By X. Cobryn. Green Mountain College.

Incidences of stomach cancer are 68 times higher among Japanese compared to Americans cheap levothroid line. However order levothroid on line amex, children of migrant Japanese settled in America show incidence rates of stomach cancer comparable to that of the American population generic 50 mcg levothroid overnight delivery. Terefore purchase levothroid online, the risk of developing cancer seems largely environmental, accounting for more than 90% of all cancers caused. In the late 18th century, Sir Percival Pott reported that scrotal cancer in chimney sweeps was linked to poor hygiene and accumulation of cancer-causing agents from soot. The Danish Chimney sweepers Guild recommended daily baths and was the most likely reason for the dramatic reduction in scrotal cancer incidence rates in Europe. In 1950, compelling epidemiological evidence showed that heavy cigarette smokers ran a 20-fold higher risk of developing lung cancer compared to non-smokers. Excessive alcohol use has been linked to liver and mouth/throat cancers in both males and females. Smoking and tobacco use signifcantly increases the risk of lung cancers equally in males and females, and there is also a slightly higher risk of mouth/throat cancers. Incidences of skin cancers (melanomas) are on the rise, especially in Australia, due to exposure to high levels of ultraviolet radiation in the suns rays and popularity of tanning salons. However the risk of developing some of these cancers can be reduced by changing lifestyles and vaccines (like Gardasil which reduces the risk of cervical carcinomas). Initiation and progression of cancer is also due to exposure to cancer-causing agents (carcinogens, mutagens). Tese are present in food and water, in the air, and in chemicals and sunlight that people are exposed to. Since epithelial cells cover the skin, line the respiratory and alimentary tracts, and metabolize ingested carcinogens, it is not surprising that over 90% of cancers originate from epithelia (carcinomas). In less than 10% of cases, a genetic predisposition increases the risk of cancer developing a lot earlier (E. Sixty percent of new cancer cases and two thirds of cancer deaths occur in persons > 65 years. By 2020, wind could provide one-tenth of our planets Brain power electricity needs. These can be reduced dramatically thanks to our systems for on-line condition monitoring and automatic lubrication. We help make it more economical to create cleaner, cheaper energy out of thin air. By sharing our experience, expertise, and creativity, industries can boost performance beyond expectations. The exponential rise in many cancers with age fts with an increased susceptibility to the late stages of carcinogenesis by environmental exposures. Lifetime exposure to estrogen may lead to breast or uterine cancer; exposure to testosterone leads to prostate cancer. The decline in cellular immunity may also lead to certain types of cancer that are highly immunogenic (e. Tere are several benefts to identifying and classifying cancers using histological sections and staining methodology 1) Diagnosis: Microscopic observation helps determine whether the tumour tissue is benign (harmless) or malignant (potentially fatal). Gross cellular morphology and tissue specifc markers are used to classify cancerous cells. Patients with simple hyperplasia in the uterine epithelium have <1% chance of developing cancer compared 82% risk in patients with atypical hyperplasia. The mesothelium is a layer of cells which cover various organs in the body protecting them and allowing organs to move against each other as the lungs expand and contract or the heart beats. However the complexity of this disease is not as simple at the cellular and molecular level. Individual cell behaviour is not autonomous, and it usually relies on external signals from surrounding cells in the tissue or microenvironment. Tere are more than 100 distinct types of cancers and any specifc organ can contain tumours of more than one subtype. How many of these regulatory circuits need to be broken to transform a normal cell into a cancerous one? Is there a common regulatory circuit that is broken among diferent types of cancers? Which of these circuits are broken inside a cell and which of these are linked to external signals from neighbouring cells in the tissue? The answer to these questions can be summarised in a heterotypic model, manifested as the six common changes in cell physiology that results in cancer (proposed by Douglas Hanahan and Robert Weinberg in 2000). This model looks at tumours as complex tissues, in which cancer cells recruit and use normal cells in order to enhance their own survival and proliferation. The 6 hallmarks of this currently accepted model can be described using a trafc light analogy (Fig 1. Almost all cancers share some or all of the 6 traits described below, depending on the tumour. Arrows on the right (orange and red) show signals that regulate normal cell behaviour. Doll, R (1999) The Pierre Denoix memorial lecture: nature and nurture in the control of cancer. Almost all types of mammalian cells carry an inbuilt circuit which controls their rate of cell division. If cells continue to divide uncontrollably without any intrinsic constraint, tissues can potentially develop to enormous sizes with lethal results for the organism. For example, humans could potentially have massive hearts or enlarged lungs or livers. In order for a clone of cells to expand to the size of a potentially fatal tumour, there must be a disruption in the inherent cellular circuitry controlling cell multiplication. It has long been known that normal mammalian cells grown in a petridish have a fnite number of cell divisions. For example, adult fbroblast cells which have been cultured in a petridish in vitro, stop multiplying when the cells reach the edge of the petridish. When a small fraction of these cells are transferred to a new petridish, they start to divide again and so on a process called passaging. However, afer a certain number of transfers, the rate of cell division slows down and ultimately stops (Fig 2. In culture, normal cells undergo a fnite number of divisions before they stop dividing completely (senescence). Leonard Hayfick was the frst to demonstrate that cells from rodent or human embryos have a fnite number of cell divsions (replicative potential) and he called this senescence. Senescent cells are viable but have lost the capacity for cell cycling and cell division. In a petridish, these cells will take up nutrients and grow (ofen looking like fried eggs because the nucleus and cytoplasm grow in size) but they will not divide. Originally cultured from a cervical adenocarcinoma from a cancer patient called Henrietta Lacks in 1951, these cells continue to grow and proliferate in hundreds of laboratories across the world to this day. This clearly suggests that these cancer cells have bypassed/disrupted the senescence regulators within the cell and acquired the capacity for unlimited division (replicative potential). The cellular mechanism controlling senescence has been discovered in the past 30 years. We now know that the ticking counter which controls fnite cell division lies at the end of all human chromosomes the telomeres. The best analogy is that telomeres are like aglets which protect the ends of shoelaces from fraying. Since every chromosome has a fnite number of these telomere repeats, successive cycles of replication result in a steady erosion of the telomeres until they cause genetic changes, chromosomal end-end fusions and disarray, and ultimately cell death. After every round of cell division, telomere lengths get progressively shorter, until it provokes the cell to stop dividing and enter senescence. Cancer cells prevent telomere shortening by producing the enzyme, telomerase, which keeps extending telomeres, thus preventing senescence. The main strategy used by cancer cells to maintain telomere lengths is by activating an enzyme called telomerase. Unlike cancer cells, actively dividing normal cells have levels of telomerase that are extremely low or undetectable. If telomerase is injected into these cells in vitro, they are transformed into cells that keep dividing limitlessly.

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Count bricks Plurals 42 mo: fetch several items Name friend Pedal order generic levothroid on line; Up stairs adult Share buy levothroid in india, turns Hop 3 steps/ Jump off 2 5 brick gate Intelligible to strangers Prepositions: between Gives age Undress indep order levothroid mastercard. Instead discount 100 mcg levothroid otc, does he do age appropriate work, need extra tuition, etc Cognitive Development Overall process: Autonomy: dependent on parents peers independent Abstract thinking (what if? Usually (80%) non-disjunction at first meiotic division 5% have different karyotypes: Mosaic Down: 3 % Robertsonian translocation t14:21: 4. Chromosomal anomalies represent 15% of congenital anomalies Risk: Maternal age at birth Down in live births 25 - 29 1:1100 30 1: 900 35 1:350 37 1:200 40 1:100 43 1:50 45 and over 1:25 Neonatal Screening: Only 30% of children with Down are born to women over 35. Boys = 3 * girls 75% show some degree of general intellectual impairment Aspergers Syndrome: Symptoms overlap with autism Social interaction and behavioural problems similar to autism but not associated with significant language or intellectual delay Effect of Chronic Disease on Development See also Chronic illness and disability in Adolescents, page 669 10 15 % of children have some chronic health condition. See Attachment Disorder, page 573 For the toddler: Watch for vulnerable child syndrome: continued parental concern after child has recovered adverse affects on child. More complicated when some ongoing vigilance is required Support appropriate attitudes and plans Mobilise family support Remain optimistic If in hospital, use separations to reinforce that parents will return. Devastation of silence Denial can also be a coping mechanism Develop an acceptance of a new identity through the crisis: Seeing how the child is different Finding positives in this new identity and helping the family value these Achieve a sense of movement through the crisis. Mark positives and achievements of the family Encouraging compliance: For the highly compliant: teaching, directions For the non-compliant (those who respond yes but. Male = female + 13 cm or average their centiles) Family history: eg constitutional delay Systems Psychosocial Development Examination: Growth parameters Dysmorphic features ? Child more vulnerable to pain and stress-induced exacerbations Occurs at least monthly for a three-month period. May slow due to maternal drugs (eg pethidine) Tone: 2 for active movement, 1 for limb flexion Response to stimuli: On suction, 2 for coughs well, 1 depressed Apnoea: Primary Apnoea: pulse < 60 and cyanosis. Takes ~ 48 hours for ductus to close Other observations: Micturition: usually soon after birth, infrequent for first 24 hours Bowel: 99. Cystic Fibrosis, Hirshprungs Jaundice: 40% develop it, but transient, resolves by day 5 Vomiting: a little is common. Same range as adults when dressed appropriately st Weight: 1 3 5 days may loose 5 10% of birth weight. See Genetic Testing, page 465 Outcome after Preterm Birth At 27 weeks, 90% survive to discharge Definitions: Prematurity: < 37 = weeks Preterm, < 33 = weeks Very preterm Birth weight (? Associated with maternal infection Paediatrics 589 Frontal, usually watershed lesion Cysts long term spastic diplegia (legs worse than arm) Retinopathy of Prematurity: Abnormal vascularisation of retina following exposure to high O2 concentrations. Parents may need reassurance Non-organic failure to thrive: Inadequate parenting/poor nutrition the most common cause (will feed and gain weight well while in hospital). Harder for older women and professional who worked up to delivery to cope with ( sense of isolation post delivery) Colic: definitions vary from crying lots to well thriving baby who develops muscle spasms, flushing face, pulls up legs, screams. No energetic games beforehand Approach to Sleep Training: Agree with partner/family what you are going to do Plan in advance (eg start on a long weekend). Pakeha lower, Maori about 4 per 1000 Epidemiological risk factors: Age (3 5 months) Maternal smoking now greatest modifiable risk factor given sleeping on back well established Prone sleeping position ? Prevent by varying position of the head when lying th th 594 4 and 5 Year Notes Neonatal Acute Airway Problems Choanal Atresia: failure of formation of nasal passages. Beware the midline lesion Pierre Robin Sequence: short jaw, cleft palate and tongue falls back and obstructs. Associated with oligohydramnios Subglottic Stenosis: due to intubation trauma in a preterm baby Hypoglycaemia of the New Born Not a big deal, but needs to be recognised and managed Causes (either big babies or small babies): Hyperinsulin: Child of poorly controlled diabetic mother. Have high index of suspicion, low threshold for antibiotics Respiratory Distress Syndrome: X-ray appearance: Ground glass + air bronchogram surfactant. Used to be due to Rhesus negative disease prior to Anti-D treatment, now numerous other causes) Lung haemorrhage: complication in premature Primary lung disease Cardiac causes of cyanosis: R to L shunt: Cyanotic heart disease or pulmonary hypertension L to R shunt and Heart failure Differentiating Heart and Lung Disease: History and exam: When did it start Relationship of cyanosis to birth. If heart, pink to start with then go blue as ductus closes (blood gets to lungs via reverse flow through ductus if right heart not functioning well) Check respiration: If apnoea heart. Second most common congenital malformation after the brain Chromosomal eg Down Syndrome Single gene eg Marfans (prolapsing mitral valve) Environmental: Infection (eg Rubella) Maternal (eg Diabetes) Substance abuse (eg alcohol) Drugs (eg phenytoin, thalidamide) Usually leads to an abnormality in tissue migration Incidence (Pathology not Paediatrics numbers! Higher in stillborn and premature births Aetiology unknown in > 90% of cases Pathogenesis: Septum primum closes foramen primum at week 5. Incidence 1 in 2000 Pathogenesis: Connects aorta to left pulmonary artery (acts as R L shunt in foetus). Go blue as ductus closes Pulmonary Valve Stenosis Similar effect to pulmonary atresia Right heart development. Prevent recurrences with -blockers or ablation of re-entry pathway Ventricular Tachycardias: rare in children. Pockets in Porirua, South Auckland Acute attacks occur mainly between 5 15 years of age. Some at risk due to longer carriage of strep antibody response Pathogenesis: Group A -haemolytic streptococci infection (eg Streptococcus Pyogenes) cross reactive antibodies substances in myocardium similar to strep antigens to significant inflammatory reaction in cardiac muscle acute rheumatic fever 1 5 weeks following infection (average 19 day latent period). Can be red and swollen Dramatic response to aspirin Never permanent joint damage Chorea (St Vitus Dance): Sudden or gradual onset. Always consider as differential in pyrexia of unknown origin Chronic Phase: recurring attacks magnify cardiac injury. Prophylaxis for deep dental work (erythromycin or clindomycin wont have any penicillin sensitive organisms on board) Valves can recover Macroscopic appearance: Acute (exudative and proliferative) phase: Pancarditis grossly visible in valves and pericardium. Valve leaflets have evenly spaced small 1 2 mm sterile/inflammatory (not infective) verrucae small vegetations resulting from deposition of fibrin along edges of value. Verrucae resolve but Aschoff bodies (areas of necrosis surrounded by macrophages) organise and fibrose. May lead to murmurs or arrhythmias Microscopic appearance: Exudative phase: fibrinoid necrosis with neutrophils, lymphocytes, plasma cells and macrophages Proliferative phase: Aschoff body in the myocardium is pathognomonic. Consists of central fibrinoid exudate/necrosis with aggregates of large mononuclear or multinuclear cells (Aschoff giant cells), fibroblasts, plasma cells, lymphocytes and oedema. May get severe obstruction Adenoid and tonsillar hypertrophy: reaches peak at 8 10 years, but relatively largest at 5 6. Generally resolve Pneumo-mediastinum angel wing appearance as air lifts up thymus Chylothorax: lymph surrounding lung in the newborn ? Also, pre-term babies less likely to pass meconium when stressed Respiratory Tract Infections in Children Reference: Mainly from Prof Grimwoods extensive infectious diseases handout Epidemiology: Common: During the first 3 years of life, a child may have up to 6 episodes of otitis media, 2 episodes of gastro-enteritis and 6 respiratory infections per year. May take out adenoids at same time eustachian tube function (Paediatricians say adenoidectomy is treatment of choice). Treatment: get rid of infection then surgical repair Pharyngitis See Acute Pharyngitis, page 63 Almost 100% given broad-spectrum antibiotics. Air-fluid levels, opacification, mucosal thickening > 4 mm Maxillary and ethmoid sinuses present at birth (although small). Varies hour to hour (ie dont send them home just yet) Lasts 3 4 days then changes to sound productive. Few side effects (< 5% with local reactions) Notifiable disease Pertussis Bordetella Pertussis = Whooping Cough Epidemiology: Highly contagious. If severe may need suction In between paroxysms looks well, is afebrile and has no chest signs Median length: 6 weeks. Can be up to 12 weeks Infectious for 2 3 weeks of paroxysmal phase Persistent cough for 3 4 months (convalescent phase bacteria cleared) Treatment: if < 4 weeks duration: erythromycin. Doesnt impact illness after paroxysmal phase is established, but will infectivity Admit if under 6 months and/or cyanosis or apnoea in paroxysms Complications: Anoxic seizures in 1 3% Encephalopathy in 0. Rate of severe neurological complications of immunisation negligible compared with the risk of encephalitis from whooping cough Vaccine: Whole cell vaccine effective in 60 90%, has higher efficacy for more severe outcomes, local reactions or fever in 50%. Cyanosis is a late sign Feeding a good indicator of respiratory distress (and one which parents can monitor at home) Recurrence common (? Evidence of poor efficacy Nedocromil (Tilade + spacer) Inhaled steroids: if it makes no difference then stop Persistent Asthma Male: female = 4:1 Preventative. Collapsible airways Can become an unhappy wheezer when they get a cold, in which case treat as for bronchiolitis Bronchiolitis: See 610 Uncommon: Inhalation: If convincing episode of inhaling a foreign body (stridor, went blue, etc) should be bronchoscoped even if they you think they brought it all back up. Only consider if lots of serious illnesses th th 614 4 and 5 Year Notes Cilia dyskinesia: usually starts with ears (middle ear has respiratory epithelium with cilia), then lungs and sinuses. Associated with dextrocardia Hypogammaglobulinaema Can confuse wheezing with soft stridor: eg laryngomalacia. Eventually Cor Pulmonale Pancreas: fibrosis around ducts, dilated ducts, islets cells relatively preserved. White spots on cheery-red buccal mucosa for 24 hours before rash (Kopliks Spots) pathognomonic nd Treatment: Supportive, antibiotics for 2 ary infection Complications: Otitis media (10%) Pneumonia (1 5%) Encephalitis (0.

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Joint swelling following an injury Symptoms may be acute due to a haemarthrosis or appear more slowly due to an effusion cheap levothroid 100mcg online. Again this Joint disorders often have pain as their presenting fea- may be a mono order levothroid us, oligo/pauci or polyarthritis generic levothroid 100mcg online. Joint pain is described as arthralgia if there is no ac- bution of joint involvement should be elicited including companying swelling or as arthritis if the joint is swollen buy generic levothroid canada. The nature of the onset, duration, timing and timing and provoking and relieving factors are impor- exacerbating factors should be noted. Arthritis may involve a ated features such as joint instability should be enquired single joint (monoarticular), less than four joints (oligo about. The relationship to exercise may be important, as inamma- tory disorders are often worse after periods of inactivity Joint stiffness and relieved by rest, whereas mechanical disorders tend Joint stiffness is another presentation usually associated to be worse on exercise and relieved by rest. A full systems enquiry is necessary as are characteristic of rheumatoid arthritis but may oc- many disorders have multisystem involvement. Less than 10 minutes in sensation including tingling or numbness are often of stiffness is common in osteoarthritis compared with due to abnormalities in nerve function. Establishment of iacstiffnessisaparticularfeatureofankylosingspondyli- the distribution helps to differentiate peripheral nerve tis. Locking of a joint is a sudden inability to complete damage from nerve root damage. Loss of function is im- amovement, such as extension at the knee caused by a portant as therapy aims to both relieve pain and establish mechanical block such as a foreign body in the joint or necessary function for daily activities. Seropositivity allows prediction of severity and the need for earlier aggressive therapy and Although some of the available tests used in diagnosis increases the likelihood of extra-articular features. Combin- ing tests may allow a clinical diagnosis to be conmed Joint aspiration (see Table 8. Rheumatoid factor: These are antibodies of any class Unexplained joint swelling may require aspiration to directed against the Fc portion of immunoglobulins. The aspiration itself may be of therapeu- The routine laboratory test detects only IgM antibodies, tic value lowering the pressure and relieving pain. It is which agglutinate latex particles or red cells opsonised often coupled with intra-articular washout or instilla- with IgG. It is the presence of these IgM rheumatoid tion of steroid or antibiotic as appropriate. Examina- factor antibodies that is used to describe a patient as tion of the synovial uid may be of diagnostic value (see seropositive or seronegative. Local spread from a soft tissue infection atively birefringent, whereas the crystals of pseudogout may also occur. Previously Haemophilus inuenzae was seen in young children, Many modalities of joint imaging and direct visualisa- but it is now rare due to vaccination. Patients with tion are used to diagnose and follow the course of mus- sickle cell anaemia are prone to osteomyelitis due to culoskeletaldisordersandareoftenusedincombination. The ndings in individual conditions will be described r Direct spread from local infection may occur with later. Streptococcus, Staphylococcus, anaerobes and gram- r X-ray: Many musculoskeletal disorders have charac- negative organisms. Pathophysiology Comparison of X-ray changes over time is especially In children the long bones are most often involved; in useful in monitoring disorders that have a degenera- adults, vertebral, sternoclavicular and sacroiliac bones tive course. In- r Ulrasound is of value in examining the joint and sur- fections from a distant focus spread via the blood stream rounding soft tissue. In children the organisms usually diagnosing the cause of a painful hip not amenable to settle in the metaphysis because the growth disc (physis) palpation. Acute inammation occurs accompanied by a rise in It can demonstrate both bone and soft tissue disor- pressure leading to pain and disruption of blood ow. In children infectious conditions prior to X-ray changes, it is of the physis acts as a physical barrier to intra-articular great value in identifying malignant bone inltration spread. Bone and joint infections Clinical features Presentationrangesfromanacuteillnesswithpain,fever, swelling and acute tenderness over the affected bone, to Acute osteomyelitis an insidious onset of non-specic dull aching and vague Denition systemic illness. Complications Age r As thebonehealsandnewboneisformed,infectedtis- Normally seen in children and adults over 50 years. Aetiology Investigations Previously, chronic osteomyelitis resulted from poorly r The X-ray nding may take 23 weeks to develop. It now occurs more fre- raised periostium is an early sign that may be seen quentlyinpost-traumaticosteomyelitis. With healing there is sclerosis and seques- Pathophysiology trated bone fragments may be visible. Blood cultures are positive in the bone may remain dormant for years giving rise to 50%. Clinical features The clinical course is typically ongoing chronic pain Management r and low-grade fever following an episode of acute os- Surgical drainage should be used if there is a subpe- teomyelitis. There may be pus discharging through a si- riosteal abscess, if systemic upset is refractory to an- nus. However, if the pus is retained within the bone or tibiotic treatment or if there is suspected adjacent join the sinus becomes obstructed, rising pressure leads to an involvement. Par- enteral treatment is often required for a prolonged period (24 weeks) prior to a long course of oral an- Investigations tibiotics to ensure eradication. Theperiostiummayberaisedwithunderlying with a third-generation cephalosporin to cover for new bone formation. Management r Adequate analgesia is essential and may be improved Discharging sinuses require dressing, and if an abscess with splints to immobilise the limb (which also helps persists despite antibiotic therapy it should be incised to avoid contractures). Prolonged combined parenteral antibiotics to reduce associated muscle disuse atrophy and to are required. In early stages the joint space is preserved, but later there is narrowing and ir- Tuberculous bone infection regularity with bone erosion and calcication within adjacent soft tissue. Incidence Patients with tuberculosis have a 5% lifetime risk of Management developing bone disease. Chemotherapy with combination anti-tuberculous agents for 1218 months (see page 105). Rest and trac- tion may be useful; if the articular surfaces are damaged, Age arthrodesis or joint replacement may be required. Geography Septic arthritis Major illness in developing countries, with increasing Denition incidence in the developed world. Aetiology Tuberculous osteomyelitis is usually due to haematoge- Aetiology nous spread from a primary focus in the lungs or gas- Joint infection arises most commonly from haematoge- trointestinal tract (see pages 105 and 154). Other mechanisms include local trauma or creased the incidence of tuberculosis and tuberculous an adjacent infective focus such as osteomyelitis. The patient complains of pain and later swelling due to Pathophysiology pus collection. Muscle spasm and wasting occur with Bacteriaareinitiallyfoundinthesynovialmembranebut limitation of movement and rigidity. Cytokine-mediated losis, pain may be mild and presentation delayed until inammationandariseinintra-articularpressurefollow thereisavisibleabscessorvertebralcollapsecausingpain the spread of bacteria. Erosion of the articular cartilage results from the In previously healthy children and adults, penicillin release of proteolytic enzymes from neutrophils within (Streptococcus cover) and ucloxacillin (Staphylococ- the inammatory exudate. A third-generation cephalosporin enzymes can result in chondrocyte and bone damage. If the hip The classical features of septic arthritis are a red, hot, is infected it should be held abducted and 30 exed. Overall the Drainage of pus and arthroscopic joint washout under knee is the most commonly affected joint, but hips are anaesthesia can be performed. There may be evidence of the r Surgical drainage may be indicated if the infection source of infection such as a urinary tract infection, skin does not resolve with appropriate antibiotics or if per- orrespiratoryinfection. Arthroscopic pro- immobilised in the position that maximises the intra- cedures allow visualisation of the interior of the joint, articular volume (e. Movement of the joint r Surgerymayalsoberequiredfortheremovalofforeign is very painful and often prevented by pain and muscle bodies or infected prosthetic material. Complications r If treatmentisdelayedthereisseverearticulardestruc- Prognosis tion, which may heal by brosis with permanent re- Outcome is related to immune status of the host, viru- striction of movement, deformity or bony union.

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