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The copyright owners grant third parties the right to use the Internal Medicine Milestones on a non-exclusive basis for educational purposes order 150 mg lyrica fast delivery. The Milestones provide a framework for the assessment of the development of the resident physician in key dimensions of the elements of physician competency in a specialty or subspecialty best lyrica 150mg. They neither represent the entirety of the dimensions of the six domains of physician competency discount lyrica 150 mg amex, nor are they designed to be relevant in any other context. They are descriptors and targets for resident performance as a resident moves from entry into residency through graduation. For each reporting period, review and reporting will involve selecting the level of milestones that best describes a resident’s current performance level in relation to milestones, using evidence from multiple methods, such as direct observation, multi-source feedback, tests, and record reviews, etc. Selection of a level implies that the resident substantially demonstrates the milestones in that level, as well as those in lower levels (See the diagram on page v). A general interpretation of levels for emergency medicine is below: Level 1: The resident demonstrates milestones expected of an incoming resident. Level 2: The resident is advancing and demonstrates additional milestones, but is not yet performing at a mid-residency level. Level 3: The resident continues to advance and demonstrate additional milestones; the resident demonstrates the majority of milestones targeted for residency in this sub-competency. Level 4: The resident has advanced so that he or she now substantially demonstrates the milestones targeted for residency. Level 5: The resident has advanced beyond performance targets set for residency and is demonstrating “aspirational” goals which might describe the performance of someone who has been in practice for several years. Answers to Frequently Asked Questions about Milestones are available on the Milestones web page: http://www. For each reporting period, a resident’s performance on the milestones for each sub-competency will be indicated by:  selecting the level of milestones that best describes the resident’s performance in relation to the milestones or  selecting the “Has not Achieved Level 1” response option Selecting a response box in the middle of a Selecting a response box on the line in between levels level implies that milestones in that level and indicates that milestones in lower levels have been in lower levels have been substantially substantially demonstrated as well as some milestones demonstrated. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. Has not Achieved Level 1 Level 2 Level 3 Level 4 Level 5 Level 1 Knows the different Applies medical knowledge Considers array of drug Selects the appropriate Participates in developing classifications of pharmacologic for selection of therapy for treatment. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. Has not Achieved Level 1 Level 2 Level 3 Level 4 Level 5 Level 1 Identifies pertinent Performs patient assessment, Determines a backup Performs indicated Teaches procedural anatomy and physiology obtains informed consent and strategy if initial attempts procedures on any patients competency and corrects for a specific procedure ensures monitoring equipment is to perform a procedure are with challenging features mistakes in place in accordance with unsuccessful (e. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. Has not Achieved Level 1 Level 2 Level 3 Level 4 Level 5 Level 1 Discusses with the patient Knows the indications, Knows the indications, Performs procedural Develops pain indications, contraindications contraindications, contraindications, potential sedation providing management and possible complications of potential complications complications and appropriate doses effective sedation protocols/care plans local anesthesia and appropriate doses of of medications used for procedural with the least risk of analgesic/sedative sedation complications and Performs local anesthesia using medications minimal recovery time appropriate doses of local Performs patient assessment and through selective anesthetic and appropriate Knows the anatomic discusses with the patient the most dosing, route and technique to provide skin to landmarks, indications, appropriate analgesic/sedative choice of medications sub-dermal anesthesia for contraindications, medication and administers in the procedures potential complications most appropriate dose and route and appropriate doses of local anesthetics used for Performs pre-sedation assessment, regional anesthesia obtains informed consent and orders appropriate choice and dose of medications for procedural sedation Obtains informed consent and correctly performs regional anesthesia Ensures appropriate monitoring of patients during procedural sedation Comments: Suggested Evaluation Methods: Procedural competency forms, checklist assessment of procedure and simulation lab performance, global ratings, patient survey, chart review Copyright (c) 2012 The Accreditation Council for Graduate Medical Education and The American Board of Emergency Medicine. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. Has not Achieved Level 1 Level 2 Level 3 Level 4 Level 5 Level 1 Prepares a simple wound for Uses medical terminology Performs complex wound Achieves hemostasis in a Performs advanced wound suturing (identify appropriate to clearly describe/classify repairs (deep sutures, bleeding wound using repairs, such as tendon suture material, anesthetize a wound (e. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. Has not Achieved Level 1 Level 2 Level 3 Level 4 Level 5 Level 1 Performs a venipuncture Describes the indications, Inserts a central venous Successfully performs 20 Teaches advanced vascular contraindications, anticipated catheter without central venous lines access techniques Places a peripheral undesirable outcomes and ultrasound when intravenous line complications for the various appropriate Routinely gains venous vascular access modalities access in patients with Performs an arterial Places an ultrasound difficult vascular access puncture Inserts an arterial catheter guided deep vein catheter (e. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. Has not Achieved Level 1 Level 2 Level 3 Level 4 Level 5 Level 1 Adheres to standards for Routinely uses basic patient Describes patient safety Participates in an Uses analytical tools to maintenance of a safe safety practices, such as time- concepts institutional process assess healthcare quality working environment outs and ‘calls for help’ improvement plan to and safety and reassess Employs processes (e. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. Demonstrates an awareness of and responsiveness to the larger context and system of health care. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. The copyright owners grant third parties the right to use the Emergency Medicine Milestones on a non-exclusive basis for educational purposes. The Subspecialty Milestones are arranged in columns of progressive stages of competence that do not correspond with post-graduate year of education. For each reporting period, programs will need to review the Milestones, identify those that best describe a fellow’s current performance, and ultimately select a box that best represents the summary performance for that sub-competency (see the figure on page v). Selecting a response box in the middle of a column implies that the fellow has substantially demonstrated those milestones, as well as those in previous columns. Selecting a response box on a line in between columns indicates that milestones in the lower columns have been substantially demonstrated, as well as some milestones in the higher column. A general interpretation of each column for subspecialty medicine is as follows: Not Yet Assessable: This option should be used only when a fellow has not yet had a learning experience in the sub-competency. Critical Deficiencies: These learner behaviors are not within the spectrum of developing competence.

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Which of the following amino acids is most likely to be decreased in this patient? Which of the following is required to transport fatty acids across the inner mitochondrial membrane? A 67-year-old man has a restricted diet that includes no fresh citrus fruits or leafy green vegetables order 75 mg lyrica with mastercard. This patient’s disorder most likely results from a defect in collagen synthesis that involves which of the following amino acids? D - 16 - Gross Anatomy and Embryology Gross Anatomy Module (125 items) Systems Blood & Lymphoreticular System 1%–5% Nervous System & Special Senses 5%–10% Musculoskeletal System 10%–15% Cardiovascular System 20%–25% Respiratory System 10%–15% Gastrointestinal System 20%–25% Renal & Urinary System 1%–5% Female Reproductive System & Breast 5%–10% Male Reproductive System 1%–5% Endocrine System 1%–5% Embryology Module (20 items) Systems Blood & Lymphoreticular System 5%–10% Nervous System & Special Senses 5%–10% Musculoskeletal System 5%–10% Cardiovascular System 5%–10% Respiratory System 5%–10% Gastrointestinal System 10%–15% Renal & Urinary System 5%–10% Female Reproductive System & Breast 1%–5% Male Reproductive System 1%–5% Endocrine System 5%–10% - 17 - 1 lyrica 75mg sale. A 45-year-old woman has a uterine leiomyoma that is 5 cm in diameter and is pressing on the urinary bladder cheap lyrica 150mg without a prescription, causing urinary frequency. A 5-year-old girl is brought to the emergency department because of fever and severe abdominal pain. In the examination room, she keeps her right hip flexed and resists active extension of the hip. The inflamed structure associated with these symptoms is most likely in contact with which of the following structures? A 61-year-old man comes to the physician because of a 3-month history of episodes of headache, heart palpitations, and excessive sweating. A 6-year-old boy has a large intra-abdominal mass in the midline just above the symphysis pubis. During an operation, a cystic mass is found attached to the umbilicus and the apex of the bladder. A 55-year-old man who has alcoholic cirrhosis is brought to the emergency department because he has been vomiting blood for 2 hours. He has a 2-month history of abdominal distention, dilated veins over the anterior abdominal wall, and internal hemorrhoids. A 3-year-old girl with mild craniofacial dysmorphosis has profound hearing deficits. Further evaluation indicates profound sensory auditory deficits and vestibular problems. Altered development of which of the following is most likely to account for these observations? A 19-year-old woman comes to the physician because of a 5-day history of increasingly severe right lower abdominal pain and bloody vaginal discharge. Which of the following is the most likely location of this patient’s fertilized egg? A 22-year-old man is brought to the emergency department because of a suprahyoid stab wound that extends from one side of the neck to the other. His tongue deviates to the right when protruded; there is no loss of sensory modality on the tongue. Resection of the tumor is scheduled, and the physician also plans to obtain samples of the draining nodes. To find these nodes, a radiotracer is injected adjacent to the tumor and images are obtained. The first draining sentinel node in this patient is most likely found at which of the following locations? This patient most likely has an abnormality of which of the following fetal structures? A 70-year-old man has a 90% blockage at the origin of the inferior mesenteric artery. Which of the following arteries is the most likely additional source of blood to the descending colon? A 30-year-old man comes to the emergency department 1 hour after injuring his left knee in a volleyball game. He says he twisted his left leg when he fell to the floor after he and a teammate accidentally collided. When the patient sits on the edge of the examination table, the left knee can be displaced anteriorly at an abnormal degree. 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.

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However generic 75mg lyrica with mastercard, the magnitude and direction of change in energy expenditure associated with these factors remain controversial due to the variable effects of exer- cise on the coupling of oxidative phosphorylation in mitochondria safe lyrica 75 mg, on ion shifts generic lyrica 150 mg without prescription, on substrates, and on other factors (Gaesser and Brooks, 1984). Spontaneous Nonexercise Activity Spontaneous nonexercise activity has been reported to be quantita- tively important, accounting for 100 to 700 kcal/d, even in subjects resid- ing in a whole-body calorimeter chamber (Ravussin et al. Sitting without or with fidgeting raises energy expenditure by 4 or 54 percent respectively, compared to lying supine (Levine et al. This suggests that the subjects had lower levels of spontaneous movement after strenuous exercise because they were more tired. Similarly, Blaak and coworkers (1992) reported no measurable change in spontaneous physical activity in obese boys enrolled in an exercise-training program. The combination of these different results indicates that the effects of planned physical activity on activity at other times are highly variable (ranging from overall positive to negative effects on overall energy expen- diture). This most likely depends on a number of factors, including the nature of the exercise (strenuous versus moderate), the initial fitness of the subjects, body composition, and gender. Gender There are substantial data on the effects of gender on energy expendi- ture throughout the lifespan. Although the energy requirement for growth relative to mainte- nance is low, except for the first months of life, satisfactory growth is a sensitive indicator of whether energy needs are being met. The energy cost of growth as a percentage of total energy requirements decreases from around 35 percent at 1 month to 3 percent at 12 months of age, and remains low until the pubertal growth spurt, at which time it increases to about 4 percent (Butte, 2000). Infants double their birth weight by 6 months of age, and triple it by 12 months (Butte et al. Progressive fat deposi- tion in the early months results in a peak in the percentage body weight that is fat at 3 to 6 months (about 31 percent) and body fatness sub- sequently declines to an average of 27 percent at 12 months (Butte et al. During infancy and childhood, girls grow slightly slower than boys, and girls have slightly more body fat (Butte et al. During adoles- cence the gender differences in body composition are accentuated (Ellis, 1997; Ellis et al. Growth velocity is a sensitive indicator of energy status and use of growth velocity charts will detect growth faltering earlier than detected using attained growth charts. Problems with measurement precision and high variabil- ity in individual growth rates over short time periods complicate the inter- pretation of growth velocity data. The timing of the adolescent growth spurt, which typically lasts 2 to 3 years, is also very variable, with the onset typically between 10 and 13 years of age in the majority of children (Forbes, 1987; Tanner, 1955). In general, weight velocity reflects acute episodes of dietary intake, whereas length velocity is affected by chronic factors. The suggested breakpoint for a more rapid decline apparently occurs around 40 years of age in men and 50 years of age in women (Poehlman, 1992, 1993). All of these determinants of energy requirements are potentially influenced by genetic inheritance, with trans- missible and nontransmissible cultural factors contributing to variability as well. Currently there is insufficient research data to predict differences in energy requirements among specific genetic groups, but as data accumu- late this may become possible. The effects of genetic inheritance on body composition are well known, with most studies reporting that 25 to 50 percent of interindividual vari- ability in body composition can be attributed to genetic factors (Bouchard and Perusse, 1993). The same group also reported that there is a genetic component to the weight- gain response to 1,000 kcal/d of overfeeding (Bouchard et al. These studies are consistent with the reports of lower levels of reported physical activity in African-American versus Caucasian adults (Washburn et al. Other Ethnic Groups In addition to African Americans and Caucasians, other ethnic groups have been investigated for potential differences in energy requirements. Similarly, physical activity levels were not different between Pima Indian and Caucasian children (Salbe et al. Thus, there are currently insufficient data to define specific differences in energy requirements between different racial groups and more research is needed in this area. The question of whether normal variations in ambient temperature influence energy requirements is therefore complex. Ambient temperature effects are probably only significant when there is prolonged exposure to substantial cold or heat. The energy cost of work was judged to be 5 percent greater in a cold environment as com- pared to a warm environment (Consolazio et al. There can also be an additional energy cost (2 to 5 percent) of both the increased weight of clothing worn and the hobbling effect of that clothing in cold weather compared with clothing worn in warm weather (Consolazio et al. In addition, temperatures low enough to induce shivering or increased muscular activity will increase energy needs because of the increase in mechanical work (Timmons et al. More recent work also suggests that the recognized increase in energy expenditure in markedly cold cli- mates may be greater in physically active individuals than in sedentary ones (Armstrong, 1998). There is an increase in the energy expenditure of standard tasks when ambient temperatures are very high (Consolazio et al. However, this increase in energy expenditure may be attenuated by continued expo- sure. Garby and colleagues (1990) reported that the extra energy expendi- ture for 2 hours of light activity at 34°C fell progressively a total of 3 to 8 percent with acclimatization over 8 days of the study compared with activity at 20°C to 24°C. More recent studies have reported a significant effect of variations in ambient temperature within the usual range on energy requirements. Lean and colleagues (1988) reported a 4 percent increase in the sleeping metabolic rate of women at an ambient tempera- ture of 22°C compared with 28°C. Instead, the effect of ambient temperature appears to be confined to the period of time during which the ambient temperature is altered. Nevertheless, the energy expenditure response to cold temperatures may be enhanced with previous acclimatization by pro- longed exposure to a cool environment (Kashiwazaki et al. Since most of the recent data has been collected in women, further research in this area is needed. There was also no significant differ- ence in season-related values for physical activity in free-living adult Dutch women, but in contrast to the values reported above for soldiers, the values tended to be higher in summer than in winter (van Staveren et al. For this reason, no specific allowance is made for ambient temperature in the requirements for energy. Altitude Hypoxia increases glucose utilization whether measurements are made on isolated muscle tissue (Cartee et al. Adaptation and Accommodation There are two key differences between nutritional adaptation and accommodation (Waterlow, 1999). First, while adaptation implies mainte- nance of essentially unchanged functional capacity in spite of some alter- ation in steady-state conditions, accommodation allows maintenance of adequate functional capacity under altered steady-state conditions. Second, whereas accommodation involves relatively short-term adjustments, such as the responses needed to maintain homeostasis, adaptation involves changes in body composition that occur over a more extended period of time. Adaptation The term adaptation describes the normal physiological responses of humans to different environmental conditions. A good example of adapta- tion is the increase in hemoglobin concentration that occurs when indi- viduals live at high altitudes (Leon-Velarde et al.

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Supportive treatment: Cytotoxic therapy and the leukaemia itself depresses normal bone marrow func- T Cell B Cell tion and causes a pancytopenia with resulting infection buy lyrica 75 mg low price, anaemia and bleeding buy 150 mg lyrica overnight delivery. Microscopy Prognosis The normal marrow is replaced by abnormal Prognosisisrelatedtoage lyrica 150mg with visa,subtypeandinverselypropor- monotonous leukaemic cells of the lymphoid cell line. Over90%ofchildren The leukaemia is typed by cytochemical staining and respond to treatment, the rarer cases occurring in adults monoclonal antibodies to look for cell surface mark- carry a worse prognosis. Full Most common in the middle aged and elderly blood count shows a low haemoglobin, variable white count,lowplateletcount. Bonemarrowaspirationshows Sex increased cellularity with a high percentage of blast cells. On examination there Proerythroblast Myeloid Stem cell Megakaryoblast may be pallor, bruising, hepatosplenomegaly and lym- phadenopathy. Myeloblast Erythrocyte Platelet Microscopy Monoblast Promyelocyte Abnormal leukaemic cells of the myeloid cell line replace the normal marrow. Monocyte Myelocyte The leukaemia is typed by cytochemical staining and Granulocyte monoclonal antibodies to look for cell surface markers. Full blood count shows a low haemoglobin, variable white count, M2 Myelocytic leukaemia with differentiation low platelet count. Bone marrow aspiration shows in- M3 Acute promyelocytic leukaemia creased cellularity with a high percentage of the abnor- M4 Acute myelomonocytic leukaemia mal cells. Bone marrow cytogentic studies allow classi- M5 Acute monocytic leukaemia proliferation of mono- fication into prognostic groups (e. Supportive treatments in- particularly prone to disseminated intravascular co- clude red blood cell transfusions, platelet transfusions agulation due to the presence of procoagulants within and broad-spectrum antibiotics. Ninety-five 70% of those under 60 years will achieve remission with percent of patients with M3 are induced into remis- combination chemotherapy although the majority re- sion by treatment with high dose retinoic acid. Gum Chronic lymphocytic leukaemia hypertrophy and hepatosplenomegaly is common Definition within this subgroup. Clinical features Often there is an insidious onset of anorexia, malaise Incidence and lethargy due to anaemia. M > F Age Pathophysiology Bimodal distribution with a peak in young adults (15–34 Although there is a proliferation in B cells they have years) and older individuals (>55). On Aetiology examination there may be lymphadenopathy and hep- Infectious agents particularly Epstein Barr virus have atosplenomegaly. Involvement with intermittent chemotherapy such as chlorambucil of mediastinal lymph nodes may cause cough, shortness or fludarabine. B symptoms may be present (fever >38◦C, drenching night sweats, weight loss of Prognosis more than 10% within 6 months). The staging of Hodgkin’s’s disease is accord- ing to the Ann Arbor system, which is suffixed by B if Chronic myelogenous Leukaemia Bsymptoms are present and A if they are absent (see See Myeloproliferative disorders page 482. Microscopy Non-Hodgkin’s lymphoma Classical Reed-Sternberg cells are large cells with a pale cytoplasm and two nuclei with prominent nucleoli said Definition to resemble owl eyes. Incidence r Mixedcellularity disease which mainly affects older 20 per 100,000 per year. Tumours arise due therapy or a combination depending on the stage of to multiple genetic lesions affecting proto-oncogenes Table12. Clinical features r Indolent: Most patients present with painless slowly Prognosis progressive lymphadenopathy. Lymph nodes may re- Indolent lymphomas have a predicted median survival duce in size spontaneously making it difficult to dis- time of 5–10 years. B symp- ◦ sponsive to chemotherapy but have a predicted median toms (fever >38 C, drenching night sweats, weight survival 2–5 years. On Paraproteinaemias examination there is lymphadenopathy and hep- atosplenomegaly. The cells are trophic to the skin particularly the hands and feet, and result Age in plaques and lumps of associated with generalised Most commonly diagnosed 60–65 years. Gas- trointestinallymphomaisparticularlycommoninthe Pathophysiology MiddleEastandisalsoseeninassociationwithcoeliac There is expansion of a single clone of plasma cells that disease. Cleavage of these immunoglobulins tribution according to the Ann Arbor system, which result in the production of Fab and Fc fragments; the Fab is suffixed by B if B symptoms are present (see fragment is termed the Bence-Jones protein and is found Table 12. Investigations There is also production of osteoclast stimulation fac- Thediagnosisismadebylymphnodebiopsy,cytogenetic tor causing lytic bone lesions, bone pain and hypercal- studies of lymphoma cells may give prognostic informa- caemia. Chapter 12: Paraproteinaemias 491 Clinical features Age r Marrow infiltration results in anaemia, thrombocy- Onset most commonly aged 60 years. Spinal cord compression occurs in approx- imately 10–20% of patients at some time during Pathophysiology the course of disease. Hypercalcaemia causes thirst, The abnormal proliferation of lymphoplasmacytoid polyuria, constipation and abdominal pain. Investigations The diagnosis of myeloma is made if there are: Clinical features r Bone marrow aspirate has at least 10–15% plasma Hyperviscosity presents as weakness, tiredness, confu- cells. Patients also often have peripheral lymphadenopa- Other investigations include: thy. Chemotherapy with single alkylating agents improves r Protein electrophoresis shows an IgM parapro- prognosis. Recently, thalidomide has been demonstrated to produce a significant response Management in 30% of patients whose disease progressed following Chemotherapy produces a variable response. Supportive care includes blood transfu- pheresis is used for symptomatic hyperviscosity. Unlike multiple myeloma there are preserved levels of 492 Chapter 12: Haematology and clinical immunology normal immunoglobulins, no lytic bone lesions and no Age renal failure. Investigations Sex Electropheresis of serum protein demonstrates a raised X linked; males only affected. Aetiology Mutations on the X chromosome including deletions, Management frame shifts and insertions. One third of cases are new Aproportionofpatients will go on to develop multi- mutations. Clinical features Type 1 and 2 causes mild disease with bleeding following Investigations injury, menorrhagia and epistaxis. Type 3 causes spon- r Activated partial thromboplastin time is raised, but taneous bleeding from early life. Clinical features Investigations Similar to haemophilia A with mild deficiency causing r Coagulation studies reveal prolonged clotting times only bleeding post surgery and trauma. Activated partial thromboplastin time is raised, but correctablewith50%normalserum(i. Patients re- quire supportive care and normally are managed in in- Management tensive care units. Definition Deficiency of vitamin K, a fat-soluble vitamin, leads to a Disseminated intravascular bleeding tendency. Deficiency occurs in obstructive jaundice and cer- widespread generation of fibrin within blood vessels and tain malabsorption syndromes. Aetiology Causes include Gram −ve and meningococcal sep- Pathophysiology ticaemia, disseminated malignant disease, haemolytic Vitamin K is a co factor in the synthesis of clotting fac- transfusion reactions, trauma, burns, surgery and P. Vitamin K is also involved in Pathophysiology producing proteins required for bone calcification.

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