Joseph Stavas, MD

• Associate Professor of Radiology
• University of North Carolina School of Medicine
• Chapel Hill, North Carolina

Neonatal alloimmune thrombocytopenia Thrombotic thrombocytopenic purpura (most cases) Non-immune Disseminated intravascular coagulation (p antibiotics for acne cause weight gain buy tetracycline with american express. The bone marrow smears may also reveal other features that indicate the nature of the disease if evidence has not already been obtained from the peripheral blood antimicrobial laundry detergent buy tetracycline 500mg with amex. Thus virus protection software purchase 500mg tetracycline mastercard, there may be a generalized aplasia of the bone marrow (aplastic anaemia) or a selective decrease in megakaryocytes caused by certain drugs antibiotic allergic reaction buy tetracycline 500mg cheap. Another cause of reduced platelet production is marked infiltration of the marrow by malignant cells antibiotic 7158 discount 500mg tetracycline. Reduced platelet production may also occur in patients with normal or increased numbers of megakaryocytes when there is ineffective megakaryocytopoiesis infection knee joint buy 250 mg tetracycline amex, as in severe vitamin B12 or folate deficiency or in myelodysplastic syndromes. The disease is almost always self-limiting when there is a history of preceding infection. Spontaneous cures are rare and the disease is characterized by relapses and remissions. The remainder also have bleeding from the following sites in decreasing order of frequency: nose, gums, vagina (menorrhagia) and gastrointestinal and renal tracts. Shortened platelet survival If the megakaryocytes in the marrow are numerous, then the thrombocytopenia is usually due to an excessive rate of removal of platelets from the peripheral circulation. Diagnosis Children with the appropriate clinical features, acute thrombocytopenia and an otherwise normal blood count. A marrow aspiration also serves to exclude other causes of thrombocytopenia, such as aplastic anaemia, leukaemia or marrow infiltration by carcinoma cells, lymphoma cells or myeloma cells. The pathogenic mechanism was previously thought to be due to IgG autoantibodies that result in a shortened platelet lifespan due to premature destruction in the spleen. It is now accepted that more complex mechanisms in which both impaired platelet production and T cell-mediated effects play a role. Corticosteroids are widely used: they increase the platelet count and so reduce the duration of thrombocytopenia. High doses of intravenous immunoglobulin (Ig) cause a rapid increase in the platelet count and are administered, with or without corticosteroids, to children with severe thrombocytopenia or life-threatening haemorrhage. Adults are often started on prednisolone 60 mg/day and the dosage reduced gradually after a remission is achieved, or after 4 weeks. However, in only a third of patients who initially have a complete remission is the remission long lived. Azathioprine, cyclophosphamide, danazol, dapsone, cyclosporine A, mycophenolate mofetil and rituximab have all been used, particularly in patients who fail to respond to splenectomy. Ig probably acts by interfering with platelet destruction by inhibiting the binding of the Fc portion of the IgG antibodies on the platelet surface to Fc receptors on macrophages. Most recently, thrombopoietin-receptor agonists (romiplostin and eltrombopag) have been shown to be effective in clinical trials. Transient but potentially serious neonatal alloimmune thrombocytopenia may occur in babies of healthy mothers. This is a serious illness characterized by widespread arteriolar platelet thrombi leading to fragmentation of red cells, thrombocytopenia, neurological symptoms and renal impairment. It is an important diagnosis to make because the untreated mortality is 90%, which can be reduced with the prompt delivery of plasma exchange. The haemolytic uraemic syndrome is an apparently similar disorder affecting infants, young children and the elderly in which the arteriolar thrombi are predominantly formed in the kidneys; in some patients, the disease follows a bout of diarrhoea caused by verotoxin-producing Escherichia coli or shiga toxin-producing Shigella dysenteriae. Drug-induced immune thrombocytopenia Certain drugs such as heparin, gold salts, quinine, quinidine, sulphonamides or penicillin cause a short- 120 Haemostasis, abnormal bleeding and anticoagulant therapy Increased splenic pooling A normal spleen contains within its microcirculation about 30% of all the blood platelets; the platelets in the splenic pool exchange freely with those in the general circulation. Another factor contributing to the thrombocytopenia in patients with splenomegaly is an increase in plasma volume. It can occur alone or in the patients with HermanskyPudlak syndrome, when it is combined with albinism and ocular defects. Platelet transfusions It is often possible to raise the platelet count temporarily by platelet transfusions. Transfusion may also be indicated in a patient with thrombocytopenia or defective platelet function prior to surgery. When thrombocytopenia results from excess destruction caused by platelet antibodies, the response to transfusion is poor. Platelets are transfused as platelet concentrates and should be given within five days of withdrawal from the donor. Abnormalities of platelet function Acquired An acquired defect of platelet function is found after ingestion of aspirin and other antiplatelet drugs. Aspirin acts by irreversibly acetylating cyclo-oxygenase and this inhibits thromboxane A2 synthesis, with a subsequent reduction in platelet aggregation. Other causes of an acquired abnormality of platelet function include chronic myeloproliferative disorders, myelodysplastic syndromes, paraproteinaemias. The essential feature of the cascade is the presence of a number of steps activated in sequence. Each step is characterized by the conversion of a zymogen (proenzyme) in to an enzyme by the splitting of one or more peptide bonds, which brings about a conformational change in the molecule and reveals the active enzyme site. Inheritance is autosomal recessive and platelets are normal in morphology and number. Bernard-Soulier disease this is a platelet disorder caused by a lack of glycoprotein Ib receptors. Storage pool diseases these are inherited conditions resulting in defective platelet granules. Thrombin splits two small negatively charged peptide fragments (fibrinopeptides A and B) from fibrinogen (factor I), thus removing repulsive forces from the molecule and allowing the remainder to polymerize and form the fibrin fibre. Hence bleeding in thrombocytopenia results from a failure of the clotting cascade as well as the lack of a platelet plug. The extent of thrombin generation is limited by a number of natural anticoagulant mechanisms. Another plasma protein, high molecular weight kininogen, is a non-enzymatic accelerator of these interactions. Small amounts of plasmin are also generated from plasminogen by urokinase, which is produced mainly by renal cells but also other cell types such as endothelial cells. Under normal conditions, any plasmin released from the fibrin in to the circulation is immediately inactivated by combining with the liver-derived plasma inhibitors, 2-antiplasmin and 2-macroglobulin. In this way, generalized breakdown of fibrinogen and other proteins does not occur. Second, there is a variation in the coagulation-potentiating activities supplied by the platelets, as platelet numbers vary considerably between individuals. Citrated plasma (which does not clot because of a lack of calcium) is obtained and to this is added a mixture of contact activator and phospholipid followed by calcium, and the time taken for the mixture to clot is measured. There is a group of patients who complain of excessive bleeding, either spontaneous or following trauma, usually starting early in life, and who frequently have a family history of a similar condition. A female with a genetic defect on one X-chromosome will transmit the disease to half her sons, and half her daughters will become carriers. Patients suspected of having haemophilia should be carefully questioned for a history of a bleeding disorder occurring in the relations on the maternal side as opposed to the paternal side. Genetic mutational analysis allows carriers to be identified with accuracy and is the method of choice. Various abnormalities in the nucleotide sequence of this gene have been identified in about half the cases of haemophilia, ranging from single-point mutations to large deletions. Daughters of males with haemophilia are obligatory carriers of the gene, since they must inherit the abnormal X-chromosome. Haemophiliacs rapidly become expert at diagnosing the onset of haemorrhage in its earliest stages, allowing treatment to be initiated at a time when it can be most effective. In addition, virtually all people treated for severe haemophilia before 1985 were infected with hepatitis C virus due to the use of non-virally inactivated factor concentrates. Treatment Treatment should be given at the earliest sign of spontaneous or post-traumatic bleeding. It should also be given prophylactically if any type of operation is contemplated. Such early therapy results in both rapid cessation of bleeding and rapid recovery. Von Willebrand disease this is the most common inherited bleeding disorder, with a prevalence of up to 1%, although most mild cases are undiagnosed. This observation is the basis of a useful laboratory test for the diagnosis of this disease. Spontaneous bleeding is usually confined to mucous membranes and skin and takes the form of epistaxes and ecchymoses, bleeding after dental extraction and menorrhagia. Acquired coagulation disorders the hepatocytes are the major cell type involved in the synthesis of all the coagulation factors. Hence, severe liver disease may result in bleeding, due both to a deficiency of several coagulation factors and to an abnormality in the structure and function of fibrinogen, as well as thrombocytopenia due to hypersplenism. The coumarin drugs are vitamin K antagonists and their administration results in only partial carboxylation of the prothrombin group of coagulation factors, which are consequently considerably less active than normal in the clotting cascade. Similar abnormalities are seen in vitamin K deficiency, which may be found in the newborn (haemorrhagic disease of the newborn), in patients with intestinal malabsorption and, since bile salts are required for vitamin K absorption, also in patients with biliary obstruction or biliary fistulae. It is a common complication following intravascular haemolysis of red cells after a mismatched transfusion. The syndrome also occurs occasionally after extensive accidental or surgical trauma, particularly following thoracic operations. Activation of the cascade leads to the generation and dissemination of large amounts of thrombin in the circulation, the activation of platelets and the formation of intravascular microthrombi. If this is sufficiently extensive, there is a reduction of the concentration of fibrinogen and other clotting factors in the plasma, which impairs haemostatic activity. As a consequence of the fibrin formation, the fibrinolytic mechanism is activated (p. They include petechiae, ecchymoses and bleeding from the nose, mouth, urinary and gastrointestinal tracts and vagina. There may be digital gangrene, adult respiratory distress syndrome, neurological signs and renal failure. The best method for the estimation of fibrinogen is based on the time taken for a diluted sample of plasma to clot in the presence of high concentrations of thrombin (the Clauss method). The thrombin time is determined by adding low concentrations of thrombin to citrated plasma and measuring the time for the appearance of a clot. D-dimers can be detected by rapid immunological tests in which latex particles coated with monoclonal antibody directed against D-dimer are agglutinated by Ddimers present in plasma. Treatment Since the activation of the clotting system is the primary initiating stimulus and fibrinolysis is mainly a secondary phenomenon, treatment is aimed at preventing further coagulation by removal of the initiating cause. It can occur in either sex, is more common in the elderly and has a high mortality. Anticoagulant drugs the two most frequently used anticoagulant drugs are heparin and vitamin K antagonists such as warfarin. Heparin does not cross the placenta and is therefore the preferred drug when anticoagulation is required during pregnancy. Long-term warfarin is also used after the insertion of mechanical heart valves and in patients with atrial fibrillation. However, the treatment of choice is now low molecular weight heparin given subcutaneously once a day with no monitoring (because of the high predictability of effect when given according to body weight). Either standard or, more usually, low molecular weight heparin is administered subcutaneously to prevent venous thrombosis in hospitalized patients at risk of thrombosis. Haemorrhage due to overdosage is managed by stopping the heparin and, if necessary, by giving protamine sulphate intravenously. Warfarin sodium Heparin Standard unfractionated heparin is an acidic mucopolysaccharide (average molecular weight 1. Examples of low molecular weight heparins currently in use are dalteparin, enoxaparin and tinzaparin. There are many possible causes for loss of control of warfarin therapy, including the simultaneous use of drugs that affect warfarin metabolism by cytochrome P450 and changes in dietary vitamin K. Bleeding is 130 Haemostasis, abnormal bleeding and anticoagulant therapy controlled by stopping the warfarin by administering vitamin K and, if necessary, administering prothrombin complex concentrates.

Obesity is a risk factor for serious diseases including ischaemic heart disease treatment for sinus infection from mold purchase cheapest tetracycline, hypertension antibiotic resistance developing countries tetracycline 500mg on-line, Drugs and endocrine disease type 2 diabetes mellitus virus yugioh buy cheapest tetracycline and tetracycline, stroke and certain malignancies antibiotic medicine order tetracycline 250mg without prescription. It is also associated with obstructive sleep apnoea antibiotic xifaxan colitis tetracycline 500mg with amex, osteoarthritis antibiotics for uti online discount tetracycline 250 mg overnight delivery, gallstones and varicose veins. It results from energy intake in excess of energy expenditure over a prolonged period of time. Genetic factors, environmental change (sedentary lifestyle with an abundance of energy-rich foods) and potentially, alterations in neurotransmitters that influence appetite. Adverse effects the most frequent adverse effects are loose oily stools and faecal urgency, and oily rectal discharge. The potential for impaired absorption of fat-soluble vitamins and concomitant medications. Bone metabolism Clinical scenario A 60-year-old postmenopausal woman attends a well woman clinic. She is a long-term smoker with no other health problems until she fractured her scaphoid 3 months previously. A bone densitometry test was done showing that she has moderately severe osteporosis with a T-score of -3 at femoral neck, and -2. A 10% weight loss is a reasonable initial aim and is associated with a reduction in mortality and morbidity. Non-pharmacological therapy A reduction in dietary calorie intake, increased energy expenditure through exercise and behavioural modification are fundamental aspects of obesity management. Introduction the drugs described in this section are used in the management of disorders of bone structure. Drug treatments of obesity Drug treatment can be used as an adjunct to diet and exercise in patients who are obese or overweight with significant co-morbidity. Several drugs have been licenced over the years but the majority have been withdrawn because of safety concerns. Calcium salts these are used in the management of: 1 Dietary deficiency 2 Prevention and treatment of osteoporosis 3 Hypocalcaemia due to malabsorption or hypoparathyroidism 4 Hyperphosphataemia 5 Cardiac dysrhythmias associated with hyperkalaemia Dietary deficiency is more likely during childhood, pregnancy and breast feeding, due to increased demand, and in the elderly, due to reduced absorption. Pancreatic lipase inhibitors (Orlistat) Mechanism Orlistat binds to the active site of pancreatic lipases and slows the breakdown of dietary fat in the gastrointestinal tract. Pharmacokinetics Orlistat is given orally, has its effect locally in the gut and is excreted in the faeces. Calcium preparations Calcium salts used orally in divided doses include calcium gluconate, calcium lactate and calcium carbonate. Calcium carbonate Clinical use and dose When used as part of a weight-control programme, average weight loss of 10% in a year has been observed. A dose of 120 mg is taken immediately before or within an hour of each main meal (up to 164 Drugs and endocrine disease binds phosphate in the gut and is used to treat the hyperphosphataemia seen in renal failure. Calcium gluconate is given intravenously in the treatment of hypocalcaemic tetany and in the treatment of cardiac dysrhythmias caused by severe hyperkalaemia. All patients receiving pharmacological doses should have monitoring of their serum calcium. Some anti-convulsants induce the enzymes that metabolise vitamin D and cause increased requirements. In humans, the main source of vitamin D (cholecalciferol/calciferol) is from the photoactivation of 7-dehydrocholesterol in the skin. This undergoes hydroxylation in the liver to 25-hydroxycholecalciferol and in the kidneys to the active metabolite 1,25-dihydroxycholecaciferol (calcitriol). A range of vitamin D compounds are available for therapeutic use, including ergocalciferol, calciferol, alfacalcidol (1-hydroxycholecalciferol) and calcitriol (1,25-dihydroxycholecalciferol). Bisphosphonates Mechanism Bisphosphonates are a family of carbon-substituted pyrophosphates that bind avidly to bone. They have an inhibitory action on osteoclasts and therefore reduce bone resorption. Substitution of different chemical moieties at the carbon atom produces compounds with differing potencies (Table 12. Between 20 and 50% of the absorbed drug binds to bone within 24 hours where it remains for many months, possibly years, until the bone is resorbed. Calcium and other chelating agents reduce the absorption of bisphosphonates from the gastrointestinal tract. Bisphosphonates should be taken with plain water on an empty stomach first thing in the morning at least 30 minutes before breakfast or, if taken at any other time of day, food and drink should be avoided for 2 hours before and after the dose. Mechanism the main action of vitamin D compounds is to facilitate intestinal absorption of calcium and phosphate. They also promote calcium mobilisation from bone and increase calcium reabsorption in the kidney tubules. Vitamin D undergoes enterohepatic circulation and is largely eliminated in the faeces. Bisphosphonates are associated with an increase in bone mineral density and a significant Clinical use and doses the clinical uses and doses of various vitamin D preparations are outlined in Table 12. Bisphosphonates have been found to reduce complications (including pathological fracture) associated with advanced multiple myeloma and metastatic bone disease. They have a number of gastrointestinal side effects including nausea, diarrhoea, and oesophageal irritation and ulceration. To minimize these effects, patients are advised to take bisphosphonates in the morning on an empty stomach, sitting or standing upright and washed down with a glass of water. Intravenous use of bisphosphonates can be associated with transient pyrexia and flu-like symptoms. Denosumab therefore inhibits osteoclast formation, decreasing bone resorption, and thereby increases bone mineral density and reduces fracture risk. Alendronate and risedronate are given as a once-daily or once-weekly regimen and oral ibandronate has a daily or monthly dosing schedule. Intravenous bisphosphonates (pamidronate, clodronate and zolendronate) are used in the treatment of severe hypercalcaemia. They should not be used until there has been adequate intravenous saline rehydration (with furosemide diuresis if salt and water retention occurs). Adverse effects Denosumab is generally well tolerated, and has been associated with hypocalcaemia. Hormone-replacement therapy Mechanism Oestrogen suppresses osteoclast-mediated bone resorption. Pharmacokinetics Orally administered oestrogens undergo extensive first-pass metabolism by the liver. Calcitonin Mechanism Calcitonin is a peptide hormone synthesised by the parafollicular cells within the thyroid gland. Calcitonin reduces bone resorption by decreasing the number and activity of osteoclasts. Calcitonin is associated with a reduction in the incidence of osteoporotic vertebral fractures. A daily dose of 100 units (subcutaneous or intramuscular injection) or 200 units (intranasally) is used. Calcitonin has potent analgesic properties and can be used in the management of acute fracture pain. Calcitonin can be used to treat severe hypercalcaemia following saline rehydration and furosemide diuresis. It is usually reserved for cases who have not responded to intravenous bisphosphonates. Bone pain in neoplastic disease can be treated with 200 units of calcitonin 6-hourly or 400 units 12-hourly. Raloxifene has agonist action on bone and the cardiovascular system and antagonist action on mammary tissue and the uterus. Their action on bone causes a reduction in osteoclast activity and an increase in bone mineral density. Raloxifene undergoes extensive first-pass metabolism and has a bioavailability of around 2%. It has a half-life of approximately 32 hours and after metabolism is excreted in the faeces. Clinical use and dose Raloxifene is used in the treatment and prevention of postmenopausal osteoporosis at a daily dose of 60 mg. Drugs and endocrine disease 167 Teriparatide Mechanism Teriparatide is a recombinant peptide composed of 34 amino acids identical to the active region of parathyroid hormone. It stimulates osteoblasts, and increased bone formation and improved bone architecture are seen. A reduction in fractures has been demonstrated in postmenopausal patients with established osteoporosis. It has a half-life of approximately 1 hour and is thought to be metabolised by the liver and excreted by the kidneys. In adults, there is some evidence that replacement improves quality of life and has favourable effects on lipid profile, bone mineral density and lean body mass. Cranial diabetes insipidus Cranial diabetes insipidus is due to deficiency of circulating arginine vasopressin (anti-diuretic hormone). In patients with an intact thirst mechanism, it presents with polyuria and polydipsia. In patients with an absent thirst mechanism (sometimes seen in head injury and hypothalamic syndromes) polyuria is seen without polydipsia, which can result in severe hypernatraemia. There is wide variation in the doses required, and monitoring of the serum sodium and osmolality is essential. The activity of this enzyme increases during pregnancy and dose requirements increase in pregnancy. Clinical use and dose Teriparatide is used in the treatment of established osteoporosis. Preclinical toxicology data showed a high incidence of osteosarcoma in rats given high doses of the drug. To date, development of osteosarcoma has not been reported in the clinical trials of teriparatide. Strontium ranelate Strontium ranelate promotes bone formation by stimulating osteoblast activity and inhibiting osteoclasts. It is associated with a reduction in vertebral and non-vertebral fractures in established osteoporosis. Drug treatment of pituitary tumours Dopamine agonists Mechanism Dopamine agonists cause activation of D2 receptors. Pituitary and adrenal cortex disease Hypopituitarism Partial or complete deficiency of anterior pituitary hormones can arise from conditions including pituitary tumours, pituitary infarction or following surgery or radiotherapy. It can result in inadequate production of thyroid hormones, adrenal steroids, sex steroids and growth hormone. Tumour shrinkage can be seen and is more likely if the tumour co-secretes prolactin. Adverse effects Gastrointestinal side effects are common and include nausea, abdominal pain and mild steatorrhoea. In primary adrenal failure there is deficiency of the glucocorticoid, cortisol and also the mineralocorticoid, aldosterone. Glucocorticoid replacement is usually with hydrocortisone although prednisolone or dexamethasone can be used. The dose is divided to mimic the normal diurnal pattern of cortisol production; a typical regimen would be 10 mg on waking, 5 mg at midday and 5 mg at 6 p. The replacement dose needs to be increased during times of intercurrent illness, surgery or major physiological stress. Fludrocortisone is a synthetic steroid that has high affinity for the mineralocorticoid receptor. It is also produced in neuroendocrine cells in the gastrointestinal tract where it inhibits the release of numerous gut peptides including gastrin, glucagon and insulin. A reduction in growth hormone is seen in approximately 60% of patients and tumour shrinkage can occur. She has had no previous pregnancies, but would like to start a family before she is 30. Both of the naturally occurring steroids, oestradiol (estradiol) and progesterone, are ineffective if taken orally because of extensive first-pass metabolism; thus, synthetic compounds are used in hormonal contraception. Synthetic progesterones (called a progestogen) are mainly derivatives of 19-nortestosterone. Introduction Hormonal contraception offers the most effective method of reversible fertility control available to women of childbearing age.

Causes or contributing factors to upper airway obstruction include aspiration bacteria unicellular purchase tetracycline 500mg mastercard, laryngeal injury medication for uti relief proven 250mg tetracycline, mandibular injury antibiotics for acne erythromycin buy generic tetracycline on-line, penetrating tracheal injury and posterior sternoclavicular injury antibiotic resistance examples generic tetracycline 500mg free shipping. There are six causes of life-threatening respiratory compromise that must be sought in the primary survey: 1 antibiotics history order tetracycline 250mg otc. Upper airway obstruction Tension pneumothorax Open pneumothorax Flail chest Massive haemothorax Cardiac tamponade oral antibiotics for acne vulgaris generic tetracycline 250 mg free shipping. The present evidence strongly supports a policy of early skeletal stabilization of all major long-bone fractures. Minor fractures or relatively stable metaphyseal or articular fractures can be splinted during the acute phase and undergo later reconstruction when the patient is stabilized. These more severely traumatized patients have a higher incidence of neurovascular injury and compartment syndrome associated with the fractures sustained, and these complications should be carefully sought during the secondary survey. Abdominal distension, absent bowel sounds, and guarding or rebound tenderness suggest an intra-abdominal injury. Abdominal ultrasonography is more sensitive but is dependent on the skill of the user. Blunt abdominal trauma with hypotension and evidence of intraperitoneal blood loss 2. The initial assessment and management of the multiple-trauma patient with an associated spine injury. Their bone is more porous and less dense than adult bone, but the periosteum is much thicker. On the other hand, the metaphyseal region is generally oval in cross-section and there is relatively less cortex with respect to the medulla. If forces are applied to the bone it is more likely to fail in the metaphyseal region and this accounts for the large number of metaphyseal injuries of long bones seen after low-velocity trauma in children. The first four will be considered here and physeal injuries in the section on growth plate injuries. The fracture patterns result from the direction and amount of energy that has been applied to the bone. Eventually the bone will fail on the tension side whilst the compression side will continue to bend, thus producing the characteristic greenstick fracture. More energy applied to the bone will cause a complete fracture of the compression side. An axial or longitudinal force applied to a long bone in a child may produce buckling of the metaphysis. Torus is the name given to the band around the base of a Grecian column and in geometry represents the shape of a doughnut. These may also be comminuted (those containing more fragments of bone other than the proximal and distal components) or segmental (the same bone has been broken at two distinct sites). Spiral fractures are produced as a result of rotational forces being applied to the bone; they are usually low-velocity injuries and may arise where one part of a limb is fixed relative to another. Oblique fractures are unstable and arise as a result Normal bone Plastic deformation Compression side Greenstick fracture Complete fracture Box 11. Physes are more susceptible to injury from rotational forces rather than angulation or traction. The type I injury is a fracture through the physis without involving the bone of the metaphysis or epiphysis. A growth arrest may cause an angular deformity because the uninjured part of the physeal plate continues to grow whilst the arrested side does not. Type V is a compression injury to the physis and, like type I injuries, it does not involve the bone of the metaphysis or epiphysis. The injury may be diagnosed only in retrospect if a partial growth arrest of the plate becomes evident later. The diagram shows how the periosteum can be used as an intact tether on the dorsal side of the fracture to assist in reducing and maintaining the reduction. Here it is not possible to reduce the epiphyseal injury because the periosteum has folded in to the fracture and this has to be retrieved from the fracture surgically. For example, a femoral fracture in a 5-year-old will have united by about 5 weeks, yet for an adult may take 20 weeks. Part of the periosteum will be torn in a fracture, but the intact part can be used to ensure fracture stability after reduction. Physeal reorientation also occurs as a result of asymmetrical forces placed across the physis due to the residual angulation. As malrotation does not remodel, it is essential that fractures, particularly of the forearm, femur and tibia, are reduced correctly. The prevalence of non-accidental fractures is between 11% and 55% of physically abused children, depending on the age of the population studied. Distinguishing abusive from accidental fractures is crucial to the protection of children, but the evidence on which to base decisions is scanty. Some 80% of children with abusive fractures are less than 18 months old, whereas 85% of accidental fractures occur in children older than 5 years. High-quality radiographs and interpretation by a skilled paediatric radiologist will increase the fracture detection rate. In one large study the distribution of affected sites were long-bone diaphyses (36%), ribs (26%), metaphyses (23%) and skull (15%). A recent systematic review of fractures in child abuse has shown that rib fractures in children without explicit explanation have the highest specificity for abuse. For other fractures, factors that should be taken in to account are: the age and developmental stage of the child; the number of fractures present; and the details of the reported mechanism of injury. Be aware of the referral pathways to senior colleagues with specialist skills to help you assess whether the child has been abused. Note that sometimes the autosomal dominant disorder hereditary multiple exostosis presents with rib exostosis, which can be misinterpreted as healed rib fractures. Discuss with a radiologist about the necessity for further radiological investigations. Where a non-accidental fracture is suspected in a child aged less than 2 years, a full skeletal survey must be performed to exclude occult fractures. A multi-agency child protection enquiry should be commenced by contacting the social services department, which should in turn discuss the case with the police. Social services have a statutory responsibility to make enquiries when concerns are expressed about a child, whereas the police have a duty to investigate. A multi-agency meeting, attended by parents (case conference), is the forum where professionals decide, based on the available information, whether the child has suffered harm. If so, the child is placed on the Child Protection Register and a Child Protection Plan is agreed to ensure the safety and wellbeing of the child. Patterns of fractures in accidental and non-accidental injury in children: a comparative study. Follow your local as well as national guidelines to ensure the safety of the child. A small proportion of these patients have high-energy trauma and in these cases there is an association with brachial plexus injuries and vascular injury. Clinical assessment should include an assessment of the neurovascular status of the upper limb. Patients should be advised to avoid overhead activity for the first 6 weeks and heavy manual work for 3 months. In adults, radiographs should be obtained at 2 weeks, 6 weeks and 3 months to ensure the fracture progresses to union. In children, complications are unusual; very few require any additional treatment and the fracture heals rapidly. Full function can be expected, but the child and parents will be aware of a swelling over the fracture for several months after healing. The lateral aspect of the clavicle is attached to the scapula by strong coraco-clavicular ligaments. If these are disrupted, the weaker acromio-clavicular joint ligaments can be disrupted allowing superior displacement of the clavicle in relation to the acromion. Patients with a vascular injury or brachial plexus palsy will usually require plating of the clavicle. Non-union occurs in 10% of adult clavicular fractures and is more common in mid-shaft fractures with more than 1 cm of displacement or with comminution. Non-union of mid-shaft fractures can be treated successfully in most cases with plating. In lateral third fractures, delayed union or non-union is the norm if the coraco-clavicular ligaments are ruptured, which results in superior migration of the medial fragment. This injury is not usually seen in the younger child, but may be seen in adolescents. However, occasionally the clavicle is widely displaced and comes to lie in a subcutaneous position. They have a well recognized association with rib fractures, clavicle fractures, brachial plexus injuries and intra-thoracic injury. The most important aspect of management is identification of the associated injuries. Although most scapular fractures can be treated non-operatively, fractures involving the glenoid fossa with significant displacement are best treated by internal fixation. There are three common the gleno-humeral joint is the most frequently dislocated major joint. The humeral head dislocates in an anterior dislocation and comes to lie medial to the glenoid, just below the coracoid process. Posterior dislocation also occurs, but is uncommon, and accounts for less than 5% of shoulder dislocations. It is often associated with high-energy trauma, an epileptic fit or as a consequence of an electric shock. There is swelling and deformity of the shoulder, and the humeral head is 142 trauma palpable in the anterior sub-coracoid position. Posterior dislocations are less obvious on physical and radiographic examination, but one key clinical feature is that the gleno-humeral joint is fixed in internal rotation. If there is a history of unusual trauma, and the shoulder is in fixed internal rotation, it should be assumed there is a posterior dislocation. Axillary or modified oblique views are better for diagnosis of posterior dislocation. Axillary nerve injury, brachial plexus palsy and rotator cuff tears are all well recognized complications of gleno-humeral dislocation and should be looked for clinically. Occasionally general anaesthesia is required and should always be used in a child. Posterior dislocations are often associated with an impaction fracture of the humeral head, which becomes locked on the edge of the glenoid, rendering closed reduction difficult. In patients over the age of 40 years this is less of a risk and early mobilization is encouraged. In younger patients the main risk is recurrent dislocation; in those under 20 years of age the risk is 80%. In patients over the age of 40 years, rotator cuff tears and nerve injury are more frequent. Nerve injuries (most commonly the axillary nerve) can be treated non-operatively as they recover spontaneously in 95% of cases. Rotator cuff tears are easily missed because they are difficult to diagnose at presentation after reduction of the dislocation owing to pain and limited motion. Most of these fractures are not markedly displaced and unite reliably with non-operative treatment in a sling in a few weeks. Wide displacement of the fragments or the presence of displaced tuberosity fragments warrants consideration of internal fixation or humeral head replacement. Non-operative treatment is associated with a high rate of mal-union and shoulder stiffness, but operative treatment in osteoporotic bone seldom produces superior functional results, except in the most displaced fracture patterns. In children the injury may involve the physeal plate (see section on physeal injuries) or the proximal metaphysis. Most injuries can be treated non-operatively and, even if there is noticeable angulation at the fracture site, the proximal humerus has excellent potential for remodelling in the child.

However bacteria 4 cheap 250mg tetracycline with amex, the success rate for redo surgery does not equal to that of the initial antire ux surgery how antibiotics for acne work cheapest tetracycline. Little et al reported that 84% of patients undergoing the rst redo antire ux surgery achieved a satisfactory result virus joint pain purchase tetracycline toronto, but only 42% of patients with three or more previous reoperations had a satisfactory result infection 1d order discount tetracycline on line. It is extremely important to identify the etiology of symptoms in order to choose an appropriate treatment option infection in bloodstream order tetracycline mastercard. However antibiotics zoloft buy cheap tetracycline 250mg on-line, good-to-excellent results can be achieved in more than 80% of patients using minimally invasive techniques at an experienced center. Since then, further evaluation and subclassi cation of hiatal hernias has occurred. Sliding hiatal hernias may be more likely to progress in patients who are obese, pregnant, or have a chronic cough. Colon, small bowel, pancreas, spleen, omentum, and liver can migrate in to the true anterior or posterior hernia sac. In addition to obstruction of the stomach, colon, or small bowel, there is the potential for compromised blood ow to the organs that are displaced intrathoracically. Other etiologies that cause increases in intra-abdominal pressures (obesity, constipation, and abdominal ascites) are also implicated. A reducible short esophagus is foreshortened, but with extensive mediastinal mobilization 2. In these cases, urgency is essential as timely diagnosis and emergent operative intervention can mean the di erence between reduction of the hernia and repair and subtotal gastrectomy or death. Laparoscopic repair significantly decreases postoperative complications and is the procedure of choice in most centers. The tenants of surgical repair include sac excision with complete reduction of the hernia from the mediastinum, establish tension-free esophageal length, repair the diaphragmatic crura, and perform an antireflux procedure. In cases where there is concern for incarceration or strangulation, exible endoscopy is a valuable diagnostic test of mucosal viability and enables gastric decompression. However, up to 80% may demonstrate improvement following surgical repair of the hiatal hernia. Esophageal manometry will determine whether there is A left posterolateral thoracotomy is performed with a planned entry at the seventh interspace. When the right crus is identi ed, the gastrohepatic ligament is divided to the level of the left gastric artery. Once the fundus is restored to its normal anatomic position, the crural approximation stitches are placed, but not tied. During mobilization of the anterior esophageal fat pad, the vagus nerves need to be identi ed and protected. A fundoplication is then performed as described in section on Nissen fundoplication. Dissection in the correct plane is generally free of hemorrhage and provides excellent visualization of the pleura, esophagus, and vagus nerves. Circumferential mobilization facilitates reduction of the entire hernia sac in to the abdomen, thus returning the stomach to its normal anatomic position. If aggressive esophageal mobilization fails to produce an appropriate length of esophagus, an esophageal lengthening procedure is performed using a stapled wedge gastroplasty. With a median follow-up of 72 months, anatomic recurrence was identi ed in 2%, postoperative morbidity in 19%, and mortality in 2%. Very early experience of small, retrospective case reports was that these reports were able to demonstrate feasibility with good outcomes over a short follow-up. Dashed line indicates the planned wedge gastroplasty in patients with less than 3bcm of tension-free, intra-abdominal esophagus. However, over the past decade there has been a considerable evolution of the technique, and the feasibility and safety of the laparoscopic approach have been well established. In the subset of these patients with a minimum follow-up of 5 years and a median of over 6 years, these results are durable and show unchanged rates of recurrence or reoperation. A 48F bougie is placed and the surgeon left hand port is enlarged to accommodate a roticulating stapler. Development of the 24-hour intraesophageal pH monitoring composite scoring system. Gastroesophageal re ux disease and connective tissue disorders: pathophysiology and implications for treatment. Esophageal mucosal damage may promote dysmotility and worsen esophageal acid exposure. Speci city and sensitivity of objective diagnosis of gastroesophageal re ux disease. Role of the lower esophageal sphincter, esophageal acid and acid/alkaline exposure, and duodenogastric re ux. Unbu ered highly acidic gastric juice exists at the gastroesophageal junction after a meal. Twenty-four hour ambulatory simultaneous impedance and pH monitoring: a multicenter report of normal values from 60 healthy volunteers. Omeprazole 10 milligrams once daily, omeprazole 20 milligrams once daily, or ranitidine 150 milligrams twice daily, evaluated as initial therapy for the relief of symptoms of gastro-oesophageal re ux disease in general practice. Combined pH-metry/impedance monitoring increases the diagnostic yield in patients with atypical gastroesophageal re ux symptoms. Acid and non-acid re ux in patients with persistent symptoms despite acid suppressive therapy: a multicentre study using combined ambulatory impedance-pH monitoring. Asthmatics with gastroesophageal re ux: long term results of a randomized trial of medical and surgical antire ux therapies. A recent paper by Stadlhuber and associates reports that complications from mesh reinforcement of the esophageal hiatus may be underreported. While open repairs using transthoracic and transabdominal approaches have resulted in low complication rates and mortality, the laparoscopic repair, in experienced hands, results in excellent outcomes and is safe. Brazilian consensus on gastroesophageal re ux disease: proposals for assessment, classi cation, and management. Nighttime heartburn is an under-appreciated clinical problem that impacts sleep and daytime function: the results of a Gallup survey conducted on behalf of the American Gastroenterological Association. Esophageal function in patients with angina-type chest pain and normal coronary angiograms. Comparison of wireless 48-h (Bravo) versus traditional ambulatory 24-h esophageal pH monitoring. Chapter 15 Gastroesophageal Re ux Disease and Hiatal Hernia (Including Paraesophageal) 347 36. High prevalence of abnormal acid gastro-oesophageal re ux in idiopathic pulmonary brosis. Gastroesophageal re ux (symptomatic and silent): a potentially signi cant problem in patients with cystic brosis before and after lung transplantation. Scintigraphic detection of gastropulmonary aspiration in patients with respiratory disorders. Pulmonary responses to tracheal or esophageal acidi cation in guinea pigs with airway in ammation. Laparoscopic fundoplication compared with medical management for gastro-oesophageal re ux disease: cost e ectiveness study. Gastro-oesophageal re ux disease in primary care: an international study of di erent treatment strategies with omeprazole. Re-examination of the cost-e ectiveness of surgical versus medical therapy in patients with gastroesophageal re ux disease: the value of long-term data collection. Clinical biology and surgical therapy of intramucosal adenocarcinoma of the esophagus. Role of clinically determined depth of tumor invasion in the treatment of esophageal carcinoma. A prospective randomized trial of two di erent endoscopic resection techniques for early stage cancer of the esophagus. Technology insight: endoscopic submucosal dissection of gastrointestinal neoplasms. Ten-year outcome of laparoscopic and conventional Nissen fundoplication: randomized clinical trial. Clinical outcome at 10 years after laparoscopic versus open Nissen fundoplication. Comparison of long-term outcome of laparoscopic and conventional Nissen fundoplication: a prospective randomized study with an 11-year follow-up. Outcomes of atypical symptoms attributed to gastroesophageal re ux treated by laparoscopic fundoplication. Outcome of respiratory symptoms after antire ux surgery on patients with gastroesophageal re ux disease. Quality of life after antire ux surgery compared with nonoperative management for severe gastroesophageal re ux disease. A physiologic approach to laparoscopic fundoplication for gastroesophageal re ux disease. Surgical reintervention after failed antire ux surgery: a systematic review of the literature. Roux-en-Y near esophagojejunostomy for intractable gastroesophageal re ux after antire ux surgery. Diaphragmatic hernia: its unsuspected frequency: its diagnosis: technic for radical cure. Esophageal hiatus hernia of the diaphragm; the anatomical characteristics, technic of repair, and results of treatment in 111 consecutive cases. Division of the hepatic branch of the anterior vagus nerve in fundoplication: e ects on gallbladder function. E ect of ambulatory 24-hour esophageal pH monitoring on re ux-provoking activities. Forty-eight-hour pH monitoring increases sensitivity in detecting abnormal esophageal acid exposure. Nissen fundoplication improves gastric motility in patients with delayed gastric emptying. Delayed gastric emptying in patients undergoing antire ux surgery: analysis of a treatment algorithm. Fundoplication and gastropexy in the surgical treatment of cardia insu ciency and hiatal hernia. Meta-analysis of randomized clinical trials comparing open and laparoscopic anti-re ux surgery. Cost e ectiveness of medical versus surgical treatment in patients with severe or refractory gastroesophageal re ux disease in the Netherlands. Esophageal function in patients with re ux-induced strictures and its relevance to surgical treatment. Division of the short gastric vessels during laparoscopic Nissen fundoplication: clinical and functional outcome during long-term follow-up in a prospectively randomized trial. Ten-year results of a randomized clinical trial of laparoscopic total fundoplication with or without division of the short gastric vessels. Chapter 15 Gastroesophageal Re ux Disease and Hiatal Hernia (Including Paraesophageal) 349 133. Laparoscopic partial fundoplication vs laparoscopic Nissen-Rosetti fundoplication. Severely disordered esophageal peristalsis is not a contraindication to laparoscopic Nissen fundoplication. A 25-year experience with open primary transthoracic repair of paraesophageal hiatal hernia. Open repair of paraesophageal hernia: reassessment of subjective and objective outcomes. Wedge gastroplasty and reinforced crural repair: important components of laparoscopic giant or recurrent hiatal hernia repair. Results of laparoscopic repair of giant paraesophageal hernias: 200 consecutive patients. Laparoscopic repair of giant paraesophageal hernia results in long-term patient satisfaction and a durable repair. Primary laparoscopic and open repair of paraesophageal hernias: a comparison of short-term outcomes. Biologic prosthesis reduces recurrence after laparoscopic paraesophageal hernia repair: a multicenter, prospective, randomized trial. Laparoscopic Nissen fundoplication with prosthetic hiatal closure reduces postoperative intrathoracic wrap herniation: preliminary results of a prospective randomized functional and clinical study. Tension-free repair of hiatal hernia during laparoscopic fundoplication: a ten-year experience. Laparoscopic hiatal hernia repair: long-term outcome with the focus on the in uence of mesh reinforcement. Mesh complications after prosthetic reinforcement of hiatal closure: a 28-case series. An even rarer event is the parahiatal hernia, where a diaphragmatic defect adjacent to the hiatus allows cephalad migration of the fundus. Close questioning reveals that most patients with this defect are either symptomatic or anemic. Far and away the most common approach to repair in the 21st century is laparoscopic hiatal hernia repair. As well, the recurrence rate of open and laparoscopic repair appears similar, despite the lack of randomized trials.

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