By R. Karrypto. Scripps College.

Both types of discursive realizations are deeply affected by populari- zation strategies buy 500 mg azulfidine with amex, which are meant not only to adjust and adapt the communication of given contents to the linguistic competence and cognitive ability of the audience purchase azulfidine 500mg without a prescription, but also to persuade them as to the reliability and validity of such meanings. In public information mate- rial (ranging from blood and organ donation to anti-smoking or anti- gambling campaigns), scientific information regarding the conditions and consequences of a given behaviour, or the requisite needed to control or change a given state, is coupled with promotional informa- tion (to persuade the recipient to perform a given action) and technical and organizational information (to guide the recipient alongside such procedures). Popularized publications, instead, are aimed at “the trans- formation of specialized knowledge into ‘everyday’ or ‘lay’ know- ledge” (Calsamiglia/Van Dijk 2004: 370). Therefore, the specificity of the expert-to-expert discourse is eschewed in favour of a less gate- keeping rhetorical representation of the content − characterized by the frequent resorting to explanations, definitions, and reformulations − which “does not alter the disciplinary content […] as much as its language” (Gotti 2014: 19). From a pragmatic standpoint, the different representations of medical discourse are used to convey meanings in the most effective and contextually appropriate way, thus adjusting the linguistic repre- sentation of the content to the competence, needs and expectations of the receiver. From a Critical Discourse perspective, besides having an informative function, medical language also serves to stigmatize certain behaviours by pathologizing them, that is, by cognitively framing them into symptoms-diagnosis-treatment paradigms, or to either sanction or proscribe given therapies and practices (Conrad/ Barker 2010). Besides contextual factors, language use in medical settings is also markedly affected by the code and the channel of its communica- tion, that is, on the one hand, the genres and text-types which are typically associated with the transmission of given contents, and, on the other, the medium employed for such communicative events. Focus on medical discourse This volume investigates how context- and medium-based factors may influence medical communication, both in synchronic and diachronic terms. Death, plagues, diseases have always been a cause of major concern, panic and terror, as is witnessed by many literary works from the past cen- turies (Virgil, Boccaccio, Chaucer, Shakespeare and many others wrote about epidemics), which were directly inspired by such power- ful feelings. These works evidence the fascination such collective apprehension generates and, at the same time, they contribute to the establishment of given views within a specific culture. Based on the assumption that language can contribute to raising fears, the chapter examines the rhetorical techniques and processes used to construct the expression of fear, first by designing a model which diachronically illustrates the evolution of the interpretation of pandemics over time and the type of fear they generate (accounting for such parameters as ‘what is to be feared? Another diachronic investigation into the ways language was used in the medical domain in order to shape up notions and frame them into cognitive terms so as to either justify or stigmatize, or 16 Michele Sala / Stefania M. With a special focus placed on the use of given expressions, metaphors and concepts by authors promoting competing views of the nature and significance of epidemics (either aligning with the Church of England’s official view or with the Puritan interpretation of the phenomenon), this chapter investigates some crucial dynamics of the ethics of medical communication about plague. The analysis illustrates how different authors − when con- fronted with devastating epidemics in both economic, demographic and social terms − exploited and manipulated discursive resources to promote either resistance to or compliance with medical treatments and public orders. The corpus-based investigation involves the analysis of two English subcorpora: on the one hand an expert-to-expert communication corpus; on the other hand, an expert- semiexpert/non-expert communication corpus. The analysis reveals that the amount and type of biomedical variants employed in each biomedical register is not only dependent upon situational factors, but also upon the writers’ intention of the recipients’ level of knowledge in each situational context. By examining variants in the two sub- corpora, the author identifies regular semantico-syntactic patterns in variant formation corresponding to each register. For instance, in the expert-to-expert register, the type of variants preferred are acronyms, whereas in the expert-semiexpert/non-expert type of communication, there is greater exploitation of terminological variants implying a re- formulation of terms composed of Greek and Latin roots than bio- medical denominations. Since new media, especially Internet-based, have an increasingly significant impact on science communication and in the dissemination of medical Introduction 17 issues to lay audiences, it is worthwhile to see how such resources are employed to communicate and recontextualize medical concepts in health and medicine news in electronic science magazines. The cross-linguistic nature of the corpus makes it possible to highlight similarities and differences in the use of pictures and captions in the three languages. Given the increasing importance − for the purpose of de- tecting and identifying language disorders − acquired by such testing methods, designed to assess the ability on the part of English speaking children to recognize and understand linguistic stimuli (presented in the written form) and elaborate in turn a response which is con- textually appropriate and pragmatically effective, this analysis hypo- thesizes the translation of such texts into Italian, anticipating possible translation problems due to either culture- or language-specific fac- tors, and offering workable solutions. The results suggest that variations do exist and that they do not merely mirror different national contexts, but rather occur within specific national contexts. Indeed, a profound contrast has been identified between institutionalised discourse, where altruism and en- lightened self-interest tend to emerge, and media reports, where self- interest clearly predominates, despite the universal positive quality, in medical term, of the giving blood procedure. In particular, they focus on the texts – the first source of information on this condition – uploaded on Italian, German and Dutch hospital websites and other similar centres, with the purpose of identifying the communicative style employed to deal with such sensitive issues and to detect, if any, cultural differences. Findings indicate variation in style: while the Italian corpus seems monologic and doctor-centred, the German and Dutch ones appear more patient-centred and reader-friendly. This calls for a more active presence of the translator in the text, who thus acquires the status “of an information broker with language counselling tasks”. She analyses authentic examples from health forum boards and, by applying a Discourse Analysis approach, she describes how participants construct position and commitment and establish credibility toward advice, opinions and suggestions. As recent research has demonstrated that the extent to which adult people trust online information depends on the topic they are looking for, in the final section Zummo presents a survey to better illustrate if and how credibility affects people’s beliefs and behaviour in relation to their health. The study she carries out focuses on the adverse outcomes resulting in health care in the United States when language barriers in doctor-patient communication exist. In particular, this chapter deals with lexical variations used by Latin American immigrants when speaking Spanish in a medical context in the United States, and the negative impact these variants have on the medical interview in terms of miscommunication, the patient´s level of trust in the physician and overall satisfaction with care. The author’s hope is that research on dialectal varia- tion may raise awareness on how easily health care may be affected and what types of solutions can be sought. The specific focus of this chapter is on the type of language and the communicative resources employed by medical expert witnesses − professionals with a spe- cialized knowledge, doctors and physicians – who are required to assist and provide their expertise in criminal trials, for the admini- stration of justice. Due to their education and experience, expert wit- nesses can provide the court with assessments or opinions within their area of competence which would not be available or even accessible to other professionals in court, such as the lawyers and the judge, on the one hand, or to the jury and the public in general, on the other.

In B cell chronic leukaemia order azulfidine 500 mg overnight delivery, the mutations in the gene are translated as a resistance to chemotherapy order 500mg azulfidine with visa. The same phenomenon is observed in ovarian cancer, where wild type p53 tumours are more sensitive to chemotherapy. Special protocols for paraffin embedded tissue are provided and should be strictly followed. Thus, this protocol is ideal for sample preservation by field molecular biologists. The result is an exponential accumulation of the specific target fragment by a factor of approximately 2n, where n is the number of cycles of amplifications performed. Problems that can be encountered are: —No detectable product or a low yield of the desired product; —The presence of non-specific background bands due to mispriming or misextension of the primers; —The formation of ‘primer-dimers’, which compete for amplification with the desired product; —Mutations or heterogeneity due to misincorporation. First of all a 50 mL reaction is set up in a microfuge tube (adequate for the available thermocycler). However, enzyme requirements may vary with respect to individual target templates or primers. If the enzyme concentration is too high, spurious non-specific background products may accumulate, and if it is too low, a low yield of products will be in evidence. As soon as the enzyme is received it should be aliquoted into 10 mL samples and stored at –20°C in Area 1 (Section 3. Deoxynucleotide concentrations between 50 and 200mM each result in an optimal balance of the yield, specificity and fidelity. An applicable annealing temperature is 5ºC below the true melting temperature (Tm) of the amplification primers. The range of enzyme activity varies by two orders of magnitude between 20 and 85ºC. Increasing the annealing temperature enhances discrimination against incorrectly annealed primers and reduces mis-extension of incorrect nucleotides at the 3¢ end of primers. Primer extensions are traditionally performed at 72°C because this temperature is near optimal for extending primers. An extension time of 1 min at 72°C is considered sufficient for products up to 2 kb in length. Typical denaturation conditions are 95°C for 30 s, but higher temperatures may be appropriate, especially for G+C-rich genomes. Denaturation steps that are too high and/or too long lead to unnecessary loss of enzyme activity. A common mistake is to execute too many cycles, which can increase the amount and complexity of non-specific background products. Higher primer concentrations may promote mispriming and accumulation of non-specific product and may increase the probability of generating a template independent artefact termed a primer-dimer. The technique has the added advantage that it is easy to prepare replicate filters, allowing many filter-bound sequences to be analysed at the same time, for example with different probes or under different hybridization and washing conditions. Dot blots do not distinguish between the number and size of the molecules hybridizing, so the hybridization ‘signal’ is the sum of all sequences hybridizing to the probe under the conditions used. Nylon membranes, due to their higher resistance, are now the most commonly used type for Southern and dot blots. This will prevent the gradual leaching-off of the nucleic acids from the surface when filters are hybridized for long periods, particularly at high temperature. Hybridization strategy Nucleic acid hybridization, the formation of a duplex between two complementary nucleotide sequences, is the basis for a range of techniques now in widespread use in modern biology. On the other hand, as the salt concentration is decreased, the stringency increases. There are various types of hybridization commonly in use, such as filter hybridization and in situ hybridization. Hybridization is followed by extensive washing of the filter to remove unreacted probe. The procedure is widely applicable, being used for Southern Blot and dot blot hybridization for example. The choice of probe depends on three factors: the hybridization strategy, the availa- bility or source of material for use as a probe and the degree to which it can be labelled. However, for nucleic acid hybridization, 32P is the isotope of choice since its high energy results in short scintillation counting times and short autoradiographic exposures. Phosphorus-32 has the advantage over other radionuclides in that high specific activities can be readily attained. However, precautions must 32 be taken when handling P because of the radiation emitted (Chapter 2). Detection by autoradiography, while sensitive, may take a long time if there are few counts in the hybrids. This method is suitable for probes and primers that are single stranded and short (20–30 bases). The probes should be boiled prior to addition to the hybridization solution in order to be single stranded. In some cases, it is preferable to apply these labelled probes directly to cells and tissues to localize the source of the signal.

Clinical Presentation • Classical presentation of pulsatile mass in the patient with abdominal pain and pulse deficits is not always present buy azulfidine 500mg on-line. Patients presenting with an abdominal aneurysm with abdominal pain are ruptured until proven otherwise and surgical consult is mandatory cheap 500mg azulfidine otc. Rupture unstable: surgical repair The differentiation between a stable and unstable rupture is trivial as the process is dynamic. The perioperative mortality is over 25% secondary acute myocardial infarction in emergent surgery compared to fewer than 5% for elective. Therefore it is preferred, but not always possible, to prime the patient for the operating room. Bowel Obstruction Risk Factors/Etiology • Small bowel obstruction is typically caused by postoperative adhesions, hernias, or tumors. It is likely due to a hereditary hypofixation of the cecum to the posterior abdominal wall. Clinical Presentation and Diagnoses • Acute onset of severe intermittent abdominal pain followed by nausea and vomiting is the common clinical manifestation. Obstipation may be absent early on or in a partial obstruction, and its absence does not exclude the diagnosis. A supine abdominal film along with either a lateral decubitus or upright abdominal films are minimally needed for diagnosis. An upright chest film may be added to search for free air under the dia- phragm indicating a perforated viscous. The small bowel is differentiated from the large bowel by the presence of “valvulae conniventes” which are numerous, narrowly spaced and cross the entire lu- men. A “string of pearls” sign is highly suggestive of small bowel obstruction and is described as a line of air pockets in a fluid filled small bowel. Air fluid levels in a stepladder pattern are also suggestive of a small bowel obstruction. If not, sigmoid volvulus can be diagnosed by the classic “birds beak” sign on barium enema. Distended large bowel in the left lower quadrant with absence of right-sided gas may indicate a cecal volvulus. The intermittent nature of the pain is suggestive of bowel obstruction but is also present in mesenteric ischemia. Treatment • Early nasogastric decompression, aggressive fluid resuscitation, broad spectrum anti- biotics including coverage of Gram negatives and anaerobes, and early surgical consul- tation are the mainstays of treatment of small and large bowel obstructions. Up to 75% of partial small bowel obstructions and up to one-third of complete small bowel obstructions will resolve with decompression and fluid resuscitation alone. Strangu- lated obstructions indicated by fever, tachycardia, and/or localized tenderness are op- erative cases. Uncomplicated obstructions are usually initially treated conservatively, with surgery reserved for treatment failures. Disposition • These patients are all admitted to the hospital, almost always under the care of a surgeon. The highest incidence occurs in 10-30 yr olds, with atypical presentations more common in the very young or very old and women of child-bearing age. Clinical Presentation and Diagnoses • The classic description is of periumbilical, epigastric, or diffuse dull pain migrating over several hours to McBurney’s point in the right lower quadrant, with the pain changing in character from dull to sharp as the overlying peritoneum becomes in- flamed. Peritoneal signs, including involuntary guarding, rigidity and diffuse percus- sion tenderness may indicate perforation. Less specific and less frequently associated symptoms include fever, chills, diarrhea, dysuria and frequency, and constipation. A pelvic appendix may irritate the bladder, result- ing in suprapubic pain or dysuria, while a retroileal appendix may irritate the ureter, causing testicular pain. More than two-thirds of appendices lie within 5 cm of McBurney’s point, with more inferior and medial. Perforation is the most common malpractice claim for ab- dominal emergencies and the fifth most expensive claim overall in emergency medicine. Abdominal plain films have little or no utility and should not be routinely ordered, as even the finding of an appendicolith are neither sensitive nor specific for appendicitis. Ultrasound has reported sensitivity up to 93% and specific- ity up to 95% and is the preferred test in children and pregnant women. Other diagnoses to consider include testicular torsion, ruptured ectopic pregnancy, peptic ulcer disease, billiary tract disease, diverticulitis, abscesses, renal colic, pyelonephritis, bowel obstruction, and abdominal aortic aneurysm. Colonic Diverticulitis Risk Factors/Etiology • 96% of patients are older than 40 yr of age.

Encouraging the mother to pant or breathe through her contractions at this stage will also help control the delivery of the head azulfidine 500mg free shipping. If cord is seen around the neck it can be left alone as the body will usually deliver through the loops discount azulfidine 500mg online. The exaggerated Sim’s position should be used to transfer the patient with cord prolapse. The mother is laid on her left side with her head Third stage of labour flat and her buttocks elevated by pillows (Figure 28. The addition The third stage of labour begins with delivery of the baby and of head-down tilt may assist in relieving the pressure of the foetal ends once the placenta has been delivered. Use your fingertips to gently push the presenting of the baby the cord may be cut after it has finished pulsating part upwards and off the cord – this must be maintained during (or immediately if resuscitation is required). Alternatively, pass a urinary catheter and fill the bladder at 3 cm and 6 cm from the baby and divided between the clamps. The increase in bladder In most cases the third stage will be physiological unless Syn- size will elevate the presenting part. Any protruding cord should be tometrine (1-mL vial intramuscularly/intravenously) is available. Owing to the risk of cord rupture and uterine inversion, prehospital application of cord traction is discouraged unless the practitioner is experienced in this technique. Once deliv- Breech presentation ered the placenta should be kept for inspection by the midwife or This is where the presenting part is the feet or buttocks and occurs in obstetrician. The safest means of delivering a breech baby is by caesarean section and if labour is not well established the mother should be transferred urgently to hospital. If the presenting Intrapartum emergencies part is visible at the introitus a vaginal breech delivery will be Cord prolapse required. Urgent midwifery assistance should be requested while Cord prolapse is the descent of the umbilical cord through preparing for delivery. It occurs in <1% of deliv- position and once the breech is visible at the introitus, pushing eries and may lead to foetal hypoxia. Spontaneous delivery of the limbs and trunk is preferable to deliver the head can result in brachial plexus injury and must (Figure 28. Fortunately, most can be managed with the first two ing pressure to the popliteal fossa (Pinard manoeuvre). Avoid trying to ‘pull’ the baby out as this can result in the extension and trapping • McRoberts manoeuvre (Figure 28. The arms should be delivered by sweeping them across the baby’s Hyperflex her legs against the abdomen. Assess the effectiveness face and downwards or by the Lovset manoeuvre – rotation of of the manoeuvre with routine traction (one attempt) before the baby to facilitate delivery of the arms (Figure 28. The baby’s body should be supported direction, just above the maternal symphysis pubis using the heel onyourarm. With the other hand, gentle traction should be aspect of the anterior shoulder towards the foetal chest. Again applied simultaneously to the shoulders, using two fingers to flex assess the effectiveness of the manoeuvre with routine traction the occiput, i. If each of these measures fails the mother should be asked to assume the ‘all fours’ position with her head as low as possible and her bottom elevated. Two attempts should be made to deliver Shoulder dystocia the posterior shoulder with gentle downward traction. Failure of This is when the anterior shoulder becomes impacted behind the delivery at this stage should trigger urgent transfer (in the left lateral symphysis pubis and it occurs in 1% of deliveries. Care of Special Groups: The Obstetric Patient 155 Postpartum emergencies Postpartum haemorrhage This is defined as a blood loss of more than 500 mL after the second stage of labour is completed and can occur within the first 24 hours (primary) or up to 6 weeks following delivery (secondary). As around a litre of blood flows to the placental bed every minute at term it can be catastrophic and life threatening. Possible aetiology includes one of the four Ts: • tone – abnormalities of uterine contraction • trauma – to the genital tract • tissue – retained products of conception • thrombin – coagulation abnormalities. Perform a primary survey including palpation of the uterus (to assess tone) and examination for tears. Estimate the amount of blood loss and then double it to provide a more realistic estimate. Earlyintra- venous access and fluid resuscitation is important but should not delay transfer to hospital. Uterine inversion Inversion of the uterine fundus may occur spontaneously or more commonly as a result of uncontrolled cord traction during the third stage. The patient will complain of severe lower abdominal pain and the uterus may not be palpable as expected around the umbilicus. If a bulging mass is visible at or outside the vaginal entrance an immediate attempt should be made to reduce the uterus manually (Figure 28.

The first course could include lectures on the basic physics of radionuclides discount 500mg azulfidine with amex, safe handling of radioisotopes purchase azulfidine 500mg without prescription, recent advances in immunoassay, separation methods, quality control and approaches to data processing. The second course could include lectures on standards and standardization, assay design and optimization, the evaluation of antisera including Scatchard analysis, iodination techniques, stability and storage of reagents, and techniques for the local preparation of simple reagents, such as standards and quality control material for selected analytes. This could also be demonstrated in practical classes and experiments carried out to validate locally produced reagents. Other practical classes could be designed to demonstrate and compare different separation methods. During the first week, participants carry out standard statistical exercises and proceed to the construction of various types of calibration curves, Scatchard plots, response–error relationships and precision profiles, with no computational assistance beyond a hand-held calculator, to ensure that all underlying concepts are well understood. The second week sees a repetition of the first week, with the difference that the work is not done manually, but using a computer and a data processing software package or packages. Advanced reagent production A further group training activity may now be organized on advanced reagent production methods, confined to participants from centres equipped, or likely to become equipped, to undertake this activity to a significant extent. Not many laboratories, especially in developing countries, have the equipment and other facilities required for the production of monoclonal antibodies. If training in this area is required, it would be better provided on an individual basis at a suitable advanced centre. Participants in an external quality assurance scheme organized at the national or regional level 64 2. A training course devoted to tumour marker assays would focus on the special problems involved (high dose hook, etc. Such missions are both popular and effective because the same expert can train many persons and training is in a local context, taking into account circumstances in the host laboratory. An expert mission also has the advantage of establishing a relationship between a centre in a developing country, which may be working in relative isolation, and the more advanced home laboratory of the expert. Participants have an opportunity to update their knowledge and acquaint themselves with recent advances. The most appropriate and cost effective option for the training of technicians in developing countries is a suitable training centre within the region. In special fields, such as steroid receptor assays for example, an expert mission followed by a short period at an advanced centre outside the region may be necessary. Academics who need to be trained for longer periods and to a higher level may need to be accommo- dated at advanced centres in developed countries. Specially identified labora- tories may be developed to become a centre of excellence for training purposes within a given country or region. Ideally, nurses should serve in diagnostic nuclear medicine sections and be present during nuclear cardiology stress testing. A nurse is the first interface with the ward nursing of inpatients and should be able to inject ward patients with radiopharmaceuticals (e. Nurses in nuclear medicine are required to perform the following duties: —General physical and mental care of patients under examination or treatment; —Examination of vital signs; —Administration of drugs and injections on the instruction of doctors; —Explanation to patients of procedures and provision of support to the receptionist; —Handling of radiopharmaceuticals and radioactive waste in cooperation with pharmacists and technologists; —Taking appropriate radiation protection measures for patients and families, especially those comforting children and elderly people. In order to carry out these functions correctly, nurses need a basic knowledge of radiation, radionuclides and the biological effects of radiation, and should receive training on the safe handling of radioactive materials as well as radiation protection. Education and training should be offered both in undergraduate courses in a school of nursing and in postgraduate training courses in hospitals. Nurses should receive a final briefing before they start working in a department of nuclear medicine. In developing countries, nuclear medicine has historically often been an offshoot of pathology, radiology or radiotherapy services. The level of nuclear medicine services is categorized according to three levels of need: Level 1: This level is appropriate where only one gamma camera is needed for imaging purposes. The radiopharmaceutical supply, physics and radiation protection services are contracted outside the centre. A single imaging room connected to a shared reporting room should be sufficient, with a staff of one nuclear medicine physician and one technologist, with backup. Level 2: This level is appropriate for a general hospital where there are multiple imaging rooms in which in vitro and other non-imaging studies would generally be performed as well as radionuclide therapy. Level 3: This level is appropriate for an academic institution where there is a need for a comprehensive clinical nuclear medicine service, human resource development and research programmes. Introduction This section deals with the establishment of a nuclear medicine service for performing diagnostic and therapeutic procedures. Recommendations related to human resources development and the procurement of equipment, specifi- cations of imaging devices and clinical protocols are expanded on in other sections. The first step in establishing a nuclear medicine service is to consider the space, equipment and staffing requirements. Space requirements will vary according to the level of the service, depending on whether a simple in vitro or in vivo imaging laboratory is envisaged or whether there are plans for a full in vitro laboratory and for in vivo imaging therapeutic procedures. Space should also be allocated for an in- house radiopharmacy if unit doses are being prepared on-site from ‘cold’ kits and 99mTc generators.

The primary stimulus for insulin secretion is the β-cell response to changes in ambient glucose 500 mg azulfidine sale. First-phase insulin release occurs within the first few minutes after exposure to an elevated glucose level; this is followed by a more enduring second phase of insulin release generic 500 mg azulfidine with mastercard. Of particular importance is that first-phase insulin secretion is lost in patients with type 2 diabetes. The generally accepted sequence of events involved in glucose-induced insulin secretion is as follows: 1. Cell-surface voltage-dependent Ca2+ channels are opened, facilitating extracellular Ca2+ influx into the β-cell. An autoimmune attack (to the β- cells of the pancreas) may be triggered by reaction to an infection, for example by one of the viruses of the Coxsackie virus family or German measles, although the evidence is inconclusive. Type 1 diabetes is a polygenic disease (different genes contribute to its expression); it can be dominant, recessive or intermediate. Pancreatic β-cells in the islets of Langerhans are destroyed or damaged sufficiently to effectively abolish endogenous insulin production. This aetiology distinguishes type 1 origin from type 2; that is, whether the patient is insulin resistant (type 2) or insulin deficient without insulin resistance (type 1). Prior research has shown that both β-cells and T-cells act to initiate type 1 diabetes. Type 1 diabetes, formerly known as ‘childhood’, ‘juvenile’ or ‘insulin-dependent’ diabetes, is not exclusively a childhood problem. A subtype of type 1 (identifiable by the presence of antibodies against β-cells) typically develops slowly and is often confused with type 2. Type 1 diabetes is treated with insulin replacement therapy, usually by insulin injection or insulin pump, along with attention to dietary management and careful monitoring of blood glucose levels. Today most insulin is produced using genetic recombination techniques; insulin analogues are a form of modified insulin with different onset-of-action times or duration-of- action times. The most definitive laboratory test to distinguish type 1 from type 2 diabetes is the C- peptide assay, which is a measure of endogenous insulin production. With type 2 diabetes, proinsulin can be split into insulin and C-peptide; lack of C-peptide indicates type 1 diabetes. The presence of anti-islet antibodies (to glutamic acid decarboxylase, insulinoma associated peptide-2 or insulin) or absence of insulin resistance (determined by a glucose tolerance test) is also suggestive of type 1. With time β-cells no longer produce enough insulin to maintain control of metabolism and type 2 diabetes results. Traditionally considered a disease of adults, it is increasingly diag- nosed in children in parallel to rising obesity rates. While the underlying cause of insulin resistance is unknown, there is a striking correlation between obesity, increased plasma lipids and resistance. Central obesity (fat concentrated around the waist in relation to abdominal organs, but not subcutaneous fat) is known to predispose individuals to insulin resistance. Abdominal fat is especially active hormonally, secreting a group of hormones called adipokines, which may possibly impair glucose tolerance. Having relatives (especially first degree) with this disorder substantially increases the risk of developing type 2 diabetes. Additionally there is a mutation to the islet amyloid polypeptide gene that results in an earlier-onset, more severe form of diabetes. Environmental exposures may contribute to recent increases in the rate of type 2 diabetes. For example, there is a positive correlation between concentration in the urine of bisphenol A, a constituent of polycarbonate plastic, and the incidence of type 2 diabetes. The term ‘diabetes’ is usually taken to refer to diabetes mellitus, which is associated with excessive sweet urine (known as ‘glycosuria’). Rarer diabetic conditions include diabetes insipidus, where the urine is not sweet; this can be caused by either kidney or pituitary gland damage. Type 2 diabetes may go unnoticed for years; visible symptoms are typically mild, non- existent or sporadic, and usually there are no ketoacidotic episodes. However, severe long-term complications can result from unnoticed type 2 diabetes, including: • renal failure due to diabetic nephropathy • vascular disease (including coronary artery disease) • vision damage due to diabetic retinopathy • loss of sensation or pain due to diabetic neuropathy • liver damage from non-alcoholic steatohepatitis • heart failure from diabetic cardiomyopathy. Type 2 diabetes may be first treated by increasing physical activity, decreasing carbohydrate intake and weight loss; insulin sensitivity can be restored with only moderate weight loss. Insulin production is initially only moderately impaired in type 2 diabetes, so oral medication can often be used to improve insulin production (e. A final resort is insulin therapy to maintain normal or near-normal glucose levels. Biguanides do not affect the output of insulin, unlike the sulphonylureas and meglitinides, and can therefore also be effective in type 1 patients in concert with insulin therapy. They can lower fasting levels of insulin in plasma, through their tendency to reduce gluconeogenesis in the liver.