Property:Explanation
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Dual antiplatelet therapy is the standard of care in patients undergoing percutaneous coronary intervention (PCI) with stent placement. Aspirin in combination with clopidogrel is one of the combinations that is most commonly used. Aspirin is an irreversible inhibitor of both COX1 and COX2 which has analgesic, anti-inflammatory, and antiplatelet (mostly at low doses) characteristics. Aspirin decreases thromboxane A2 production leading to a decrease in platelet aggregation. Clopidogrel on the other hand is an ADP receptor blocker that inhibits ADP mediated expression of GpIIb/IIIa on the surface of platelets required to bind fibrinogen. Antiplatelet therapy is essential after stent placement due the risk of associated in-stent thrombosis that often leads to death or a large myocardial infarctions. Stent thrombosis occurs due to several factors including patient- and lesion-related factors, as well as the thrombogenicity of the stent itself.<br/>
'''Educational Objective:''' Both aspirin and clopidogrel play a role in decreasing platelet aggregation, aspirin via decreasing thromboxane A2 and clopidogrel via blocking ADP receptors and decreasing GpIIbIIIa expression.<br/>
'''References:''' Savi P, Nurden P, Nurden AT, Levy-toledano S, Herbert JM. Clopidogrel: a review of its mechanism of action. Platelets. 1998;9(3-4):251-5.<br>
Vane J, Botting R. The mechanism of action of aspirin. Thrombosis Research. 2003;110(5-6):255-258. +
Phosphodiesterase III (PDE3) inhibitors such as cilostazol and dipyridamole are potent vasodilators that can be used in the treatment on intermittent claudication. By inhibiting PDE3, cAMP accumulates leading to the activation of protein kinase A (PKA). PKA in turn leads to the inhibition of myosin light-chain kinase (MLCK) causing the vascular smooth muscle to relax. Another important effect of PDE3 inhibition and cAMP accumulation is the inhibition of platelet aggregation. PDE3 inhibitors have also been used clinically for TIA and stroke prevention and have been shown to be a potent antithrombotic agent when compared with aspirin or ADP receptor blockers.<br/>
'''Educational Objective:''' PDE3 inhibitors cause cAMP accumulation leading to vasodilation as well as a decrease in platelet aggregation.<br/>
'''References:''' Schror K. The pharmacology of cilostazol. Diabetes Obes Metab. 2002;4(s2):S14-S19. +
Polyarteritis nodosa (PAN) is a systemic illness characterized by medium-vessel vasculitis involving vessels of the kidneys, gastrointestinal tract, skin, nerves, joints, and muscles sparing the lungs. Pathologically, PAN is described as a transmural necrosis of medium-sized vessels with lesions of varying age leading to a disruption of visceral blood flow and ischemia. Patients with PAN usually present with constitutional symptoms with associated symptoms related to the involved organ systems. Patients can have some form of neurologic impairment, skin changes including rashes and nodules, abdominal pain and GI bleeding, as well as symptoms related to renal impairment. PAN can be idiopathic in many patients; however, both hepatitis B and hepatitis C have been linked to its development. Hepatitis B positivity can be seen in up to a quarter of patients with PAN. Treatment includes corticosteroids mainly combined with cyclophosphamide in certain cases.<br/>
'''Educational Objective:''' PAN is a medium vessel vasculitis characterized by transmural fibrinoid necrosis, classically associated with hepatitis B infection.<br/>
'''References:''' Pettigrew HD, Teuber SS, Gershwin ME. Polyarteritis nodosa. Compr Ther. 2007;33(3):144-9. +
Fontanelles as membranous separations between bones of the skull. They allow for stretching of the cranial cavity to accommodate the rapidly expanding brain early on. Posterior fontanelles usually ossify very early on, within 2-3 months of birth. Anterior fontanelles on the other hand typically close between 4 months and 2 years, half of which occur in the first year. Craniosynostosis is defined as premature complete ossification of the sutures that leads to increased intracranial pressure and deformation of the skull. The bones of the skull, unlike the rest of the skeletal system, are derived from neural crest cells. Other bones are generally derived from the mesodermal layer. Other derivatives of neural crest cells include:
<li> Chromaffin cells of the adrenal medulla
<li> Parafollicular C cells of the thyroid
<li> Schwann cells
<li> Cranial nerves
<li> Majority of ANS
<li> Odontoblasts
<li> Aorticopulmonart septum
<li> Pia and arachnoid mater
<li> Melanocytes
<li> Celiac ganglion<br/>
'''Educational Objective:''' Both the arachnoid mater and the bones of the skull are derived from the neural crest cells.<br/>
'''References:''' Crane JF, Trainor PA. Neural crest stem and progenitor cells. Annu Rev Cell Dev Biol. 2006;22(1):267-86.<br>
Aisenson MR. Closing of the anterior fontanelle. Pediatrics. 1950;6(2):223-6.<br>
First Aid 2014 page 553 <br> +
Several embryologic anomalies in organ development and maturation can be encountered. Typically the anomalies are classified according to either the presence or absence of primordial tissue or the time period during which they most likely occur. In general, 5 common error can be described. Malformation refers to an error that occurs anywhere during the embryonic period between 3 to 8 weeks of embryogenesis. A deformation is anything that occurs after 8 weeks. Before 3 weeks defects are usually fatal. In terms of primordial tissue, agenesis refers to absent organ development due to absent primordial tissue, while aplasia is absent organ development despite the presence of primordial tissue. Hypoplasia refers to incomplete organ development. Spina bifida is a neural tube defect by which the bony spinal canal fails to close completely due to the failure of the neuropores to close at 4 weeks of development. It usually presents with a tuft of hair on the lumbar area. Spina bifida is a classical example of a malformation.<br/>
'''Educational Objective:''' Spina bifida is an example of malformation that occurs usually around 4 weeks of gestation.<br/>
'''References:''' Spranger J, Benirschke K, Hall JG, et al. Errors of morphogenesis: concepts and terms. Recommendations of an international working group. J Pediatr. 1982;100(1):160-5. +
Metyrapone is an agent used mainly for diagnosing adrenal insufficiency via blocking steroid synthesis and monitoring the hypothalamic-pituitary-adrenal axis for increase in steroidogenesis. Failure of detecting an increase in ACTH or 11-deoxycortisol levels support the diagnosis of adrenal insufficiency. Metyrapone acts by inhibiting the last step in cortisol synthesis by blocking the enzyme 11β-hydroxylase. It is also used in the treatment of Cushing's disease (not very common practice) to decrease the corticoid load. Typically, if 11β-hydroxylase is inhibited, it's substrate would accumulate. After initiation of therapy, serum levels of 11-deoxycortisol would be expected to increase. Urine levels of 17-hydroxysteroids, the breakdown products of 11β-hydroxylase are also expected to increase.<br/>
'''Educational Objective:''' Metyrapone inhibits the last step in cortisol synthesis by blocking the enzyme 11β-hydroxylase.<br/>
'''References:''' Avgerinos PC, Yanovski JA, Oldfield EH, Nieman LK, Cutler GB. The metyrapone and dexamethasone suppression tests for the differential diagnosis of the adrenocorticotropin-dependent Cushing syndrome: a comparison. Ann Intern Med. 1994;121(5):318-27.<br>
First Aid 2014 page 317 +
Vitamin B6 or pyridoxine is an essential vitamin required as a co-factor in many metabolic reactions including heme, GABA, and niacin synthesis among others. Typically, vitamin B6 deficiency presents with irritability, hemolysis, sideroblastic anemia, and peripheral neuropathy. In infants, convulsions can also be seen with significant deficiency. Vitamin B6 deficiency can be seen in patients with severe inflammatory diseases, malnutrition, celiac disease, sickle cell disease, and as a side effect of drugs namely isoniazid, D-penicillamine and OCPs. Pyridoxine is an important cofactor for transforming homocysteine into cysteine. With pyridoxine deficiency, cysteine levels decrease and levels of homocysteine and methionine increase.<br/>
'''Educational Objective:''' Vitamin B6 deficiency, often seen in patients on izoniazid therapy, leads to decreased levels of cysteine.<br/>
'''References:''' +
This is a case of antibiotic-associated colitis or otherwise called pseudo-membranous colitis. Pseudomembranous colitis is an infection of the colon often caused by the bacterium Clostridium difficile. It is characterized by offensive-smelling watery diarrhea, fever, and abdominal pain. It can be severe, causing toxic megacolon, or even fatal. The Clostridium difficile bacteria are normally seen in the intestine. However, it may overgrow when you take antibiotics. The bacteria release a powerful toxin that causes the lining of the colon to become inflamed and bleed.
The image shown above reveals the presence of pseudomembranes.
The most common antibiotics associated with this condition are penicillin, clindamycin, fluoroquinolones, and cephalosporins (broad spectrum). Other antibiotics implicated are macrolides, trimethoprim, sulphonamides, and rarely implicated drugs such as aminoglycosides, tetracyclines, metronidazole and vancomycin.
Pseudomembranous colitis is rare in infants younger than 12 months old and uncommon in children. It is most often seen in hospitalized patients on prolonged antibiotic treatment. However, it can also be community acquired.
The initial step in management involves discontinuing the offending antibiotic agent and placing the patient on contact precaution. Oral metronidazole 500mg three times daily for 10-14 days is recommended for the treatment of mild forms of the disease i.e., with a WBC count of less than 15,000/cm3, temperature <38.5C, a creatinine less than 1.5 times of the normal. Oral vancomycin is usually reserved for the severe forms. There is no place for intravenous vancomycin in the treatment of pseudomembranous colitis since the drug is not excreted into the colon in appreciable quantity. Alternative drugs include fidoxomicin, which has a lower recurrence rate compared with vancomycin, and rifaximin.<br/>
'''Educational Objective:''' Oral metronidazole remains the first line of therapy for antibiotic-associated clostridium difficile infection, and also in cases of relapse. Oral vancomycin is usually reserved for severe cases of primary infection and subsequent relapses. Other choices of medication in situations of recurrence are fidoxomicin and rifaximin.<br/>
'''References:''' http://www.wikidoc.org/index.php/Pseudomembranous_colitis
Clostridium difficile is an organism normally seen in the intestine. However, it may overgrow when you take antibiotics which kill a lot of gut flora which impede their growth in the intestine. The bacteria release a powerful toxin that causes the lining of the colon to become inflamed and bleed. The symptoms experienced during an acute infection are offensive-smelling watery diarrhea, fever, and abdominal pain. Toxic megacolon may result in severe cases which involves surgery.
A positive Clostridium difficile toxin assay may signify an acute infection or a recent infection. However, treatment is not indicated for an asymptomatic patient with a positive assay.
Educational Objective: No treatment is indicated for patients who have a positive C. diff toxin assay without symptoms.<br/>
'''Educational Objective:''' <br/>
'''References:''' +
The patient in this vignette is an elderly man who has recently lost a dependable partner. He expressed symptoms suggestive of major depression – loss of appetite, fatigue, feeling of guilt and weight loss. He suffered an abrupt onset of memory loss within two weeks. All this symptoms are suggestive of an entity called Dementia syndrome of depression, formerly known as pseudodementia. This can be defined as the combination of an affective disorder with dementia.
The typical cardinal signs of pseudodementia proposed by Wells are:
*Preoccupation with the cognitive deficit
*Excessive dependency
*Abrupt onset
*Preserved attention
*Poor effort on exam performance with “I don’t know” answers
The history of cognitive impairment in pseudodementia is often short and abrupt onset, while in dementia it is more often insidious. Clinically, people with pseudodementia differ from those with true dementia when their memory is tested. They will often answer that they don't know the answer to a question, and their attention and concentration are often intact, and they may appear upset or distressed. Those with true dementia will often give wrong answers, have poor attention and concentration, and appear indifferent or unconcerned.
Investigations such as SPECT imaging of the brain show reduced blood flow in areas of the brain in people with Alzheimer's disease, compared with a more normal blood flow in those with pseudodementia.
Antidepressants are effective in reversing the mood and cognitive symptoms. It is important to note that patients with cognitive impairment secondary to major depression may be at higher risk of converting to an irreversible dementia syndrome such as Alzheimer’s disease.<br/>
'''Educational Objective:''' Elderly patients with symptoms of major depression may also show signs of cognitive impairment. They are overly concerned with their cognitive impairment, and the mini-mental state exam is usually normal with a normal attention and concentration. This is often a reversible cause of dementia amenable to antidepressants.<br/>
'''References:''' Wilson RS. et al., 2002. Neurology. “Depressive symptoms, cognitive decline, and risk of AD in older persons”. 59 (3): 364-70
This patient is experiencing symptoms suggestive of stroke or cerebrovascular accident (CVA). The term 'stroke' is used to describe pathological conditions caused by brain ischemia or hemorrhage. Therefore, the etiology of the patient’s symptoms may either result from brain ischemia (embolus, thrombus or systemic hypoperfusion) or hemorrhage into the brain parenchyma (intracerebral hemorrhage) or cerebrospinal space (subarachnoid hemorrhage).
In the acute setting, an urgent confirmation of the etiology is required, especially in cases with an onset <3 hours, who may be eligible for intravenous thrombolytic administration (i.e., recombinant TPA). Based on this, non-contrast enhanced CT is usually preferred due to its ability to exclude or confirm hemorrhage, easy access, ease of interpretation, speed of acquisition, widespread availability and cost effectiveness.
Educational Objective: Non-contrast enhanced CT is the preferred immediate brain imaging to rule out or confirm hemorrhage in cases of suspected stroke. It is also easily accessible, and the most cost-effective strategy, when compared with other modalities.<br/>
'''Educational Objective:''' <br/>
'''References:''' +
The image above shows loss of gray-white differentiation, one of the subtle changes appreciable very early after an infarct. Another feature of an ischemic infarct is the swelling of the gyri that produces sulcal effacement (not appreciable in this image).
Non-contrast enhanced CT (NCCT) is the preferred immediate brain imaging to rule out or confirm hemorrhage in cases of suspected stroke, especially in the acute setting. Areas of hemorrhage on NCCT appear lighter (hypodensity) while areas of infarct are usually darker (hyperdense).
Educational Objective: NCCT is used to rule out hemorrhage during an acute stroke. It is important to know how to differentiate a bleed from ischemic areas on a CT or MRI.<br/>
'''Educational Objective:''' <br/>
'''References:''' +
This is a case of acute ischemic stroke presenting after two hours of symptom onset. She is a good candidate for thrombolysis, but her blood pressure is elevated. An elevated blood pressure is not uncommon in cases of stroke, and great caution has to be taken in the management of blood pressure because the perfusion of the ischemic areas in the brain is largely dependent on the systemic blood pressure. Elevated blood pressure increases the risk of hemorrhage following administration of thrombolytics. The blood pressure of a candidate for thrombolysis must be ≤180/110 mmHg, and must be maintained below 180/105 mmHg for the first 24 hours post thrombolysis. Commonly used agents include labetalol, nicardipine, and in extreme cases, sodium nitroprusside.
In patients with contraindication to thrombolysis, elevated blood pressure is generally not treated until it is >220/120 mmHg, or when BP is <220/120 mmHg with evidence of end organ damage (e.g., myocardial infarction, aortic dissection, pulmonary edema, and hypertensive encephalopathy)
Educational Objective: The blood pressure must be controlled before IV thrombolytics can be administered. The following are the don’ts of acute ischemic stroke:
*Do not treat hypertension except the blood pressure is >220/120 mmHg, and not until CT/MRI have been performed.
*Do not initiate anticoagulation treatment within the first 24 hours.
*Do not commence oral administration of medications before speech and swallow evaluation.
*Do not delay sending the patient to CT for any reason.
Reference: http://www.wikidoc.org/index.php/Stroke_resident_survival_guide<br/>
'''Educational Objective:''' <br/>
'''References:''' +
This is a case of acute ischemic stroke. There was a history of stroke 2 months prior to presentation. The present stroke, despite anticoagulation with warfarin, may be explained by the intake of st. John’s wort (the herbal tea) which is known to increase the metabolism of warfarin, thereby reducing its anticoagulant actions.
The presence of a prior stroke less than 3 months ago, current intake of warfarin, and an elevated BP>180/110 mmHg makes the patient an unsuitable candidate for thrombolysis. Conservative management is usually indicated in the management of patients with an acute ischemic stroke ineligible for thrombolysis within the first 24 hours. In patients with contraindication to thrombolysis, elevated blood pressure is generally not treated until it is >220/120 mmHg, or when BP is <220/120 mmHg with evidence of end organ damage (e.g., myocardial infarction, aortic dissection, pulmonary edema, and hypertensive encephalopathy). The exclusion criteria for IV rTPA administration must be reviewed carefully before thrombolysis. They are:
Exclusion Criteria for IV Recombinant TPA Treatment
*Less than 3 hours of onset
Significant head trauma or prior stroke in previous 3 months
Symptoms suggest subarachnoid hemorrhage
Arterial puncture at noncompressible site in previous 7 days
History of previous intracranial hemorrhage
Intracranial neoplasm, arteriovenous malformation, or aneurysm
Recent intracranial or intraspinal surgery
Elevated blood pressure (systolic >185 mm Hg or diastolic >110 mm Hg)
Active internal bleeding
Acute bleeding diathesis, including but not limited to
Platelet count <100,000/mm³
Heparin received within 48 hours, resulting in abnormally elevated aPTT greater than the
upper limit of normal
Current use of anticoagulant with INR >1.7 or PT >15 seconds
Current use of direct thrombin inhibitors or direct factor Xa inhibitors with elevated
sensitive laboratory tests (such as aPTT, INR, platelet count, and ECT; TT; or appropriate factor Xa activity assays)
Blood glucose concentration <50 mg/dL (2.7 mmol/L)
CT demonstrates multilobar infarction (hypodensity >1/3 cerebral hemisphere)
*Relative exclusion criteria
Only minor or rapidly improving stroke symptoms (clearing spontaneously)
Pregnancy
Seizure at onset with postictal residual neurological impairments
Major surgery or serious trauma within previous 14 days
Recent gastrointestinal or urinary tract hemorrhage (within previous 21 days)
Recent acute myocardial infarction (within previous 3 months)
*Between 3 and 4.5 hours of onset
Aged >80 years
Severe stroke (NIHSS>25)
Taking an oral anticoagulant regardless of INR
History of both diabetes and prior ischemic stroke
Educational Objective: Patients with acute ischemic stroke, who also have contraindications to thrombolysis treatment, are best managed conservatively within the first 24 hours of symptom onset. Elevated blood pressure is generally not treated until it is >220/120 mmHg, or when BP is <220/120 mmHg with evidence of end organ damage (e.g., myocardial infarction, aortic dissection, pulmonary edema, and hypertensive encephalopathy).
Reference: http://www.wikidoc.org/index.php/Stroke_resident_survival_guide<br/>
'''Educational Objective:''' <br/>
'''References:'''
Coronary artery disease (CAD) present with chest pain that doesn’t change with body position and respiration. Stress test is done when the case is equivocal, and you are not certain of the diagnosis. Angiography is done when the stress test is abnormal.<br/>
'''Educational Objective:''' <br/>
'''References:''' +
Coronary artery disease (CAD) present with chest pain that doesn’t change with body position and respiration. Stress test is done when the case is equivocal, and you are not certain of the diagnosis. According to ACC/AHA class I recommendations for angiography, if the stress test shows an area of reversible ischemia, angiography is done as the best next step.<br/>
'''Educational Objective:''' <br/>
'''References:''' +
Lactase, also known as β-D-galactosidase, is a glycoside hydrolase found predominantly along the brush border membrane of enterocytes that breaks down the disaccharide lactose into its two monosaccharide components: galactose and glucose. Lactase deficiency is a major cause of lactose intolerance presenting with gastrointestinal discomfort, bloating, and diarrhea following the consumption of any food products that contain lactose (primarily milk but also other dairy products). Lactase deficiency may be either congenital or acquired. Although the acquired form is more common, the congenital form may be more severe preventing newborns from having human milk. Diagnosis is made using the hydrogen breath test, which consists of administering up to 25g of lactose orally after an overnight fast and measuring the amount of hydrogen in the exhaled air. As lactose cannot be digested, it is metabolized by the gut bacteria releasing gases, such as hydrogen gas and methane, that are responsible for the symptoms of lactose intolerance.<br/>
'''Educational Objective:''' β-D-galactosidase (Lactase) is a intestinal brush border enzyme responsible for the hydrolysis of the disaccharide lactose into its monosaccharide components: galactose and glucose.<br/>
'''References:''' Swajerty DL Jr. Lactose intolerance. Am Fam Physician. 2002 May 1;65(9):1845-50. +
Sleep terror is a type of parasomnia which is most likely to occur during stages 3 and 4 of non-rapid eye movement (NREM) sleep. NREM sleep is also known as delta sleep or slow wave sleep and is characterized by the highest amplitude and the lowest frequency waves among all sleep stages. The most common age group affected by sleep terrors is 4 to 12 years. Commonly, sleep terrors are associated with waking up in panic, inconsolable crying, autonomic arousal (tachycardia, sweating and hyperventilation), no memory of the episode, and no recollection of any nightmare. Reassurance is often recommended with improvement of sleep hygiene. Other parasomnias such as bed wetting and sleep walking also occur during the delta sleep stage.<br/>
'''Educational Objective:''' Sleep terror is a type of parasomnia which is most likely to occur during stages 3 and 4 of non-REM sleep (delta waves stage).<br/>
'''References:''' Ohayon MM, Guilleminault C, Priest RG. Night terrors, sleepwalking, and confusional arousals in the general population: their frequency and relationship to other sleep and mental disorders. J Clin Psychiatry. 1999;60(4):268-76. +
The patient in this vignette has classical symptoms of major depressive disorder. Sleep disturbances are very common in cases of depression. It is estimated that 90% of patients with depression complain about problems with sleep quality. Sleep pattern changes in depression include early morning awakenings, decreased REM latency, increased total REM duration, and decreased slow wave sleep. Sleep disturbances often affect disease prognosis and patient outcomes after treatment (i.e. patients with sleep disturbances have recurrent depression and may not respond to cognitive-behavioral therapy). By treating major depression, the sleep disturbances slowly improve; however, temporary administration of hypnotics may be helpful. Remember that the diagnosis of major depressive disorder is made if at least 5 of the following symptoms are present for 2 weeks or more, depressed mood or lack of pleasure should at least be one of the 5 symptoms.<br>
'''S''' - Sleep disturbance (lack or excess of sleep)<br>
'''I''' - Loss of interest in previously enjoyable activities<br>
'''G''' - Feeling of excess guilt<br>
'''E''' - Loss of energy<br>
'''C''' - Inability to concentrate<br>
'''A''' - Appetite change (could be increased or decreased<br>
'''P''' - Psycho-motor agitation<br>
'''S''' - Suicidal tendency<br><br/>
'''Educational Objective:''' Sleep pattern changes in depression include early morning awakenings, decreased REM latency, increased total REM duration, and decreased slow wave sleep.<br/>
'''References:''' Nutt D, Wilson S, Paterson L. Sleep disorders as core symptoms of depression. Dialogues Clin Neurosci. 2008;10(3):329-36. +
Acute promyelocytic leukemia (APML) is a rare subset of acute myeloid leukemia (AML). APML is characterized by a chromosomal translocation involving the retinoic acid receptor-alpha gene on chromosome 17 (RARA). APML cells undergo a differentiation arrest, which can be reversed with all-trans retinoic acid. Arsenic is thought to act by inhibiting the enzyme thioredoxin reductase, an enzyme that is essential for cell growth and survival and that is upregulated in APML cells. Histologically, APML is notable for leukemic cells containing rod-like cytoplasmic inclusions called “Auer rods”. Treatment of APML can precipitate release of these inclusions causing disseminated intravascular coagulopathy (DIC). Prolonged therapy with arsenic trioxide, a known carcinogenic agent, increases the risk of certain cancer particularly squamous cell carcinoma of the skin as well as angiosarcoma of the liver.<br/>
'''Educational Objective:''' Angiosarcoma is a potential late complication of exposure to arsenic.<br/>
'''References:''' Watts JM, Tallman MS. Acute promyelocytic leukemia: what is the new standard of care?. Blood Rev. 2014;28(5):205-12.<br>
Pershagen G. The carcinogenicity of arsenic. Environ Health Perspect. 1981;40:93-100. +