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It does not anxiety xr cheap generic bupropion uk, however bipolar depression elderly purchase bupropion 150 mg with amex, report fraud-specifc Public policy to anxiety from coffee trusted bupropion 150mg ensure post-trial access; com Myers Squibb performs strongly in encour risk assessments remitted depression definition order bupropion once a day, nor does it demonstrate evi mits to registering trialed products. Bristol aging employees to work towards access-re dence of a monitoring system for non-compli Myers Squibb has a publicly available policy for lated objectives. It is one of 14 companies to ance in the workplace, or procedures to segre ensuring post-trial access to treatments for clin have both fnancial and non-fnancial incentives gate duties, to ensure decisions are checked by ical trial participants. The policy is aligned with in place to motivate employees to perform on another party. These incentives include Once a product is approved, Bristol-Myers awards for performance and public recogni Above average transparency regard Squibb commits to registering it in all countries tion by senior company leaders in internal meet ing access-related practices. Bristol-Myers where clinical trials for the product have taken ings and through internal social media for objec Squibb publicly discloses its policy positions on place. It discloses policies for responsible this C medicines that are available in countries in engagement within its Principles of Integrity. It Commits publicly to equitable pricing but does scope, the company reports tracking the number does not publicly disclose its policy approach to not report a commitment to fle to register new of patients benefting from its medicines. Bristol-Myers Squibb does Furthermore, it is part of the Access Accelerated countries in scope. Squibb publicly discloses which stakeholder Publicly commits to R&D to meet public Its public commitments also apply to intra-coun groups it engages with on access issues, but health needs. Bristol-Myers Squibb has pub try equitable pricing strategies, albeit to only does not publicly share its process for select licly committed to R&D for diseases and coun some of its products. It does incorporate middle-income countries is informed by an evi Some new products in scope fled for regis local stakeholder perspectives into the develop dence-based public health rationale linked to tration in the majority of priority countries. Has measures to ensure third-party compli the smallest pipelines in the Index with 25 pro However, it does not publicly share registration ance with ethical marketing and anti-corrup jects. Bristol-Myers Squibb has a exist, Bristol-Myers Squibb is active in two pro code of conduct relating to ethical marketing jects; both of these target priority R&D gaps. It demon tiatives across all areas for assessment; Bristo product to patients once the programme has strates evidence of having equitable pricing Myers Squibb submitted 22. Most of these strate Bristol-Myers Squibb has initiatives that meet product, etc. Most of these initiatives are table pricing strategy to one further product focused on health system strengthening in the No best or innovative practices were identifed informed by a public health rationale. Globally consistent recall guidelines for coun tries in scope but no processes to track prod Most initiatives meet most good practice ucts. While its cesses to track the distribution of products in health system strengthening projects have good countries in scope to facilitate rapid and efec governance structures in place, some initiatives tive recalls. Like most of its peers, Bristol the prevention and handling of counterfeit med Myers Squibb publicly discloses the patent sta icines. Bristol-Myers Squibb atazanavir sulfate (Reyataz ), encompasses 97 donated medicines on the request of relief agen countries including 66 middle-income countries cies. It has not issued any non-assert decla sis, it donated products in response to the 2017 rations for products in scope. Bristol-Myers Squibb reported existing Relief to ensure products are rapidly delivered. The programme is carried out in part nership with the the Max Foundation and has No public commitment not to enforce patents been ongoing since 2016. Bristol-Myers Squibb does programme for chronic myeloid leukemia sup not have a public policy available that sets out plies dasatinib (Sprycel ) in 15 countries. In 2017, its approach to fling for or enforcing patents in Bristol-Myers Squibb reports to have reached low and middle-income countries. Bristol Ensures long-term access through transition Myers Squibb has eight capacity building ini planning. Bristol-Myers Squibb has transition tiatives that were included for analysis by the plans in place for its dasatinib (Sprycel ) dona Index: i. With a mid-ranking performance, it lacks a process to develop access plans during R&D, but considers access for a Average Leader key paediatric product. One of only two companies without a public commitment to not enforce and/or fle patents in countries in scope. Focus on pharmacovigilance, with no initia tives meeting all good practice standards. Bayer can also vector control products and to continuing to publicly disclose the status of its patents, clearly showing where products are on and develop new vector control products to control of-patent, and when patents are due to expire. Commits to expand its successful youth-centric the company has equitable pricing strategies for two products in the scope of the health programmes under the umbrella of the Index. Bayer can develop a clear approach to establish access plans for R&D projects earlier in the development phase that take into account the specifc considerations necessary for each project. It can develop this approach for both in-house and collaborative projects for all diseases in scope, with a clear timeline for developing, refning and executing access plans to ensure broad and rapid access. Bayer can improve its commitment to ensure responsible sales practices by decoupling sales incentives from sales targets. Removing an emphasis on sales targets is recognised as a mechanism for ensuring rational pre scribing, and critical for a company like Bayer that produces antibiotics and other prod ucts which are often inappropriately used. Clinical candidates: 9, including fnerenone for the treatment of diabetic Portfolio focus: maternal & neonatal health conditions (contraceptive kidney disease and tedizolid (Sivextro ) for the treatment of pneumonia. Bayer does focus on family planning and maternal and neo pliance following an annual audit plan. The highest level of responsibility not report conducting fraud-specifc risk assess to treatments for clinical trial participants. However, Bayer does not countries where clinical trials for these products incentives to reward employees. Bayer publicly discloses its mem Does not publicly commit to equitable pric objectives. It discloses its policies for commit to fling its newest products for regis urement. Bayer measures and monitors progress responsible engagement within its code of con tration in countries in scope within one year of and outcomes of access-to-medicine activi duct. It also publicly reports on commitments, for disclose its policy approach to payments made publicly commit to implement equitable pric example, it reports to commit to supply medi to healthcare professionals in countries in scope. Bayer publicly Bayer has made a specifc commitment to R&D ucts for registration to date in more than half of discloses which stakeholder groups it engages for diseases and countries in scope, but it is not the relevant priority countries (disease-specifc with on access issues, as well as its process for publicly available. Its R&D strategy for low and subsets of countries with a particular need for selecting who to engage with. It selects by a pro middle-income countries is informed by an evi access to relevant products). However, it does cess based on expertise, activity and geographic dence-based public health rationale based on not publicly share registration information for coverage. It publicly shares its policy for ensur pleting R&D projects for diseases in scope and 12% of products have equitable pricing strate ing responsible engagement; namely with its evaluates progress toward these targets. These strategies apply to an average of 9% of prior Has measures to ensure third-party compli Access provisions in place for 11% (1/9) of late ity countries. One of these strategies applies ance with ethical marketing and anti-corrup stage candidates. Bayer does not have a clear inter-country pricing; this strategy, for contra tion standards. Bayer has a policy relating to process in place to develop access plans during ceptive methods, takes into account one socio ethical marketing and anti-corruption, and pro R&D. Bayer also applies an equitable vides regular compliance training for employ R&D projects for diseases in scope, namely for pricing strategy to one further product informed ees. Bayer donated Unlike most of its peers, Bayer does not disclose medicines on the request of relief agen the status of its products for diseases and coun cies. The company discloses that No use of non-assert or licensing arrange such ad hoc donations are aligned with inter ments. Bayer reported existing agreements with Three donation programmes covering diseases product development partnerships such as the and countries in scope.

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Check that you really have found the perform a gastrojejunostomy mood disorder journals buy discount bupropion 150 mg, proximal enough to mood disorder otherwise not specified cheap bupropion online amex avoid stomach depression symptoms rating scale proven 150 mg bupropion, and not the transverse colon by mistake! If medical treatment fails mood disorder definition psychology buy bupropion 150 mg line, or is too expensive, you may be Make a small stab incision lateral to the midline and use a able to help a poor patient by operating. If there is haemostat to pull a Ch20 or Ch24 Malecot or Foley uncontrollable pain and dyspepsia, or if the quality of life catheter through it. Make the gastrostomy high on the has been spoilt over the years by nagging pain, heartburn, anterior wall of the stomach, midway between its greater and indigestion, there may be still a place for a truncal and lesser curves, and as far from the pylorus as you can. The gastrostomy must be leak-proof, so that gastric juice does not enter the peritoneal cavity, so test it by flushing water through the tube. If there is no leak, anchor the stomach above and below the tube to the posterior rectus sheath. Before the patient leaves the theatre, instil some fluid through the tube, to make sure it is patent. If stomach content leaks later around the tube, and there is no abdominal pain, this may be due to some pressure necrosis of the gastric wall from the balloon, or infection of the adjacent abdominal wall. Try a course of gentamicin; if the leak persists, remove the tube and allow the gastrostomy to drain naturally. It will start to close, and before the stoma is completely shut, re-insert a catheter if the gastrostomy is still needed. If the gastrostomy tube falls out or is blocked, re-insert a new one through the same track, if necessary with a guide wire. If you use a paediatric gastroscope or uroscope, you can pass this through the stoma to view the stomach directly. If there is bleeding from the gastric tube, it is probably due to irritation from small vessels around the stoma; insert and inflate a larger catheter balloon to tamponade these vessels. If this fails, perform an endoscopy to rule out gastric ulceration, and treat this with cimetidine or omeprazole. If there is persistent vomiting after gastric tube feeds, or the upper abdomen swells, or undigested food comes out via the tube, the tube and it balloon has probably migrated and got stuck in the pylorus. Deflate it, and re-inflate it just after its entrance into the anterior wall of the stomach. C, pick up the stomach with probably because the tube was inadvertently inserted into Babcock forceps. If peritonitis develops, there may be a leak into the Make a small incision between the forceps, aspirate the abdomen from the open stomach, or a perforation of a gastric contents and push the catheter through this. Encircle it with 2 purse string sutures, and invaginate the stomach wall as you tie them If necrotizing fasciitis (6. Take the bites of the inner purse string suture through the full thickness of the stomach wall, so as to control If you find a pneumoperitoneum on an erect chest bleeding: the main dangers are haemorrhage and leaking. There will probably be a filling defect, or an ulcer, which you can see quite easily on screening. Carcinoma of the stomach presents usually in a male Inhibited peristalsis suggests a tumour. Vomiting after food; a distal gastric carcinoma causes Suggesting non-ulcer dyspepsia: diffuse tenderness, protracted vomiting, like that of pyloric stenosis due to a no mass, less weight loss, and a variable appetite. If the tumour is within 5cm of the gastro-oesophageal (8) Other symptoms of secondary spread. Gastric carcinoma may take the form of: (1) a cauliflower type of growth; Before deciding on major surgery, remember that although (2);a malignant ulcer with raised, irregular everted edges, a partial gastrectomy might be feasible, if you do not especially in the distal third of the lesser curve; manage to remove all the tumour and metastatic nodes, (3);diffuse infiltration, either in its antrum, causing pyloric you can only palliate the condition. If there are signs of progressive pyloric obstruction, You may not be able to perform a partial or total causing daily vomiting, with no signs of advanced disease gastrectomy, so try to: (except perhaps metastatic cervical nodes), perform a (1) Make the diagnosis as best you can. Choose a part of the stomach (2) Select out any resectable and potentially curable cases. Try to refer the patient last days a little more bearable, stop him vomiting, afterwards for definitive surgery. A firm, or hard, slightly mobile, irregular epigastric gastrectomy which is very major surgery. Explore the whole abdomen looking for node, especially in the supraclavicular fossa, biopsy it. Clamp and divide the gastrocolic omentum in stomach with a long narrowed stricture extending to the sections including the left gastro-epiploic vessels and first pylorus with complete loss of rugosity and lack of motility 2 short gastric arteries on the left side, and the right gastro (hour-glass stomach). Close the duodenal stump in 2 layers with Because of gross malnourishment, perform a simple long-acting absorbable suture. Do not perform a Lift up the mobilized stomach and apply non-crushing pyloroplasty because the thickened scarred pylorus does clamps (preferably Lane’s) proximally across it, not hold sutures well. Do not try a gastrectomy unless and crushing clamps just distal to these; divide between nutrition is satisfactory; if gastric carcinoma has them. Bring up a loop of proximal jejunum 10-12cm from developed it is best to feed first by a jejunostomy and then the duodeno-jejunal flexure so that the afferent loop lies arrange a partial gastrectomy (13. Approximate the gastric stump and jejunum and make an end-to-side anastomosis (11-9). There is no evidence that a nasogastric tube is helpful Most ingested foreign bodies will pass through the pylorus postoperatively. Do not put one in after the operation, and exit via the anal canal, although their passage is often because you may perforate the anastomosis with it! Most of the time these do not result If there is significant bleeding after gastrectomy, in gastric outlet obstruction, but may cause obstruction in place a pack, press and wait 5mins. Occasionally they may cause bleeding or even perforation, especially alkaline disc If you cannot close the duodenal stump, insert a Ch20 batteries, or potassium tablets. Bezoars are concretions of ingested material: trichobezoars, principally hair (chewed by long-haired girls), or phytobezoars, (unripe persimmons or citrus 13. These form a glutinous mass in the stomach which eventually can occupy the whole organ, and cause Swallowing a corrosive causes damage to the oesophagus obstruction, as well as bleeding, anaemia, weight loss, (30. If you use antacids in the acute (2) Haematemesis and/or melaena, situation, the acid is neutralized in a highly exothermic (3) Multiple foreign bodies accumulating in the stomach, reaction which burns the gastric mucosa further. A bezoar may show up as a mottled density, but is has a history of acid ingestion. If it is acute, the result is non-productive retching after Allow smooth foreign bodies to pass naturally: be patient recent foods had been swallowed. A nasogastric tube does not usually Endoscopy may not be so easy because you may have pass into the stomach. There is usually dysphagia you can pass a protective plastic sheath over the foreign and an inability to burp. Gastric peristalsis is noisy after body before pulling it out together with the endoscope en meals, but less so on lying down; the patient may need to bloc, especially with ingested heroin packets which may adopt strange postures to get his food down. However, usually you will only make the diagnosis after contrast studies, or endoscopy. Metoclopramide 10mg qid or erythromycin with a double fluid level on an erect film. Palpate for the foreign body in the stomach and examine the duodenum and small bowel for further foreign bodies, especially broken-up bezoars; if you find these, try to break them up and push them into the colon. Open the stomach longitudinally proximal to the pylorus, and extract the foreign body, taking care not to cause further damage if the object is sharp. Continue nasogastric drainage postoperatively till the aspirate is no longer blood-stained. Endoscopy however may be helpful and may allow spontaneous untwisting, but not in the chronic case because the abnormal orientation of the stomach is very difficult to interpret. Barium studies show the greater curve facing superiorly and the body of the stomach assuming a globular shape, if the volvulus is incomplete and some contrast passes into the stomach. There may be associated motoneurone disease or similar myopathy in the chronic type. Try passing a nasogastric tube to deflate the stomach: this will buy you time in a chronic or incomplete case. At laparotomy you may have difficulty seeing the stomach as it is tucked away in the left hypochondrium; you will need to decompress the distended twisted stomach by a needle or small-bore suction tube before you can untwist it. For organo-axial volvulus, fixing the greater curve to the duodeno-jejunal flexure seems to be successful. In Tanner’s gastropexy you have to detach the transverse colon from the stomach, and place the colon under the left hemidiaphragm. The history is likely to be that the symptoms began as above, then the patient began to feel better, the pain 14. He now looks Appendicitis is becoming the commonest abdominal fairly well and has only a mild fever (37·5ºC).

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In conclusion bipolar depression research buy cheap bupropion 150mg line, cftr function measurements in intestinal organoids were used to 7 anxiety disorders buy bupropion 150 mg with mastercard screen for cftr activating drugs depression test short purchase 150 mg bupropion otc, and subjects with cftr variants that respond to depression game cheap bupropion uk these drugs in vitro were selected for in vivo treatment. Human organoid cultures rectal crypt isolation and organoid expansion was performed with some adaptations of previously described methods 20, 21. Hereafer, the droplets were immersed in pre-warmed complete culture medium and cultures were expanded for at least three weeks before assaying cftr function. Quality of the conditioned media was assessed by dot blots, elIsa and luciferase reporter constructs (toPflash and foPflash) 22, 23. Pulses (1-mV amplitude, 1-s duration) were delivered every 90 s to monitor resistance. We included patients aged ≥18-years-old with a cftr-a455e or a cftr-r117H mutation on at least one allele of whom rectal biopsies and organoid cultures showed residual cftr function in previous studies 20. Patients were excluded if they had an acute pulmonary exacerbation or an increased risk of side efects of salbutamol. Patient plasma-induced organoid swelling Patient plasma was collected before and afer treatment with salbutamol and incubated (40% plasma) with organoids derived from a cf patient with high residual function (r117H/f508del). Inhaled vivo nasal potential diference: techniques and bronchodilators for cystic fibrosis. Recognition of the total or luminal organoid area (xy plane) by Volocity imaging software is shown. The luminal surface(a) representative confocal images of calcein-green areas (in μm and %) of the total organoid surface area (100%) are indicated in the bottom left corner. Sweat chloride concentrations were obtained from individuals expressing 2from the Dutch registry database. Icm values were normalized to healthy control (Hc) responses to correct for the use of two diferent protocols (see methods). Importantly, high sla (>20%) of organoids is negatively associated with the relative area increase of organoids upon forskolin stimulation (forskolin-induced swelling, fIs)17, leading to underestimation of wild type cftr function (s2b). In conclusion, organoid-based swelling measurements can be used to semi-quantitate individual residual cftr function over a large dynamic range, and significantly correlate with known in vivo and ex vivo cftr-dependent biomarkers. We observed the strongest positive correlation between the response to therapy in organoids at 0. However, a significant correlation between drug-induced sla and clinical trial data was only observed when r117H-7t data was excluded (all genotypes, s6d, r = 0. Importantly, the subject-specific responses were maintained throughout culture for at least 6 months and afer 4 months of liquid nitrogen storage (fig. Per experiment, the cultures were assessed simultaneously to limit technical variation. Responses were averaged from 3 and forskolin-induced organoids derived from two individual f508del homozygous subjects with or without 24independent experiments performed with weekly interval (week 1 3; see S7a-c for the results of the independent experiments). The responses are normalized to the average response of the 5 cultures per experiment (100%). In e and g the sd represents the variation from 3 independent wells; in f and h the sd represents variation between diferent experiments. We clearly observed diferences between residual function and response to therapy between organoids with identical cf-causing mutations that were stable over over extended culture periods with diferent media preparations (28 weeks) and independent of biobanking (figs. We found the highest positive correlation with clinical responses at a suboptimal forskolin dose (0. We therefore expect that combination treatment of subjects with a455e in vivo will yield better results than combination treatment of f508del homozygous subjects. It might very well be that experimental conditions rather than intrinsic tissue diferences explain these observations. Importantly, we provide the first proof-of-principle that individual in vitro functional measurements can be used to preclinically select in vivo responders to cftr-modulating drugs. Crypt isolation and organoid culture from rectal suction biopsies methods were slightly adapted from protocols described previously12,17. In short, crypts were isolated, and seeded in 50% matrigel (growth factor reduced, phenol-free, bd bioscience) in 24-well plates (~10–30 crypts in three 10 µl matrigel droplets per well). In short, the biopsies were collected in phosphate-bufered saline on ice and directly mounted in sliders (aperture 0. Identification of the cystic fibrosis cystic fibrosis and the g551d-cftr mutation. Ivacafor in severe cystic fibrosis assessment of cftr function in rectal biopsies lung disease and a g551d mutation. The data were derived from three independent wells of the same experi was quantitated in a blinded fashion. Representative confocal images of calcein-green-labeled organoids at the indicated timepoints of forskolin stimulation. Each data point represents responses of F508del / Class I organoids derived from six different individuals, measured at f508del / class I organoids. In e and g the sd indicates the variation from 3 independent wells; in f and h the sd indicates variation between diferent experiments. Increased camP levels induce rapid swelling of such organoids by opening the cystic fibrosis transmembrane conductor receptor (cftr). Here we use the crIsPr/cas9 genome editing system to correct the cftr locus by homologous recombination in cultured intestinal stem cells of cf patients. Intestinal organoids or ‘miniguts’ comprise nearly intact physiology; self-renewing lgr5+ stem cells and the niche supporting Paneth cells are located in a domain that resembles the crypt, and enterocytes as well as goblet and enteroendocrine cells move upwards to build a villus-like domain that lines the central lumen. We established sI and lI organoids from two diferent pediatric cf patients, respectively. Unlike wild type organoids, the cftr f508del patient organoids did not expand their surface area upon forskolin treatment (fig. Within the intronic sequence, we incorporated a puromycin resistance cassette (fig. We confirmed site-specific knock-in events and correction of the f508del allele by sequencing the recombined allele (fig 1I). It has been reported that sgrnas can potentially tolerate mismatches in the 20bp protospacer target sequence, which can lead to the generation of undesirable ‘of-target’ indels 19,41,42. We identified 29 potential of-target sites for sgrna1, of which 25 were sequenced and analyzed in an individual clone. Quantification of swelling by automated image analysis demonstrated a relative increase of the total organoid surface area to 177% (+/ 1. We next tested whether the forskolin-induced swelling of the corrected organoids was sensitive to chemical inhibition of cftr by cftrinh-172 43. Indeed, forskolin-induced swelling was fully abolished in presence of the inhibitor (fig. The total organoid surface area is normalized to t0 min and f508del: uncorrected control organoids of the corresponding patient. Note that after transfection only stem cells that integrated the selection cassette can grow clones (d). In summary, we have isolated and expanded adult intestinal stem cells from two cf patients, corrected the mutant f508del allele using the crIsP/cas9 mediated homologous recombination, and demonstrated functionality of the corrected allele in the organoid system (fig. Mouse material for organoid cultures experimental setup was approved by the animal welfare committee (dec) of the royal dutch academy of sciences (KnaW). Organoid culture crypts were isolated from mouse and human intestinal tissues by incubating for 1 hour with 2mm edta in Pbs at 4 °c, and plated in drops of matrigel1,8. Human intestinal growth medium additionally contains Wnt conditioned media (50%, produced using stably transfected l cells), tgf-β type I receptor inhibitor a83-01 (tocris), nicotinamide (sigma-aldrich) and P38 inhibitor sb202190 (sigma-aldrich). Organoid Transfection the organoid lipofection protocol is described in detail in32. In short: mouse organoids were cultured in medium plus nicotinamide and Wnt-conditioned medium to enrich for stem cells. Human organoids were grown in expansion media, and trypsinized for 10 min at 37°c. Vector construction the human codon-optimized cas9 expression plasmid was obtained from addgene (41815). Forskolin-induced organoid swelling assay organoids from a 7-day old culture were seeded in a flat-bottom 96-well culture plate (nunc) in 5 µl matrigel containing 20–80 organoids and 100 µl culture medium.

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Analysis of these images provides of the lens causes it to depression only at night buy 150 mg bupropion amex be deeper on one side than on the other organic depression definition purchase bupropion 150 mg mastercard. In infammatory conditions of the uveal tract where the permeability of the vessels is increased depression symptoms wife generic bupropion 150mg with amex, the aqueous may contain particles of protein or foating cells bipolar depression hotline numbers purchase bupropion with american express. The curvature of the anterior surface of the cornea can be measured by a keratometer and the corneal thickness by an Contents optical pachymeter on a slit-lamp or an ultrasonic pachym eter. The topography of anterior and posterior surfaces of Protein transudation from the iris or ciliary vessels pro the cornea are assessed by a digital analysis of over a thou duces an opalescence of the aqueous, an aqueous fare sand points on the cornea (see Fig. The aqueous cells are recorded as: Hyphaema: A similar collection of blood may occur after contusions or spontaneously (hyphaema). Micro-flariae l trace if 1–5 are present may be observed in the anterior chamber in eyes with l 11 if 5–10 onchocerciasis. A dull iris with an ill-defned pattern or ‘muddiness of Very large, non-reactive pupils will suggest that a myd the iris’ suggests atrophy from iridocyclitis and sectoral riatic has been used, perhaps inadvertently, as when a pa patches of atrophy suggest an acute angle-closure glaucoma tient has been using an ointment containing atropine, and or herpes zoster. The Tremulousness of the iris or iridodonesis is seen when pupils are usually immobile, and the patient complains of the eyes are moved rapidly if this tissue is not properly sup dimness of vision, especially for near work. This occurs in absence, shrinkage, or the pupils are also large and immobile in bilateral le subluxation of the lens, and is best appreciated in a dark sions affecting the retina and optic nerve causing blindness room with oblique illumination, on asking the patient to (see Fig. Bilateral dilated pupils, in bilateral in Down syndrome and pedunculated nodules (Lisch) in blindness, can be distinguished from a bilateral efferent neurofbromatosis. Flat nodules at the pupillary margin pupillary defect, pupilloplegia, by eliciting the near refex. It is equally important to the position of the iris must be examined next, espe remember that the presence of a direct reaction to light does cially the plane in which it lies. Special attention should be not eliminate the possibility of the patient actually being paid to any adhesions or synechiae, anterior to the cornea blind due to a central lesion affecting the visual pathways or posterior to the lens capsule. The size of the pupil is determined by the afferent and effer Dilated and immobile pupils also result from third nerve ent pathways for pupillary light refexes, and the function of palsies (absolute paralysis of the pupil); if the paralysis the sphincter and dilator pupillae muscles. Dilatation of the also affects the third nerve fbres to the ciliary muscle, ac pupils with retained mobility is found sometimes in myopia commodation is also paralysed (ophthalmoplegia interna). This results in lesions affecting the third nerve nucleus, Conversely, the pupils are small in babies and in old people. This may be due to conditions hand and watch the pupil, noting if its constriction to light such as swollen lymph nodes in the neck, apical pneumo is well maintained. Replace this hand and remove the other, nia, apical pleurisy, cervical rib and thoracic aneurysm. Most of the conditions causing an process is repeated while observing the other pupil. When all sympathetic function on to an absence of natural light or diffuse illumination. More one side is lost, resulting in miosis, a narrowed palpebral over, when the reaction to light is feeble and the pupils are fssure and slight enophthalmos (due to loss of tone already small, it is diffcult to be certain of the results in of Muller muscle), sometimes associated with unilateral bright, diffuse daylight. In such cases the examination absence of sweating, the condition is called the Horner should be carried out in a dark room and light concentrated syndrome. By slight lateral movements the focus of light sluggish pupil with ‘muddiness’ of the iris is associated can be moved on or off the pupil, the pupillary movements with an active iritis. Still fner observations can be iritis with posterior synechiae, and should be investigated made with the slit-lamp, when the microscope is focussed with a mydriatic such as cyclopentolate to ascertain if the on the papillary margin and the beam is abruptly switched pupil dilates regularly. If there is no irritation of the third nerves, arousing suspicion of a central movement in these conditions it may be concluded that the nervous disease in their vicinity. The light is focused frst on the large, immobile and oval, with the long axis vertical. The best source of illumination for this purpose is the focal beam of Pupillary Refexes the slit-lamp reduced to a spot. If the reaction is present During routine examination of the eyes, the pupils should the pupil will react briskly when one half of the retina is be examined at an early stage, before any mydriatic is em illuminated, but very slightly when the other half is illumi ployed. This is so because it is impossible to prevent diffusion and is best carried out with low background illumination of light onto the sensitive half of the retina, so the test is using a bright focused light with the patient looking into the rarely unequivocal. After 2–3 seconds, the should be kept in mind: light is rapidly transferred to the opposite pupil. This swinging to-and-fro of the light is repeated several times l Illumination in the examination room should be low while observing the response of the pupil to which the light l the patient should look into the distance, and is transferred (Fig. The patient is asked to look consensual response has the same magnitude as a direct into the distance to prevent accommodative constriction of response. Note the size, shape and contour of each pupil, input from that side is less than that from the normal side. In that case when the light is transferred to the diseased eye these refexes are: (i) constriction of the pupil to direct both pupils will dilate, and on swinging back to the normal or consensually presented light and (ii) accommodation— side both the pupils will constrict. This is referred to as light near determined by asking the patient to look to the far end dissociation. While he does so an accommodation target the tonic pupil (of Adie) somewhat resembles the is suddenly held up vertically at about 15 cm from the Argyll Robertson pupil; it is of unknown aetiology, not patient’s nose and he is told to look at it. The movement of associated with syphilis, occurs usually in young women, is the pupils is studied while he converges. This When properly conducted, the above method provides pupil is slightly dilated and always larger than its fellow; reliable information as to the shape and relative size of the the unilateral Argyll Robertson pupil is always smaller. A few of the common conditions Although in the tonic pupil the reaction to light seems ab are considered here. The reaction of the pupil on convergence is sluggish with a long latent period and is Abnormal Reactions of the Pupil unduly sustained. As mentioned pine; the Argyll Robertson pupil does not; fnally, the tonic earlier, loss of light refexes results from a lesion in the retina pupil constricts with 0. A lesion in the third due to the pupil size, which do not last longer than a few nerve abolishes both light and convergence refexes. The affected More complex lesions may result from damage to the eye usually has a slight accommodative paresis and astheno relay paths in the tectum between the afferent and efferent pia is often induced by near effort. The most important of these is the Argyll Robertson get the two eyes to work together when reading and are best pupil, usually caused by a lesion, almost invariably syphilitic, advised to use dilute pilocarpine and fx with the other eye. Any opaci Diffuse illumination allows an observer to obtain a direct ties in the pupillary area can be seen by inspection, aided by and tangential view of the anterior segment of the eye. The Diffuse illumination allows determination of general fea haze is much more pronounced in an old person and the tures, such as colour, size and relative position of structures. This is followed by tangential illumination with a large It is probable that the patient has a cataract, but examina angle of illumination, which helps to increase contrast and tion by distant direct ophthalmoscopy shows a clear red highlight the texture of ocular tissues. The explanation is that the refractive index of the lens substance increases with age, and scattering of light from its surface is greater. The milkiness is due to rays Focal Illumination of light which are refected from the lens and enter the Focal illumination is used for direct observation of the observer’s eye. Various forms of cataract are view of the eye illuminated by a slit-lamp beam of light of diagnosed according to their distribution and nature but moderate width, entering the eye from the left side. Opti observation must always be confrmed by ophthalmoscopic cally the homogeneous media appear quite black; struc examination, and the opacities localized with the help of the tures such as the cornea, lens and suspended particles in slit-lamp (see Figs 11. On the left the pupil, looking as if it were on the surface of the lens, of both Fig. The black space on the right is the anterior appearance over the whole pupillary area suggests a total or chamber. A mature cataract; if it is yellowish-white, with white spots of dim central interval can be distinguished, formed by the calcifcation and the iris is tremulous, a shrunken calcare embryonic nucleus with its Y-sutures. Finally, the pupil may the successive ‘zones of discontinuity’— the fetal nucleus, be blocked with uveal exudates forming an infammatory the infantile nucleus, the adult nucleus and the cortex. Ocular problems can be identifed by different meth ods of examination, which differ in the positioning of the illuminating light and the angle between the illumination and observation arms. Various permutations and combina tions of these techniques are used, some simultaneously and others sequentially. Specular Refection Specular refection allows the observer to visualize the cor neal endothelium by viewing light refected back from this interface. The illuminating and viewing arms are adjusted so that each forms an angle of about 30° to the central per pendicular, the slit-lamp beam is narrowed to a height of 2 mm and focused onto the central corneal endothelium. This is placed immediately adjacent to the refection of the slit-lamp bulb on the cornea. A golden sheen with darker lines outlining the hexagonal endothelial cells is seen (Fig.

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