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Neurology 2012; 78: 1207– tration does not increase blood loss during temporal lobectomy lisinopril 17.5 mg amex. Reversible cerebral atrophy: radiologic correlate of cular risk factors in valproate-treated women purchase lisinopril american express. Successful initiation of combined therapy with valproate so- matic fractures: a population-based analysis generic 17.5 mg lisinopril mastercard. May also be of value as adjunctive therapy for focal and secondarily generalized seizures refractory to other drugs in children and adults Usual preparations Tablets: 500 mg Powder (sachets): 500 mg Usual dosages 75–150 mg/kg/day (infantile spasms). For focal seizures, maintenance dosages are generally in the range of 1000– 3000 mg/day (adults), 500–1000 mg/day (children weighing 10–15 kg), 1000– 1500 mg/day (children weighing 15–30 kg) and 1500–3000 mg/day (children weighing over 30 kg). Because of the risk of irreversible visual feld constriction, vigabatrin is rarely used in other indications Introduction factor from µg/mL to µmoL/L is 7. The applica- Pharmacology and toxicology tion was extended in 1990 to treatment for children with refractory epilepsy, and later to as monotherapy for infantile spasms. Howev- Activity in experimental models of seizures and epilepsy er, afer the discovery of serious retinal toxicity, the indication was The onset of anticonvulsant activity of vigabatrin in seizure and restricted primarily to the treatment of infantile spasms. Vigabatrin shows protective activ- ity against bicuculline-induced myoclonic seizures, strychnine-in- Chemistry duced tonic seizures, isoniazid-induced generalized seizures, Vigabatrin is a white to of-white crystalline amino acid which is light-induced seizures in baboons and amygdala kindled seizures in highly water-soluble and only slightly soluble in ethanol and metha- rats, whereas it is inactive in models such as maximal electroshock nol (Figure 52. Animal toxicology data In preclinical safety studies, microvacuolation was observed in brain white matter tracts of rats, mice and dogs at dosages of 30– Glutamine 50 mg/kg/day. Microvacuolation is caused by a separation of the outer lamellar Glutamate sheath of myelinated fbres, a change characteristic of intramyelinic oedema. Krebs cycle In neonatal rat brains, vigabatrin (50, 100 or 200 mg/kg twice daily on three consecutive days) elicited apoptotic neurodegener- Figure 52. The elimination half-life is 5–7 h for both enanti- converts it to a reactive intermediate. Restoration of normal enzyme activity afer withdrawal of active S-enantiomer of vigabatrin were signifcantly lower for the vigabatrin takes several days. Vigabatrin also signifcantly reduces active S-(+)-enantiomer than for the R-(–)-enantiomer following the activity of plasma alanine aminotransferase by 20–100% [7]. Seven of these children were treated with add-on vi- pharmacokinetic analysis [19]. Disease states The vigabatrin-treated children had signifcantly lower hemispher- In renal disease, the clearance of both vigabatrin enantiomers is re- ic fumazenil volume of distribution in all cortical regions and the duced in proportion to the degree of renal impairment, as assessed cerebellum. Since about 60% Pharmacokinetics of the drug was removed from the blood during haemodialysis, it was recommended that in these patients vigabatrin should be ad- Adults ministered afer the dialysis. The drug is rapidly absorbed and peak plasma concentra- tions are reached within 0. Felbamate leads to a slight increase in the levels of the active of those of the R-(+)-enantiomer, whereas areas under the plas- S-(+)-enantiomer of vigabatrin [21]. Food does not infuence nytoin levels by about 25% on average, without altering phenytoin vigabatrin absorption. The mechanism of this Vigabatrin is widely distributed in the body and is not bound interaction is unclear. In children with epilepsy, the fall in pheny- to plasma proteins, The volume of distribution calculated from the toin levels can be even more pronounced [23]. In patients randomized to vigaba- trin (150 mg/kg/day), efcacy in terms of cessation of spasms was 100% (11 out of 11), while less than half of patients (5 out of 11) randomized to hydrocortisone responded. All seven patients who Serum level monitoring crossed over from hydrocortisone to vigabatrin (six for inefca- As vigabatrin has an irreversible mode of action, the time course cy, one for adverse events) became seizure-free. The mean time to of plasma vigabatrin concentrations is dissociated from the time reach seizure cessation was 3. A low-dose (18–36 mg/kg/day) or high-dose (100–148 mg/kg/day) poor relationship between plasma vigabatrin concentrations and vigabatrin, followed by an open-label extension phase of up to 3 clinical efects has also been found in other studies, and there seems years [37]. Primary responders were defned as subjects who were to be no indication for monitoring vigabatrin levels, except as a spasm-free and showed absence of spasms and hypsarrhythmia in check for compliance [28]. A spasm-free pe- riod of 7 consecutive days at any time of the study or remaining Randomized trials spasm-free for the duration of the study (on caregiver’s assessment) Infantile spasms are currently the primary indication for vigabatrin. Studies on the efcacy of vigabatrin as treatment for infantile infants randomized to vigabatrin (100–150 mg/kg/day), 28 (54%) spasms have been the topic of many reviews [29,30,31,32,33,34]. The short-term efcacy of vigab- In a double-blind study, 40 infants with newly diagnosed in- atrin was lower than that of hormonal treatment. At the end of a 5-day double-blind phase, sev- Of the 55 infants allocated to hormonal therapy, 27 were treated en (35%) vigabatrin-treated infants were spasm-free and fve (25%) with vigabatrin afer day 14 because of failure to achieve cessation had resolution of hypsarrhythmia, compared with two (10%) and of spasms (n = 12), seizure relapse (n = 14) or appearance of focal one (5%), respectively, in the placebo group (P = 0. In the group initially allocated to vigabatrin, 22 curred in four (20%) of the vigabatrin-treated patients. Adverse events were of the study, 42% of the 36 patients who entered a 24-week open-la- reported in 54% (28 of 52) of the infants on vigabatrin (mainly bel phase were spasm-free on vigabatrin monotherapy. No patient drowsiness and gastrointestinal symptoms) and in 55% (30 of 55) withdrew from the study because of adverse efects. At re-assessment Using a cross-over design, the alternative drug was administered to at 12–14 months of age [39], freedom from spasms was similar in infants who did not respond within 20 days or were intolerant to the both treatment groups (vigabatrin 76%, hormonal treatment 75%). Cessation of spasms was observed in 48% (11 out of Five children died during the follow-up period, one due to Staph- 23) of infants in the vigabatrin group, with a slightly higher efcacy ylococcus aureus septicaemia on day 15 of prednisolone treatment, in cryptogenic than in symptomatic cases (57% versus 44%), and in and four due to the underlying disease. Relapse rates in vigabatrin-treated infants in the three active-con- trol randomized trials summarized here ranged between 8% and Efcacy versus aetiology: infantile spasms 20%. Complete cessation of (11 of 11) of vigabatrin-treated patients compared with 45% (5 of spasms occurred in 68% of patients (131 of 192), 19% had a reduc- 11) of hydrocortisone-treated patients. Relapses occurred in 21% (28 of Response was observed within 1 week in the majority of patients. At the mentioned in all studies) varied between 50% and 100% in crypto- fnal evaluation (follow-up at least 3. A signifcant diference in seizure outcome low, ranging from single cases to a maximum of 14%. Efcacy in and intellectual development was found between infants treated terms of complete cessation of spasms did not difer between newly with vigabatrin within the frst weeks afer seizure onset, and in- diagnosed infants (43%, 45%) [43,44] and infants who were initially fants with a treatment delay of 3 weeks or more. Sometimes was present in 61% of children in the early treatment group and in response was observed afer one or two doses [50]. The for qualifying responders was proposed in diferent controlled and degree of intellectual disability correlated with seizure outcome. In group 1 of spasms and hypsarrhythmia at doses ranging from 25 to 135 mg/ (‘standard therapy’, 31 of 45) vigabatrin was started early afer the kg/day in 12 of 20 infants.

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It may be complete or incomplete (based on whether both cortices are involved) order lisinopril 17.5mg visa, or open or closed (based on whether the overlying skin is intact) buy lisinopril 17.5mg online. Reactive phase – Fracture and inflammatory phase order lisinopril 17.5 mg without a prescription, followed by granulation tissue formation Reparative phase – Callus formation and lamellar bone deposition Remodelling phase – Remodelling to the original bone contour What classification do you know for proximal femoral fractures? The treatment of bone fractures depends upon the type and location of the fracture and the patient’s age and medical history. However, four phases can be identified (4 R’s): Resuscitation Reduction (open or closed) Restriction (immobilisation) (cast splintage, functional bracing, continuous traction, internal fixation, external fixation) Rehabilitation (Physiotherapy) What are the complications of fractures? Early complications Local: Vascular injury causing haemorrhage (internal or external) Visceral injury causing damage to the surrounding organs (i. Sterilisation refers to the process that kills or eliminates transmissible viable microorganisms (i. Physical sterilisation: Heat sterilisation Moist heat (pressurised steam autoclaves) 134°C Dry heat – 160°C Radiation sterilisation Chemical sterilisation: Ethylene oxide Ozone Chlorine bleach Formaldehyde Glutaraldehyde Hydrogen peroxide Peracetic acid Ethanol (70%) Give some examples of sterilisation? Moist heat sterilisation (steam autoclaves) – Trays of surgical instruments Dry heat sterilisation – Non-aqueous liquids and ointments Ionising radiation – Swabs, catheters, syringes Ethylene oxide – Sutures, electrical equipment Formaldehyde – Plastics Glutaraldehyde – Endoscopes Does sterilisation destroy prions? All instruments need to be cleaned and thoroughly dried before they are sterilised. There are three main cleaning methods: Hand scrubbing, ultrasonic cleaning and automated washing. It has potent antiseptic activity against Gram-positive and Gram-negative organisms and some viruses, but only moderate activity against the tubercle bacillus. There is some activity against bacterial spores and good activity against tubercle bacilli. Iodine has some residual effects but these are not sustained for more than 4 hours. They are effective in destroying Gram-positive and Gram-negative bacteria, fungi, viruses and tubercle bacilli. Hands and forearms are washed systematically three times, the hands being held above the level of the elbows throughout. The folded gown is lifted away from the trolley and allowed to unfold (inside facing the wearer), whilst the top is held. Arms are inserted into the armholes simultaneously, hands remaining inside the gown until gloves are donned: the gown is secured by an unscrubbed staff member. Gloves are put on using a one- or two-person technique: From this point on, hands remain above waist level at all times. Anti-fungal Surgical iodine is not free but scrub in combined with dilute polyvinylpyrrolidone solutions in (povidone) open wounds Cetrimide Aqueous Handwashing Pseudomonas spp. Ammonium compounds have good detergent action (surfaceactive agent) Alcohols 70% ethyl, Skin Should be reserved for isopropyl preparation use as disinfectants Hypochlorites Aqueous Instrument Toxic to tissues preparations and surface (Eusol, cleaning Milton, (debriding Chloramine agent in T) open wounds) Hexachlorophane Aqueous Skin Has action against bisphenol preparation Gramnegative Handwashing organisms Figure 4. An antibiotic is a substance produced by or derived from a microorganism that destroys or inhibits the growth of other microorganisms. There is evidence to support the use of prophylactic antibiotics in clean- contaminated and contaminated operations. Biliary tract surgery – Risk factors include emergency surgery, > 70 years of age, jaundice, obesity, exploration of the common bile duct and concomitant alimentary procedures, biliary instrumentation without surgery (i. Colorectal surgery – Surgery involving the bowel has a high rate of primary or secondary sepsis associated with anastomotic dehiscence. Appendicectomy Vaginal or abdominal hysterectomy Urogenital surgery Exogenous contamination: Lower limb surgery in the presence of peripheral vascular disease Prosthetic joint replacements Prosthetic heart valves Neurosurgical shunts Extensive trauma and burns Surgical procedures and instrumentation in rheumatic and valvular heart disease Mesh insertion in hernia repair Host immune system suppression: Diabetes mellitus Chronic renal failure Leukaemia Aplastic anaemia Malnourishment Carcinomatosis Obstructive jaundice Steroids therapy (Figure 4. Choice of antibiotics for prophylaxis Empirical cover against expected pathogens with local hospital guidelines. Continue as therapy if there is unexpected contamination or if a prosthetic is implanted in a patient with a septic source. Benzylpenicillin should be used if Clostridium gas gangrene infection is a possibility. Patients with heart valve disease or a prosthesis should be protected from bacteraemia caused by dental work, urethral instrumentation or visceral surgery. Cardiovascular – Hypertension, angina and atherosclerosis Cerebrovascular – Stroke Peripheral vascular – Large blood vessel diseases (macroangiopathy), gangrene Renal – Uraemia and hypertension Eyes – Proliferative and non-proliferative retinopathies and cataracts Metabolic – Hyperglycaemia and ketoacidosis Nerves – Peripheral neuropathy (increased risk of pressure sores) Skin – Poor wound healing and infections How should a diabetic patient be managed during surgery? Full medical assessment is performed to evaluate diabetic control and identify potential complications. A patient should not fast for prolonged periods, they should be scheduled first on an operating list. Diet-controlled diabetic patients For minor surgery, no additional precautions are required. For major surgery, monitor blood glucose and if elevated commence an insulin sliding scale. Oral hypoglycaemic-controlled diabetic patients For minor surgery, the morning dose of the oral hypoglycaemic agent should be omitted. For major surgery, patient should be commenced on an insulin sliding scale when they are nil by mouth and stopped when they have resumed eating and drinking. Insulin-controlled diabetic patients For all surgeries, the insulin dose should not be given whilst the patient is fasted. Intra-operative period: Anaesthesia combined with surgical stress has a definite hyperglycaemic effect. Post-operative period: Aim to have the patient’s blood glucose levels within normal range. Oral fluids once started should be followed by a soft diet and then a diabetic diet. The patient was neuropathic but not ischaemic and it was possible to salvage a functional foot by ‘filleting’ the hallux and using the soft tissues to cover the defect. Whilst treating patients, we are commonly exposed to bodily fluids (including blood). This can occur with needle stick injuries, mucosal contact and bodily fluid spillages and splashes. Route Estimated infections/10,000 % exposures to an infected source Blood transfusion 9000 90 Needle-sharing 67 0.

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Pancreatic pseudocyst : Pseudocysts are collections of fluid in a localized space that lack epithelial lining (hence the name pseudo) and persists for more than 4 weeks buy generic lisinopril 17.5 mg. Pseudocysts are usually asymptomatic and disappear with the resolution of the pancreatitis 17.5mg lisinopril visa. Prolonged hyperamylasemia buy lisinopril us, recurrent pain with refeeding and persistent ileus should raise the suspicion of larger than usual pseudocyst. If cysts do not resolve spontaneously, they are drained, surgically, percutaneously or endoscopically. This necrotic tissue has high chances of getting infected and carries a high mortality. These patients often develop systemic complications as renal and pulmonary insufficiency. Appropriate antibiotics and percutaneous surgical drainage is the treatment of choice. Others: Other systemic complications include coagulopathy, subcutaneous nodules, polyarthritis, hyperglycemia, and hypocalcemia. Mortality according to one study is around 10 to15%, often from multiorgan failure. The commonest causes according to different studies are infections (mumps), trauma, secondary to systemic illness, and idiopathic. An increase in serum amylase and lipase may help in the diagnosis, but they have their limitations in children. Severe Acute Pancreatitis is inflammation of pancreas, associated with multiple organ system failure, and may include local complications such as necrosis, abscess, or pseudocyst. The commonest causes according to different studies are infections ( mumps), trauma, secondary to systemic illness, and idiopathic. Large amount of liberated trypsin overwhelm the defense mechanism of the pancreas and the system as a whole, and activate other enzymes. The mortality of infected pancreatic necrosis with multi system involvement is high in patients managed conservatively, but can be reduced significantly if timely necrosectomy is done. More than 1500 children die every year from burns and three times the number are permanently disabled. Toxic chemicals associated with inhalation injury are those that are absorbed systemically and those that cause direct injury to the tracheo-bronchial lining. Similarly Polyvinyl chloride found in fire retardant material, aldehydes, hydrochloric acid and chlorine found in rubber and ammonia released by nylon, rubber, silk, wool and petroleum products. Symptoms and signs of sore throat, hoarseness, dysphagia, cough, carbonaceous sputum, stridor, nasal flaring, tachypnea, retractions, restlessness, confusion or irritability should be looked for. Findings may include singed nasal hair, facial burns and rales or wheezes on auscultation of the chest. The oxygen hemoglobin dissociation curve is shifted markedly to the left leading to severe cerebral hypoxia and myocardial ischemia. It may be unsafe in the presence of severe edema, a lubricated endotracheal tube placed over the bronchoscope will allow immediate control of the airway if required. Arterial blood gas analysis is usually normal until vary late in the course, at which time it may be too late to intubate and emergency tracheostomy may be required. In the presence of severe bronchospasm a bronchodilator such as aminophylline may have to be administered. Humidification of the inspired gas and good pulmonary toilet are the mainstays of treatment. Steroids have no place in the treatment of inhalation injury and antibiotics should be given only in cases in which a documented infection is present. Lungs with a low V/Q will cause hypoxemia and hypercapnia due to pulmonary shunting and increase in the dead space ventilation. The airway should be controlled with a low pressure, high volume cuffed endotracheal tube. A volume cycled ventilator with an initial tidal volume of 10 to 15 ml/kg of body weight should be ideal. Continuous positive airway pressure or positive end expiratory pressure are begun when an adequate PaO cannot be maintained. Steroids fail to improve pulmonary function and are associated with an increased incidence of infection. The energy or heat produced by electric shock is a function of voltage, ampere and time. Tissues with high resistance such as dry skin and bone, generate high temperatures when high voltage is applied. Heat injury results in muscle necrosis, diffuse vascular injury and intense swelling in the fixed muscle compartment. Vascular injury is a progressive phenomenon and aneurysms of the aorta may develop late. Late neurologic disability may be caused by progressive vascular occlusion and demyelination. Low voltage alternating current can cause ventricular fibrillation and cardiac arrest, as well as tetany of the muscles of respiration with suffocation. A majority of electrical injuries in children are low voltage and usually occur in the home. It is not necessary to admit children with low voltage injuries to the hospital if no abnormalities are noted on examination. Controversy exists about the best treatment for commissure injuries, that is, early versus late repair and splint versus no splint. A non-operative conservative approach to these lesions has excellent long term results, and significant labial artery hemorrhage is rare. Myoglobinuria and elevated creatinine phosphokinase values often indicate a deep injury covered by viable skin. Muscle compartments must be carefully assessed and early fasciotomy carried out to prevent a compartment syndrome.

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