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Angina of effort (moderate to low tolerance to physical exertion): · Aspirin, 150 mg orally once a day. Add beta-adrenergic blockers or calcium channel blockers, as well as one of the following drugs: · isosorbide dinitrate, 10 mg orally 3 times a day, or · isosorbide mononitrate, 60 mg orally once a day. Clinical Practice Guidelines for General Practitioners 21 Chest Pain Unstable angina Hospitalization is indicated. Then coronary angiography is performed and decision is made as to whether balloon coronary angioplasty or coronary bypass surgery is indicated. The above treatment scheme used in exertional angina may be supplemented by calcium antagonists: · nifedipine, 20 mg orally 2-3 times a day (drug of choice), or · verapamil, 40-160 mg orally 2-3 times a day, or · diltiazem, 30-90 mg orally 4 times a day, or · amlodipine, 2. Myocardial infarction In myocardial infarction, pain lasts 15-20 minutes and does not respond to nitroglycerin. Painless forms of myocardial infarction are developed mostly in patients with diabetes mellitus, in the elderly, as well as in recurrent myocardial infarction. In case of suspected myocardial infarction, specialized emergency care should be provided, with subsequent cardiology referral. Aortic dissection Aortic dissection is characterized by sudden occurrence of very severe retrosternal pain. Diagnostic sign of importance is unequal pulse at carotid, radial, and femoral arteries. Aortic dissection is often complicated by occlusion of coronary and renal arteries, aortic insufficiency, and cardiac tamponade. In case of suspected aortic dissection, cardiologist should be called for organizing patient management, and emergency care should be provided. Pulmonary thromboembolism Pulmonary thromboembolism is accompanied by retrosternal pain, dyspnea, and syncope. In severe cases, hypotension, acute right ventricular failure, and cardiac arrest may develop. Lesions of the trunk and large branches of pulmonary artery often have fatal outcome. In 10% of cases, pulmonary thromboembolism is complicated by pulmonary infarction, which is manifested by pain worsened during respiration, and the spitting up of blood. Diagnosis of pulmonary thromboembolism presents great difficulties when the only sign is suddenly occurring dyspnea. In case of suspected pulmonary thromboembolism, specialized emergency care should be provided! Pericarditis Pericarditis is manifested by: · pain worsened by cough and deep breathing, and sometimes related to swallowing; · continuous squeezing retrosternal pain resembling angina; · throbbing pain in the cardiac area and left shoulder. Pneumothorax In case of suddenly occurring pain and dyspnea, pneumothorax should be considered, especially in patients with bronchial asthma and emphysema. Worsening of dyspnea and pain is indicative of tension pneumothorax; in this case, emergency pleural puncture is indicated. In case of suspected pneumothorax, pulmonology referral is indicated and emergency medical care should be provided. Pulmonary conditions Pleurodynia (pleurisy), caused by inflammation of pleura, often accompanies viral or bacterial respiratory infections. It may also occur in collagen 24 Clinical Practice Guidelines for General Practitioners Chest Pain vascular disorders. History suggesting pleurodynia includes acute onset of sharp pain associated with breathing or movement, sometimes accompanied by systemic symptoms of infection. A chest X-Ray should be obtained to exclude pneumonia, pleural effusion, or other intrathoracic processes. Gastrointestinal conditions Reflux esophagitis is characterized by burning retrosternal or epigastric pain radiating to the lower jaw. Pain occurs or worsens in recumbent position and front bend, especially after a meal; sleep is often disturbed. Post-prandial chest discomfort, especially if associated with radiation to the back or abdomen and accompanied by nausea, is suggestive of gallbladder disease.

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In the case of an academic medical center, such uses of the patented gene fragments and associations would be arguably commercial in nature because any test that was ultimately developed from these experiments would be offered as a laboratory-developed test. Even if this use somehow was not commercial, one could argue that the use of the gene fragment or association to develop a genetic test would not be eligible for the exemption because it would relate to the legitimate business of an academic medical center in developing clinically useful diagnostics that improve patient care. One jurist has observed that such limitations on research are at odds with the role of patents in disclosing knowledge: the purpose of a patent system is not only to provide a financial incentive to create new knowledge and bring it to public benefit through new products; it also serves to add to the body of published scientific/technologic knowledge. The requirement of disclosure of the details of patented inventions facilitates further knowledge and understanding of what was done by the patentee, and may lead to further technologic advance. The right to conduct research to achieve such knowledge need not, and should not, await expiration of the patent. Yet today the court disapproves and essentially eliminates the common law research exemption. The case did not involve the common law research exemption-instead, it was about the statutory research exemption, which is discussed in subsequent paragraphs of this report. This statutory exemption is found in the Hatch-Waxman Act and provides an exemption from patent infringement liability for using a patented invention for the purpose of developing and submitting information under a Federal law regulating drugs. In sum, it appears that test manufacturers are eager to develop-and clinicians are eager to use- multiplex tests, rather than single-gene tests, to carry out genetic testing. Patent claims on isolated genes and association patent claims, however, appear to have already created a thicket of intellectual property rights that may prevent innovators from creating these multiplex tests. Similar concerns arise when envisioning the clinical application of whole-genome sequencing. Such scenarios threaten to diminish the usefulness of these promising technologies and their application to patient care. The creation of a patent pool or clearinghouse is a possible, but uncertain, solution to the patent thicket facing multiplex tests and whole-genome sequencing. Such information would enable technology developers to more easily determine the necessary licenses for planned innovations. As multiplex testing and whole-genome sequencing become commonplace in medicine, challenges to innovators in obtaining access to licensing information may discourage the development of advanced tests and their application to medicine. Several public commenters were of the view that recent legal decisions have obviated any need for change; others suggested that the decisions did not alter what were viewed as existing threats to patient access. In that case, Judge Learned Hand held that adrenaline purified from a gland was patentable. In finding the invention patentable, Judge Hand reasoned that purified adrenaline differed "not in degree, but in kind" from the adrenaline 189 190 the case was decided in March 2010 after the approval of this report. No major opinion apparently has addressed whether the exclusion of laws of nature from patent-eligibility is constitutionally mandated, although this may be the case, because patents on laws of nature would not serve to promote the progress of useful arts. The isolation and purification exception to the general unpatentability of products of nature. Oysters and oligonucelotides: concerns and proposals for patenting research tools. Purification and isolation here refer not to absolute purity, but to the general absence of other large molecules and biological substances. Supreme Court considered a different inquiry: whether a living thing that did not occur naturally was patentable. A case that was closely watched by the biotechnology community, Charkrabarty concerned the patentability of a bacterium that had been genetically altered by introducing plasmids that enabled it to degrade oil. No case, however, has squarely considered the question of whether isolated, purified nucleic acid molecules are patentable subject matter. At least some cases before Parke-Davis that considered whether claimed inventions derived from nature were patentable found that they were not patentable-see, for example, American Wood-Paper Co. Even some cases after Parke-Davis found such inventions not to be patentable-see, for example, General Electric Co. Different perspectives on the evolution of "products of nature" jurisprudence can be found in Gipstein, op. Back to the future: rethinking the product of nature doctrine as a barrier to biotechnology inventions (Part I). Journal of the Patent & Trademark Office Society 85:371-398; and L Andrews and J Paradise. Paper presented at the Conference on Living Properties: Making Knowledge and Controlling Ownership in the History of Biology.

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Symptoms may worsen when patients are forced to receive medications at predetermined dosing times such as those used in hospitals and nursing homes. The patient states that the pain began several hours after eating a double-sized cheeseburger, french fries, and a chocolate milkshake at a local fast food restaurant. The pain intensified and was associated with escalating nausea followed by several episodes of vomiting. The vomiting finally ceased but the abdominal pain has persisted and is made worse after meals. Since the initial episode, his appetite has decreased and he has been avoiding fried or fatty foods. Practice parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review). What feasible pharmacotherapeutic alternatives are available for the treatment of acute pain? What economic, psychosocial, and ethical considerations are applicable to this patient? At the end of the first hospital day, the patient states that the medication "eases the pain some" but the pain is inadequately controlled, with each dose lasting only last about 2 hours. Describe the pathophysiology and management of opioidinduced respiratory depression. Describe the advantages and disadvantages of single and multidimensional pain assessment instruments. She has frequent complaints of joint pain after walking or other activities and experiences stiffness in the morning when she awakes or after sitting during bridge games. She lives at a retirement community that has multiple levels of care, from independent living to skilled nursing care. Narcotic analgesic effects on the sphincter of Oddi: a review of the data and therapeutic implications in treating pancreatitis. At her 2-week follow-up appointment the patient reported some pain relief but new complaints of dizziness. Considering that she describes her pain as 6 out of 10, would you alter your treatment plan? If this patient were to require an alternative therapy for osteoarthritis, what would you recommend? Long-acting opioids for chronic pain: pharmacotherapeutic opportunities to enhance compliance, quality of life, and analgesia. Antidepressants and anticonvulsants for diabetic neuropathy and postherpetic neuralgia: a quantitative systematic review. She states that she used to get about two migraines every month; however, she recently got divorced and started a new job. Since then, the frequency of her migraines has increased to about four to five per month. She states her migraines usually occur in the morning, and there is no identifiable relationship with her menses. Her typical headache evolves quickly (within 1 hour) and involves severe throbbing pain, which is unilateral and temporal in distribution and preceded by an aura, which consists of nausea and pastel lights flashing throughout her visual field. She reports experiencing severe migraine attacks that cause her to miss 2 days of work each month. She is not able to complete household chores for the 2 days she has severe migraine attacks, and she misses working out at the gym. She also complains of having mild migraine attacks lasting 3 days per month during which her productivity at work and at home is reduced by half. She typically has to retreat to a dark room and avoid any noise, or the severity of the migraine increases. She rates her migraines as 7­8 on a headache scale of 1­10, with 10 being the worst. At her previous visit to the Neurology Clinic 2 months ago, she was prescribed naratriptan 2.

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Changes in bronchial and pulmonary arterial blood flow with progressive tension pneumothorax. The clinical validity of normal compression ultrasonography in outpatients suspected of having deep venous thrombosis. Incidence of pericardial effusions in patients presenting to the emergency department with unexplained dyspnea. Assessment of left ventricular function and hemodynamics with transesophageal echocardiography. Atypical presentations and echocardiographic findings in patients with cardiac tamponade occurring early and late after cardiac surgery. Correlation between clinical and Doppler echocardiographic findings in patients with moderate and large pericardial effusions. Consecutive 1127 therapeutic echocardiographically guided pericardiocenteses: clinical profile, practice patterns and outcomes spanning 21 years. Superiority of visual versus computerized echocardiographic estimation of radionuclide left ventricular ejection fraction. Determination of left ventricular function by emergency physician echocardiography of hypotensive patients. Echocardiographic predictors of survival and response to early revascularization in cardiogenic shock. Diagnostic accuracy of identification of left ventricular function among emergency department patients with nontraumatic symptomatic undifferentiated hypotension. Outcome in cardiac arrest patients found to have cardiac standstill on bedside emergency department echocardiogram. Does the presence or absence of sonographically identified cardiac activity predict resuscitation outcomes of cardiac arrest patients? Use of transthoracic Doppler echocardiography combined with clinical and electrographic data to predict acute pulmonary embolism. Quantitative two dimensional echocardiography in massive pulmonary embolism: emphasis on ventricular interdependence and leftward septal displacement. Prospective evaluation of two dimensional transthoracic echocardiography in emergency department patients with suspected pulmonary embolism. Value of transthoracic echocardiography in the diagnosis of pulmonary embolism: results of a prospective study in unselected patients. Short term clinical outcome of patients with acute pulmonary embolism, normal blood pressure and echocardiographic right ventricular dysfunction. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolus. Noninvasive estimation of right atrial pressure from the inspiratory collapse of the inferior vena cava. Sonospirometry: a new method for noninvasive measurement of mean right atrial pressure based on two dimensional echocardiographic measurements of the inferior vena cava during measured inspiration. Respiratory changes in inferior vena cava diameter are helpful in predicting fluid responsiveness in ventilated septic patients. The respiratory variation in inferior vena cava diameter as a guide to fluid therapy. Trauma ultrasound examination versus chest radiography in the detection of hemothorax. Emergency department paracentesis to determine intraperitoneal fluid identity discovered on bedside ultrasound of unstable patients. Accidentally created tension pneumothorax in patient with primary spontaneous pneumothorax-confirmation of the experimental studies, putting into question the classical explanation. Occult traumatic pneumothorax: diagnostic accuracy of lung ultrasonography in the emergency department. Accuracy of transthoracic sonography in detection of pneumothorax after sonographically guided lung biopsy: prospective comparison with chest radiography. Rapid detection of pneumothorax by ultrasonography in patients with multiple trauma. A prospective comparison of supine chest radiography and bedside ultrasound for the diagnosis of traumatic pneumothorax.

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In general the standardized purified protein derivative intradermal test is used with evaluation by a health care provider 48 to 72 hours after injection. For most patients, Table 9-2 Lead Poisoning Risk Assessment Questions to be Asked between 6 Months and 6 Years Children and adolescents who have a family history of cardiovascular disease or have at least one parent with a high blood cholesterol level are at increased risk of having high blood cholesterol levels as adults and increased risk of coronary heart disease. Total cholesterol of less than 170 mg/dL is normal, 170 to 199 mg/dL is borderline, and greater than 200 mg/dL is elevated. Sexually Transmitted Infection Testing Does the child spend any time in a building built before 1960. Is there a brother, sister, housemate, playmate, or community member being followed or treated (or even rumored to be) for lead poisoning? Does the child live with an adult whose job or hobby involves exposure to lead. Does the child live near an active lead smelter, battery recycling plant, or other industry likely to release lead? A full adolescent psychosocial history should be obtained in confidential fashion (see Section 12). Part of this evaluation is a comprehensive sexual history that often requires creative questioning. Not all adolescents identify oral sex as sex, and some adolescents misinterpret the term sexually active to mean that one has many sexual partners or is very vigorous during intercourse. Young women should be assessed for human papillomavirus and precancerous lesions by Papanicolaou smear at 21 years of age. Children and adolescents who have a family history of high cholesterol or heart disease 2. Pediatricians may identify gross abnormalities, such as large caries, gingival inflammation, or significant malocclusion. All children should have a dental examination by a dentist at least annually and a dental cleaning by a dentist or hygienist every 6 months. Dental health care visits should include instruction about preventive care practiced at home (brushing and flossing). Other prophylactic methods shown to be effective at preventing caries are concentrated fluoride topical treatments (dental varnish) and acrylic sealants on the molars. Pediatric dentists recommend beginning visits at age 1 year to educate families and to screen for milk bottle caries. Fluoridation of water or fluoride supplements in communities that do not have fluoridation are important in the prevention of cavities (see Chapter 127). All children younger than 13 years should be restrained in the rear seats of vehicles for optimal protection. This is specifically to protect them from airbags, which may cause more injury than the crash in young children. A dietary history should be obtained because the content of the diet may suggest a risk of nutritional deficiency (see Chapters 27 and 28). Anticipatory guidance that is age relevant is another part of the Bright Futures guidelines. Bright Futures has a "toolkit" that includes the topics and one-page handouts for families (and for older children) about the highest yield issues for the specific age. It is important to review briefly the safety topics previously discussed at other visits for reinforcement. Safety Issues the most common cause of death for infants 1 month to 1 year of age is motor vehicle crashes. No newborn should be discharged from a nursery unless the parents have a functioning and properly installed car seat. Many automobile dealerships offer services to parents to ensure that safety seats are installed properly in their specific model. Most states have laws that mandate use of safety seats until the child reaches 4 years of age or at least 40 pounds in weight. The following are ageappropriate recommendations for car safety: · Infants and toddlers should ride in a rear-facing safety seat until they are 2 years of age, or until they reach the highest weight or height allowed by the safety seat manufacturer.

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Using both arms for support, the patient should stand up and bend their torso forward as far as possible, until the joints are extended to the locked position. Therapeutic Application and Gait Training Ottobock 25 Sitting down with the FreeWalk orthosis Two different ways of sitting down that can be practised in daily life. This method is particularly safe and is appropriate for situations in which the patient has to concentrate on the surface of the seat. The lock cannot be manually released on FreeWalk orthoses which have the three-phase switch installed. With their hand on the side of the orthosis, the patient can then press the button on the knee joint to unlock the knee. This causes pre-tension of the orthosis-side knee joint and ankle joint which are in extension and dorsiflexion respectively. With a light rocking movement, the patient can then unlock the knee joint and sit down. All exercises should be repeated several times with the assistance of the therapist. Please note that not every Free Walk user is suited to the dynamic method, or indeed is comfortable using this method of sitting down. Nevertheless, this method offers the advantages of being safe and gentle on the body. As with the FreeWalk orthosis, this method is appropriate for situations in which the patient has to concentrate on sitting down. Before releasing the knee joint, the patient must be in a position with the knee extended. Some patients are able to extend their knees in a normal stance, but other patients have to consiously make a knee-extending movement. As with the FreeWalk orthosis, the movement should be practised with the help of the therapist to enable the patient to get accustomed to it. With enough practice and if there is some remaining muscle function, it may be possible to sit down with both joints opened. To prevent abnormal movements when the first steps are being taken, balancing exercises should be practised to determine the best possible weight-distribution on the supported limb. Posture is the ideal alternative to the inevitably inaccurate scales normally used for checking for correct weight distribution. With the help of the visualised load-line and the hand-held control unit, the therapist or orthotist can give the patient precise instructions for movements in order to determine the position of optimum load assumption. Following this exercise the patient must practise standing on two legs stably and with uniform weight distribution. StabilisingExercise: the clinician applies a resisting force to the shoulder and/or pelvic girdle to help the patient practise achieving a stable stance. Therapeutic Application and Gait Training Ottobock 29 Stabilising exercises outside the parallel bars these exercises are to be carried out with the legs in parallel or in stride position to involve the various muscle groups of the trunk and lower limbs. Practising initial heel contact up to the stance phase If possible, the exercises for the individual step cycles should be done between the parallel bars. The parallel bars give patients an increased sense of security, allowing them to better concentrate on the exercises. The individual step cycles should be repeated several times independently of each other, until the movements become routine for the user. The first exercise teaches the patient to place trust in the function of the orthosis in the stance phase. This is performed using either the residual functions of the hip flexors or a tilting movement of the pelvis. Upon weight-bearing, the patient should try to unload the contralateral leg completely. Then, to practise the transition from the midstance phase to the terminal phase, the patient unlocks the orthosis. At the beginning of the exercise, the therapist should guide the affected leg during the swing phase to give the patient a feel for the correct step length.

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In some nations indigenous peoples have been marginalized, and have poor health and live in poverty. Indigenous peoples are threatened, with either extinction or assimilation, as the rest of the world continues to expand. This was the case for the Huaorani Indians of Ecuador and Peru, who live in the Amazon rainforest (see photo, top). We know little about their genetics, but we do know that they suffer from infections brought in by the missionaries, and skin disorders, hair loss, and sore throats thanks to pollution from the oil industry. Human Ancestry © the McGraw-Hill Companies, 2010 (Continued) knew to be dangerous to people who had had no contact with the outside world. Hundreds of Yanomami died, as Neel prevented anyone from helping them-he supposedly wanted to observe the effects of introducing an infectious disease to an isolated group. Blood was sampled from the Yanomami for comparison to other modern populations to assess genetic diversity, but the people were not informed that the this Maasai chief wears the samples might be used in research traditional headware and after their deaths. The controversy continues as the people attempt to take back their blood samples from research labs. Geneticists have attempted to describe the genetic diversity among nine indigenous groups in Africa, but so far have not been able to distinguish them. The man in the photo (right) is a chief of a Maasai tribe, who live in Kenya and Tanzania and are one of the nine groups being studied. The Maasai have low body weight and blood pressure, and excellent lipid profiles, despite a very fatty diet. Their healthy hearts and blood vessels are likely due more to their very active nomadic lifestyle than to inheriting protective gene variants, researchers think. The most celebrated case was that of the Yanomami, who live near streams in southern Venezuela and northern Brazil. In 1968, a team of anthropologists led by geneticist James Neel gave the Yanomami a measles vaccine that they Questions for Discussion 1. Read reviews of the book and discuss what the research team did, and whether or not you think their actions were justified. The more alike a gene or protein sequence is in two species, the more closely related the two are presumed to be-that is, the more recently they shared an ancestor. Knowing the mutation rates for specific genes provides a way to measure the passage of time-a sequence-based molecular clock, of sorts. The mutant gene is very similar in sequence in cats, horses, mice, and minks, who have light coats and eyes and are deaf. The related species presumably inherited the gene from a shared ancestor, and a change in that gene would not persist in a population unless it provided a selective advantage. At the same time, natural selection weeded out proteins that did not promote survival to reproduce. The inset shows the corresponding information on the stylized version of a tree in figure 16. In contrast, some genome regions that vary widely among species do not affect the phenotype, and are therefore not subject to natural selection. Complementary pieces bind, and some hybrid molecules form, with one strand of the double helix from one species, the other from the other species. The premise is that the higher the temperature required to separate hybrid double helices, the more of the sequence is shared, because more complementary base pairs attract (figure 16. Genome similarity can be estimated by tracking "indels," which stands for "insertions and deletions. If small insertions and deletions that distinguish the human and chimp versions of the same gene are considered, then our degree of genome similarity is only about 96. The degree of similarity may even be as low as 94 percent if sequences not in the human genome are considered. A mutation in mice (a), cats (b), humans (c), and other types of mammals causes light eye color, hearing or other neurological impairment, and a fair forelock. Human Ancestry © the McGraw-Hill Companies, 2010 * * Chimp A T C G T A T A C G T A G C T A G C T A A T C G C G G C Human A T C G T A T A C G A T G C T A G C T A A T A T C G G C * * * * * Chicken A T C G A T T A C G C G G C T A G C T A G C C G G C G C actually have great effects on appearance, physiology, and development.

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Identify the advantages of using lorazepam in status epilepticus, and perform a literature search to identify articles that support its use over diazepam. Write a concise paper outlining the proper procedure for administering Diastat to a person in status epilepticus. Prepare a short paper summarizing the hematologic adverse effects of all of the antiepileptic drugs. Women with epilepsy who take antiepileptic drugs may consider self-discontinuing their medication when they become (or want 160 to become) pregnant. Describe the potential risks to the mother and baby from antiepileptic drugs and from uncontrolled seizures. Witnesses report that he was initially lethargic and in severe pain at the scene and has become progressively less responsive since the incident. Intravenous valproate is well tolerated in unstable patients with status epilepticus. Upon painful stimuli, he does not speak or open his eyes but does exhibit extensor posturing. The left pupil is 6 mm and nonreactive, and the right pupil is 3 mm and slowly reactive. Inspection and palpation around the eyes reveal multiple orbital fractures with crepitus. The head has an open 4-cm scalp laceration over the left frontal region of the skull with some swelling. Discuss the therapeutic management of traumatic brain injury and increased intracranial pressure associated with acute brain injury. Recommend appropriate therapy to prevent medical complications after brain injury. Ext No non-traumatic edema is noted Neuro There is no response other than extensor posturing to pain 161 н Labs Na 132 mEq/L K 3. What is the role of corticosteroids and nimodipine as neuroprotective therapies in patients with traumatic brain injury? There is evidence of subarachnoid blood within the sulci of the frontal and parietal regions. Outline a pharmacotherapeutic plan for prevention of medical complications that may occur in this patient. What medication education should this patient receive if he is discharged on phenytoin? Review the different types of neurologic monitoring devices that are available and how drug therapy might influence these monitoring parameters. Evaluate the role of serum biomarkers in predicting outcome after traumatic brain injury. Review the guidelines for managing the neurobehavioral sequelae of traumatic brain injury. Does this patient have any factors that may complicate assessment of the neurologic examination? Effect of nimodipine on outcome in patients with traumatic subarachnoid haemorrhage: a systematic review. Propofol in the treatment of moderate and severe head injury: a randomized, prospective doubleblinded pilot trial. What are the goals of fluid resuscitation and hemodynamic monitoring for this patient? What therapeutic alternatives are available for fluid resuscitation, and which would be the most appropriate for this patient? Intensive insulin therapy reduces microdialysis glucose values without altering glucose utilization or improving the lactate/pyruvate ratio after traumatic brain injury. A randomized, doubleblind study of phenytoin for the prevention of post-traumatic seizures. Intracranial hypertension and cerebral perfusion pressure: influence on neurological deterioration and outcome in severe head injury. Cerebral blood flow and metabolism in severe brain injury: the role of pressure autoregulation during cerebral perfusion pressure management. Comparing the bispectral index and suppression ratio with burst suppression of the electroencephalogram during pentobarbital infusions in adult intensive care patients.


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