Property:Explanation
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Prostate cancer is the most common cancer in men, and the second most common cause of cancer deaths in the in men following lung cancer. Prostatic adenocarcinoma is a slow growing neoplasm whose incidence increases dramatically with increasing age. In fact, the prevalence among patients above 80 years of age may be as high as 80%. The most common location for prostate cancer to develop is the peripheral zone, making the digital rectal exam (DRE) a good method of screening for prostate cancer. In 2011, PSA was removed from the universal screening guidelines given the lack of evidence supporting its benefit. PSA is not used for the diagnosis of prostate cancer, but rather for follow-up after cancer resection. Several derivatives of PSA have been used to increase the sensitivity and specificity of the test. Free/Total PSA is one example. In men with prostate cancer, there is a lower proportion of free PSA causing a lower ratio of free/total PSA. Definitive diagnosis is made by transrectal ultrasound guided biopsies of the prostate gland. Current treatments include transurethral resection or radical prostatectomy both of which may be associated with erectile dysfunction and urinary incontinence. Metastatic disease may be seen in elderly patients presenting for back pain secondary to neoplastic seeding to the lumbar spine (classically osteoblastic). Advanced disease often requires radiation therapy and androgen ablation. It is important to note that prostate cancer does not arise from benign prostatic hyperplasia, and presence of the latter does not increase the risk of cancer.<br/>
'''Educational Objective:''' Prostate adenocarcinoma is the most common cancer in men. It arises most commonly in the peripheral zone of the prostate. Diagnosis is by transrectal ultrasound guided biopsies of the prostate. Universal screening for prostate cancer with PSA is no longer recommended, the use of PSA should be tailored to individual cases and discussed with patients.<br/>
'''References:''' Hayes JH, Barry MJ. Screening for prostate cancer with the prostate-specific antigen test: a review of current evidence. JAMA. 2014;311(11):1143-9.<br>
Jain S, Bhojwani AG, Mellon JK. Improving the utility of prostate specific antigen (PSA) in the diagnosis of prostate cancer: the use of PSA derivatives and novel markers. Postgrad Med J. 2002;78(925):646-50.<br>
Nelson WG, De marzo AM, Isaacs WB. Prostate cancer. N Engl J Med. 2003;349(4):366-81.
Finasteride is a selective inhibitor of 5-alpha-reductase that suppresses serum dihydrotestosterone (DHT) levels by inhibiting the conversion of testosterone to DHT. Finasteride may be used alone or in combination with alpha-blockers to treat benign prostatic hyperplasia (BPH). Another indication finasteride is slowing the progression of androgenetic alopecia. As androgenetic alopecia is partly caused by the effect of DHT at the pilosebaceous unit, decreasing DHT production is associated with slower progression of hair loss. Finasteride actively delays hair loss while the medication is being administered; however, similarly to other medical options for the treatment of alopecia, its effect does not last once the drug is discontinued. Common side effects include erectile dysfunction, decreased libido, and breast enlargement.<br/>
'''Educational Objective:''' Finasteride is a selective inhibitor of 5-alpha-reductase used in the treatment of androgenetic alopecia.<br/>
'''References:''' Kaufman KD, Olsen EA, Whiting D, et al. Finasteride in the treatment of men with androgenetic alopecia. Finasteride Male Pattern Hair Loss Study Group. J Am Acad Dermatol. 1998;39(4 Pt 1):578-89. +
Calcium homeostasis is essential for muscular and neural function as well as osteogenesis. It is maintained in physiological concentrations under the control of parathyroid hormone (PTH). Low serum calcium promotes the secretion of PTH into the circulation allowing 3 main processes to occur: (1) increased calcium and phosphate release from bone, (2) increased calcium reabsorption/phosphate excretion in the renal tubules, and (3) increased calcium and phosphate reabsorption from the small intestine secondary to the PTH mediated increase in 1,25(OH)Vitamin D3. Accordingly, PTH increases the serum concentrations of calcium. The increase in calcium above a set threshold acts as an inhibitor of PTH secretion by a negative-feedback loop. In the kidneys, PTH inhibits the sodium/phosphate co-transporter in the proximal convoluted tubules to promote phosphate excretion (decrease its reabsorption). In converse, it increases the calcium/sodium exchanger in the distal convoluted tubule to increase calcium reabsorption and thus increase the serum concentrations of calcium.<br/>
'''Educational Objective:''' PTH increases the calcium/sodium exchanger in the distal convoluted tubules to increase the reabsorption of calcium.<br/>
'''References:''' Molina P. Endocrine Physiology, Fourth Edition. Chapter 5. Parathyroid Gland and Ca<sup>2+</sup> and PO<sub>4</sub><sup>-</sup> Regulation. McGraw Hill Professional; 2013.<br>
First Aid 2014 page 314 +
The transtheoretical model (TTM) describes the stages most individuals go through in the process of change. These 6 stages are important to identify before implementing a plan to curb an addictive behavior. The model was initially established by observing patterns in alcoholics before, during, and after they attempted to modify their addiction. The patient in this vignette is in a stage of contemplation. Contemplation is a stage characterized by acknowledgement of the problem, with or without seeking help, without any real commitment to change. People who are in the contemplation stage are often very ambivalent. Tailoring therapy to the the stage of change an individual is in has been associated will improved overall outcomes and higher likelihood of success.<br>
The stages of change in order are as follows:<br>
1- Precontemplation<br>
2- Contemplation<br>
3- Preparation/Determination<br>
4- Action/Will power<br>
5- Maintenance<br>
6- Relapse<br/>
'''Educational Objective:''' Contemplation is a stage of the ''stages of change model'' whereby individuals acknowledge the presence of a problem and may seek help, but have not yet made a commitment to take action or change.<br/>
'''References:''' Norcross JC, Krebs PM, Prochaska JO. Stages of change. J Clin Psychol. 2011;67(2):143-54.<br>
First Aid 2014 page 513 +
During a normal pregnancy, fertilization is considered to occur at day 0. The fertilization process typically occurs in the ampullary-ischmic junction of the fallopian tubes. After fertilization, the oocyte proceeds with meiosis II, which was previously arrested following ovulation. The fertilized egg continues to descend along the fallopian tube as mitotic division of the embryo proceeds and gives rise to the morula on day 3 and the blastocyst on day 5. On day 6, the blastocyst reaches the endometrium, and implantation starts. Soon after implantation takes place, hCG is secreted and pregnancy then becomes detectable by serum and urinary concentrations of hCG within 10-14 days post-fertilization.<br/>
'''Educational Objective:''' Blastocyst implantation occurs on day 6 post-fertilization.<br/>
'''References:''' Cunningham F, Leveno K, Bloom S et al. Williams Obstetrics 24/E. Chapter 5: Implantation and Placental Development. McGraw-Hill Professional; 2014.<br>
First Aid 2014 page 552 +
Patients receiving warfarin therapy, such as the case in mechanical valve replacement, must be monitored and dose adjusted to maintain their anticoagulation within a certain therapeutic range. The prothrombin time (PT) or its more standardized counterpart, the international normalized ratio (INR), are used as measures of the extrinsic pathway inhibited by warfarin administration. Patients with bioprosthetic valve replacement require anticoagulation with an INR maintained at 2.0 - 3.0. Those with mechanical valve replacements require a slightly higher range of 2.5 - 3.5. The introduction of new medications must always take into account possible interactions with warfarin. P-450 inhibitors will prevent the elimination of warfarin in the liver and cause prolonged effects and possibly bleeding. On the other hand, P-450 inducers will increase warfarin metabolism and elimination and predispose the patient to thrombotic events. Among the list of antibiotics, ciprofloxacin is an inhibitor of P-450 system. Drugs that inhibit P-450 (and cause more warfarin bleeding effect): Macrolides, amiodarone, isoniazid, cimetidine, ritonavir, ciprofloxacin, ketoconazole, sulfonamides, gemfibrozil, quinidine. Newer oral anticoagulant have been approved in the past decade that do not require monitoring and that have very limited drug interactions.<br/>
'''Educational Objective:''' Levofloxacin is an inhibitor of the P-450 system, decreasing warfarin elimination and prolonging its half-life, predisposing patients to a higher risk of bleeding.<br/>
'''References:''' +
Whenever significant bleeding happens in the early postoperative period, the presumption should always be towards an error in the surgical control of blood vessels in the operative field. Hematologic disorders that are not apparent during the long operation are most unlikely to surface as problems postoperatively. The low platelet count here could be due to post transfusion hemodilution.
'''Educational Objective:'''
Whenever significant bleeding happens in the early postoperative period with normal coagulation profile, the presumption should always be towards an error in the surgical control of blood vessels in the operative field. Hematologic disorders that are not apparent during the long operation are most unlikely to surface as problems postoperatively.<br/>
'''Educational Objective:''' <br/>
'''References:''' +
Griseofulvin is a fungistatic antifungal drug used mostly in the treatment of fungal skin infections. It is deposited in keratin precursor cells and tightly bound to keratin, which explains its efficacy in dermatologic infections. It acts by inhibiting mitosis strongly in fungal cells and weakly in mammalian cells by affecting mitotic spindle microtubule function. It binds to microtubules and inhibits their ability to polymerize leading a decrease in the effective mitotic spindles. It is among the fastest reversible drugs acting on microtubules. Common side effects include urticaria and drug induced rashes. A more severe but rare adverse effect is severe liver toxicity. Treatment is indicated for resistant infections affecting skin, body, hair, or nails, including tinea capitis, tinea corporis, and tinea pedis.<br/>
'''Educational Objective:''' Griseofulvin is a fungistatic agent that inhibits microtubule polymerization halting mitotic divison.<br/>
'''References:''' Odds FC, Brown AJ, Gow NA. Antifungal agents: mechanisms of action. Trends in Microbiology. 2003;11(6):272-279. +
The patient in this scenario is presenting with symptoms consistent with heart failure. Physical examination of the patient reveals a third heart sound, S3, that is described as a low-pitched, early diastolic sound that is heard due to the increased filling pressure in a dilated ventricle. The patient also has jugular venous distention and pitting edema of the lower extremities, both of which signify the presence of right heart involvement. Elevation of the jugular venous pressure (JVP) and the presence of a third heart sound (S3) are 2 physical examination findings that are considered important prognostic features in patients with heart failure as they are associated with worse outcomes. Patients with S3 are more likely to have worse New York Heart Association (NYHA) functional class than those with absent S3 sound.<br/>
'''Educational Objective:''' Presence of S3 is associated with worse outcomes in patients with heart failure.<br/>
'''References:''' Rame JE, Dries DL, Drazner MH, et al. The prognostic value of the physical examination in patients with chronic heart failure. Congest Heart Fail. 2003;9(3):170-5, 178.<br>
First Aid 2014 page 270 +
The patient in this scenario is most likely presenting with aortic regurgitation (AR). Murmur of AR is best described as a blowing diastolic decrescendo murmur. It is usually caused by aortic root dilation, bicuspid aortic valve, rheumatic heart disease, or endocarditis. Patients with AR often have a widened pulse pressure (PP = SBP - DBP) as observed in this patient. This wide difference between systolic and diastolic pressures causes head bobbing, which is head nodding that accompanies one's heart beat (De Musset's sign). Additionally, patients with AR have positive Quincke's sign, which are pulsations in the capillary beds of the nails. Other signs include a bounding carotid pulse (Corrigan’s pulse), pulsation of the uvula (Muller’s sign), pistol-shot sounds during auscultation of the femoral artery (Traube’s sign), and bruit during compression of the femoral artery (Duroziez sign).<br/>
'''Educational Objective:''' Murmur of AR is best described as a high-pitched diastolic decrescendo murmur. Patients usually present with shortness of breath, fatigue, and head bobbing (De Musset's sign). Physical examination findings include a wide pulse pressure and a positive Quincke's sign.<br/>
'''References:''' Bekeredjian R, Grayburn PA. Valvular heart disease: aortic regurgitation. Circulation. 2005;112(1):125-34.<br>
First Aid 2014 page 273 +
Seborrheic dermatitis is an inflammatory skin disease with sebum secretions due to the ''Malassezia furfur'' fungus that occurs most often on the face, scalp, and chest. On histologic examination, seborrheic dermatitis is best characterized by parakeratosis (retained nuclei in stratum corneum), orthokeratosis (formation of anuclear keratin layer), and follicular plugs. Cyclical "squirting" of granulocytes from the dermal papilla may also be observed. Seborrheic dermatitis is best treated using any of several topical antifungal medications and keratinolytic agents, such as selenium sulphide. The patient presents with physical examination findings that suggest Parkinson's disease; which is also confirmed by the use of ropirinole, a non-ergotamine dopamine agonist. Patients with Parkinson's disease often have resting or "pill-rolling" tremor, cogwheel rigidity upon active flexion of the limbs, and bradykinesia. The association between Parkinson's disease and seborrheic dermatitis is well established; however, the pathophysiology is poorly understood. The level of seborrhea, however, does not seem to correlate with the degree of Parkinson's disease. Other factors associated with seborrheic dermatitis are HIV/AIDS, mood disorders, and winter weather.<br/>
'''Educational Objective:''' Seborrheic dermatitis is an inflammatory skin condition that commonly affects the face, scalp, and chest. It is caused by Malassezia furfur and is commonly associated with Parkinson's disease.<br/>
'''References:''' Gupta AK, Bluhm R. Seborrheic dermatitis. Journal of the European Academy of Dermatology and Venereology. 2003;18(1): 13-26 +
Ketamine is a phencyclidine (PCP) analog used as an intravenous anesthetic drug. Ketamine acts as a non-competitive N-methyl-D-aspartate (NMDA) receptor blocker. Ketamine is known to cause dissociative anesthesia, a state of profound analgesia with only superficial sleep and spontaneous ventilation. It does not usually suppress respiratory drive unless used at very high doses.
Because ketamine increases intracranial pressure, it is contraindicated among patients with brain injury. Other systemic effects of ketamine are generally also increased. Following ketamine, there is an increased heart rate, blood pressure, CVP, CO2 baroreceptor function, bronchodilation, respiratory rate, uterine tone, salivation.<br/>
'''Educational Objective:''' Ketamine causes systemic effects by stimulating hemodynamic and respiratory systems. Following ketamine, there is an increased heart rate, blood pressure, cerebral blood flow, CVP, CO2 baroreceptor function, bronchodilation, respiratory rate, uterine tone, salivation.<br/>
'''References:''' Stevenson C. Ketamine: a review. Update in Anaesthesia. 2005;20:25-9. +
Hemispatial neglect or hemineglect syndrome is often caused by a stroke to the non-dominant right parietal lobe. It is characterized by a patient's inability to recognize, perceive, or acknowledge stimuli on the contralateral side of the body. Reports of hemineglect on the ipsilateral side are also described. Patients who are left-handed (right dominance) tend to have less hemineglect when their non-dominant parietal lobe is affected following a stroke. In this case, the patient has left hemineglect due to a stroke of the right parietal lobe of the brain. Patients with hemineglect often complain of recurrent falls, resulting from their inability to visualize objects that are on the affected side. Also, patients frequently neglect half of environmental activities, such as neglecting half their food or shaving only half of their face.<br/>
'''Educational Objective:''' Right (non-dominant) parietal lobe stroke frequently causes hemineglect on the contralateral side.<br/>
'''References:''' Bailey MJ, Riddoch MJ. Hemineglect part 1: the nature of hemineglect and its clinical assessment in stroke patients: an overview. Physical Therapy Reviews. 1999;4(2):67-75(9). +
Cluster headache is characterized by episodic unilateral headaches that often lasts for several months with periods of remission. Cluster headaches are best described as excruciating episodes of unilateral headaches in the peri-orbital region that last for 15 minutes up to 3 hours. They are associated with lacrimation, rhinorrhea, and nasal blockage. Cluster headaches usually occur at night and patients complain of restlessness and agitation during the episodes. The first line therapy for acute attacks of cluster headaches is inhalation of high-dose, high-flow oxygen at 100% for 15 minutes. Oxygen therapy is preferred over other drugs because of its rare side effects and its remarkable therapeutic effects in cluster headaches.<br/>
'''Educational Objective:''' 100% oxygen therapy for 15 minutes is recommended to relieve symptoms of patients with cluster headaches.<br/>
'''References:''' Cohen AS, Burns B, Goadsby PJ, et al. High-flow oxygen for treatment of cluster headache: A randomized trial. J Am Med Assoc. 2009;302(22):2451-2457. +
A subdural hematoma is characterized by the rupture of a bridging vein. Because the venous pressure system is a low-presure system as compared to the arterial system, the build-up of blood following subdural hematoma is slow and gradual increase in hematoma size develops over a prolonged period of time. On CT scan, subdural hematoma appears as a crescent-shaped hemorrhage that does not cross the falx cerebra but may cross the suture lines.<br/>
'''Educational Objective:''' Upon CT scan, subdural hematoma, resulting from a rupture of bridging veins, appears as a crescent-shaped hemorrhage that crosses the suture lines but is unable to cross the falx cerebri.<br/>
'''References:''' First Aid 2014 page 462 +
Chromatin is composed of repeated nucleosomes, which are in turn composed of DNA molecules bound to a histone tetramer. Core histones of the nucleosome are H2A, H2B, H3, and H4, all of which are tripartite proteins. These histones have helix-strand-helix motifs on different ends of a long central helix, which form a "helix fold". The H1 histone is also a tripartite protein that is not located in the core nucleosome. It connects two nucleosomes and is referred to as a "linker histone". The combination of the nucleosome (DNA, H2A, H2B, H3, H4) and H1 linker histone is called a chromatosome. The H1 histone and its particular position within the chromatin structure facilitates the nucleosomal stability and protection from nuclease digestion.<br/>
'''Educational Objective:''' Histone H1, a tripartite protein, is referred to as a linker protein because it links 2 nucleosomes. It provides stability of the DNA stem and prevents nuclease digestion of the nucleosome.<br/>
'''References:''' Arents G, Burlingame RW, Wang BC, Love WE, Moudrianakis EN. The nucleosomal core histone octamer at 3.1 A resolution: a tripartite protein assemble and a left-handed superhelix. Proc Natl Acad Sci 1991; 88:10148-10152.<br>
Whitlock JP, Simpson RT. Removal of histone H1 exposes a fifty base pair DNA segment between nucleosomes. Biochemistry. 1976; 15:3307-3314.<br>
Harshman SW, Young NL, Parthun MR, Freitas MA. H1 histones: current perspectives and challenges. Nucl Acids Res. 2013; 41(21):9593-609. +
Opioid analgesic overdose is life-threatening and affects multiple organ systems. Opioids increases the activity of G-protein-coupled transmembrane mu, delta, and kappa opioid receptors in various organs. Heterodimer and homodimer receptors form to activate endogenous and exogenous compounds. Patients with opioid overdose are frequently present with a comatose-like condition with signs of cardiopulmonary depression, such as low heart rate, low respiratory rate, and low blood pressure. Upon physical examination, patients with chronic abuse of opioids may have visible track marks on their arms and characteristic pinpoint pupils.
Opioid receptors in the brain stem mediate the respiratory depression in patients with opioid toxicity. Pinpoint pupils occur following the activation of the opioid receptor in the Edinger-Westphal nucleus of the oculomotor nerve.<br/>
'''Educational Objective:''' The opioid receptor, in the Edinger-Westphal nucleus, mediates the pupillary constriction in opioid toxicity.<br/>
'''References:''' Boyer EW. Management of opioid analgesic overdose. N Eng J Med. 2012;367:146-55. +
The patient has von Hippel-Lindau (VHL) disease, an autosomal dominant disorder caused by germline mutation of one copy of the VHL tumor suppressor gene on chromosome 3. VHL is characterized by hemangioblastomas of the retina, cerebellum, and medulla. Also patients frequently present with bilateral renal cell carcinomas or other tumors, such as pheochromocytomas. A common manifestation of VHL in young patients are headaches with neurological symptoms. Symptoms of other tumors may also manifest, such as hypertension in the case of pheochromocytoma.<br>
VHL encodes a ubiquitin ligase that targets the HIF (hypoxia inducible factor) protein for degradation. In the absence of VHL protein, renal cell carcinoma cells turn on a transcriptional program mimicking that of an oxygen-deprived state. The cells begin to highly express genes such as VEGF (vascular endothelial growth factor) that induce tumorigenesis. Recall that the kidneys are responsible for coordinating the erythropoetic response to low oxygen tension. Accordingly, renal cell carcinomas express high levels of erythropoietin and patients often develop high hematocrits.<br/>
'''Educational Objective:''' Polycythemia is associated with VHL, due to an overproduction of HIF.<br/>
'''References:''' Kaelin WG. The von Hippel-Lindau tumor suppressor gene and kidney cancer. Clin Cancer Res. 2004; 10(18 Pt 2):6290S-5S +
Schizotypal personality disorder is a pervasive pattern of being usually beginning in early adulthood characterized by weird and eccentric appearance, magical beliefs, bizarre fantasies or preoccupations, and odd thinking and speech. Patients can also have some form of social withdrawal, lack of friends, and inappropriate affect. Patients with schizotypal personality disorder do not have visual or auditory hallucinations, and not have social, personal, and intellectual decline seen in patients with schizophrenia.<br/>
'''Educational Objective:''' Schizotypal personality disorder is characterized by weird and eccentric appearance, magical beliefs, and bizzare preoccupations. Patients usually do not have visual or auditory hallucinations.<br/>
'''References:''' American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA:American Psychiatric Publishing. +
Clostridium botulinum is a gram positive spore forming bacillus that produces an exotoxin known as the botulinum toxin. Clostridium botulinum thrives in anaerobic conditions and foodborne illness occurs due to the ingestion of preformed botulinum toxin usually found in home canned vegetables prepared without following required methods. Infant botulism is seen in babies less than 12 months that are fed honey that contains the bacteria. Botulinum toxin is inactivated by high temperatures, so boiling home-canned food for 10 minutes prior to eating is preferred. Botulinum toxin acts by blocking acetylcholine vesicle release from the pre-synaptic cleft leading to flaccid paralysis of all muscles including the diaphragm.<br/>
'''Educational Objective:''' Botulinum toxin inhibits acetylcholine vesicles from being release in the pre-synaptic cleft leading to flaccid paralysis. It is produced by Clostridium botulinum an anaerobic gram positive bacillus.<br/>
'''References:''' Cherington M. Clinical spectrum of botulism. Muscle Nerve. 1998;21(6):701-10. +