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Less frequent adminis- trations reduce the oscillation in hemoglobin levels outside the optimal range of hemoglobin as defined by best practice guide- lines discount lexapro 10mg online, which is often seen with existing short-acting compounds (epoetin lexapro 20 mg free shipping, darbepoetin) discount 5 mg lexapro otc. Such excursions are associated with ad- verse events and considered to contribute to further deterio- ration of cardiac and renal functions buy generic lexapro 5mg on-line. It is believed that less fre- quent administrations represent a significant gain in quality of life for patients but also allow overworked nephrologists and nurses to concentrate on the other serious medical conditions affecting many of these patients such as hypertension, diabetes, chronic heart failure and obesity. The principle of Improved efficacy of proteins can be achieved pegylation: Pegasys with the help of specific modifications. It is essential to select the proper moiety that will confer Main avenues of research 43 to the active protein the de- A pegylated protein: Pegasys sired properties. The choice of linker is also very impor- tant as its rigidity (or lack thereof) will influence the ultimate properties of the new medicine. Roche has successfully applied this principle to develop a drug for the treatment of hepati- tis C and B. In this method the drug is enveloped in one or two highly branched molecules of polyethylene glycol. It has been used for de- cades for treating hepatitis C, a widespread infection which causes inflammation of the liver. To date no treatment exists that is able to eradicate the hepatitis C virus from the body. As a result, drug levels in the patients’ blood- stream undergo significant fluctuations in a two-day rhythm, giving rise to side effects and limit efficacy. It is also considered that fluctuation is instrumental promoting the appearance of resistant viruses. Thanks to a carefully selected pegylation with the appropriate bond with the protein,Pegasys is broken down much more slow- ly than simple interferon and therefore remains active in the body longer. This has several advantages for patients: Firstly, Pegasys only has to be given once weekly. Secondly, the dose does not have to be adjusted gradually – at least not to the same degree – according to the patient’s age, hepatic status and renal function, a time-consuming process. Thirdly, interferon levels in the bloodstream are subject to less fluctuation, making the side effects more tolerable and improving patient compliance. First approved in 2002, Pegasys quickly became the internation- al market leader in the hepatitis C sector. The drug was also the first pegylated therapeutic protein in the world to be approved for the treatment of chronic hepatitis B. A new drug class: Therapeutic antibodies form a relatively new therapeutic antibodies drug class that was only made possible by modern biotechnology. These Y-shaped proteins bear on their two short arms two identical regions that recognise a specific foreign structure. The long stem of the molecule interacts with other components of the immune sys- tem, which then initiate destruction of the intruders. In 1972 César Milstein and Georges Köhler, who later received the Nobel Prize, found a way to produce copies of identical antibody molecules in unlimited amounts. Within a few years these so-called monoclonal antibodies had revolutionised bio- logical research, allowing any desired molecule to be reliably identified and marked. However, it took more than 20 years for monoclonal antibodies to find widespread use in therapy. Not until the late 1990s did researchers succeed in exploiting the specificity of monoclonal antibodies for therapeutic purposes. For example, monoclonal antibodies can be designed to bind to specific molecules and block their disease-causing effects. However, drug developers were unable to use antibodies ob- tained from standard mammalian (usually mouse) cells. Because the molecules differ in structure from one species to the next, mouse antibodies proved to be of very limited benefit in humans. Re- searchers therefore turned their attention to what are known as chimeric and humanised antibodies, where only the recognition regions are based on mouse genes. It is now possible to insert all the human genes required to produce antibodies into laboratory Main avenues of research 45 A new drug class: therapeutic antibodies Mouse Chimeric Humanised Human Each antibody bears on its two short arms identical regions render them harmless. Whereas early therapeutic anti- that recognise a specific foreign structure, to which they bodies were still partly derived from mouse genes (yellow bind.

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Once perforation has occurred there is r Under general anaesthetic the abdomen is opened migration of the bacteria into the peritoneum (peritoni- by an incision along the skin crease passing through tis) buy lexapro 10mg amex. Theoutcomedependsontheabilityoftheomentum McBurney’s point (one third of the distance from a and surrounding organs to contain the infection buy 10 mg lexapro visa. The muscle fibres in each muscle layer Clinical features are then split in the line of their fibres (grid iron in- This is a classic cause of an acute abdomen cheap lexapro 5mg mastercard. The mesoappendix is divided with ligation of tially periumbilical generic 20 mg lexapro amex, then migrates to the right iliac fossa. The appendix is ligated at its There is mild to moderate fever, nausea and anorexia. The wound is then ment of the disease may be over hours to days partly closed in layers. In most cases, the appendix is tally particularly if the omentum is wrapped around the removed to avoid confusion if patients ever re-present appendix, or an abscess has formed. Macroscopy Prognosis The appendix appears swollen and the surface vascula- Uncomplicated appendicitis has an overall mortality of ture is yellow. Microscopy Meckel’s diverticulum Initially there is acute inflammation of the mucosa, which undergoes ulceration. As the condition progresses the inflammation An ileal diverticulum occurring as a result of persistence spreads through the wall until it reaches the serosal sur- of part of the vitellointestinal duct. Chapter 4: Disorders of the small bowel 165 Incidence due to ulceration of the adjacent ileum. Age Investigations Congenital Presence of gastric mucosa can be detected by scintiscan- ning with 99mTc labelled sodium pertechnetate, which is Sex taken up by parietal cells (the Meckel’s scan). Persistence of the Malabsorption syndromes ductmayresultinaMeckel’sdiverticulum(persistenceof Absorption of food occurs within the small bowel. The the ileal end of the duct), an umbilical sinus (persistence process involves breakdown of macromolecules by en- of the umbilical end of the duct) or an umbilical ileal zymes and transport across the specialised small bowel fistula (see Fig. The most common causes of Pathophysiology malabsorption are pancreatic insufficiency, coeliac dis- The diverticulum arises from the antimesenteric border ease, resection of the ileum, Crohn’s disease and liver of the ileum 2 ft from the ileocaecal valve and is on aver- disease (see Fig. Acid secreting gastric mucosa is found in 50% of cases which may result in Coeliac disease ulceration of the surrounding mucosa. Clinical features Ninety-five per cent of cases are asymptomatic, symp- Incidence tomatic patients present most commonly with bleeding 1in2000. There is lymphocytic infiltration of the lamina propria, and an increase in intra-epithelial lymphocytes (which Geography bear the γδ eceptor). Loss of normal villous architecture Common in Europe, (1 in 300 in Ireland) rare in Black ranges from blunting (partial villous atrophy) to com- Africans. Aetiology Investigations Thought to be an autoimmune disease with genetic and r Serology: Screening by IgG gliadin and IgG anti- environmental components. Management Clinical features Aglutenfree diet leads to a restoration of normal villous Patients may present with irritability and failure to thrive structure and resolution of dermatitis herpetiformis (see in childhood, delayed puberty, short stature, or vomit- page 394). Haemoglobin and antiendomysial antibodies ing, diarrhoea, anorexia or abdominal distension at any may be checked at routine follow-up to look for inad- age. Complications Whipple’s disease There is an association with development of small bowel lymphomaandasmallincreasedriskinthedevelopment Definition of small bowel adenocarcinoma. Chapter 4: Inflammatory bowel disease 167 Aetiology Disorders of the large bowel Caused by an infection by Tropheryma whippelii,anacti- and inflammatory bowel nomycete. Diverticular disease Clinical features Patients present with steatorrhoea, abdominal pain and Definition systemicsymptomsoffever,weightloss,lymphadenopa- Adiverticulum is a mucosal out-pouching, diverticular thy and arthritis. Investigations and management Incidence Electron microscopy can demonstrate the organism. Tropical sprue Definition Aetiology AseveremalabsorptionsyndromeendemicinAsia,some Diverticulae are associated with high intraluminal pres- Caribbean islands and parts of South America. There is a relationship with a low fibre diet and Aetiology/pathophysiology chronic constipation.

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It will be many years before the virtual version of this easy peer connection can be fostered in the medical part of the Internet 10 mg lexapro free shipping, again in part due to medical-legal concerns buy lexapro 20 mg on-line. Medicine is so fragmented discount 10mg lexapro otc, and the knowledge base so diverse buy lexapro 10mg line, that a workable peer-to-peer so- lution to locating and retrieving medical knowledge seems unlikely to appear any time soon. In the meantime, the Internet will make it easier for physicians to communicate with each other and foster network relationships that extend beyond the walls of the specific institutions in which physicians practice. Groupware like Lotus Notes has long made it possible for clinical and research teams that are dispersed geograph- ically to work on common projects. Physicians’ natural curiosity and gregariousness seem likely to find new outlets in virtual collab- oration on the Internet. Medical journals have raced to make their content available to physicians and other subscribers online. When physicians subscribe to their service, which is called Cog- niQ, they list all of the medical journals they follow. Physicians can scan the new articles and choose those of interest to be archived in their box on the Unbound Medicine server, in abstract or full-text form. Physicians 83 Thus, questions that would have been lost end up getting an- swered and stored in an easily retrievable fashion. Over time, the server retains the entire stream of answers to questions and relevant journal articles as a personalized “knowledge archive,” making it unnecessary for the physician to retain the new knowledge in his or her memory. This service will evolve from being modem dependent to being wireless as it becomes more widely available. As this occurs, physicians will be freed from the need to return telephone calls or to give verbal orders, enabling them to practice medicine “anytime, anywhere. In many institutions, physician mistrust of hospital motivations and strategies is a dominant theme. Mistrust Although competitive tensions between physician-sponsored enter- prises and hospitals have contributed to this problem, many physi- cians view the hospital as a battleship whose wake is sufficient to swamp the small boats it operates. The fact that hospitals and physi- cians have completely separate information domains complicates the ability to implement new clinical information systems. The Hospital as Potential Information Source Hospitals are presently committing major capital resources to com- puterize both operations and clinical services. As argued above, physician practices, even many large groups, are capital poor and thus lag in automating their processes and services. It is entirely possible given the present course that hospitals will complete this Physicians 85 process a decade or more ahead of physicians, leaving what physi- cians “know” about their patients locked up in paper records and their memories. When physicians do automate, if no compatibility standards are set in advance, they will use incompatible software and be unable to move clinical information between their systems and those of the hospital. Optimal patient care would require that the clinical team be able to access important clinical information about a patient at any place and at any time. Because hospitals have capital, and physicians, generally speaking, do not, hospitals could be a potential source for modern digital clinical information systems, as well as patient care support tools like disease management, for their physicians. If hospitals could help bring about a shared record format across their medical staffs, it would be easier for physicians to send patient information to one another for consultative purposes. Historically, physicians have been extremely reluctant to permit hospitals access to their private practices. Many experiments by hos- pitals during the 1990s with salaried employment of physicians and with practice management support ended in costly failure. Physi- cians resisted installing inexpensive software that enabled them to perform remote order entry or retrieval of test results from hospi- tals because they thought it opened a portal that enabled hospital executives to understand their practice’s economics. Legal and Regulatory Barriers Besides the mistrust discussed above, legal and regulatory barriers make linking hospitals and physicians difficult. Federal Medicare regulations forbid hospitals from offering physicians anything of value (including software and services) if it would influence their patterns of hospital utilization. These statutes were intended to pre- vent hospitals from, in effect, bribing physicians to bring their pa- tients in. If compatible clinical software made it easier for physicians 86 Digital Medicine with a choice to use the facility that provided them the software, it might trigger fraud and abuse investigations. Tax laws provide another barrier to the sharing of clinical soft- ware between hospitals and physicians. The Internal Revenue Code and state laws forbid not-for-profit hospitals (recall that 85 percent of all community hospitals are not-for-profit) from giving physicians (or anyone else) anything of value.

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It is administered by dripping the ether onto a gauze square or piece of absorbent material held over face by a wire frame to prevent direct contact of the ether with the skin and to facilitate airflow order 5 mg lexapro with mastercard. The patient’s face and eyes should be covered with gauze to protect them – if available Vaseline should be applied to exposed skin generic lexapro 10 mg with amex. One common ether mask was the Schimmelbusch mask (figure 1) lexapro 5 mg online; this provides an example of what we are aiming for in making an improvised mask order lexapro 20 mg with visa. The ether is poured onto the gauze (you would need multiple layers) – the gauze should be saturated with ether. The gauze may need to be changed frequently as when the ether evaporates off as it causes “frost” to form on the gauze interfering with its effectiveness. Gauging the depth of anaesthesia with ether is an art in itself – when is the patient deep enough to begin the operation, how much to give them to keep them asleep, how not to give too much and kill the patient. But rough guidance over drip rates are given below (to give an idea of the pattern of increasing volume during the anaesthetic) slowly increasing depth of anaesthesia to reach a level where surgery can be performed and then reducing slightly as the body becomes more saturated with it. Ether Time (drops per minute) (minutes) 12 1 24 2 48 3 96 4-15 50 15-30 20-30 after 30 It is difficult to induce anaesthesia in an adult using the “open-drop” technique due to problems reaching high enough concentrations around the mask. This is essentially a metal column which sits over the mask, holding the vapour at a higher concentration close to the face which increases the concentrations being breathed in. It is also worth getting the patient used to the smell of ether first as it is highly potent and can cause coughing fits. It can take a considerable period for a patient to wake up after an ether anaesthetic. It is reasonable to stop administering it slightly before the operation is finished. Ether also causes excess production of secretions in respiratory system and this potentially can cause problems with breathing – where possible Atropine should be administered to prevent this from occurring. It tends to give a much smoother induction but also can cause more cardiovascular instability. Less is required than with ether; with chloroform the gauze is damp, with ether it’s saturated. This limits your options with light sources somewhat in that open flames are a potential hazard. It is possible to use ether safely - 107 - Survival and Austere Medicine: An Introduction with open flames if you have no alternatives by keeping the ether and naked flame as separate as possible and ensuring adequate ventilation. Provided there is air circulating the ether is going to very rapidly be diluted with the surround air. A certain concentration of ether is required to induce anaesthesia (about 5%) which exceeds the flammable concentration (about 1. A safe minimum distance to exposed flames would be 50 cm in a well-ventilated room but the process still carries a small risk. Static electricity from the operating team also provides a potential ignition source and should be considered. All in all – if you possibly can avoid using ether with naked flames – the risks probably outweigh the benefits. Physical therapy focuses on maintaining and rehabilitating musculoskeletal function – stretching, massage, and muscle-strengthening exercises. Occupational therapy is focused on rehabilitating people to perform the activities required to look after themselves – eating, dressing, and personal hygiene. It is beyond the scope of this book to discuss either in great detail – but if your goal is to rehabilitate a seriously injured or ill person back to full function within your community this aspect of care cannot be underestimated. Most communities will not be able to carry many people who cannot contribute meaningfully to the group. The goal of physical and occupation therapy is to maximise a patient’s physical functioning, and get them to a point where they can look after themselves, and contribute. If you have a group member who has suffered a serious injury or illness early on you should focus on what they are likely to be able to do and tailor their rehabilitation to being able to perform that role.

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