By T. Tom. Westminster Theological Seminary in California.

This is particularly important in radiation therapy deltasone 5 mg amex; the only application of radiation in which very high radiation doses are deliberately given to patients to achieve cure or palliation of disease order 40mg deltasone mastercard. Notwithstanding the above, disseminating lessons learned from serious incidents is necessary but not sufficient when dealing with new technologies. It is of the utmost importance to be proactive and continually strive to answer questions such as: ‘What else can go wrong? While the recommendations specifically apply to new external beam therapies, the general principles for prevention are applicable to the broad range of radiotherapy practices in which mistakes could result in serious consequences for the patient and practitioner. The recommendations provide elements for mobilizing for future effective work as outlined below. Independent verification should be performed of beam calibration in beam radiation therapy. Independent calculation should be performed of the treatment times and monitor units for external beam radiotherapy. Prospective safety assessments should be undertaken for preventing accidental exposures from new external beam radiation therapy technologies, including failure modes and effects analysis, probabilistic safety assessment, and risk matrix, in order to develop risk informed and cost effective quality assurance programmes. Moderated electronic networks and panels of experts supported by professional bodies should be established in order to expedite the sharing of knowledge in the early phase of introducing new external beam radiation therapy technologies. A collaborating team of specifically trained personnel following quality assurance procedures is necessary to prevent accidents. Maintenance is an indispensable component of quality assurance; external audits of procedures reinforce good and safe practice, and identify potential causes of accidents. Accidents and incidents should be reported and the lessons learned should be shared with other users to prevent similar mistakes. The available data on doses received by people approaching patients after implantation show that, in the vast majority of cases, the dose to comforters and carers remains well below 1 mSv/a. Moreover, due to the low activity of an isolated seed and its low photon energy, no incident/accident linked to seed loss has ever been recorded. A review of available data shows that cremation can be allowed if 12 months have elapsed since 125 103 implantation with I (3 months for Pd). If the patient dies before this time has elapsed, specific measures must be undertaken. However, although the therapy related modifications of the semen reduce fertility, patients must be aware of the possibility of fathering children after such a permanent implantation, with a limited risk of genetic effects for the child. Patients with permanent implants must be aware of the possibility of triggering certain types of security radiation monitor. Considering the available experience after brachytherapy and external irradiation of prostate cancer, the risk of radio-induced secondary tumours appears to be extremely low, but further investigation might be helpful. Only the (rare) case where the patient’s partner is pregnant at the time of implantation may need specific precautions. Specific recommendations should be given to patients to allow them to deal adequately with this event. As far as cremation of bodies is concerned, consideration should be given to the activity that remains in the patient’s ashes and the airborne dose, potentially inhaled by crematorium staff or members of the public. Specific recommendations have to be given to the patient to warn the surgeon in case of subsequent pelvic or abdominal surgery. The wallet card including the main information about the implant (see above) may prove to be helpful in such a case of triggering certain types of security radiation monitor. The risk of radio-induced secondary tumours following brachytherapy should be further investigated. Avoidance of radiation injuries from medical interventional procedures Interventional radiology (fluoroscopically guided) techniques are being used by an increasing number of clinicians not adequately trained in radiation safety or radiobiology. Many of these interventionists are not aware of the potential for injury from these procedures or the simple methods for decreasing their incidence. Many patients are not being counselled on the radiation risks, nor followed up when radiation doses from difficult procedures may lead to injury. Some patients are suffering radiation induced skin injuries and younger patients may face an increased risk of future cancer. Interventionists are having their practice limited or suffering injury, and are exposing their staff to high doses. In some interventional procedures, skin doses to patients approach those experienced in some cancer radiotherapy fractions. Injuries to physicians and staff performing interventional procedures have also been observed. Acute radiation doses (to patients) may cause erythema, cataract, permanent epilation and delayed skin necrosis. Protracted (occupational) exposures to the eye may cause opacities in the crystalline lens.

Cultivation of rat marrow-derived mesenchymal stem cells in reduced oxygen tension: effects on in vitro and in vivo osteochondrogenesis cheap deltasone 20mg online. Incubation of murine bone marrow cells in hypoxia ensures the maintenance of marrow-repopulating ability together with the expansion of committed progenitors cheap deltasone 10mg mastercard. Extensive in vivo angiogenesis following controlled release of human vascular endothelial cell growth factor: implications for tissue engineering and wound healing. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Role of vascular endothelial growth factor in bone marrow stromal cell modulation of endothelial cells. The role of bone grafting in the treatment of delayed unions and nonunions of the tibia. The osteogenic potential of culture-expanded rat marrow mesenchymal cells assayed in vivo in calcium phosphate ceramic blocks. Bone formation in vivo: comparison of osteogenesis by transplanted mouse and human marrow stromal fibroblasts. Culture expanded canine mesenchymal stem cells possess osteochondrogenic potential in vivo and in vitro. The effect of implants loaded with autologous mesenchymal stem cells on the healing of canine segmental bone defects. Autologous bone marrow stromal cells loaded onto porous hydroxyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones. Healing of segmental bone defects with granular porous hydroxyapatite augmented with recombinant human osteogenic protein-1 or autologous bone marrow. Repair of large bone defects with the use of autologous bone marrow stromal cells. The use of percutaneous autologous bone marrow transplantation in non-union and concentration of progenitor cells. Percutaneous bone marrow grafting of delayed union and nonunion in cancer patients. The use of percutaneous autologous bone marrow transplantation in non-union and concentration of progenitor cells. Bensaid W, Oudina K, Viateau V, Potier E, Bousson V, Blanchat C, Sedel L, Guillemin G, Petite H. De novo reconstruction of functional bone by tissue engineering in the metatarsal sheep model. Analysis of ectopic and orthotopic bone formation in cell-based tissue-engineered constructs in goats. Successful healing of Refractory Tibial Non-union by combined Calcium Sulphate and Stromal Cell Implantation. Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage, and lung in irradiated mice. Mesenchymal stem cells are capable of homing to the bone marrow of non-human primates following systemic infusion. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta. Microfracture technique for full- thickness chondral defects: technique and clinical results. Results after microfracture of full-thickness chondral defects in different compartments in the knee. Repair of human articular cartilage after implantation of autologous chondrocytes. Relationship between cell shape and type of collagen synthesized as chondrocytes lose their cartilage phenotype in culture. Mesenchymal cell- based repair of large, full-thickness defects of articular cartilage. Autologous bone marrow stromal cell transplantation for repair of full-thickness articular cartilage defects in human patellae: two case reports. Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees. Reduced chondrogenic and adipogenic activity of mesenchymal stem cells from patients with advanced osteoarthritis. Caridiomyocytes of noncardiac origin in myocardial biopsies of human transplanted hearts. Transitional cell carcinoma of the bladder following augmentation cystoplasty for the neuropatic bladder. Metabolic consequences and long-term complications of enterocystoplasty in children: a review. Bladder regeneration by bladder acellular matrix combined with sustained release of exogenous growth factor.

When the patient sits on the edge of the examination table buy deltasone 10mg overnight delivery, the left knee can be displaced anteriorly at an abnormal degree buy generic deltasone 5 mg online. A 70-year-old man is brought to the emergency department because of a 1-week history of increasingly severe left-sided lower abdominal pain and passing gas in his urine. A 60-year-old man has tenderness in the region distally between the tendons of the extensor pollicis longus and extensor pollicis brevis (anatomical snuffbox) after falling on the palm of his right hand. A 20-year-old man is brought to the emergency department 1 hour after he was involved in a motorcycle collision. On auscultation, a harsh continuous murmur is heard at the left of the sternum between the first two ribs. Arterial blood oxygen content is slightly higher in the right hand than in the left hand. A 50-year-old woman is brought to the emergency department because of severe upper abdominal pain for 24 hours. Physical examination shows jaundice and tenderness of the right upper quadrant of the abdomen. Serum studies show a bilirubin concentration of 5 mg/dL, alkaline phosphatase activity of 450 U/L, and lipase activity of 400 U/L (N=14–280). A 6-year-old boy is brought to the physician by his parents for a follow-up examination because of a heart murmur that has been present since birth. A grade 3/6 pansystolic murmur is heard maximally at the lower left to mid left sternal border. He undergoes cardiac catheterization and is found to have a higher than expected oxygen level in the right ventricle. A 32-year-old woman, gravida 2, para 2, develops fever and left lower abdominal pain 3 days after delivery of a full-term male newborn. During a study of bladder function, a healthy 20-year-old man drinks 1 L of water and delays urination for 30 minutes after feeling the urge to urinate. C - 23 - Histology Systems General Principles of Foundational Science 30%–35% Biochemistry and molecular biology Biology of cells (excludes signal transduction) Apoptosis Cell cycle and cell cycle regulation Mechanisms of dysregulation Cell/tissue structure, regulation, and function Biology of tissue response to disease Pharmacodynamic and pharmacokinetic processes Immune System 1%–5% Blood & Lymphoreticular System 1%–5% Nervous System & Special Senses 5%–10% Skin & Subcutaneous Tissue 1%–5% Musculoskeletal System 1%–5% Cardiovascular System 1%–5% Respiratory System 1%–5% Gastrointestinal System 5%–10% Renal & Urinary System 5%–10% Pregnancy, Childbirth, & the Puerperium 1%–5% Female Reproductive System & Breast 1%–5% Male Reproductive System 1%–5% Endocrine System 5%–10% - 24 - 1. Which of the following changes is most likely to occur in the endometrium after 1 year of treatment? Which of the following muscle cell components helps spread the depolarization of the muscle cell membranes throughout the interior of muscle cells? A new drug is developed that prevents the demyelinization occurring in the progress of multiple sclerosis. The drug protects the cells responsible for the synthesis and maintenance of myelin in the central nervous system. Tissue remodeling begins at this site with degradation of collagen in the extracellular matrix by which of the following proteins? A 22-year-old man is brought to the emergency department in respiratory distress 15 minutes after he was stung on the arm by a wasp. His pulse is 100/min, respirations are 30/min, and blood pressure is 100/60 mm Hg. Secretion of the molecule causing this patient’s symptoms is most likely mediated by which of the following? He is informed that he will require treatment with intramuscular vitamin B12 (cyanocobalamin) for the rest of his life. This therapy is necessary because this patient lacks which of the following types of cells? Beginning with protein synthesis in membrane-bound ribosomes, hepatocytes secrete proteins into the circulation via which of the following mechanisms? Which of the following is required to transport fatty acids across the inner mitochondrial membrane? An experiment is conducted in which the mitochondrial content of various tissues is studied. It is found that the mitochondrial content is directly proportional to the amount of energy one cell is required to generate and expend. The mitochondrial content is most likely greatest in which of the following types of cells? A 45-year-old man without a history of bleeding or excessive bruising dies suddenly due to rupture of an aortic dissection. A 42-year-old woman comes to the physician for a follow-up examination after two separate Pap smears have shown dysplastic epithelial cells. The viral E6 protein binds to the cellular p53 tumor suppressor gene, causing it to be degraded. Which of the following best describes the mechanism by which the E6 protein causes cervical cancer? Which of the following is the correct sequence of events in the initiation of contraction of a skeletal muscle fiber? Conformational Release of Ca2+ from Change in Acetylcholine Depolarization Troponin-Tropomyosin Sarcoplasmic Propagation into Binding to of Sarcolemma Complex Reticulum Transverse Tubules Receptors (A) 1 2 3 4 5 (B) 2 5 4 3 1 (C) 3 5 2 4 1 (D) 4 2 5 3 1 (E) 5 3 4 1 2 14. A 90-year-old woman is brought to the emergency department 30 minutes after she fell while climbing the steps into her house.

There are other situations when the presenting history and physical are much more vague purchase deltasone 5 mg online. In these cases buy discount deltasone 5 mg on-line, it is likely that the total pretest probability can add up to more than 100%. This occurs because of the desire on the part of the physi- cian not to miss an important disease. Therefore, each disease should be con- sidered by itself when determining the probability of its occurrence. This proba- bility takes into account how much the history and physical examination of the patient resemble the diseases on the differential diagnosis. The assigned proba- bility value based on this resemblance is very high, high, moderate, low, or very low. In our desire not to miss an important disease, probabilities that may be much greater than the true prevalence of the disease are often assigned to some diagnoses on the list. Physicians must take the individual patient’s qualities into consideration when assigning pretest probabilities. For example, a patient with chest pain can have coronary artery disease, gastroesophageal reflux disease, panic disorder, or a combination of the three. In general, panic disorder is much more likely in a 20- year-old, while coronary artery disease is more likely in a 50-year-old. When con- sidering this aspect of pretest probabilities, it becomes evident that a more real- istic way of assigning probabilities is to have them reflect the likelihood of that disease in a single patient rather than the prevalence in a population. This allows the clinician to consider the unique aspects of a patient’s history and physical examination when making the differential diagnosis. Constructing the differential diagnosis The differential diagnosis begins with diseases that are very likely and for which the patient has many of the classical symptoms and signs. Next, diseases that are pos- sible are included on the list if they are serious and potentially life- or limb- threatening. These are the active alternatives to the working diagnoses and must be ruled out of the list. This means that the clinicians must be relatively certain from the history and physical examination that these alternative diagnoses are not present. Put another way, the pretest probability of those alternative diseases is so vanishingly small that it becomes clinically insignificant. If the history and physical examination do not rule out a diagnosis, then a diagnostic test that can reliably rule it out must be performed. Diseases that can be easily treated can also be included in the differential diagnosis and occasionally, the diagnosis is con- firmed by a trial of therapy, which if successful, confirms the diagnosis. Last to be included are diseases that are very unlikely and not serious, or are more difficult and potentially dangerous to treat. These diseases are less possible because they 224 Essential Evidence-Based Medicine Fig. A good example of this would be a patient with chest pain and no risk factors for pulmonary embolism who has a low transcu- taneous oxygen saturation. Now one should begin to look more closely for the diagnosis of pulmonary embolism in this patient. When considering a diagnosis, it is helpful to have a framework for consid- ering likelihood of each disease on one’s list. This only helps to get an overview and does not help one determine the pretest probability of each disease on the differential diagnosis. In this schema, each disease is considered as if the total probability of disease adds up to 100%. One must tailor the probabilities in one’s differential diagnosis to the individ- ual patient. Bear in mind that a patient is more likely to present with a rare or unusual presentation of a common disease, than a common presentation of a rare disease. As stated earlier, the first step in generating a differential diagnosis is to sys- tematically make a list of all the possible causes of a patient’s symptoms. This skill is learned through the intensive study of diseases and reinforced by clinical experience and practice. When medical students first start doing this, it is useful to make the list as exhaustive as possible to avoid missing any diseases. Think of all possible diseases by category that might cause the signs or symptoms. There are several helpful mnemonics that can help get a differential diagnosis started. The values of pretest probability are relative and can be assigned according to the scale shown in Table 20.

In such a setting discount 40mg deltasone with visa, Society does not appreciate a self-protective collegiality that a collegial faculty would be one that values a commitment to circles the wagons around questionable professional behav- the sharing of knowledge generic 10 mg deltasone with visa. And so it is important to remember that, like everyone else, physicians get sick and grow old, and that in the process their competence can be compromised. As is discussed elsewhere in this handbook, certain aspects of the culture of medicine, together with typi- cal attributes that otherwise hold physicians in good stead, can make physicians reluctant to admit when they fnd themselves in diffculty. However, the physician’s responsibility to maintain his or her own health in order to practise safely also extends to a collegial duty to be aware of the health and ftness of others. Case resolution In the past, ill physicians, worried that their medical licence It is important for any organization or group to cultivate might be put in jeopardy, remained silent until a complaint was collegiality and mentorship. In this case, rumours are reported to a regulatory body or an adverse event occurred. The resident Even now, despite the availability of organized physician health might have a substance use disorder, a signifcant depres- programs in every Canadian province to assist physicians in sion, an adjustment disorder or some other reason for the diffculty, we cannot ignore our collegial responsibility to sup- apparent change in behaviour. Nor is it a colleague’s role wait until problems are of such severity that regulatory bodies to try to diagnose or to treat the resident. Workplaces should have mechanisms in however, for a trusted colleague or colleagues to respect- place to ensure that potentially impaired practitioners promptly fully ask to meet with the resident privately and to present cease practice until their ftness to practise can be assessed. It would be appropriate to offer assistance Too often, however, a misguided sense of collegiality makes in connecting the resident with a personal physician if the physicians hesitate to respond to a colleague in diffculty or resident doesn’t have one. In this case it would be appropriate for the colleague or colleagues to research contact information for the local An organized and responsible method for dealing with mat- physician health program and assist the resident in orga- ters of potential physician impairment would involve early nizing an appointment with medical staff there. It might identifcation of physicians who might require assistance and even be ftting for a colleague to accompany the resident to the provision of timely and caring intervention when it is such an appointment, but not to be part of that meeting. Help could include offering encouragement, covering Alternatively, it might be appropriate to follow up with practice duties, referral to remedial assistance and, eventually, the resident to try to ensure that they had indeed made mentorship for physicians returning to work after an absence. Academic departments or group It is to be hoped that incapacitated colleagues will respond practices should cultivate a resource list of primary care appropriately to support and advice, but at the end of the day physicians who are community based and not necessarily we cannot ignore our legal and ethical obligations to report associated with academic departments. These providers to the appropriate bodies impaired physicians who insist on should have experience in caring for physician colleagues practising despite reasonable offers of assistance. A supportive collegial group works proactively as a team to ensure the optimal function of all members. It is not focused Key references only on the individual practitioner’s health, but also on the Brown G, Rohin M, Manogue M. Effective Learning & Teaching in Medical, Dental & Veterinary contribute to the stress of health care staff, but also encour- Education. Although confict in acterization of confict, medical workplaces and academic settings is common, it can • describe factors that infuence styles of dealing with con- be diffcult to deal with, especially when its determinants fict, and are poorly understood. Given that interpersonal confict is • discuss collaborative attitudes and communication skills potentially all around us, it is important to learn strategies that that support the creative resolution of confict. Case Most instances of confict appear to have had an immediate, Two enthusiastic and ambitious residents seem to have observable trigger, a hot-button issue of some kind. In reality, butted heads regularly on several issues during their three the problem is usually more complex. Conficts occur repeatedly, other variables, of which the parties involved might not be whether it surrounds organizing the on-call rota, holiday fully aware. Such variables include the power relationships, true schedules, or topics for grand rounds. The confict seems needs as opposed to apparent wants, and styles in dealing with to be escalating, and each sees the other’s behaviour confict. As is typical of unresolved it is important to be aware of our own typical responses to confict, the situation is becoming personalized, and both confict—our “confict styles. It is normal The situation is becoming diffcult for the department as to make presumptions and assumptions on the basis of experi- a whole, as both residents each seek to recruit colleagues ence. In this module we focus on interpersonal con- When we are in confict we can demonstrate behaviour that fict, which occurs when human need or interest is frustrated. A defensive style is usually more has been defned as “a situation in which one or both persons adversarial, and refects the extent to which we are attempting in a relationship are experiencing diffculty in working or living to satisfy our own needs. This usually occurs due to different or in- ness, and refects the extent to which we are willing to satisfy compatible needs, goals or styles” (Fisher 1977). Kilmann described fve personal relationships do not have confict-free relationships. They are conscious of their personal modating (smoothing), avoiding (withdrawing), collaborating communication techniques and are aware that confict makes (problem-solving) and compromising (sharing). Because these facets of can make sense when you understand the other person’s unmet confict resolution are so complex, a better designation might needs. In order to appreciate somebody’s needs we need to set be confict management, since not all confict ends up being an environment of trust and honesty. Given that so many factors infuence our personal behaviour in confict it is wise to remember that when in confict it really is “all about me,” rather than the other person.

Women who carry these mutations can reduce their risk of death from cancer through increased cancer screening or through prophylactic surgeries to remove their breasts or ovaries (Roukos and Briasoulis 2007) buy deltasone 40 mg with amex; until these mutations were identified it was not possible to determine who carried the mutations or to take proactive steps to manage risk deltasone 5mg amex. In addition, epidemiological studies and other data have raised the possibility that H. The human genome and microbiome projects are only two examples of emerging biological information that has the potential to inform health care. It is similarly likely that other molecular data (such as epigenetic or metabolomic data), information on the patient’s history of exposure to environmental agents, and psychosocial or behavioral information will all need to be incorporated into a Knowledge Network and New Taxonomy that would enhance the diagnosis and treatment of disease. Traditionally, lung cancers have been divided into two main types based on the tumors’ histological appearance: small- cell lung cancer and non-small-cell lung cancer. Non-small-cell lung cancer is comprised of three sub-groups, each of them defined by histology, including adenocarcinoma, squamous- cell carcinoma, and large cell carcinoma. Since 2004, knowledge of the molecular drivers of non-small-cell lung cancer has exploded (Figure 2-1). Drivers are mutations in genes that contribute to inappropriate cellular proliferation. If the inappropriate function of the mutant protein is shut down, dramatic anti-tumor effects can ensue. These receptors were known to send signals that promote cellular proliferation and survival, and increased signaling was thought to contribute to some cancers. However, the dramatic tumor shrinkage in some patients was enough for Food and Drug Administration approval in 2003, even though the molecular basis for the response was then unknown. Without the ability to recognize the responding patients as a biologically distinct subset, these agents were tried unsuccessfully on a broad range of lung-cancer patients, doing nothing for most patients other than increasing costs and side effects. In retrospect, some clinical trials with these agents probably failed because the actual responders represented too small a proportion of the patients in the trials (Pao and Miller 2005). This made it possible to predict which patients would respond to the therapy and to administer the therapy only to this subset of patients. This led to the design of much more effective clinical trials as well as reduced treatment costs and increased treatment effectiveness. Since then, many studies have further divided lung cancers into subsets that can be defined by driver mutations. Not all of these driver mutations can currently be targeted with drugs and cancer cells are quick to develop resistance to targeted drugs even when they are available. Nonetheless, this new information makes it possible to develop new targeted therapies that can extend and improve the quality of life for cancer patients. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease 24 Source: Pao and Girard 2011 Figure 2-2: Knowledge of non-small-cell lung cancer has evolved substantially in recent decades. The traditional characterization of lung cancers based on histology has been replaced over the past 20 years by classifications based on driver mutations. However, the sophistication of this system for molecular classification has improved with the advent of more genetic information and the identification of many more driver mutations. Similar approaches could improve the diagnosis, classification, and treatment of many other diseases. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease 25 The Urgent Need to Better Understand Phenotype-Genotype Correlations While dramatic progress in understanding the relationship between molecular features and phenotype is being made, there is an urgent need to understand these links better and to develop strategies to deal with their implications for athe individual patient. Of these, 1,167 were judged by the database’s curators as likely to be clinically significant, while most of the rest were categorized as of “unknown” clinical significance. Among the mutations that are believed to be clinically significant, some are thought to confer a higher risk of cancer than others (Gayther et al. To what extent does their mutation increase their risks of breast and ovarian cancer and how do these risks change with age? All of these real-life decisions carry heavy personal consequences as well as implications for health care costs. These treatment decisions do not need to be made based on such fragmentary information. It would be possible to assess the extent to which prophylactic surgeries reduced risk. It would be possible to assess the effectiveness of increased cancer screening, the best ways to screen these patients, and the complications that arise from the inevitable false-positive results that come from increased screening. Efforts along these lines have so far been based on modest numbers of patients or cohorts that are not fully representative of the larger population because it has not been practical to integrate genetic information, treatment decisions, and outcomes data for large numbers of unselected patients. However, recent advances in genomic and information technologies now make it possible to systematically address these issues by integrating large data sets that already exist. Even if only a subset of this variation has significant implications for disease risk or treatment response we have the potential to improve the detection, diagnosis, and treatment of disease dramatically by large-scale efforts to assess phenotype-genotype correlations.