The Tiffinian Journal of General Medicine - Winter 2016 by Zak Mouyer

The Tiffinian Journal of General Medicine Issue 3â&#x20AC;&#x201D;Winter 2016 Created by Zak Mouyer

Made in association with www.tbsmb.co.uk/

A Message from the Editor-in-Chief The Tiffinian Journal of General Medicine is a termly medical publication directed at, but not limited to, aspiring medical students and human biologists. The aim is to provide informative and thoroughly researched articles on a variety of clinical and biological cases. Since the magazine was first published, the publishing team have focused on conveying undergraduate knowledge to Aâ&#x20AC;&#x201C; Level students in wellwritten, coherent articles. Every term we receive thirty-five articles, however only the most intriguing are selected for the final edition. To maintain the high quality of our published material, our journalists are advised to utilise and quote data from reliable sources such as research papers and other renowned medical journals. I hope that you enjoy reading through our articles and other material. The Publishing Team and I are extremely grateful for your support by reading our journal and I hope you are eager for the upcoming issues. This journal was made in association with the The British Studentsâ&#x20AC;&#x2122; Medical Blog (www.tbsmb.co.uk), an online medical blog which highlights current advances and hot topics in the medical field. Thank you, Zak Mouyer Editor-in-Chief and Head of the Tiffin Anatomical Society

Contents: The Publishing Team..............................................4-5 Tiffin Anatomical Society...........................................6 Mr James Laban........................................................7 Autosomal Dominant Polycystic Kidney Disease........8 Adrenoleukodystrophy...............................................9 Multiple Sclerosis................................................10-11 Dementia.................................................................12 Stem Cell Research..................................................13 Cystic Fibrosis and Orkambi.....................................14 Gastroenteritis.........................................................15 Strokes...............................................................16-17 Proliferation, causes and the treatment of Cancer.....18 Orthopaedics and Femoral Fractures........................19 Parkinsonâ&#x20AC;&#x2122;s Disease.................................................20 Intraocular Lenses...................................................21 Atrial Fibrillation and Catheter Ablation..................22 Pleural Effusion......................................................23 Root Canal Surgery..................................................24 Osteoporosis............................................................25

The Publishing Team

Zak Mouyer Editor-in-Chief and Journal Designer

Malachi Saccomani

Vith Ketheeswaranathan

James Hong

Neil Narayan

Muse Berhe

Abhijeet Neeti

Yunis Fazaldin

Denis Efovi

Mohammad Hakimi

Rohit Vijjhalwar

Rohan Vijjhalwar

Rajan Patel

Narmathan Rajeswaran

The Tiffin Anatomical Society By Zak Mouyer The Anatomy Society has seen a lot of change this past term. Be it the hand-over of leadership from outgoing Head Senthooran to myself or the new influx of members from Year 12. Among other things, we have seen a change in the syllabus , where each term focuses on the anatomy and pathology of only two bodily systems; this allows for greater detail and more content to be covered over the year. Also the teaching style has evolved, very much emulating the Oxbridge tutorial system. Perhaps our greatest triumph (pictured above) was the ox heart dissection, which attracted great attention across this yearâ&#x20AC;&#x2122;s cohort of biology students. Hopefully many more dissections are to come!

Mr James Laban, Consultant Neurosurgeon By Zak Mouyer

What responsibilities as a neurosurgeon do you have?

The below is the transcript of an interview we gave to Mr Laban:

There are three aspects to this: the clinical one, the academic one and the managerial one. He says that he spends half his time in consultation with patients explaining management pathways and diagnoses. And the other half is the surgical aspect where he would be in theatre or in ward carrying out the clinical aspect. With regard to academia, there is large amount of research and teaching involved. And lastly the managerial aspect involves the patient being able to flow through the hospital smoothly and legally.

Why did you choose to study medicine? Mr. Laban was always interested in how the body works and as a little child, he remembers flicking through various different anatomical children’s pop-up books. But most clearly remembers looking at the abdominal organs and questioning himself “well, what’s in between the organs, is it just air?” Hence the main reason for going into medicine was that he was quite innocently curious to know how the body functioned.

Why did you choose to study Neuroscience and Neurology and hence become a Neurosurgeon? After his youthful fascination within the body, he became especially intrigued by how the mind worked in particular. So came the decision for him to pick neurology, neurophysiology or neurosurgery. But Mr. Laban claims to be a ‘doer’ and he likes to get answers, he also loves theatre, so this passion lead him into neurosurgery.

What part of surgery, if there is one, takes the greatest toll on you? Of course, surgery requires hours of arduous and intense concentration but this isn’t the hardest part. He believes that, from his experience in theatre, the hardest part of the surgical process is the decision-making. He claims this since, whilst under immense pressure, you need to accumulate all of your knowledge about the situation and make a decision which will bring out the greatest good for the patient.

Can you give us an insight to the multi-disciplinary team caring for a patient in the neurosurgical department? An example of this in effect is clear post-surgery of a very simple procedure such as freeing a trapped vein or fixing a slipped spinal disc. Post-surgery, a pain management team is needed and so is a physiotherapist. In some cases an occupational therapist is needed which tries to optimise and make as painless as possible the home living experience. There is also a very clear link between his department and the oncology department, where post-op of cranial tumour removal, an oncologist is needed to look after and make sure the patient shows no other worrying signs.

What do you like to see in an aspiring medical student? Most importantly enthusiasm and of course intelligence are key in a medical student. But determination and being self-critical are vital in the role of doctor, hence he expects to see this. Also being personable is essential since it is a doctor’s role to be able to convey messages to other people in a friendly and likeable manner.

Autosomal dominant Polycystic Kidney disease kidneys reduced filtration capabilities. To add to this, a fever is a common symptom of ADPKD due to pyelonephritis (kidney and urinary tract infections) or the rupturing of cysts which can last few weeks sometimes. However, the most common symptom of ADPDK is hypertension due to the abnormalities in the vascular systems caused by the formation of aneurysms and cysts on blood vessels. [1]

By Rohit Vijjhalwar Polycystic Kidney disease (or ADPKD) is a dominant monogenic disorder in which multiple cysts form on the renal tubules as a result of an excessive proliferation of renal tubular epithelial cells[1]. The proliferation is due to mutations in the PKD1 gene (expressed in the MDCKD cells) or the PKD2 gene which is important for regulating gene transcription and renal tubular development leading to the growth of fluid-filled cysts on the kidneys[2]. This genetic disorder is estimated to affect over 12.5 million people worldwide and is a progressive disease eventually leading to renal failure[3]. This is because the cysts begin to develop over healthy kidney tissue and thus this leads to the progressive decline in the function of the kidney. Currently, it is an incurable disease.

ADPKD is usually an adult-onset condition to which many patients remain asymptomatic to the renal functional decline. What is worst is that this disease can lead to cysts forming on other organs such as the liver and pancreas. In rare cases, it can even cause heart failure due to coronary aneurysms rupturing. This invasive nature of this disease makes it extremely difficult to treat. [1] Symptoms of this disease include low-grade flank, abdominal and lower back pain due to the cystic enlargement as well as the bleeding of one or more of the cysts. A normal kidney weighs approximately 150g; an ADPDK kidney can grow almost as big as 20 to 30 lb thus causing this pain [4]. In addition to this, due to the functional decline of the kidneys, there may be the presence of blood in the urine (known as Haematuria) due to the

Therefore, from the above, it is apparent that this disease cannot be cured however the progression of this invasive disease can be slowed down. The drug in question is called Tolvaptan which can slow the annual rate of kidney growth as well as a reduced rate of renal functional decline in treated patients. According to a drug trial carried out on 51 patients over a 3 year period, it was shown that this drug was able to decrease the steepness in the eGFR curves insinuating that it was able to reduce the rate at which the renal function was declining [5]. The eGFR reading stands for the Glomerular filtration rate which helps to estimate the functional capability of the kidney. The benefit of Tolvaptan is that it reduces the rate of renal decline thus slowing down the degeneration of the kidneys caused by the ADPKD disorder. Currently, this drug is only available in Canada, Japan, Korea and Switzerland for treating ADPKD. [5] The only issue with this drug is that although it can impact the progressive nature of this illness, it will not combat the cystic formation. It only slows the rate of progression of the condition but doesn’t combat the condition itself- the progression will still continue, just at a slower rate. In addition to this, as part of the current treatments, they use antihypertensive agents in order to control hypertension that is usually common with ADPKD sufferers. Furthermore, due to the frequency of pyelonephritis, antibiotics have to be constantly prescribed in order to contain these issues. These all mean that ADPKD is extremely difficult to treat and live with. However, in the recent few months, revolutionary research at Royal Holloway University has identified a possible treatment for this currently incurable disease. Professor Robin Williams and his team at Royal Holloway have identified a dietary flavonoid present in grapefruit called Naringenin that specifically targets the PDK1 gene to prevent cyst formation. [6] Naringenin has been identified as having anti-inflammatory properties that can help counteract the growth of cysts on organs. The PDK1 gene is expressed in a group of cells called the MDCKD cells that are essential for the cystic growth on organs. However, Naringenin was able to inhibit the growth of these MDCKD cells at the concentration of 100 μM after just 6 days. [6] This means it was able to combat the formation of cysts thus could be a future therapeutic agent against Autosomal dominant polycystic kidney disease. It is clear that this can be the key to combating ADPKD in the future- currently it is awaiting drug trials. Unlike Tolvaptan, this chemical is able to fully inhibit the progression of ADPKD thus combating the condition itself. References 1. Luciano, R.L. (2014) ‘Extra-renal manifestations of Autosomal dominant polycystic kidney disease (ADPKD): Considerations for routine screening and management’, . 2. WILSON, P.D. (2001) ‘Polycystin: New aspects of structure, function, and regulation’, Journal of the American Society of Nephrology.

3. Chapman, A.B., Devuyst, O., Eckardt, K.-U., Gansevoort, R.T., Harris, T., Horie, S., Kasiske, B.L., Odland, D., Pei, Y.P., Perrone, R.D., Pirson, Y., Schrier, R.W., Torra, R., Torres, V.E., Watnick, T. and Wheeler, D.C. (2015) ‘Autosomal dominant Polycystic kidney disease (ADPKD): Executive summary from a kidney disease: Improving global outcomes (KDIGO) controversies conference’, . 4. Available at: http://www.medicinenet.com/ polycystic_kidney_disease/page2.htm (Accessed: 26 October 2016.) 5. Tolvaptan for ADPKD: Interpreting the NICE decision (2016) Available at: http://www.renal.org/docs/ default-source/guidelines-resources/ tolvaptan_in_adpkd-rawg2015_commentary-030216.pdf (Accessed: 26 October 2016). 6. Waheed, A., Ludtmann, M.H.R., Pakes, N., Robery, S., Kuspa, A., Dinh, C., Baines, D., Williams, R.S.B. and Carew, M.A. (2014) ‘Naringenin inhibits the growth of Dictyostelium and MDCK-derived cysts in a TRPP2 (polycystin-2)-dependent manner’, 7. Image provided kindly by - The beginning of A new era in ADPKD (2015) Available at: https:// ajkdblog.org/2015/10/29/the-beginning-of-a-new-era-in -adpkd/ (Accessed: 26 October 2016).

Adrenoleukodystrophy

By Rohan Vijjjhalwar Ardenoleukodystrohpy (ALD) is a deadly genetic neurodegenerative disease, more specifically a demyelinating disease. ALD is caused by the mutation of the ABCD1 gene on X-chromosome resulting in a progressive demyelination of neurons leading to the impairment of signal conduction. ALD can present itself in various ways however a symptom attributed to this disease is commonly occurring seizures and hyperactivity. These symptoms rapidly mature into patient falling into a vegetative state shortly followed by death. Unlike many genetic illnesses, ALD has not been shown to affect any particular country or ethnic group however females (1 in 16,800) are shown to be more at risk of being affected by this genetic disease than men (1 in 21,000)[1]. ALD affects a transporter protein which is responsible for transporting very long fatty acids (VLCFA) to the peroxisome (which catabolises the VLCFA as mitochondria cannot break it down). The mutation of the gene ABCD1 leads to a transporter protein failing to transport these large fatty acid chains into the peroxisome leading to an aggregation of fatty acid within tissues as VLCFA are not being broken down. The behaviour of VLCFAs is such that they begin to progressively damage the myelin sheath surrounding the axon until the neuron has no myelin sheath. The myelin is responsible for the signal propagation speed and for insulating signals. As a result, the patient will have seizures, hyperactivity and later on rapid deterioration of their motor skills and metal aptitude. As ALD is a genetic illness, multiple factors often play part in its onset; however two-thirds of the patients will have the onset in their childhoods (3 to 10 years).[2] The diagnosis of ALD is particularly difficult as ALD is rapidly occurring illness along with the fact that the illness has a highly variable onset meaning that identifying the illness before it becomes severe is difficult. When ALD is suspected, there are a variety of tests the doctor will often conduct such as performing a blood test to determine the VLCFA levels in the blood. The level of VLCFA in plasma is determined through gaschromatography mass spectrometry [3]. This test is not a conclusive of ALD however it ensures that other illnesses are removed from question. Additionally, gas chromatography of plasma often fails as many women affected by ALD show no abnormal VLCFA levels in plasma as the physician expects to see. VLCFA levels in women often seem normal in tests because ALD is a genetic illness in which x-chromosome’s gene is mutated and since women have 2 X chromosomes even if one abcd1 gene is mutated another is functional. This result in some of the VLCFA’s to be correctly broken down by the peroxisome due to the unmutated gene in the pair of Xchromosomes thus VLCFA levels are often lower and the ABCD1 gene mutation does not significantly alter the phenotype. In many cases, the physician will often follow up with the plasma analysis with a more preferable method: Genetic analysis. Genetic analysis will target the ABCD1 gene to see for mutations.

Genetic analysis is not used earlier as ALD is an extremely rare genetic illness so physicians are often unsuspecting of the illness as being ALD. [4]

As of today, there are two treatments which are effective in resisting the progression of ALD however neither have been able to repair the damages that the illness has previously caused. The first treatment that is shown to be effective is using Lorenzo’s oil. Lorenzo’s oil is oil which is a mixture of specific fatty acids which will be able to reduce the VLCFA levels in the body thus reduce the progression rate of the illness. In 2005, a study followed 89 boys who had been screened for ALD and had shown the mutation (marker of ALD) however during the study the subjects were given Lorenzo’s oil prior to onset of ALD as well as low-fat diet for 7 years. The results of this study showed that 74% of the boys had showed no signs of ALD. [5] As a result, Lorenzo’s oil is often used on patients with ALD in order to try preventing onset of ALD. In addition, another treatment in dealing with ALD is stem cell transplantation. Stem cell transplantation (SCT) involves providing the patient with modified stem cells which can produce a functional ALD protein which reduces VLCFA levels. As a result, progression of ALD can be arrested. A drawback of this treatment is SCT could lead to the body rejecting the implanted cells leading to severe immune responses. This is combated through administration of immunosuppressant drugs to reduce immune system’s sensitivity; however it leads to the patient becoming vulnerable to foreign infections due to suppressed immune system. Ergo, current research on treating ALD is focusing on autologous transplants (transplanting modified patient’s stem cells) as it can overcome rejection from the body thus becoming a safer treatment option. [6]

References

[1] Steinberg, S., Moser, A., Raymond, G., Pagon, R., Adam, M., Ardinger, H., Wallace, S., Amemiya, A., LJH, B., Bird, T., Fong, C., Mefford, H., RJH, S. and Stephens, K. (2015) ‘X-linked Adrenoleukodystrophy’, .

[2] Engelen, M. and Kemp, S. (2009) Facts on ALD « xlinked Adrenoleukodystrophy database. Available at: http://www.x-ald.nl/clinical-diagnosis/facts-on-x-linkedadrenoleukodystrophy/ (Accessed: 30 October 2016).

[3] Takemoto, Y., Suzuki, Y., Horibe, R., Shimozawa, N., Wanders, R. and Kondo, N. (2003) ‘Gas chromatography/mass spectrometry analysis of very long chain fatty acids, docosahexaenoic acid, phytanic acid and plasmalogen for the screening of peroxisomal disorders’, Brain & development., 25(7), pp. 481–7.

[4] Moser, H.W., D, P. and Kemp, S. (2003) Diagnosis of ALD « x-linked Adrenoleukodystrophy database. Available at: http://www.x-ald.nl/clinical-diagnosis/diagnosis -of-x-ald/ (Accessed: 30 October 2016).

[5] Moser, H.W., Raymond, G.V., Lu, S.-E., Muenz, L.R., Moser, A.B., Xu, J., Jones, R.O., Loes, D.J., Melhem, E.R., Dubey, P., Bezman, L., Brereton, N.H. and Odone, A. (2005) ‘Follow-up of 89 asymptomatic patients with Adrenoleukodystrophy treated with Lorenzo’s oil’, Archives of Neurology, 62(7), p. 1073. doi: 10.1001/ archneur.62.7.1073.

[6] Current treatment research (no date) Available at: http://www.stopald.org/current-treatment-research/ (Accessed: 30 October 2016).

Multiple Sclerosis The next diagnostic test for MS is to take a lumbar puncture (LP) where a sample of the cerebrospinal fluid is taken and tested via gel electrophoresis. Since the cerebrospinal fluid is part of the CNS, it is still very much prone to the effects of MS. And since MS is autoimmune, the LP contains immune system remnants like antibodies which can, if elevated, show the presence of MS. With regard to the gel electrophoresis test, it will help separate and visualise the contents of the LP. The results of this, as shown in the image on the left, depict a set of lines. In the normal patient, the thin lines indicate proteins. In the MS patient, the thicker lines (oligoclonal bands) indicate a higher protein presence from antibodies; this hence directly points towards MS.

By Zak Mouyer Multiple Sclerosis is an example of an autoimmune disease which affects the brain, specifically its neurons by damaging the insulating layer known as myelin around it. By it being autoimmune, multiple sclerosis (MS) works by using the bodyâ&#x20AC;&#x2122;s immune system to directly degrade the myelin layer. Hence MS presents through a variety of symptoms with neurological roots. When looking for MS, there are some tell-tale signs and symptoms to look out for. For example the patient often presents with impaired or weakened vision where distant objects cannot be seen and double vision is common. And since this condition directly affects the CNS, there is often stuttered speech and a difficulty in breathing. Also in the peripheral extremities like the hands, there is often a lack of sensation or even paraesthesia present. In some cases as well, there is muscular paralysis or spasticity, and it is very common that there is a lack of bladder control and it is difficult to maintain sexual arousal. Lastly associated with MS is cognitive dysfunction, where paying attention, working memory or decision making are significantly impaired. Diagnosis: Having the above signs and symptoms are not enough when it comes to giving a full diagnosis of MS, instead significant testing is needed. The first and most common test is an MRI scan. In the MRI scan, it is very clear that MS could be present when lesions are seen in the white matter of the brain. As shown in image above, these lesions/plaques are the white spots where damage has occurred from the MS condition. Also the white matter shown is mainly just the axons covered in the myelin insulator, so these lesions tell us that MS causes damage to the axons, but specifically to the myelin layer.

The last diagnostic test, which is more confirmatory than anything else, is a visual evoked potential test. Here the patient has some electrodes placed on their scalp above where lesions have been seen on their MRI and a lit chequered screen is placed in front of them. This screen alternates the black area into white by lighting them rapidly. This should induce a detectable amount neural activity to which can be plot on voltagetime graph. If there was a lesion on one of the optic nerves for example, the voltage-time graph should show a delay for the output of an electrical impulse from the damaged neuron. And since MS damages the myelin, all electrical impulses from neurons that have degraded myelin will not be able to transmit impulses as well as normal neurones. Risk Factors: When it comes to finding a cause for MS, it is very difficult since there is not one single, outstanding factor. However there are some very clear risk factors that put one more prone to MS than others. MS is not a genetic disease but definitely has genetic components leading to its arrival in a patient. In twin studies, where identical twins (same DNA) are compared with fraternal twins (different DNA), there is a clear link to the passing down of MS. Recent studies have shown that there are around fifty genes related to the cause of MS. But one that is very prevalent in MS patients is the autoimmunity gene in chromosome 6, namely HLA-DRB1. The HLA stands for Human Leukocyte Antigen, and since this antigen determines what is and what is not meant to be in the body, in MS patients the HLA-DRB1 gene is damaged. Aside from genetic risk factors for MS, there have been studies to show that there are environmental factors as well. For example for most MS cases, people who live north of the equator are much more likely to get this disease. And as you go further and further north,

you are exposed to less sunlight. Sunlight on the skin is what produces vitamin D which is thought to lead to autoimmunity. There is also a correlation in getting MS as an adult when in your childhood had one of the following viruses: Epstein-Barr, herpes, mumps or measles. Lastly it is evident in people who have MS and smoke, that when they quit smoking, their treatment works a lot better. Pathophysiology: MS at its heart is the degradation of the myelin around the axon of a neuron caused by the bodyâ&#x20AC;&#x2122;s own immune system. But how does the immune system get to the neurons in the first place since there is a blood brain barrier to prevent this from happening. Normally the blood brain barrier (BBB) prevents any viruses or immune system components from entering the brain since the endothelial cells are joined together very well at points called tight junctions. In MS however, parts of the immune system are able to enter the brain and slip through the BBB. In most cases a T-cell breaches the barrier and when it reaches neurons, it detects the protein structures coming out of the myelin as foreign and it releases a chemical known as cytokines. Cytokines can do a number of three things. Firstly they degrade the BBB further such that it becomes more permeable. It also calls for other immune system components like macrophages or B cells which both are able to break down the myelin further. And lastly the cytokines are directly toxic to the myelin and can actively degrade it themselves. All of this attacking and the presence of the immune system in the brain leads to an increased amount of inflammation called neuro-inflammation

The body does however have its own recovery system where cells come to the damaged myelin and are able to replenish the degraded sheath around the neuron. These cells are not neurons themselves and are known as oligodendrocytes. The process which allows them to replenish the myelin on the neurons is called remylelination. However since the immune system is so robust, the oligodendrocytes are in a losing battle as the amount of myelin degradation ends up outweighing the myelin regeneration.

Treatment: Unfortunately, since there is no known cause to MS, there is no single cure to it as well. However treatment is available via drugs called ‘disease-modifying drugs’. The most common type of MS, relapse-remitting MS, is the type of MS that responds best to treatment. And since the drug is ‘disease-modifying’, it decreases the relapse time and also the remission but it greatly increases the time in which the next relapse begins. This is why the life expectancy of a person with MS is only shortened by a few years at most.

When it comes to the drugs used there are two types. One being an immunosuppressant like corticosteroids and the other are Beta Inerferons which suppresses inflamation. The immunosuppressants are very effective as they are able to initially prevent any T-cells from leaking through the BBB into the brain. Also they are able to stop any T-cells from reacting vigorously at the presence of proteins on the myelin and hence release

cytokines. With a reduced amount of cytokines released, fewer macrophages and B-cells come to further degrade the myelin. This treatment specifically targets the autoimmune response of MS by dampening the immune activity in the brain. But when it comes to treating the presenting symptoms, not only the pathophysiological ones, a lot of therapy is needed. Whether it be physiotherapy for the muscle numbness and pain, or cognitive stimulaiton to maintain a reasonable amount of cognitive activtity. It is clear however that the treatment for these symptoms is extremely subjective to each patient. Epideomology of MS: There are currently 2.3 million people who have MS in the UK but it is difficult to count the exact number since MS is a non-reportable disease which means that doctors do not have to tell the government that their patient has MS, unlike HIV. In the general poplulation there is a 0.1% chance of having MS but when it comes to being directly related to a MS patient, this chance increases to 2.5%-5%. However, even if you have an identical twin with MS, chances which should increase to 100% of acquiring the condition, only go up to 25% which suggests that it is not an entirely genetic disease. MS is most common in Caucasians around the world and there is a slight tendency towards females than males within the twenty to fifty year old age range. Reference: Khan AcademyTM UK MS Society

Dementia leading to symptoms such as memory failure, personality changes, problems carrying out daily activities and other symptoms of Alzheimer's disease stated above. [4]

By Narmathan Rajeswaran Dementia affects 850,000 people in the UK. [1] It is not a disease in its own right and it is not a natural part of ageing. The word dementia describes a set of symptoms that may include memory loss and difficulties with thinking, problem-solving or language. [2] In simple terms dementia is caused by loss of nerve cells in the brain which makes dementia a progressive condition because when nerve cells die they cannot usually be replaced. Therefore, when more cells die it causes the brain to shrink which is called brain atrophy. The common symptoms for dementia are memory loss, impaired cognition and loss of physical coordination; however, the symptoms are dependent on the area of the brain that is affected. For example, if there were apoptosis of nerve cells in the temporal lobe the person will have difficulties with language. Similarly, apoptosis of nerve cells in the occipital lobe will result in problems with vision. Dementia is mainly caused by neurodegenerative diseases but, as well as progressive brain cell death, dementia can be caused by a head injury, a stroke or a brain tumour. This article will look at the common types of dementia. [3] Alzheimer’s disease is the most common cause for dementia and accounts for 60 to 80 percent of dementia cases. [4] Generally, the symptoms of Alzheimer's disease are divided into three main stages. In the early stages, the main symptom of Alzheimer's disease is memory lapses. For example: forgetting recent conversations, forgetting names of places and objects and having trouble thinking of the right word. This is known as agerelated cognitive decline and these symptoms are usually unnoticed as they are seen as natural causes of ageing. In the middle stage symptoms, Alzheimer's disease develops and memory problems progressively get worse meaning that they struggle to recognise their family and friends, increasingly become confused, disorientated and have problems with speech or language (aphasia). By this stage someone with Alzheimer’s disease would need support. In the later stages of Alzheimer’s disease, the symptoms become increasingly severe as they have difficulty eating and swallowing (dysphagia), gradual loss of speech and have significant problems with memory. In the severe stages of Alzheimer's disease, people may need full-time care and assistance with eating, moving and using the toilet. [5] During the course of the disease, proteins build up in the brain to form structures called 'plaques' and 'tangles'. Plaques are deposits of a protein called betaamyloid that builds up in the spaces between nerve cells. Tangles are twisted fibres of a protein called tau that builds up inside cells. At the moment, scientists are unsure what exact role plaques and tangles play in Alzheimer's disease, however they believe that the plaques and tangles block communication among nerve cells and disrupting processes that cells need to survive leading the nerve cell to die causing brain atrophy

Another common type of dementia is vascular dementia. This is caused by cerebrovascular diseases: conditions caused by problems that affect the blood supply to the brain. In vascular dementia there is a reduced blood flow to the brain, which damages and eventually kills the brain cells. This can happen due the narrowing of the small blood vessels inside the brain known as subcortical vascular dementia. This may also happen due to a stroke which is also known as singleinfarct dementia or happen due to many “mini-strokes” which is known as multi-infarct dementia. [6] On CT or MRI scans of a brain, damage to the white matter regions of the brain can be seen as thinning. This is called ’leukoaraiosis’ which is caused by white matter infarcts. White matter composes a large volume of the brain, which run like “tracts of communications cables throughout the brain, connecting different regions” of the brain allowing the coordination to exchange information. Therefore, damage to the white matter results in impairment of brain functions which requires complex interactions between regions. There are a number of things that can put someone at risk of developing vascular dementia. Age is the strongest risk factor for vascular dementia since a person's risk of developing the condition doubles approximately every five years over the age of 65. However, cardiovascular diseases can also cause vascular dementia. If someone has high blood pressure (hypertension), high blood cholesterol, poor diet, obese and lack exercise they will be at a high risk of vascular dementia. [7] Dementia with Lewy bodies (DLB) is a type of dementia that shares symptoms with both Alzheimer's disease and Parkinson's disease. Lewy bodies are named after the German doctor, Dr Friedrich Heinrich Lewy, who first identified them. They are tiny deposits of a protein (alpha-synuclein) that appear in nerve cells in the brain. In the healthy brain, alphasynuclein plays an important role in nerve cells especially at synapses. In dementia with Lewy bodies, alphasynuclein forms into clumps inside neurons which cause neurons to work less effectively and, eventually cause them to die. Although scientists do not have a full understanding of why Lewy bodies appear, it could be understood that that Lewy bodies link to two factors: low levels of chemical messenger such as acetylcholine and dopamine that carry messages between nerve cells and a loss of connections between nerve cells. People with dementia with Lewy bodies not only experience problems with memory and judgement, like those with Alzheimer's disease, but are also likely to have difficulties with concentration, visual perception and sleep disturbances. This is because Lewy bodies affect several different brain regions: the cerebral cortex, which controls many functions, including many higherorder brain functions such as processing, perception, thought, and language, the brain stem, which is important in regulating sleep and maintaining alertness and the hippocampus, which is essential to forming new memories .[8] The final type of dementia which we will be looked at in this article is called frontotemporal dementia. Frontotemporal dementia is one of the less common types of dementia yet affecting around 16,000 people in the UK. Frontotemporal dementia affects the frontal lobes and the temporal lobes of the brain. [9] Symptoms of frontotemporal dementia include changes in personality and behaviour, and difficulties with language. [10]

The frontal lobes are large and complex having an 'executive function'. The frontal Lobes play an integral role in memory formation, emotions, decision making, reasoning and personality. The executive function has different aspects which are dealt with by different parts of the frontal lobes. The upper parts of the outer surfaces of the frontal lobes, known as the dorsolateral frontal cortex, are where we organise and plan actions and learn new tasks. The upper parts of the middle surfaces of the frontal lobes are important for our interest and motivation. The area on the underside of the front of the brain called orbitofrontal cortex controls our social behaviour. An area called the Broca’s area, found on the left frontal lobe, controls facial neurons, speech, and language comprehension and at the back of the frontal lobes is the motor cortex which deals with the planning of movements and the control of certain muscles. The temporal lobes are found on either side of the brain and play an integral role in hearing, organisation and comprehension of language and information retrieval. The primary auditory cortex is responsible for hearing. The Wernicke’s area is responsible for language comprehension which is located on the left temporal lobe. [11]

In all forms of frontotemporal dementia, the frontal and/or temporal lobes shrink. There are two main variants of frontotemporal dementia, behavioural variant and language variants. Behavioural variant frontotemporal dementia is the most common type of frontotemporal dementia and mainly affects the frontal lobes such as the orbitofrontal cortex meaning that the person with lose their inhibitions: behave in socially inappropriate ways and act in an impulsive or rash manner. The person may also lose interest in people. It is also common for a person with behavioural variant frontotemporal dementia to struggle with planning, organising and making decisions due to the damage to the dorsolateral frontal cortex. In language variants of frontotemporal dementia there are two types, progressive non-fluent aphasia and semantic dementia. The main reason for this is due to the damage to the Broca’s area as well as the Weimicke’s area. In progressive non-fluent aphasia, these problems are with speech. They speak slowly and hesitantly, have frequent error in grammar and have impaired understanding of complex sentences, but not single words. In semantic dementia, speech is fluent but people begin to lose their vocabulary and understanding of what objects are. [10] References [1] Alzheimer’s Society, 2014. Dementia 2014 infographic. [2]NHS Choices, 2015. About Dementia. [3] Alzheimer’s Society, 2014. What is Dementia? [4]Alzheimer Association, 2016. What Is Alzheimer's? [5] NHS Choices, 2015. Alzheimer's Disease. [6] NHS Choices, 2015. Vascular Dementia. [7]Health Exchange, 2016. Causes of Vascular Dementia. [8]National Institution on Aging, 2015. Lewy Body Dementia. [9] NHS Choices, 2015. Frontotemporal Dementia. [10] Alzheimer Association, 2016. What Is Frontotemporal Dementia? [11] Harvard University, 2005. The Human Brain

Stem Cell Research differentiate into almost any cell in the body. ‘Hematopoietic Stem Cells’ are stem cells which are manufactured in the bone marrow: these have the ability to specialise into any of the cells found in the blood. And ‘Mesenchymal Stem Cells’, which are found in many different parts of the body and are typically taken from: bone marrow, skin and fat tissue. (MS Society, 2015, Page 1).

By Muse Berhe ‘Stem Cell Research’ is the research into a type of cell commonly regarded as a ‘stem cell’. What gives these cells such value is that stem cells have the remarkable potential to develop into many different cell types in the body during early life and growth. (National Institutes of Health, 2016, Page 1). This makes them highly sought after, as they can be used to repair impaired tissues and various other structures within our bodies. Their most valuable asset is that certain types of stem cells, which we refer to as ‘embryonic stem cells’, have the ability to specialise into any other cell in the body, this means that they can be used to aid the reparation of any structure in our body, hence the high value of stem cell research. However, this isn’t the only objective of stem cell research, as the research into it continues to advance knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms. (National Institutes of Health, 2016, Page 1). It furthers our understanding of the complex nature behind evolution, so we can effectively use our knowledge of stem cells to help us gain a clearer understanding of how life began on Earth. We also gain a more in depth understanding of the human anatomy and we are able to apply this new found knowledge into medicinal research. However, stem cell research is highly regarded as a controversial topic: some believe that embryos, from which stem cells can be obtained, are living organisms. Thus, by using these embryos, you are effectively murdering a human being. There are two ways in which this controversy can be avoided: deriving embryonic stem cells without destructing the foetus and obtaining embryonic stem cells without actually creating a foetus. (Murnaghan, Stem Cell Controversy, 2016, Page 1). It is paramount that we place equal emphasis on obtaining stem cells from other areas in the body, such as the bone marrow, to further our understanding of the therapeutic properties of stem cells. There are three different types of stem cells: ‘Pluripotent Stem Cells, ‘Hematopoietic Stem Cells’ and ‘Mesenchymal Stem Cells’. ‘Pluripotent Stem Cells’, sometimes regarded as ‘true’ or ‘embryo’ stem cells, can

At the moment, the most widely used stem cell treatment is transplanting blood cells, which have specialised from stem cells, to treat blood related diseases and conditions or to restore the blood loss after specific cancer treatments. (Luca, 2015, Page 1). More than 26,000 patients are treated in Europe alone with the aid of blood stem cells, and this figure will gradually increase as the attitudes towards stem cell research become less apprehensive. (Luca, 2015, Page 1). Unfortunately, there are not many embryonic stem cell donors, as embryonic stem cells are only produced during a human’s embryonic stage of development so we have to make use of the less versatile ‘Mesenchymal’ and ‘Hematopoietic’ stem cells. A fascinating property that heightens their usage is stem cells have the ability to renew themselves through mitosis for long periods of time, unlike specialised cells. This means they can offer a ‘virtually’ unlimited source of cells needed in embryonic research. However, this only applies to embryonic stem cells, which generate the most controversy between the various stem cells. (ABC News, 2005, Page 1). This also emphasises the importance of increased acceptance towards stem cells. We can’t necessarily use stem cells that were not produced in our own bodies, as they wouldn’t have the same genes as us. This is because our body recognises them as being ‘foreign’ objects so are thus rejected and die. However, this can be remedied by cloning one of your own cells to produce an embryo, which we would then take stem cells from. This is referred to a ‘theurapeutic cloning’. (BBC, 2014, Page 2) Reference National Institutes of Health, 2016, Stem Cell Basics I, https://stemcells.nih.gov/info/ basics/1.htm, Date accessed: 15/10/2016 Murnaghan, IM, 29 September 2016, Stem Cell Controversy, http:// www.explorestemcells.co.uk/ StemCellControversy.html Date accessed: 17/10/2016 ABC News, 2005, Fast Facts on Stem Cells, http://abcnews.go.com/Health/US/story? id=785936 Date accessed: 29/10/2016 Luca, ML, 1 September 2015, What diseases and conditions can be treated with stem cells?, http://www.eurostemcell.org/faq/ what-diseases-and-conditions-can-betreated-stem-cells, Date accessed: 23/10/2016 MS Society, 2015, Stem Cells, https:// www.mssociety.org.uk/ms-research/ emerging-areas/stem-cells#Top, Date accessed: 24/10/2016

Cystic Fibrosis and Orkambi However, not only can there be organ damage, but often transport tubes in the body can become so blocked by mucus that nothing can travel through them, leading to further problems. There are many different cases of this, but some of the most severe are as follows; the tubes in the pancreas that transport the enzymes to the stomach can become so blocked that the enzymes can no longer fit through, so food cannot be properly digested. This can lead to malnutrition, so CF sufferers may need to take at least fifty pills a day to help digest their food [2]. Furthermore, as the pancreas also produces insulin, sufferers can become diabetic, further decreasing their quality of life due to the required treatments – this is known as cystic fibrosisrelated diabetes mellitus (CFRDM). In males the tubes that transport semen out of the testes can become so blocked that they can cause infertility, this condition is known as ‘congenital bilateral absence of the vas deferens’.

By Malachi Saccomani Cystic Fibrosis is an inherited condition that causes the human body to produce thicker, stickier mucus that can block and damage many of the body’s organs, typically those in the respiratory and digestive system. Hence, just half of people who suffer from cystic fibrosis will live to forty-one [1]. However, a recent 96 weeklong study suggested that a treatment consisting of a combination of the drugs lumacaftor and ivacaftor (marketed and developed as Orkambi by Vertex) was extremely effective in reducing the damaging effects of cystic fibrosis, reducing the rate of lung decline by 42%, and so reducing the number of lung transplants needed.

According to the Cystic Fibrosis Trust, one in twenty-five [2] Brits carry the faulty, recessive CFTR allele that causes cystic fibrosis. As the allele is recessive, it will not be visible in the phenotype of a human carrying one copy. However, when two carriers produce offspring, there will be a one in four chance of the child having cystic fibrosis, as seen to the right. The CFTR gene provides instructions for the production of a transport protein called the cystic fibrosis transmembrane conductance regulator, which transports chloride ions into and out of cells; the protein is a channel protein and is imbedded in the phospholipid bilayer of a cell surface membrane. In a healthy human, this flow of chloride ions controls the flow of water between the inside and outside of cells, through the process of osmosis. This helps to keep the mucus, produced by goblets cells, thin and easily flowing. However, typically due to a mutation called delta F508, a faulty allele can be present. This allele then produces the faulty CFTR channel protein, which is missing an amino acid at position 508, and so causes the protein to fail immediately, making it redundant at transporting chloride ions. Thus this causes thicker, stickier mucus to build up in the lungs and other organs, which leads to chronic infections and ultimately organ damage.

Due to these conditions, the quality of life of CF sufferers is greatly diminished, and so as there is no known cure, huge amount of money are being invested into medication and treatment to reduce the negative effects of the disease. One private pharmaceutical company, Vertex Pharmaceutical Incorporated, have just concluded a 96 weeklong study into the effects of the drug “Orkambi”. Although Orkambi has been developed as a treatment for those who suffer from CF due to the faulty CFTR gene, who make up just 4-5% of all CF sufferers [3] (2750 are eligible for Orkambi in the UK [4]), large amounts of money have already been spent, and so the current cost of the drug, per person, per year, is £104,000 [4]. Due to this price, the UK government, as well as many others, is still in ongoing negotiations. Orkambi is the combination of two drugs; lumacaftor and ivacaftor.

Lumacaftor acts as a pharmacological chaperone, a small molecule that moves into cells to act as a scaffold for protein construction, to increase the number of CFTR channel proteins that successfully form and bind to the cell membrane, thus increasing the rate at which chloride ions can be transported.. Ivacaftor is not limited to treatment of just one type of cystic fibrosis (Orkambi is limited to only cystic fibrosis caused by the delta F508 mutation), but of nine [5]. Ivacaftor is a potentiator which increases the likelihood that the defective channel proteins, which have been able to bind to the cell surfaces of epithelial cells, successfully transport chloride ions by binding to the protein and changing the way it gates.

In combination, the efficacy of the drugs appeared to increase, and the study was very promising. Researchers reported that those who took the drug, could expect the declination of their lungs’ function decreased from 2.3% annually, to just 1.3% [6]. The study suggested that it would also be safe for 12 year olds to take, as it was “generally well tolerated” [1], and the same was said for 6 to 11 year olds. This is important as if children are able to take Orkambi from the age of six, then their lungs and other organs can be partially saved from greater damage, reducing the need for transplants, and so likely increasing life expectancy and quality of life.

Vertex Pharmaceuticals Incorporated, published: 27/10/16, accessed: 03/11/16, http://investors.vrtx.com/ releasedetail.cfm?ReleaseID=995880 “What is CF”?, accessed 03/11/16, www.cysticfibrosis.org.uk/what-is-cysticfibrosis Jones AM, Helm JM published 10/09, "Emerging treatments in cystic fibrosis". Drugs. 69 (14): 1903 https:// dx.doi.org/10.2165%2F11318500000000000-00000 National Institute for Health and Care Excellence, published 17/06/2016, accessed 03/11/16 https:// www.nice.org.uk/news/press-andmedia/cost-of-cystic-fibrosis-treatmenttoo-high-for-benefit-offered-says-nice Ivacaftor Label, last revised 03/15, accessed 03/11/16, http:// www.accessdata.fda.gov/ drugsatfda_docs/ label/2015/203188s017lbl.pdf James Gallagher, published 28/10/16, “Doctors excited by cystic fibrosis therapy”, BBC News Health Page, accessed 03/11/16, http:// www.accessdata.fda.gov/ drugsatfda_docs/ label/2015/203188s017lbl.pdf

Gastroenteritis Dehydration is another symptom, since little water is absorbed into the bloodstream. If one experiences these three defining symptoms, then they may have acute gastroenteritis. Other symptoms may include stomach pain/cramps, tiredness, body aches, and a fever.

By Akila Wickramathilaka Gastroenteritis refers to the inflammation of the stomach and the small intestine due to either a viral or bacterial infection. Other, more colloquial names for gastroenteritis include: “stomach flu”, “stomach bug” and “stomach virus”. There are two distinct types of gastroenteritis: the common acute gastroenteritis, and the less common chronic gastroenteritis. Acute gastroenteritis lasts for a short period of time, usually a few days to a week. It can be described as the sudden inflammation in the lining of the stomach. Conversely, chronic gastroenteritis is persistent, and will last for a long time. It may be painless and occurs slowly over time. Often associated with ulcers, and an increase in the risk of stomach cancer (most commonly adenocarcinoma), this is a condition that should not be underestimated. However, the main focus of this article will be the unexceptional acute gastroenteritis. In general terms gastroenteritis results in the inability to digest food, resulting in the expulsion of undigested food, via the oesophagus (vomiting), or through means of diarrhoea. This condition is caused by a pathogenic infection. Common viruses that may trigger this condition include the likes of rotavirus, norovirus and hepatitis A. Common bacterial causes are the Enterotoxigenic E.coli, Salmonella, Campylobacter and Shingella bacteria. Less commonly (although very common in developing countries), it can also be caused by parasites such as Giardia and Cryptosporidium. These pathogens can be found in food, water, soil, animals and in human faeces. In theory, these pathogens get into our body system via Fecal-Oral transmission. A common pathway of infection involves a lack of hygiene following the passing of a stool. If one fails to wash their hands effectively, the pathogen will not be washed away and their hands will be contaminated. Via means of contact, this germ can spread from one place to another, until eventually it enters our body orally. Once it is in the body system, the pathogen starts to attack a region of the gastrointestinal system called the gastrointestinal wall. The wall consists of a layer called the epithelium, which is composed of specialized cells involved in digestion and absorption. Pathogens contained in the partially digested food will invade the epithelium and the specialized cells, causing apoptosis (cell death). Some of the dead epithelial cells will then break off the lining, as deposit into the “slurry” of partially undigested food. Since the presence of epithelial cells is starkly reduced, the efficiency of the digestion of food and water will deplete. Therefore, much of the important nutrients (including water) will not be absorbed, and will remain in the mixture of partially digested food. Incrementally, white blood cells near the epithelium will also be deposited into the mixture of food, leading to inflammation. This, in turn, causes a plethora of symptoms including vomiting and diarrhoea, as the partially digested food needs to be expelled from the body due to the destruction of the epithelium, meaning that food cannot be digested and absorbed.

In order to confirm this, doctors will usually carry out scientific tests to find out which specific pathogen is causing the symptoms. The doctor may use a stool sample to evaluate which pathogen is contaminating the faeces. They may also carry out a blood test, which is designed to check for signs of dehydration. Marked signs include high levels of sodium (Na+) ions, or high levels of creatinine- a compound produced by metabolism of creatine and excreted in the urine. These two tests can be used to confirm whether or not a person has acute gastroenteritis. Treatment of acute gastroenteritis involves Oral Rehydration Therapy. The patient should consume vast quantities of liquid containing mineral salts and sugars. This is to combat dehydration. If the condition of the patient is severe, they can be put on an IV fluid. This is known as intravenous therapy, which involves the infusion of liquid substances directly into a vein. Dehydration is especially dangerous for babies and the elderly. If the case is caused by a bacterium, then the doctor may prescribe antibiotics. This is not a liable form of treatment if the case involves a virus, since viruses are not affected by antibiotics. Even if the case involves a bacterium, the drug may still kill other, more useful bacteria in the gastrointestinal system that aid the digestion and absorption of food. It could also be seen as a waste, because the symptoms will clear up by themselves, after a few days. Whether or not to prescribe antibiotics must therefore be derived from the condition of the patient and the nature of the pathogen. One should also try to avoid anti-vomiting or antidiarrhoeal medications unless prescribed or recommended by a doctor. In essence, there is no medicine to treat/cure acute gastroenteritis as the normal functioning of the body will eventually flush out the pathogens To prevent gastroenteritis, one should endeavour to practise means of good hygiene. This includes washing hands thoroughly after using the bathroom. One should also take care to drink water that has been decontaminated and is clean, and to cook food properly to ensure that it is not contaminated with pathogens, which might infect someone that eats it. The best way to combat acute gastroenteritis is to prevent it, and means of doing so are relatively easy, in comparison to most other conditions. References: 1.

www.khanacademy.org

www.nhs.uk/conditions/gastroenteritis

www.healthywa.wa.gov.au

Strokes fragments could become lodged somewhere in the brain. The severity of a stroke is solely determined by the place of the damaged brain tissue. For example if a clot were to occur in the brain stem, a vital component of controlling heart rate and blood pressure, a person could fall into cardiac arrest and then death. However if there were to be a clot at the very end of the ACA, ischemia would still occur, but would not result in such consequences as mentioned previously. When it comes to detecting strokes, there are a plethora of neurolgical examinations that can be done (usually testing the limbs for motor function), but these test can only merely determine which hemisphere the stroke is on; since all motor action apparent on one half of the body will always have been coordinated from the opposing hemisphere within the brain. Finding the location, size and type of stroke can only be done by highly sophisticated imaging techniques.

Figure 2 shows a CT scan forty-eight hours after a stroke has occurred. There are some worrying signs that damage has been done in this patient. Two obvious signs are that on the left side of the brain, the well delineated curves have disappeared, and the easily distinguishable white and grey matters have now become indistinguishable. The loss of curves suggests heavily that that part of the brain has swollen due to cell death. To confirm that a stroke has occurred on the left part of the cereberrum (most likely the middle cerebral artery), loss of motion or strength could be present on the right side of the patient. Lastly it can be seen that brain appears to not be so symmetrical and that the left side is pushing into the right, this is most probably due to the swelling and is a definitive sign that a stroke has occurred in the area of the middle cerebral artery.

By Zak Mouyer The human brain is split into three main areas: the cerebrum, cerebellum and the brain stem, each having their own specific function. The largest part of the brain, the cerebrum is further split into lobes: frontal lobe, parietal lobe, temporal lobe and the occipital lobe. And since the brain is made of billions of neurons, it needs a constant supply of glucose and oxygen for respiration (since ATP is a vital part of neurotransmission) and also ions for electrical impulses to occur. Hence it is logical that the brain has a diverse and dense set of arteries and veins to supply it with blood. The brain’s blood supply consists of five main arteries: the right and left internal carotid arteries (ICA), the right and left vertebral arteries (VA) and finally the basilar artery (this forms from the two vertebral arties joining together near the brain stem). Within the brain, the two ICAs feed into different parts of the cerebrum. From these arteries comes out the Anterior Cerebrum Artery (supplies the very front and superior half of the frontal lobe), Middle Cerebrum Artery (supplies the centre of the frontal lobe, most of the temporal and parietal lobes) and the Posterior Cerebrum Artery (supplies the Occipital lobe and the Temporal lobe). The two VAs, also called the basilar artery supply the cerebellum via the Superior Cerebellar Artery, the Anterior Inferior Cerebellar Artery and the Posterior Inferior Cerebellar Artery. Lastly the brain stem has direct supply from the VAs via the Anterior Spinal Arteries and again a direct supply from the basilar artery via the Pontine Branches. This assorted and detailed network of arteries are absolutely necessary in keeping all parts of the brain alive and any impediment to these arteries could result in a fatality. The most common form of vascular impediment to the brain’s arteries would be via a stroke. There are two types of stroke: haemorrhagic and ischemic. The former refers to a leakage from a burst vessel hence internal bleeding occurs, this results in the brain receiving a malnourished blood supply and the fluid build-up could put pressure on and damage certain parts of the brain. The latter implies the death of brain cells via a starvation of oxygen from there being a physical barrier stopping blood from moving within the brain. Causes of ischemic strokes vary a lot; a less common cause would be from atrial fibrillation or quivering in the heart. The reduced pumping motion in the heart allows for blood to stagnate and hence clot. These clots can eventually travel to the brain and block arteries. However the most common cause is by a thrombotic or embolic atherosclerosis. A build of atherosclerotic plaque in arteries can eventually break up under hypertension and these little

Figure 1 shows an image of a healthy brain via a CT scan (computerised tomography). This brain is shot by x -rays from many different angles on an axial view. Distinguished factors of this brain are that there are clear delineated curves on the outside edges of the cerebrum which is sign of vitality. Another sign is that both hemispheres are in symmetry. Lastly there is a clear distinction between the grey matter on the surface and the white matter which is on the inside. One issue with CT scans is that it takes around twelve to eighteen hours for the effects of a stroke to appear on the scan. This is not ideal since intervention of the dying brain tissue needs to happen as soon as possible after the stroke.

Figure 3 shows another type of CT scan called a CT angiography (a type of fluroscopy) where a dye is added intravenously into the patient. This dye shows up very clearly and the computer software can be orientated to only show vascular tissue in the brain. In this case it is very clear that there is some sort of vascular impediment on the right side of the patient’s brain (as shown on Figure 3) and this would be enough evidence to begin treatment on the patient. A final type of scanning would be that of MRI (Magnetic resonnance image). MRIs are superior to CT scans in the sense that a stroke can appear on the images as soon as it has occurred. Also these images have greater resolution than CT scans and can give clearer evidence to where and how the brain has been damaged. However MRI scanners are not in as much abundance as CT scanners and it often takes a long time to find an available scanner, hence CT is considered to be a viable alternative. The entire aim of treatment is to try to save what is left of the core around the area of the stroke, but to definitely save the tissue around the core tissue, called the penumbra. This tissue still receives some blood from arterioles and capillaries but a fully oxygenated flow from an artery is needed. Hence all sorts of treatment can be done to end the death process of cells. Treatment for strokes vary immensely between the two types, ischemic and haemorrhagic strokes. After sufficient testing has been done to assure the medical professional that it is an ischemic stroke, treatment can begin. In an ischemic stroke, there is some sort of embolism/ thrombosis in the brain causing blood to halt, hence an anti-coagulant like aspirin is given to stop any further clotting. To remove the clot and resume blood flow as soon as possible, the clot needs to be broken down. Hence a thrombolytic plasminogen activator is used. This drug works by activating our body’s natural ‘clot-busting’ drug: plasmin and increases its effect massively so that the embolism/thrombosis can be broken down.

Figure 4:Transcatheter Aneurysm Coiling

Treating a haemorrhagic stroke requires a completely different approach. Firstly the aim is to stop bleeding from continuing in the brain, hence it is necessary for a clot to occur, but only in that specific area which makes this task a lot more difficult. Another problem is that as a natural reflex to bleeding, the heart pumps faster and harder, increasing heart rate and blood pressure. This is a bad response since any kind of make-shift clot created over the vessel could now break due to the high pressure blood flowing over it. Therefore initial treatment begins with an anti-hypertensive and an eradication of any anti-coagulant the patient may have taken. Another problem to be solved is that due to the increase in of the brain’s volume, pressure can build and hence disrupt electrical flow; in very severe cases this can lead to a seizure. Doctors in this case can give an anti-convulsant drug to oppose the chance of a seizure. A much simpler method would be to sit the patient up right so that blood flow via the jugular veins is increased due to gravity, therefore reducing the brain’s volume.

breaks it up. Hence slowly the clot is broken down and sucked away. In the UK, a stroke occurs every three minutes and globally there is a stroke once every two seconds. Women have less of a chance of strokes than men, and Black people are twice as likely to have strokes compared to Caucasian people. Strokes kill twice as many people than breast, testicular and prostate cancers combined. Strokes are responsible for 7% of all UK deaths but the death rate of strokes has declined by 46% since 1990. One shocking fact among all of the above is that it only costs £48 per patient per annum for medical research as opposed to the £241 needed for a cancer patient in the UK. Hence it is clear that a lot can be done, and is needed to be done, in order to reduce the amount of unnecessary deaths caused by strokes

Interventional procedures can be done to stop strokes, and this is more important for haemorrhagic strokes since initial treatment consists of mainly managing complications. One method of treatment for aneurysms of arteries which have burst is to simply put a tight clip on it. Another method to prevent any further bleeding is to thread a catheter up to the point of the aneurysm and to consistently coil wire into it. This huge amount of coils of wire should physically prevent blood from continuing through it and should promote clotting to occur (Figure 4). The interventional procedure for treating ischemic strokes is only done if the thrombolytic plasminogen activator treatment has failed. The first interventional procedure that can be done is that of a MERCI retriever (mechanical embolus removal in cerebral ischemia, shown in Figure 5). This device is wired to the area of the clot via a catheter and a wire is slipped round and past the clot where it coils. This coil is then wrapped around the clot and is then pulled away. The next method is called the suction method. This involves wiring a suction device up to the clot, and while sucking just under the embolus, a small prong hits the clot continuously and

Figure 5: MERCI Retriever

Proliferation, causes and the treatment of Cancer

By Mohammad Hakimi 2012 saw 8.2 million deaths attributed to this genetic disease. It occurs when information in cellular DNA is corrupted, which in turn leads to abnormal expressions of genes. Alterations in the genes cause a change in its functions. Alterations can be caused by the accumulation of mutations, but also through non-mutational processes (epigenetic). These aberrant (different to the norm) gene expressions can lead to fundamental changes in the biological processes of cells. To understand the proliferation of cancer cells, one must understand the fundamental differences between a healthy cell, and one that is cancerous. This difference can be traced back to protein synthesis where transcription and translation take place. During transcription mRNA can be degraded by small non-coding RNA molecules called microRNA’s (miRNA’s) pre translation. Compelling evidence shows that in cancer cells, miRNA is dysregulated through various mechanisms. These dysregulated miRNA’s are thought to affect the hallmarks of cancer. These include resisting cell death, evading growth suppressors and activating invasion and metastasis. Metastasis is when cancer cells break away from where they first formed (primary cancer) and travel through the blood or lymphatic system to form new metastatic tumours. This new tumour is the same type of cancer as the primary tumour. When mRNA reaches the ribosome, specific protein molecules are translated due to the triplet code of bases. The phenotypic changes recognised as cancer are a result of these protein products of genes. In summation, the proliferation of cancer may be due to the miRNA molecules present during transcription, which alter the process of protein synthesis. Furthermore, the mutation of two types of genes, oncogenes and tumour suppressor genes, are what usually result in cancer (TSG). In normal cells, these two provide an essential function. Oncogenes are a result of mutated versions of normal cellular genes, known as protooncogenes, which encode for proteins that function to stimulate survival, invasion/motility, cell proliferation and apoptosis. Uncontrolled cell division occurs when proto-oncogenes are mutated. Typically, these genes expressions are carefully regulated to avoid uncontrolled cell growth. The mutated nature of these oncogenes

thus results in the increased production of said proteins, leading to increased cell division, and the inhibition of apoptosis. Due to their phenotypical nature, only a single mutated copy of a proto-oncogene is required for the promotion of cancer. Therefore they are not usually associated with inherited cancer syndromes. TSG’s on the other hand are normal cellular genes which function to inhibit cell proliferation and survival. Programmed cell death (apoptosis), and cell cycle progression are both affected by TSG’. TSG’s become problematic when they are inactivated, and so don’t regulate these cellular processes. This is the opposite of oncogenes which become overly expressed. Another difference in these genes is also the fact that TSG’s are phenotypically recessive, and so both copies must be functionally altered to promote cancer. Their phenotypical nature also means they are responsible for inherited cancer syndromes. In this case, individuals inherit a germline mutation of one allele of a TSG, causing every cell in the body to be affected. As a result, there is a high likelihood of at least one cell suffering complete loss of TSG function, as only one copy has to be altered.

Iridium-192. The short bursts are used to protect workers from unnecessary overexposure. With HDR brachytherapy, thin catheters with the HDR sources are placed inside the tumour so that the radiation is focused intensely on just the tumour. Low-dose rate (LDR) brachytherapy on the other hand works by delivering radiation at a continuous rate over the course of one or two days. This also means that the patient will have to stay at the hospital overnight so the delivery device used in the procedure can remain in place throughout the treatment. With this treatment, the radiation is delivered radioactive isotope decays over time. EBRT on the other hand uses high energy X-ray beams such as photon beams, or other types of radiation such as particle beams. Unlike brachytherapy, EBRT is non-invasive. The treatment works by damaging the DNA within the cancerous cells, and by doing this the cell cannot carry out its usual functions like replication. The treatment may either damage the DNA directly, or create free radicals (charged particles) that then damage the DNA. This will ultimately lead to the cells death as the cancer cells aren’t able to replicate themselves due to their damaged DNA. Reference http://www.cancerresearchuk.org/about-cancer/ cancers-in-general/treatment/radiotherapy/external/ about-external-radiotherapy

http://www.radiologyinfo.org/en/info.cfm?pg=brachy

http://www.medicinejournal.co.uk/article/S13573039(15)00281-9/pdf

http://www.cancer.org/cancer/cancercauses/ geneticsandcancer/genesandcancer/genes-andcancer-oncogenes-tumor-suppressor-genes

http://www.medicinejournal.co.uk/article/S13573039(15)00270-4/pdf http://www.moloncol.org/article/S1574-7891(12) 00098-1/fulltext There are various treatments for cancer; however the attention of this article will be dedicated to radiotherapy, as it is one of the most common treatments. There are in fact two types of radiotherapy: external beam radiation therapy (EBRT), and internal radiation therapy (brachytherapy). Brachytherapy involves the placement of a single or multiple radioactive sources inside the patient’s body. There are also different types of this treatment. Contact brachytherapy involves the implantation of the radioactive source in a cavity/space adjacent to the tumour. One of the main differences between EBRT and brachytherapy is that brachytherapy allows physicians to use a higher total dose in order to treat a smaller area, in a shorter space of time. The other form of this type of treatment is interstitial brachytherapy which involves the implantation of radioactive sources directly into the tumour. With interstitial there are two methods which can be applied. High-dose rate (HDR) brachytherapy involves a specific dose of radiation to be delivered to the tumour in a short burst. This is accomplished by a remoteafterloading machine which stores powerful isotopes of

http://www.cancercenter.com/terms/metastasis/

Orthopaedics and Femoral Fractures where the articular surface (the surface of a bone which makes contact with another bone to form a joint) is changed, replaced, remodelled or realigned. A hemiarthroplasty is performed when only one side of the joint is being replaced, for example only the head of the femur as opposed to the femur and the acetabulum. Total knee and hip replacements are common arthroplastic procedures.

By Abhijeet Neeti Orthopaedics is a study of medicine which involves the musclo-skeletal part of the body. It can involve surgery and physiotherapy to treat musclo-skeletal trauma, diseases and injuries. Orthopaedic surgeons undertake many surgical procedures which include, but isn’t limited to, arthroscopies, arthroplasties, meniscectomies, tenotomies and tenectomics, chondroplasties, fracture repairs and total joint replacements (a sub category of arthroplasty). Orthogeriatrics is a sub branch which mainly involves treating skeletal trauma etc. of elderly inpatients. Generally, they are more vulnerable to injuries due to a frailer frame, more brittle bone, a lower bone density (can be caused by osteoporosis) and complications caused by arthritis (or a combination of both - osteoarthritis). Although these can sometimes be avoided by increasing intake of certain nutrients (e.g. calcium, vitamin D, isoflavins) and decreasing intake of others (e.g. sodium, protein, caffeine) which can alter bone densities, ageing is unavoidable and can often bring with it unwanted conditions. One of the most common fracture areas is the hip as there are many delicate areas and weight can be distributed unevenly, especially when combined with osteoporosis. Fragility fractures have a very high mortality rate, 10% die within a month and 32% die within a year; therefore it is vital that research and study is done in this field. Health and social aftercare costs for the first two years after hip fracture average £13,000, further research may reduce costs. One of the most common procedures is a knee arthroscopy (also known as a keyhole surgery) which is minimally invasive and involves the treatment of the many orthopaedic conditions that can occur to the knee’s meniscus such as torn cartilage, anterior cruciate ligament reconstruction. Arthroscopies use a fibre optic camera that is inserted into the knee cavity by making a small 10mm incision on the knee surface. This means that there will be a very quick healing times and this is especially useful for professional athletes where time is money. Although arthroscopies are possible for almost any joint, knees, elbows, hips and shoulders are the most common. An arthroplasty is a surgical procedure

One of the most common fractures in the elderly involves the acetabulum and the femur in hips. The mortality rates are double among the women who'd suffered a broken hip in the first year after injury, compared to women of similar age who have not suffered a hip fracture, as suggested in a meta-analysis published in 2010 in the Annals of Internal Medicine. The femur is affected normally and is classified by using the terminology as shown on the next page. The anatomy of the femur is also on the next page. All of the fractures shown can be fixed using a variety of orthopaedic surgical methods. Any intracapsular fractures (those that break into the capsule that surrounds the acetabulum and femoral head), must require an arthroplastic procedure. This is because these types of fractures can disrupt blood supply from, but not limited to the common femoral artery and any branches of it. This can cause necrosis (death) of the bone which can cause serious problems. Arthroplastic procedures may include insertion of a metal/plastic implant which completely replaces the joint. These implants generally last 10-20 years, depending upon the activity levels of the patient. Extracapsular fractures can be fixed using orthopaedic metal work such as an IM nail or a DHS. Sometimes, a hemiarthroplasty may be preferred to reduce pain or when dealing with elderly patients. A neck of femur fracture is a common orthogeriatric condition, with many hospitals having whole wards dedicated to just patients with this fracture. A hemiarthroplasty or a full arthroplasty is carried out as treatment. During this procedure the articular surface of the bone is ground down and an implant is placed on the surface. Cement is sometimes used to ensure fixation, although this can cause problems in some patients. Capital and subcapital fractures are also fixed with these procedures.

the medullary cavity) may be performed in order to align comminuted pieces of bone before the IM nail is hammered. This metal work can be left inside post operation, however in rare cases complications may arise. Sometimes, a combination of both can be used in order to achieve the desired effect (see example b on the left) or reattach many broken pieces together. During a trochanteric fracture (greater or lesser), which can affect muscle contraction, only a single nail needs to be hammered vertically and put in a splint. A speedier recovery should occur as this is a smaller fracture.

Reference British Orthopaedic Association. The Care of Patients with Fragility Fractures. London: British Orthopaedic Association; 2007 National Clinical Guideline Centre. The management of hip fracture in adults. London: National Clinical Guideline Centre; 2011 Wilkinson K, Martin IC, Gough MJ, Stewart JAD, Lucas SB, Freeth H, Bull B, Mason M. An Age Old Problem: a review of the care received by elderly patients undergoing surgery. London: National Confidential Enquiry into Patient Outcome and Death; 2010 National Clinical Guideline Centre - Acute and Chronic Conditions. Venous thromboembolism: reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in patients admitted to hospital. London: National Clinical Guideline Centre; 2010 Wilson H, Harding K, Sahota O. Best Practice Tariff: Making Ends Meet. British Geriatric Society Newsletter June 2010 [cited 2012 Nov 12]. Available from: http:// www.bgs.org.uk/index.php?option=com_ 7

A solution to intertrochanteric fractures is the use of a dynamic hip screw (DHS) (examples c and d on bottom most image), an orthopaedic implant which will be fixed the proximal (closest to where the limb begins) end of a femur. A lag screw is inserted into the neck of the femur, a sideplate and four cortical screws (c) which fix to the proximal femoral shaft to hold the sideplate in place. The idea behind the DHS is that any movement along one plane is locked into place and this means that the screw can only get tighter and tighter resulting in a robust and secure joint which doesn’t require arthroplastic remodelling. The native femur will then undergo primary healing with the cells joining and regrowing along boundaries.

Gaillard, F. (2005) Femoral neck fracture classification | Radiology case. Available at: https://radiopaedia.org/ cases/femoral-neck-fracture-classification (Accessed: 30 October 2016).

Intertrochanteric fractures and fractures that surpass the trochanteric line (subtrochanteric) and are transverse, oblique, spiral or comminuted can be fixed with an intramedullary nail which involves the hammering of a metal nail down the proximal femur through the medullary cavity. K-wire fixation (wire insertion through

Various (2016) Different types of bone fractures. Available at: http://www.newhealthadvisor.com/differenttypes-of-fractures.html (Accessed: 30 October 2016).

Singh, A.P. (2015) Femur Anatomy and Attachments. Available at: http://boneandspine.com/femur-anatomyand-attachments/ (Accessed: 30 October 2016). Gray, H. (1858) Gray’s anatomy - the arteries of the lower extremity - Yahoo! Reference. Available at: https:// web.archive.org/web/20041230094036/http:// education.yahoo.com/reference/gray/subjects/subject? id=157 (Accessed: 30 October 2016).

Parkinsonâ&#x20AC;&#x2122;s Disease The average age of onset of PD is around 60 years, but 5 -10% of cases begin between 20 and 50. Some studies suggest that men are more likely to develop PD than women. Scientists have also concluded that Parkinson's arises due to a combination of genetic and environmental factors. An increased risk of PD has been seen within people who live in rural locations and are exposed to large amounts of pesticide from agricultural endeavours. On the genetic side, the disease has certainly been identified as a result of mutated genes. These genes code for alpha-synuclein (SNCA), parkin and other chemicals. SNCA is a protein which accumulates into Lewy bodies within neurones; detecting these in a microscope is an indicator of PD. Mutation of parkin results in the apoptosis of dopaminergic cells. Reducing the risk of contracting PD is possible with exercise, caffeine and even tobacco smoke (this is probably not prescribed).

By Neil Narayan Parkinson's disease (PD) is a long-term disorder of the motor aspect of the central nervous system (CNS). It affects around one in every 500 people in the UK; this is equivalent to 127,000 people who have the progressive neurological condition. The name is derived from James Parkinson, an English apothecary (similar to a pharmacist), who published An Essay on the Shaking Palsy in the early 19th century, describing symptoms similar to that of PD. From a pathological perspective, the disease involves a degeneration of neurons in the substantia nigra, located in the midbrain. It is a major component of the basal ganglia and is instrumental in the planning of movement. The neurons in the substantia nigra coordinate movement with the help of a neurotransmitter called dopamine. The brain contains many dopamine pathways where the neurotransmitter is transferred from one region of the brain to the other. One pathway, known as the nigrostriatal pathway, is specifically involved in motor function and begins at the substantia nigra and ends at the caudate nucleus. Unfortunately, a form of cell death known as apoptosis causes the loss of these dopamine neurons in the nigrostriatal pathway, resulting in severe problems in movement. However, the reason and mechanism for the disappearance of these neurons still remains a mystery; the root cause of PD is still unknown.

It is difficult for doctors to recognise and diagnose the disease as symptoms occur very gradually. There are no medical or laboratory tests that can be carried out to determine whether a person has PD, although some medical imaging can be carried out. While results from brain scans in the form of MRIs and CT scans usually appear to be normal, they are still invaluable as they rule out other disorders with similar symptoms to PD, such as Alzheimer's, stroke or hydrocephalus. Consequently, a neurologist will diagnose the disease based on the medical history of the patient and a detailed physical examination through clinical observation. They will ask the person to complete tasks to assess the agility of the arms and legs, muscle tone, gait and balance. According to the Parkinson's Disease Foundation, the doctor will specifically look at some of these motor aspects: It is difficult for doctors to recognise and diagnose the disease as symptoms occur very gradually. There are no medical or laboratory tests that can be carried out to determine whether a person has PD, although some medical imaging can be carried out. While results from brain scans in the form of MRIs and CT scans usually appear to be normal, they are still invaluable as they rule out other disorders with similar symptoms to PD, such as Alzheimer's, stroke or hydrocephalus. Consequently, a neurologist will diagnose the disease based on the medical history of the patient and a detailed physical examination through clinical observation. They will ask the person to complete tasks to assess the agility of the arms and legs, muscle tone, gait and balance. According to the Parkinson's Disease Foundation, the doctor will specifically look at some of these motor aspects:. The expression on the face is scanned to see if it is animated.. The arms are observed for tremor; it is present either at rest or in an extended position.. The neurologist will test the rigidity of the limbs and the neck. The gait of the patient will be seen as he/she walks for a short distance.. In order to examine postural stability, the 'pull' test is carried out. The neurologist 'pulls' the shoulder backwards with some force. The expected response is a quick step backward but a person with parkinsonism* shuffles even further backward and would probably fall without support from the doctor. This involuntary backwards movement is known as retropulsion. As PD is a progressive illness, patients eventually begin to feel the cardinal manifestations of PD. The most prominent of these is tremor, i.e. involuntary shaking of particular parts of the body. Other symptoms include the stiffness of muscles (rigidity), problems in maintaining a firm posture and bradykinesia, the slowness of movement. These primary symptoms are collectively known as parkinsonism*. The disease continues to

hinder a person's motor system, and they may find trouble in chewing and swallowing food. They may also face problems in sleeping - insomnia - as well as a loss of the olfactory sense - anosmia. While Parkinson's is generally a movement disorder, there may be severe effects on mental health, with the occurrence of significant psychological effects such as depression and anxiety. Dementia may also occur in the advanced stages of PD, causing memory problems. There is currently no cure for Parkinson's disease, but a number of measures have been taken in the attempt to treat and prevent it. The first line of managing the disease involves levodopa (L-DOPA), a chemical substance which is absorbed into the bloodstream from the small intestine. From there, it crosses the blood-brain barrier (as pure dopamine cannot) and is converted into dopamine within the brain. Levodopa is usually given as a capsule or tablet, but in combination with other drugs. The most famous is carbidopa, which is useful because it delays the conversion of L-DOPA into dopamine until it reaches the brain. Other drugs are given as a supplement to levodopa, including COMT and MAO-B inhibitors, which block enzymes (COMT and MAO-B respectively) that break down dopamine in the brain. Another form of medication comes in the form of dopamine agonists, which do not actually form dopamine but replicates its effects. These compounds work by binding to dopamine receptors, deceiving the brain so that it thinks it is receiving dopamine. They are given because L -DOPA can cause side-effects such as dyskinesia, i.e. difficulty in performing voluntary movements. Less commonly used drugs such as anticholinergics and amantadines can reduce tremors. If a patient is not responding well to medication, the second line of management is surgical therapy. One process is deep brain stimulation (DBS). It involves inserting electrodes through small perforations in the skull and placing them on both sides of the brain, typically the subthalamic nucleus, which is near the substantia nigra. Long extension wires pass under the skin to a battery-powered stimulator in the chest. The stimulator sends electrical impulses to the electrodes to alleviate symptoms such as tremors. The main advantage of this procedure is that these impulses do not damage any brain tissue, so they are relatively safe to use. However, it is important to state that this surgical therapy does not actually cure Parkinson's and cannot stop its progressive nature. Other surgical treatments include pallidotomy and thalamotomy, where a high frequency current is used to destroy a part of the globus pallidus and the thalamus respectively. This may ease tremors and stiffness as activity in those areas of the brain are lessened. Reference https://www.parkinsons.org.uk/content/whatparkinsons http://www.ninds.nih.gov/disorders/ parkinsons_disease/parkinsons_disease.htm http://www.nhs.uk/conditions/parkinsons-disease/ Pages/Introduction.aspx https://en.wikipedia.org/wiki/Parkinson%27s_disease https://en.wikipedia.org/wiki/James_Parkinson https://en.wikipedia.org/wiki/Substantia_nigra http://www.pdf.org/en/diagnosis https://www.youtube.com/watch?v=sJqKvajUC3k http://www.pdf.org/parkinson_prescription_meds https://medlineplus.gov/druginfo/meds/a601068.html http://www.parkinson.org/understanding-parkinsons/ treatment/Medications-for-Motor-Symptoms/Carbidopa -levodopa http://www.mayfieldclinic.com/PE-PD.htm https://www.michaeljfox.org/understandingparkinsons/living-with-pd/topic.php?deep-brainstimulation&navid=deep-brain-stimulation

Intraocular Lenses

By Denis Efovi An intraocular lens is an artificial lens which can be implanted in the eye to correct vision. Mainly, this method is applied to patients suffering from cataracts (cloudy crystalline lens), where a pseudophakic IOL (a “fake lens”) is embedded in the eye after the removal of the cataract, which provides a clear path for the light rays to enter the eye and focus on the retina correctly. However, less common uses of intraocular lenses include the treatment of myopia (short-sightedness); in this case, the eye’s natural lens is not removed, so the IOL applied is prefixed by “phakic”. This is done to aid the already existing lens in focusing the light accurately. Intraocular lenses were first implemented on the 8th of February 1950 by an English doctor from London called Dr. Harold Ridley at St. Thomas’ Hospital. This was rendered possible by his experiences in World War II since Ridley was caring for injured RAF pilots, who often had fragmented pieces of their aircraft’s cockpit lodged inside their eyes. He noticed that, surprisingly, this did not trigger an inflammatory response, meaning that the material used (polymethylmethacrylate) to build the cockpits could be safely used in contact with the eye. Dr. Ridley tried to make lenses out of this plastic and insert them into a patient’s eyes after cataract removal surgery, however, his attempts were quite unsuccessful. In the following years, many ophthalmologists worked to improve the lens as it could be very useful in treating different eye conditions. It was not until the 1970s that a new method to embed the lens was adopted. This was a process developed by doctors all over the world, including the European Dr. Worst and Dr. Binkhorst as well as Dr. Shearing from America who decided it would be a better solution if the intraocular lens was placed inside the capsule of the pre-existent cataract, which facilitated natural support from the outer envelope and significantly improved the success rates of the surgery. Concurrently, Dr. Charles Kelman was establishing phacoemulsification. This is a process derivative from extracapsular cataract extraction (ECCE), which involves the lens being removed while leaving the elastic capture which covers the lens partially intact to support the IOL. The disadvantages of ECCE are that the incisions required can be up to 10mm across, meaning that the patient would be required to stay in hospital for a week, with limited physical activity in the upcoming weeks in order to recover fully. Modern extracapsular cataract extraction requires the surgeon to extract the lens fibres, which make up the nucleus and cortex of the cataract, so that only the capsule remains, which prevents the vitreous humour from infiltrating the anterior chamber.

Phacoemulsification was the newly developed method to remove a cataract, and is still in use today. It works by splitting up, or emulsifying, the cataract into small pieces using an ultrasound tip. This was innovative as the recovery times were cut considerably, due to the incisions being of a lesser size. The primary concern that ophthalmologists now had was to be able to somehow fit the intraocular lens inside the new 3mm incision made in the eye (a third of the original cut). The solution revolved around being able to fold the lens to halve its original size and this became possible after lenses started to be manufactured out of silicone, permitting the surgeon to implant a folded IOL and successively unfolding it inside the capsule. The continuous amelioration of the procedure contributed to increasing success rates, thus, making the surgery more popular amongst the population. A standard procedure for implanting IOLs is as follows: First of all, the patient is anesthetized using a local anaesthetic, which is interpolated into the lower eyelid using a needle. The surgeon will then apply a slight amount of pressure on the eyeball to prevent any bleeding as well as lowering the pressure between the lens and the cornea which reduces the chances of any complications. Then, a small opening is cut in the cornea and a viscoelastic fluid is applied, which increases shock absorption and stability. The next procedure is capsulorhexis, where a microscopic circular incision is made in the membrane surrounding the cataract to insert the ultrasound tip (titanium needle) and emulsify the cataract to disintegrate it and remove it by suction; starting from the nucleus and going outwards due to its higher density. The surgeon will ensure the posterior capsule is left intact, after removing the cortex, as that will be needed for support when installing the intraocular lens. Subsequently, a finer vacuum suction cleaner is used to make sure the capsule is completely clear of any cloudy crystalline lens. The folded intraocular lens is inserted into the eye through an injector which passes through the same small incision in the cornea. As the lens reaches the eye it unfolds and the surgeon repositions it to align in the correct position relative to the centre of the eye (to maximise vision). The viscoelastic fluid is vacuumed out of the eye and the edges of the wound are hydrated to seal it and prevent leaks/ infections.

In a scenario where the patient does not suffer from cataracts, the procedure remains the same excluding the removal of the eye’s natural lens. In this case, the IOL implanted reinforces the current lens and is placed in front of it. Due to prior development, today we have the opportunity to choose from specialty lenses which allow us to see both far and near. In some cases, glasses may still be required, however, the addition of intraocular lenses significantly improves vision for most. This procedure is a great alternative to procedures such as laser eye surgery, which may sometimes not be a viable option due to factors such as a high prescription (ranging from -3 to -15), thin corneas or dry eyes. There are risks to using intraocular lenses and although they are not major, they shouldn’t be left unconsidered. After surgery, there is a 0.03-0.05% chance of eye infection risk, a 0.6% risk of corneal detachment and a 0.4% possibility of corneal swelling. IOLs are undoubtedly a great invention which has revolutionised a major part of cataract and general vision correction surgeries in the field of ophthalmology. Reference http://www.surgeryencyclopedia.com/Pa-St/ Phacoemulsification-for-Cataracts.html http://www.surgeryencyclopedia.com/Ce-Fi/ Extracapsular-Cataract-Extraction.html http://emedicine.medscape.com/article/1844198overview http://www.nhs.uk/Conditions/Cataract-surgery/Pages/ How-it-is-performed.aspx http://www.aao.org/eye-health/treatments/iolsintraocular-lens https://en.wikipedia.org/wiki/Intraocular_lens http://www.flei.com/blog/the-fascinating-historybehind-the-intraocular-lens/

Atrial Fibrillation and Catheter Ablation After entering the left atrium, heparin (a blood thinner) is given to the patient. This reduces the chances of blood clotting during the procedure, and perhaps the outcome of a stroke. A 3-D map of the left atrium is produced via the use of a Lasso catheter, which is inserted through the trans-septal puncture. This catheter has several electrodes on its surface, enabling it to rapidly pick up information about its surroundings. This is done so that the catheter can be guided by looking at the 3-d image given.

By Vith Ketheeswaranathan The most common type of cardiac arrhythmia, an irregular heartbeat, is atrial fibrillation. It is when the atria dilate due to a loss in coordinated systolic function, where consistency is replaced by chaos.

The next step is to isolate the pulmonary vein – a process known as PVI. There are two methods for this, the first being segmental ostial isolation. This is when a barrier is created around each individual vein by ablation, preventing any electrical signals from the pulmonary vein to the left atrium and radiofrequency energy (heat) is utilised. The second method is known as wide area circumferential ablation (WACA) where a barrier is created, on a pair of pulmonary veins further out, by a line of lesions. The end point of both methods is to eliminate electrical signals from the pulmonary vein which affect the atria.

A normal heart beat begins with an electrical impulse fired from the SA node in the right atrium. As this travels it spreads throughout the atria causing them to contract, and hence push blood into the ventricles. The impulse reaches the AV node where it pauses, allowing time for blood to enter the ventricles. The impulse then spreads throughout both ventricles via the AV node, and they contract to push blood out of the heart. The most common cause of AF are extra wavefronts, which originate from the pulmonary veins in over 80% of cases. Due to these having such a high frequency, the atrial myocardium is forced to break them into multiple wavefronts. These disperse across the atria, triggering them to beat irregularly and quickly – atrial fibrillation caused by this is paroxysmal. After each paroxysm, the properties of myocytes are likely to change resulting in persistent AF. Catheter ablation is by far the most common source of treatment of persistent AF after anti-arrhythmic drugs have failed to treat it. A transesophageal echocardiogram (TOE) is performed, in order to detect any thrombus or other structural problems within the atria. During the procedure itself, percutaneous access for the catheter is usually carried out through the femoral vein in the upper leg. In order to gain access to the left side of the heart, a trans-septal puncture is performed, where a hole is created through the inter-atrial septum by a long metal needle.

WACA pulmonary vein isolation where ablations have been delivered point-by-point.

Vascular injury (2-4%) may also be a result as the catheter is inserted usually through a vein in the leg. The catheter may damage the femoral artery by causing an aneurysm. It is usually characterised by swelling directly after the ablation procedure, and can also be detected via an ultrasound. A drug known as thrombin may be given to the patient, which forces the blood within this artery to clot, hence relieving pressure from the wall. There are also many benefits in using catheter ablation to treat atrial fibrillation. It brings normality and regularity to the heart rhythm, and many people no longer need antiarrhythmic medication after this. This procedure provides a less invasive and traumatic alternative to surgery, hence why it is described as the ‘bread and butter’ of electrophysiology. Reference Emedicinehealth.com, (2016). Atrial fibrillation [online]. Available at: http://www.emedicinehealth.com/ atrial_fibrillation/page2_em.htm Uhs.nhs.uk, (2015). Pulmonary vein isolation (PVI) radiofrequency ablation [online]. Available at: http:// www.uhs.nhs.uk/Media/Controlleddocuments/ Patientinformation/Heartandlungs/ Pulmonaryveinisolationradiofrequencyablationpatientinformation.pdf Segal,O (2015). AF Ablation. [Online]. Oliversegal.com. Available at: http://www.oliversegal.com/heartconditions/af-ablation-2/

3D image of left atrium with pulmonary veins in different colours Currently, WACA is considered a more effective and efficient method than the segmental ostial isolation. However, the latter is being developed with new technology such as the cryoballoon, which aims to create a barrier of the entrance of a vein with just a single ablation delivery. This is done by inflating a balloon within the left atrium and inserting into each pulmonary vein. A major disadvantage with this procedure however, is that the patient has a chance of over 50%, of undergoing the same process again. This is because, due to the barrier being created by the point-by-point method, if one of these points recovers, then the whole barrier is deemed useless. A complication which may occur after AF ablation is cardiac tamponade (2%). A hole maybe created by the ablation, and this leads to a build of fluid between the myocardium and the pericardium. Due to this, the heart may not be able to expand to its full potential, leading to it not pumping enough blood to the body. Symptoms include sharp chest pain, dizziness and grey/blue skin. Furthermore, another complication could be phrenic nerve palsy (1-4%). Due to the positioning of this nerve, it is vulnerable during the ablation of the pulmonary vein and may lead to paralysis of the right hemidiaphragm which leads to breathlessness. The risk of this occurring is greater with the use of the cryoballoon.

Earley, M. (2009). How to perform a transseptal puncture. Journal, [online} p. 86. Available at: ht.tp:// heartrhythmuk.org.uk/files/file/Docs/Guidelines/How% 20to%20perform%20a%20transeptal%20puncture% 20EiH.pdf Sharecare.Inc, (2015). What are the benefits of ablation for atrial fibrillation? [Online]. Available at: https:// www.sharecare.com/health/arrhythmia/the-benefitsablation-atrial-fibrillation

Pleural Effusion There are two types of fluid that can be found in the pleura: transudate and exudate. Transudative pleural effusions occur when there is an increase in pressure in the vessels carrying the fluid. This is easiest described in the case of a disorder, such as congestive heart failure. If the left side of the heart was to fail, there would be a pressure increase in the vessels carrying blood from the lungs to the heart (via the pulmonary vein). If this pressure is high enough, fluid may be forced out of the vessel between the endothelial cells. This is described as fluid ‘leaking’ into the pleural space.

By Yunis Fazaldin The most common types of lung disorders, like asthma and COPDs (emphysema and chronic bronchitis), occur inside of the lung, in the bronchi, bronchioles or the alveoli. For this reason, the walls of the lungs tend to be overlooked, and so are disorders associated with them. Our lungs are surrounded by two walls. The inner wall is called the visceral pleura (visceral refers to the viscera, the internal organs of the body), and the outer called the parietal pleura. Outside of the parietal pleura are the ribs and intercostal muscles. Between the two pleura membranes, there is space, called the pleural space or the pleural cavity. This space is where pleural fluid is found, a lubricant that allows the visceral and parietal pleura membranes to glide smoothly during inspiration and expiration. There should normally be approximately 10 - 20 cc of pleural fluid between in the pleural cavity, or a few teaspoons.

A pleural effusion occurs when there is an abnormally high volume of pleural fluid in the pleural cavity, which leads to a higher pressure inside pleura, causing the lung to be pushed inward instead of outward (prevented by the presence of the ribs and muscles surrounding the parietal pleura). This would cause symptoms such as dyspnea (difficulty breathing), chest pain (due to the increase in pressure in the pleural space) and a dry cough. A dry cough may be noticed, due to the body’s attempt to get rid of any obstruction in the bronchioles which may be causing the reduced lung volume, however this is futile as the fluid build up is in the wall of the lung. So what are the reasons for the pleura producing more fluid than usual? Our lymph system regularly removes the pleural fluid to prevent a build up. A pleural effusion is usually the result of another disorder, such as a congestive heart failure, pulmonary embolism and even cancer (usually lung or breast cancers). With something like kidney failure, our lymphatic system cannot remove the fluid as quickly as it could prior to the failure, leading to this build up of pleural fluid as the fluid may leak into pleural space or may be forced out of the vessels holding it (due to an increase in pressure in these vessels).

Exudative pleural effusions are different to transudative ones in terms of what causes them, and the composition of the pleural fluid. Exudative effusions are caused by inflammation, tumors or blocked blood or lymph vessels. When there is inflammation, the lymph and blood vessels dilate. This increases the inter-endothelial space, and in tandem with an obstruction in the vessels and hence a higher pressure, both fluid and protein leak out of the vessels into the pleural space. In transudate, there is no protein as the endothelial cells are still close together, so proteins cannot fit between them to leave the vessel. Exudative pleural effusions require drainage, and are much more dangerous than transudative effusions. In order to differentiate which type of pleural effusion has occurred, the pleural fluid must be examined for protein, and then white blood cells (a sign of an infection). A thoracentesis can be carried out to ascertain the pleural fluid for examination. This involves the insertion of a small needle and a catheter into the pleural space (between the ribs), and fluid can be extracted for both analysis and to temporarily relieve related symptoms (if large amounts of fluid are removed). However, from a medical perspective, this stage only comes after identifying whether there is a pleural effusion or not. This can be done initially by percussion (tapping on the chest and listening for a duller sound on the side with the pleural effusion) and auscultation (using a stethoscope to listen for breathing sounds, which may sound more dull or distant on the side with the effusion). However, most effusions are diagnosed using an imaging test. On X-rays, the space with the pleural effusion appears white on the X-ray film. Furthermore, a decubitus X-ray can also be used, where an X-ray is taken while the patient is lying on his/her side. This identifies whether the fluid is able to flow freely. A CT scan can also be used, which would identify the pleural effusion as well as any other abnormalities in the lungs (if there are any present). A CT scan consists of multiple X-rays being fired at the thorax from multiple angles, producing a very detailed image of the chest. Reference "Fluid In The Chest (Pleural Effusion)". Healthline. Web. 30 Oct. 2016. "Pleural Effusion Diagnosis And Treatment". Khan Academy. Web. 24 Oct. 2016. "Pleural Effusion: Causes, Symptoms, And Treatment". WebMD. Web. 30 Oct. 2016. "The Symptoms, Treatment, And Prognosis Of Stage 4 Non-Small Lung Cancer". Verywell. Web. 30 Oct. 2016. "Transudate Vs Exudate". Khan Academy. Web. 24 Oct. 2016. "What Is A Pleural Effusion?". Khan Academy. Web. 24 Oct. 2016. "What Is Non-Small Cell Lung Cancer?". Cancer.org. Web. 30 Oct. 2016.

Root Canal Surgery and so will use this to verify a need for treatment. The only ways to treat this form of bacterial infection are root canal surgery and removal of the tooth, however a dentist will always advise the former.

By Rajan Patel Root Canal Surgery is a dental surgery that is performed to save a tooth from severe bacterial infection. This surgery is often performed in place of a tooth removal as it is usually preferable to retain as many natural teeth as possible. Teeth consist of two parts: the crown that is visible in the mouth, consisting primarily of enamel; and the root that is located beneath the gums and extends to the bone, holding the tooth in place. The root of the tooth is further separated into dentine: a softer part of the tooth that is found beneath the enamel and forms the rest of the tooth; the dental pulp: a very soft part of the tooth that contains the nerves and blood vessels in the tooth which can be found in the root canals; and cement: a hard material that coats the surface of the root. A severe bacterial infection is one that can be found in the dental pulp and extends to the very root of the tooth.

Root canal treatment often takes a long time to perform and so is often performed across a number of sessions. The dentist starts by taking a number of X-rays of the tooth to allow them to assess the level of damage and to give them a better idea of the shape of the tooth. During the operation, a local anaesthetic will often be provided to numb the area that will be operated on with the exceptions of cases in which the tooth is dead and so no pain will be felt. A rubber sheet is then placed around the tooth to ensure that it remains dry and to ensure that no chemicals are breathed in or swallowed during the procedure. A hole is then drilled in the tooth through the crown of the tooth and any infected pulp is removed as well as any dental abscesses (pus filled swellings) being drained. Once the infected pulp has been removed, the root canals will be enlarged using a number of small files to allow the dentist to ensure that any bacteria has been properly removed and then the canals will be filled with a small amount of medication to prevent any further bacterial infection, followed by a temporary filling. Once all canals have been properly treated, the temporary fillings are removed and replaced with permanent root canal filling, along with another filling to prevent any further reinfection. Treated teeth are often much more liable to damage than unrestored teeth and so it is likely that the dentist will recommend a crown to follow the surgery. A crown is a porcelain or metal cap that covers the real tooth to provide additional strength to the tooth. This requires another procedure, involving trimming the tooth down and replacing what is removed with the crown. Root canal treated teeth have been found to last an additional 8-10 years after the surgery. Crowns and good oral hygiene have been found to be critical to the rate of survival, however and so this figure is liable to variation depending on these factors. It is also possible for the infection to return but it is usually possible to repeat the surgery if this does occur but failing this, it may be necessary to remove the root tip instead to remove the infection. Reference http://www.nhs.uk/Conditions/Root-canal-treatment/ Pages/How-it-is-performed.aspx http://www.nhs.uk/conditions/Root-canal-treatment/ Pages/Introduction.aspx

A severe bacterial infection in a tooth usually causes pain while eating or when the tooth comes into contact with hot or cold food. It can also cause a loose tooth. If ignored these symptoms will eventually go away for a period of time but will return if left untreated with added symptoms including swelling of the gum and face around the infected tooth as well as pus from the gum and the tooth becoming a darker colour. These infections can be caused by tooth decay, a leak in a filling or trauma to the tooth due to something such as a fall. A dentist can see an infection of this kind through an X-ray

http://www.aae.org/patients/treatments-andprocedures/root-canals/root-canals.aspx http://www.webmd.com/oral-health/picture-of-theteeth#1

Osteoporosis ment or have an unbalanced diet. Many people today spend hours indoor, rather than going outdoors and fewer children walk to school on a regular basis. This highlights how osteoporosis can affect not just the elderly, but also the younger generations as well. DEXA (DXA) scan is used to measure your bone mineral density. It's a short, painless procedure that takes about five minutes, depending on the part of the body being scanned. During a DEXA scan, Xrays are passed through your body. Some radiation is

By James Hong Osteoporosis is the medical condition in which the bones become brittle and fragile from loss of tissue, typically as a result of hormonal changes, or deficiency of calcium or vitamin D. It develops over several years and is commonly diagnosed when a minor fall or a sudden impact causes a bone (or bones) to fracture. The most common injuries in people with osteoporosis are wrist fractures, hip fractures and fractures of the vertebrae (spine). However, these fractures can appear on other bones. Such examples are the arm and ribcage when sneezing. Osteoporosis isn't usually painful until a fracture occurs, but spinal fractures are a common cause of longterm (chronic) pain. Although a fracture is the first sign of osteoporosis, some older people develop the characteristic stooped (bent forward) posture. It happens when the bones in the spine have fractured, making it difficult to support the weight of the body. In the UK, at least 3 million suffer from this condition and More than 500,000 people receive hospital treatment for fragility fractures (fractures that occur from standing height or less) every year as a result of osteoporosis. The bones in our body naturally lose bone and density after you are about 40 years old. Women are more susceptible to osteoporosis because bone loss becomes more rapid for several years after the menopause (when stop going though the menstrual cycle and are no longer able to get pregnant naturally), when sex hormone levels decrease. Women generally have smaller bones than men and with loss of bone tissue continuing, makes fragility fractures more likely. Osteoporosis doesnâ&#x20AC;&#x2122;t just affect women. One in five men break a bone after the age of 50 years because of low bone strength. Although this generally affects the elderly as losing bone mass is a normal part of the ageing process. However, this does not mean younger men and women are not affected by osteoporosis. Vitamin D is necessary for strong bones and muscles. Without Vitamin D, our bodies cannot effectively absorb calcium, which is essential to good bone health. Vitamin D is really not a vitamin. Vitamins are special nutrients that the body needs but cannot make, so they must be obtained from what we eat or by supplements. Because

our bodies can make Vitamin D in our skin when it is exposed to good sunlight, Vitamin D is considered a prohormone. The deficiency of vitamin D usually occurs to people who arenâ&#x20AC;&#x2122;t very active or suffer from malnourish-

absorbed by thicker tissue such as the bone. Detectors in the DEXA scanner measure how much radiation passes through your bones, and this information is sent to a computer. Your bone density measurements will be compared with the bone density of a young healthy adult or an adult of your own age, gender and ethnicity. The difference is calculated as a standard deviation (SD) and is called a T score. Standard deviation is a measure of variability based on an average or expected value. A T score of: above -1 SD is normal, between -1 and -2.5 SD is defined as decreased bone mineral density compared with peak bone mass and below -2.5 is defined as osteoporosis. This procedure must not be used on women who are pregnant. Despite being a safe procedure, DEXA scans and X-rays can damage the health of an unborn child due to x-rays being highly ionizing. If you're at risk of developing osteoporosis, you should try to help keep your bones healthy. This may include: taking regular exercises (at least two and a half hours of aerobic exercise a week), healthy eating especially food which are rich in vitamin D or calcium or alternatively taking daily supplement containing 10 micrograms (mcg) of vitamin D and making lifestyle changes â&#x20AC;&#x201C; such as giving up smoking and reducing your alcohol consumption.

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