite of Roman housewives seeking retribution against their less than faithful husbands and a staple of the witch’s potion cupboard. Little wonder how belladona became known as the Devil’s plant. Curiouser still it’s also the antidote for other poisons, most notably the organophosphates or nerve gases. On account of its non-selective antagonism, atropine produces a constellation of effects: the inhibition of salivary, lacrimal and sweat glands occurs at low doses; dry mouth and skin are early markers. Pyrexia is a central effect exacerbated by the inability to sweat. Flushing of the face due to skin vessel vasodilatation. Low parasympathetic tone causes a moderate sinus tachycardia. Vision is blurred as the eye becomes dilated, unresponsive to light and accommodation is impaired. Mental disorientation, agitation and ataxia give the impression of drunkedness or a delirium tremens like syndrome. Visual hallucinations, often of butterflies or silk blowing in the wind, are a late feature. It was then that Mr Agutter, seemingly untroubled by the sight of his wife’s problematic situation, proceeded to leave a message with the local practitioner. How fortunate they were to have the vigilant locum check the answering machine and come round to the Agutter’s lodge accompanied by an ambulance crew. The attending paramedic had the presence of mind to pour the remainder of Mrs Agutter’s beverage into a nearby jam jar, while Mr Agutter handed over what he suspected to be the offending ingredient: the bottle of Indian tonic water. As it soon transpired there were seven other casualties in the surrounding countryside of East Lothian – all involving an encounter with tonic water. In fact by some ironic twist of fate, two of the victims were the wife and son of Dr Geoffry Sharwood-Smith, a consultant aneasthetist. Obviously very familiar with the typical toxidrome of anticholinergic agents, he was quick to suspect atropine poisoning. Although for a man of his position with daily access to a sweetshop of drugs, it was not something to draw attention to. Through no small amount of cunning had the poisoner(s) devised the plan. It was elegant; atropine is very bitter. So much so that it can be detected at concentrations of 100 parts per million (0.001%). Those foolish enough to try the berries of belladonna during walks in the woods are often saved by the berry’s sour taste. They are soon spat out. But the quinine in the tonic water was a worthy disguise. The lethal dose for an adult is approximately 90-130mg, however atropine sensitivity is highy variable. In its salt form, atropine sulfate, it is many times more soluble: >100g can be dissolved in 100ml of water. So 1ml may contain roughly tenfold the lethal dose. There ensued a nationwide scare; 50 000 bottles of Safeway branded Indian tonic water were sacrificed. Only six bottles had been contaminated. They had all been purchased, tops unsealed, from the local Safeway in Hunter’s Tryst. Superficially this looked like the handiwork of a psychopath with a certain distaste for the supermarket brand, and amidst the media furore, it did have some verisimilitude: one of the local papers received a letter from 25 year old, Wayne Smith admitting himself as the sole perpetrator. The forensic scientist, Dr Howard Oakley analysed the contents of the bottles. They all contained a non-lethal dose, 11-74mg/litre of atropine except for the Agutter’s, it contained 103mg/litre. The jam jar holding Mrs Agutter’s drink bore even more sinister results, the atropine concentration was 292mg/L. It would appear Mrs Agutter had in some way outstayed her welcome. But she lived. A miscalculation on the part of the person who had added an extra seasoning of atropine to her drink. According to the numbers she would have had to swallow a can’s worth (330ml) to reach the lethal dose. Thankfully she had taken no more than 50mg. The spotlight suddenly fell on Dr Paul Agutter. He was a lecturer of biochemistry at the nearby University of Napier, which housed a research syndicate specialising in toxicology. CCTV footage had revealed his presence at the Safeway in Hunter’s Tryst and there was eye witness evidence of him having placed bottles onto the shelves. Atropine was also detected by the forensic investigators on a cassete case in his car. Within a matter of two weeks he would be arrested for the attempted murder of his wife. Despite the calculated scheme to delay emergency services and to pass the blame onto a non-existent mass poisoner, he had not accomplished the perfect murder. Was there a motive? Allegedly his best laid plans were for the sake of a mistress, a mature student from Napier. He served seven years of a twelve year sentence. Astonishingly, upon his release from Glenochil prison in 2002, he contacted his then former wife proclaiming his innocence and desire to rejoin her in their Scottish home. A proposition she was not very keen on. Dr Agutter was employed by Manchester University as a lecturer of philosophy and medical ethics. He is currently an associate editor of the online journal Theoretical Biology and Medical Modelling. We will never know the true modus operandi as Dr Agutter never confessed to the crime. Perhaps all this story can afford is weak recompense for the brave followers of the Dry January Campaign. Oddly these sort of incidents never appear in their motivational testimonials. Acknowledgements Emsley J. Molecules of Murder. 2008, Cambridge, RSC Publishing, p.46-67. Lee MR. Solanaceae IV: Atropa belladona, deadly nightshade. J R Coll Physicians Edinb. March 2007; 37: 77-84. Illustrator Edward Wong This blog post is a reproduction of an article published in the The Medical Student Newspaper January issue, 2014 http://www.themedicalstudent.co.uk/
almost 8 years ago
Easy glycolysis mnemonic for beginning students. You may need to pause/watch it more than once - and there's a self-paced FLASHCARD TUTORIAL at: http://www.helphippo.com/flash/flashcards.html All cellular respiration tutorials can be found in our playlist: http://www.youtube.com/playlist?list=PLIPkjUW-piR0Bsauys9qL-UNZ2dPVPeGE This tutorial introduces simplified intermediates structures/ ATP/NADH steps - the next part of our tutorial has the full structures/enzyme names. Please SUBSCRIBE for new videos: more cool stuff coming as we get more Hippo Helpers! This explanation also explains the difference between the investment and pay-off stages of glycolysis, as well as the important regulatory step, the "committed" step of phosphofructokinase-1. http://www.helphippo.com - for more video tutorials organized by topic/year.
almost 8 years ago
I started medical school in 2007 wanting to 'making people better'. I stopped medical school in 2010 facing the reality of not being able to get better myself, being ill and later to be diagnosed with several long term health conditions. This post is about my transition from being a medical student, to the other side - being a patient. There are many things I wish I knew about long-term health conditions and patients when I was a medical student. I hope that through this post, current medical students can become aware of some of theses things and put them into practice as doctors themselves. I went to medical school because I wanted to help people and make them better. I admired doctors up on their pedestals for their knowledge and skills and expertise to 'fix things'. The hardest thing for me was accepting that doctors can't always make people better - they couldn't make me better. Holding doctors so highly meant it was very difficult for me to accept their limitations when it came to incurable long-term conditions and then to accept that as a patient I had capacity myself to help my conditions and situation. Having studied medicine at a very academic university, I had a very strict perception of knowledge. Knowledge was hard and fast medical facts that were taught in a formal setting. I worked all day and night learning the anatomical names for all the muscles in the eye, the cranial nerves and citric acid cycle, not to mention the pharmacology in second year. Being immersed in that academic scientific environment, I correlated expertise with PhDs and papers. It was a real challenge to realise that knowledge doesn't always have to be acquired through a formal educational but that it can be acquired through experience. Importantly, knowledge acquired through experience is equally valid! This means the knowledge my clinicians have developed through studying and working is as valid as my knowledge of my conditions, symptoms and triggers, developed through experiencing it day in day out. I used to feel cross about 'expert patients' - I have spent all these hours in a library learning the biochemistry and pharmacology and 'Joe Bloggs' walks in and knows it all! That wasn't the right attitude, and wasn't fair on patients. As an expert patient myself now, I have come to understood that we are experts through different means, and in different fields. My clinicians remain experts in the biological aspects on disease, but that's not the full picture. I am an expert in the psychological and social impact of my conditions. All aspects need to be taken into account if I am going to have holistic integrated care - the biopsychosocial model in practice - and that's where shared-decision making comes in. The other concept which is has been shattered since making the transition from medical student to patient is that of routine. In my first rotation, orthopaedics and rheumatology, I lost track within the first week of how many outpatient appointments I sat in on. I didn't really think anything of them - they are just another 15 minute slot of time filled with learning in a very busy day. As a patient, my perspective couldn't be more different. I have one appointment with my consultant a year, and spend weeks planning and preparing, then a month recovering emotionally. Earlier this year I wrote a whole post just about this - The Anatomy of an Appointment. Appointments are routine for you - they are not for us! The concept of routine applies to symptoms too. After my first relapse, I had an emergency appointment with my consultant, and presented with very blurred vision and almost total loss of movement in my hands. That very fact I had requested an urgent appointment suggest how worried I was. My consultants response in the appointment was "there is nothing alarming about your symptoms". I fully appreciate that my symptoms may not have meant I was going to drop dead there and then, and that in comparison to his patients in ICU, I was not as serious. But loosing vision and all use of ones hands at the age of 23 (or any age for that matter) is alarming in my books! I guess he was trying to reassure me, but it didn't come across like that! I have a Chiari malformation (in addition to Postural Orthostatic Tachycardia Syndrome and Elhers-Danlos Syndrome) and have been referred to a neurosurgeon to discuss the possibility of neurosurgery. It is stating the obvious to say that for a neurosurgeon, brain surgery is routine - it's their job! For me, the prospect of even being referred to a neurosurgeon was terrifying, before I even got to the stage of discussing the operation. It is not a routine experience at all! At the moment, surgery is not needed (phew!) but the initial experience of this contact with neurosurgeons illustrates the concept of routines and how much our perspectives differ. As someone with three quite rare and complex conditions, I am invariable met in A&E with comments like "you are so interesting!". I remember sitting in the hospital cafeteria at lunch as a student and literally feasting on the 'fascinating' cases we had seen on upstairs on the wards that morning. "oh you must go and see that really interesting patient with X, Y and Z!" I am so thankful that you all find medicine so interesting - you need that passion and fascination to help you with the ongoing learning and drive to be a doctor. I found it fascinating too! But I no longer find neurology that interesting - it is too close to home. Nothing is "interesting" if you live with it day in day out. No matter what funky things my autonomic nervous may be doing, there is nothing interesting or fascinating about temporary paralysis, headaches and the day to day grind of my symptoms. This post was inspired by NHS Change Day (13th March 2013) - as a patient, I wanted to share these few things with medical students, what I wish I knew when I was where you are now, to help the next generation of doctors become the very best doctors they can. I wish you all the very best for the rest of your studies, and thank you very much for reading! Anya de Iongh www.thepatientpatient2011.blogspot.co.uk @anyadei
Anya de Iongh
almost 9 years ago
I am an Anatomy Professor who has taught anatomy to the medical school students in discipline based medical education system for first 10years of academic life. When I started teaching Anatomy in system-based medical education in the later half of my academic life I was surprised to find out that my students in system-based education can retain a lot of anatomy knowledge as they can visualize the application of the contents in the pathology, clinical science contents, PBL triggers and clinical skills sessions. Surprisingly, medical schools in India still follow the discipline-based medical education. Mostly the students are forced to retain the factual knowledge of Anatomy in this system. When they are in Year 1,they study only Anatomy,Physiology and Biochemistry. Hence it is very difficult for the student to imagine the application of the knowledge of Anatomy learnt in lecture or dissection room. For example, the students in discipline-based system learn the gross anatomy of the sternum and anterior thoracic wall. They need to memorize the importance of sternal angle without visualizing it as they are still not practising palpation of anterior thoracic wall for apex beat. I know that they learn it provided they are lucky to get a tutor who is a medical doctor, who obviously takes them to the task of palpating intercostal space through palpation of sternal angle in skeleton or over their own body surface marking. But the lack of Clinical skills practice in traditional discipline based medical education in year 1 does not allow the student to apply their anatomy knowledge automatically. Dr Nilesh Mitra
Nilesh Kumar Mitra
almost 9 years ago
A video tutorial on fluid balance. This tutorial includes basic biochemistry and physiology of electrolytes followed by an outline of clinical conditions such as hypovolaemia, hypervolaemia, hypocalcaemia, hypercalcaemia and syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH).
over 10 years ago