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By E. Abbas. University of Scranton.

Many of these random events can be described by the normal distribution purchase 50 mg atenolol with amex, which we will discuss in Chapter 9 buy generic atenolol 50 mg online. An imprecise instrument will get slightly different results each time the same event is measured. For example, serum sodium measured inside rat muscle cells will show less random error than the degree of depression in humans. There can also be innate variability in the way that 70 Essential Evidence-Based Medicine different researchers or practicing physicians interpret various data on certain patients. Systematic error represents a consistent distortion in direction or magni- tude of the results. Systematic or systemic error is a function of the person making the measurement or the calibration of the instrument. For example, researchers could consistently measure blood pressure using a blood-pressure cuff that always reads high by 10 mmHg. More commonly, a measurement can be influenced by knowledge of other aspects of the patient’s situation lead- ing to researchers responding differently to some patients in the study. Another source of systematic error can occur when there is non- random assignment of subjects to one group in a study. For instance, researchers could preferentially assign patients with bronchitis to the placebo group when studying the effect of antibiotics on bronchitis and pneumonia. This would be problematic since bronchitis almost always gets better on its own and pneu- monia sometimes gets better on its own, but it is less likely and occurs more slowly. Then, if the patients assigned to placebo get better as often as those tak- ing antibiotics, the cause of the improvement is uncertain since it may have occurred because the placebo patients were going to get better more quickly anyway. The researcher’s job is to minimize the error in the study to minimize the bias in the study. Researchers are usually more successful at reducing systematic error than random error. Overall, it is the reader’s job to determine if bias exists, and if so to what extent and in what direction that bias is likely to change the study results. Instruments and how they are chosen Common instruments include objective instruments like the thermometer or sphygmomanometer (blood-pressure cuff and manometer) and subjective instruments such as questionnaires or pain scales. By their nature, objective measurements made by physical instruments such as automated blood-cell counters tend to be very precise. However, these instruments may also be affected by random variation of biological systems in the body. An example of this is hemodynamic pressure measurements such as arterial or venous pres- sure, oxygen saturation, and airway pressures taken by transducers. The actual measurement may be very precise, but there can be lots of random variation around the true measurement result. Subjective instruments include questions that must be answered either yes or no or with an ordinal scale (0, 1, 2, 3, 4, or 5) or by placing an x on a pre-measured line. Measures of pain or anxiety are Instruments and measurements: precision and validity 71 common examples and these are commonly known to be unreliable, inaccurate, and often imprecise. Overall, measurements, the data that instruments give us, are the final goals of research. They are the result of applying an instrument to the process of sys- tematically collecting data. Common instruments used in medicine measure the temperature, blood pressure, number of yes or no answers, or level of pain. The quality of the measurements is only as good as the quality of the instrument used to make them. The researcher must select instruments that will measure the phenomena of inter- est. If the researcher wishes to measure blood pressure accurately and precisely, a standard blood-pressure cuff would be a reasonable tool. The researcher could also measure blood pressure using an intra-arterial catheter attached to a pres- sure transducer. This will give a more precise result, but the additional precision may not help in the ultimate care of the patient. If survival is the desired out- come, a simple record of the presence or absence of death is the best measure. For measuring the cause of death, the death certificate can also be the instru- ment of choice but has been shown to be inaccurate. When subjective outcomes like pain, anxiety, quality of life, or patient satis- faction are measured, the selection of an instrument becomes more difficult. Some patients will react more strongly and show more emotion than others in response to the same levels of pain. There are standardized pain scores available that have been validated in research trials. A 10-cm line is placed on the paper with one end labeled “no pain at all,” and the other end “worst pain ever. If this exercise is repeated and the patient reports the same level of pain, then the scale is validated. The best outcome measure when using this scale becomes the change in the pain score and not the absolute score. Since pain is quantified differently in differ- ent patients, it is only the difference in scores that is likely to be similar between patients. In fact, when this was studied, it was found that patients would use con- sistently similar differences for the same degree of pain difference. Another type of pain score is the Likert Scale, which is a five- or six-point ordi- nal scale in which each of the points represents a different level of pain. A sample Likert Scale begins with 0 = no pain, continues with 1 = minimal pain, and ends 1 K. The minimum clinically important difference in physician-assigned visual analog pain scores. The reader must be careful when interpreting stud- ies using this type of scoring system. A patient who puts a 3 for their pain is counted very differently from a patient who puts a 4 for the same level of pain.

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The combination of molecular imaging and the unique idea of new scanners provides exciting potential of integration of diagnosis and radiotherapy atenolol 50 mg online. Late effects after the treatment The worldwide spread of high precision radiotherapy has led to increased opportunity to treat a variety of cancers discount atenolol 100 mg visa. The therapeutic outcome has improved for locally advanced cancers that were not curable with conventional methods. Many of these patients now survive for longer periods and, thus, more attention must be paid to radiation effects from a long term perspective [8]. In the past, radiation oncologists focused mainly on curing cancers with little consideration for secondary cancer. Recently, the situation has been changing; while high precision photon radiotherapy methods are superior to conventional radiotherapy in the dose distribution delivered to the tumour, a large volume of surrounding normal tissues may be exposed to low levels of dose. Ion beam radiotherapy with protons or carbon ions further contributes to localizing the dose to the tumour, and the extra dose received in surrounding normal tissues is further reduced. The increasing use of radiation in young patients requires evidence of age dependent biological effects of radiation [10]. Late deterministic effects after radiotherapy, such as retardation of growth, hormonal deficiencies, organ dysfunctions, and intellectual and cognitive functions are more severe in children than in adults. It should also be noted that children have distinctly different organ susceptibility from adults [12]. Protection of personnel Protection of occupational staff can be achieved according to the general principles of radiation protection [13, 14]. Specific consideration should be given to the management of the treatment facility and devices for each method. The use of a high energy accelerator for ion beam radiotherapy requires a control of activated devices and air in the treatment room to avoid unnecessary radiation exposure of staff members. Exposure of patients’ family members is also a concern, but is sufficiently low in ion beam radiotherapy [15]. It is now expanding rapidly within the medical community, with significant benefits to patients. In addition to the general guidance for radiation protection of patients, unique problems specific to each treatment method have to be solved for the efficient and safe use of new technology in radiotherapy. Education, sufficient knowledge and training of personnel involved in the treatment procedure are essential for patient protection. Health care professionals should also be aware of the possible risks and consider the necessary procedures for patient protection when new technologies are introduced in clinical practice. The discussion will cover the process from the decision to treat until the patient has completed the radiotherapy course. Prescription The prescription is one of the most important steps in the process and should be one of the first substeps, and in this case it is shown in parallel with the imaging sessions. Based on the information from previous steps in the health care process, and together with information that can be collected during the patient’s visit, radiation oncologists have to decide according to the department’s guidelines about which protocol the patient should be treated with. The guidelines and the protocol should include information about total dose, fractionation (dose per fraction, timing, e. Tools Guidelines and protocols should be evidence based when possible, and detailed to facilitate further development in the consecutive steps in the process. During the development of protocols, one must also include priorities for all these dose–volume criteria to facilitate the planning but especially the plan review process. In Table 1, an example of priorities is given for treatment of prostate cancer patients. It is also advantageous if there is a consensus in the radiotherapy world regarding naming conventions. The Global Clinical Trials Quality Assurance 1 of Radiation Therapy Harmonisation Group has published a suggestion that would be favourable if it were adopted by professional organizations within radiation oncology, and if it were disseminated to all radiation oncologists, medical physicists, dosimetrists and radiation therapy technologists. Imaging Imaging for radiation therapy used to be performed using a ‘simulator’ where two orthogonal X ray projections were produced. Together with other X ray examinations and anatomical atlases, a cross-section (sometimes several) was applied to construct typical target volumes and organs at risk. Today, a full spectrum of imaging devices is available, sometimes even at the radiotherapy department. The protocol should also ensure that the patient’s position is correct both macroscopically, i. In an environment where several imaging devices are available, the registration tools and methods must also be assured. This is a large task for a department, especially gaining an understanding of devices used in other departments. This probably leads to an increase in cooperation between imaging and therapy staff, e. Volumes The delineation of the volumes in radiotherapy that will be used for treatment planning and/or optimized intensity modulated radiotherapy is one of the most crucial steps in the whole radiotherapy process. Several papers in the literature have shown the spread among radiation oncologist delineation of target volumes. Planning Many hazards exist in planning; thus, thorough protocols and guidelines must exist that describe the process for most of the treatments given at the department. The quality of the treatment plan is strongly dependent on the information given at the prescription, which has to be combined with the planning directives present in the guidelines. The first physicist did it correctly, but his colleague did it slightly differently, resulting in severe overdosing [2]. Experience is, of course, an important parameter when creating robust and accurate treatment plans, and combining inexperienced dosimetrists with ambiguous guidelines and a lack of experienced supervisors will lead to unsafe conditions in the treatment planning process. The Glasgow accident, in which a young girl was overdosed, was partly a consequence of a situation of this sort. For all purposes, it is important that the results of such comparisons are not biased due to limitations or uncertainties of the evaluation method itself or by the individuals involved. The red stars represent plans for which one cannot improve any of the two criteria without diminishing the other. It is observed that a radiation treatment prescription commonly contains multiple, mutually conflicting objectives. In general, the goal of full target coverage is set against the need to spare healthy tissues and organs at risk. The relative weighting of these different treatment objectives represents a trade-off that is seldom expressed specifically in the prescription. Instead, this trade-off is usually explored by investigating multiple treatment plans, either from a pre-calculated database or, more often, in an iterative process.

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Ashammakhi Summary tem cells have a capacity for self-renewal and capability of proliferation and differentiation to various cell lineages. The use of amniotic fluid derived cells, umbilical cord cells, fat and skin tissues and monocytes might be an adequate “ethically pure” alternative in future. Stem cells can improve healthcare by using and augmenting the body’s own regenerative potential. Hopefully, this will help to provide therapeutic treatment for conditions where current therapies are inadequate. Human body has an endogenous system of regeneration through stem cells, where stem cells are found almost in every type of tissue. Regenerative medicine comprises the use of tissue engineering and stem cell technology. This review is not meant to be exhaustive, but aims to highlight present and future applications of stem cells in this exciting new discipline. We will briefly discuss tissue engineering and stem cell technology including their different sources. He was unsuccessful but his experiments were among the first attempts at what we now describe as tissue engineering. He had positively concluded that with the advent of biomaterials science it would be possible to regenerate and produce new tissues by loading viable cells onto “smart” engineered scaffolds (1). These forums recommended that tissue engineering be designated as an emerging engineering technology. The new speciality was then famously described in an article by Langer and Vacanti in Science. They wrote (3): “Tissue engineering is an interdisciplinary field that applies the principles of engineering and the life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function”. Since then the novel speciality has successfully expanded and excited scientists and clinicians alike. They injected bone marrow cells into irradiated mice, nodules developed in the spleens in proportion to the number of bone marrow cells injected. Later on, they obtained evidence that these cells were capable of infinite self-renewal, a central characteristic of stem cells (4). Thus, stem cells by definition have two defining properties the capacity of self-renewal giving rise to more stem cells and to differentiate into different lineages under appropriate conditions. Their potential to differentiate into different cell types seems to be more limited (5) (Table 1). The capability for potency and the relative ease to isolate and expand these cells are invaluable properties for regenerative medicine. Several ideas have been put forward to explain stem cell lineage and fate determination. This three-dimensional (3D) microenvironment is thought to control genes and properties that define “stemness”, i. Further studies on the niche might give us a better understanding on the control of stem cell differentiation. Stem cells might be appropriately differentiated cells with the potential to display diverse cell types depending on the host niche. Furthermore, stem cells implanted into a totally different niche can potentially differentiate into cell types of the new environment (7). For example, human neuronal stem cells produced muscle cells when they were implanted in skeletal muscle (8). Bone marrow cells differentiated into neuronal cells when they were transplanted into a neural environment (9,10). This can have clinical implications for example since both liver and pancreas develop from the same embryological line, specific growth factors and culture Topics in Tissue Engineering, Vol. Stem cells for regeneration techniques achieved the “transdifferentiation” of liver cells to islet cells (11). Stem cell Definitions Stem cell A cell with the ability for self-renewal and differentiation potential. Self-renewal Asymmetric cell division which leads to at least one daughter cell which is equal to the mother cell. Commitment Engaging in a defined pathway which leads to differentiation and inability for self- renewal. Progenitor cell A proliferative cell with the capacity to differentiate but with no self-renewal ability. Multipotency Ability to form multiple cell lineages which form an entire tissue, usually specific to one germ layer, e. Plasticity Controversial possibility for adult stem cells to show higher potency in response to different microenvironments. On 17 January 1912 in one of his experiments he placed part of chicken’s embryo heart in a fresh nutrient medium. Every January 17 , the doctors and nurses would celebrate with Carrel, singing “Happy Birthday” to the chicken tissue (12). Even though these cells were unlikely to be embryonic and possibly more related to cord-derived cells, this experiment showed the future potential of tissue culture. The hypoblast forms yolk sac, while the epiblast differentiates into three classical layers of the embryo; ectoderm, mesoderm and endoderm with potential of forming any tissue (Fig. Before their clinical use, ethical and scientific questions need to be resolved, e. In 1869, Paul Langerhans as a medical student observed for the first time beta islet cells as microscopic islands of a different structure in the pancreas (16).

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In males the hairline recedes initially in the temporal regions before hair loss at the Clinical features Symptoms begin with recurrent flushing of the face discount atenolol 100mg fast delivery, which worsens on exposure to hot drinks atenolol 50mg mastercard, alcohol, stress Table9. Thismayprecede,byyears,erythemaofthe Diffuse non-scarring Androgenic alopecia, metabolic, nose and cheeks. Scarring Discoid lupus, burns, radiation, foreign body in the eye, telangiectasia and inflammation lichen planus. Chapter 9: Hair and nail disorders 397 Anagen, Growth phase lasts two to three years. Catagen, Release of hair shaft involutional phase lasts two to three weeks Telogen, resting phase, lasts three to four months Figure 9. Topical minoxidil produces some response in up Idiopathic Possible steroidogenic abnormality to 30% of cases. Finasteride is also used in androgenic Iatrogenic Danzol, some oral contraceptive pills alopecia in males. Pituitary Hyperprolacinaemia r Telogen effluvium occurs when the normally asyn- Adrenal Congenital adrenal hyperplasia, Cushing’s chronous cycles in follicles synchronises after child- syndrome Ovarian Polycystic ovaries, hyperthecosis, some tumours birth, surgery or severe illness. Hir- develop well-demarcated circular patches of hair loss, sutism is caused by increased androgen production or, which may coalesce causing alopecia totalis. Pathog- more rarely, increased sensitivity of hair follicles to an- nomonic is the presence of exclamation mark hairs, drogens (see Table 9. Women with a normal menstrual cycle are unlikely to Hirsutism have an endocrine cause. Other features may include Definition acne, seborrhoea, androgenic alopecia, deepening of the Hirsutism is the androgen-dependent growth of hair in voice and clitoromegaly. The abdomen should be exam- awoman, which is in the same distribution as in males. Increased incidence Systemic illness Hypothyroidism, anorexia nervosa, of impetigo is seen in conditions damaging the integrity malnutrition, porphyria cutanea of skin such as eczema, and its spread is facilitated by tarda overcrowding and poor hygiene. Paraneoplastic syndrome Clinical features Impetigo appears as erythematous erosions with a char- Investigations acteristic golden brown crusting. There may be associ- Dependent on the level of virilisation and menstrual ated localised lymphadenopathy. Bullous impetigo de- anomaliesfound;hormoneprofileandabdominalimag- scribes punched-out blistering lesions with crusting due ing may be required. Management Management r Any underlying cause for excess androgen production Swabs should be taken. Of- r Physical methods of hair removal include shaving, ten the condition requires treatment with oral penicillin chemical depilatories, bleaching, electrolysis and laser (Streptococcus) and flucloxacillin (Staphylococcus). Cellulitis Hypertrichosis Definition Definition Cellulitis is an acute diffuse spreading infection of the Hypertrichosis is excessive hair in a non-androgenic dis- skin extending into the soft tissues. Clinical features Aetiology/pathophysiology Patients present with fine terminal hair diffusely on the The main causative organisms are β-haemolytic Strep- face, limbs and trunk. The mechanisms of infection are not clearly understood but may involve bacterial exotox- Infections of the skin and ins and cytokine release. There is warmth Impetigo andtendernesstotouch,oftenwithlocallymphadenopa- Definition thy. If untreated, there is spreading of the erythema, Impetigo is a contagious superficial skin infection oc- abscess formation and secondary septicaemia. Chapter 9: Infections of the skin and soft tissue 399 Complications Investigations Abscess formation, septicaemia, toxic shock-like syn- r Imaging may allow detection of gas in muscle too deep drome. Management Management Prevention of clostridial infections involves adequate Initial management with penicillin (Streptococcus) and wound care at the time of original trauma including ex- flucloxacillin(Staphylococcus);erythromycinisusefulfor cision and debridement of necrotic tissue. In vanced or if it fails to respond to oral therapy, parenteral established cases penicillin is the drug of choice. Aggres- penicillin and flucloxacillin are used, and clindamycin, sive surgical intervention with wide excision, opening of if penicillin allergic. It is useful to outline the erythema fascial compartments, and meticulous debridement of to allow the condition to be followed. Clostridial myonecrosis (gas gangrene) Definition Leprosy Gangrenereferstodeathoftissue,andmyonecrosisrefers specifically to muscle. Clostridial infection of wounds Definition may result in significant infection of muscle, which de- Leprosy is a chronic indolent mycobacterial infection velops rapidly and is potentially life-threatening. Com- Geography promise of the blood supply as a result of the traumatic Leprosy is found primarily in Africa and Asia. It is thought that τ-toxin pro- Leprosy is caused by an intracellular acid-fast bacillus, duced by Clostridium prevents the normal inflamma- Mycobacterium leprae. The mode of transmission is un- tory cell infiltration and therefore allows the infection certain and the incubation may be many years. Fivepatternsofdiseasearerecognisedthataredependent on the immunological response of the individual (see Clinical features Table 9. Patients develop severe pain due to myonecrosis at a site There are two immunological reactions that may oc- of trauma with induration, blistering and oedema. It is characterised by fever and mul- most individuals are seropositive by adult life. Im- munocompromised patients are at particular risk for recurrent and disseminated infection. Afterprimary infection, the latent non-replicating virus resides within the dorsal root ganglion, shielding the Management virus from the immune system. Symptomatic infection usually manifests as acute gingivostomati- tis with vesicles on the lips and painful ulcers within Viral skin infections the mouth accompanied by fever and malaise. Local herpes inoculation into a site of injury may present Herpes simplex as a herpetic whitlow–apainful vesicle or pustule on a digit. Ocular infections and encephalitis (see page Definition 304) may occur with or without kin lesions. Aetiology/pathophysiology Latent infection occurs and recurrence is often her- There are two subtypes: alded by a burning or tingling sensation. It usually Chapter 9: Infections of the skin and soft tissue 401 occurs at the site of the primary infection and in ad- the rash. Theyheal Patients with atopic eczema may develop eczema her- over 2–3 weeks leaving scars. Corneal ulcers and corneal scarring may result from trigeminal infection with ocular involvement.

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