Property:Explanation
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Turner syndrome is caused by the a complete or partial loss of one copy of the X chromosome, an abnormal structure of the X chromosome, or mosaicim of a 45,XO cell line with another cell line. The karyotype of patients with Turner syndrome is 45,XO. Turner syndrome affects 1/2000 to 1/3000 live-born girls. It has a variable phenotypic expression, but some features are common.
Facial characteristics include abnormalities caused by lymphatic obstruction, such redundant neck folds, low posterior hairlines, and neck webbing (pterygium colli). Other signs of obstructive lymphedema include cystic hygroma, acral congenital lymphedema, and interstitial congestion. Also, patients have posteriorly rotated ears, downward slanting of the eyes, and epicanthal folds. Skeletal features include short stature, congenital hip dislocation, scoliosis, broad shield-shaped chest with a square torso and widely spaced nipples, and cubitus valgus (increased carrying angle of the elbow). Patients often also have dental crowding, micrognathia or prognathia, and a posterior rotation of the mandible.
Females with Turner syndrome typically experience gonadal dysgenesis (or less commonly agenesis), which results in amenorrhea, infertility, and the presence of a hypoplastic uterus due to low estrogen levels. Consequently, the loss of negative feedback inhibition results in elevated FSH and LH levels. Turner syndrome is also associated with cardiac abnormalities such as pre-ductal coarctation of the aorta (delayed femoral pulses), and bicuspid aortic valve. Turner syndrome is also associated with the presence of a horseshoe kidney, a renal fusion anomaly that leads to trapping of the fused kidney low in the abdomen under the inferior mesenteric artery.<br/>
'''Educational Objective:''' Turner syndrome is characterized by unique facies that include abnormalities caused by lymphatic obstruction, such redundant neck folds, low posterior hairlines, and neck webbing (pterygium colli). It is associated with gonadal dysgenesis/agenesis, pre-ductal coarctation of the aorta, and bicuspid aortic valve. Turner syndrome is also associated with horseshoe kidney, a renal fusion anomaly that leads to trapping of the fused kidney low in the abdomen under the inferior mesenteric artery.<br/>
'''References:''' Doswell BH, Visootsak J, Brady AN, Graham JM. Turner syndrome: an update and review for the primary pediatrician. Clin Pediatr. 2006;45:301-13.<br>
First Aid 2014 page 574
Epispadias in males results from the the faulty positioning of the genital tubercle that leads to an abnormally located dorsal (superior) urethra during development. Due to the involvement of the urinary sphincter, patients typically present with urinary incontinence, which may include involuntary urine loss and continuous urine dripping through the meatus. Epispadias is associated with bladder and cloaca exstrophy; the combination of both diseases is referred to as the exstrophy-epispadias complex. Other genitourinary and abdominal anomalies may also be associated with the exstrophy-epispadias complex. Diagnosis is usually made clinically at birth; but prenatal ultrasound may demonstrate a repeatedly empty bladder and may help in the early diagnosis. Management includes surgical genital reconstruction, but additional surgeries may be necessary in the presence of associated diseases.<br/>
'''Educational Objective:''' Epispadias in males results from the the faulty positioning of the genital tubercle that leads to an abnormally located dorsal urethra during development. Due to the involvement of the urinary sphincter, patients typically present with urinary incontinence, which may include involuntary urine loss and continuous urine dripping through the meatus. Epispadias is associated with bladder and cloaca exstrophy.<br/>
'''References:''' Ebert AK, Reutter H, Ludwig M, et al. The exstrophy-epispadias complex. Orph J Rare Dis. 2009;4:23.<br>
First Aid 2014 page 562 +
Inclusion cell disease or I-cell disease (mucolipidosis type II) is a lysosomal storage disease characterized by a defective phosphorylation of mannose residues due to a defect of GlcNAc-phosphotransferase, which is normally found on the Golgi apparatus. Consequently, lysosomal enzymes are secreted out of the cell, rather than being directed into the lysosomes, resulting in vacuolization of the cytoplasm due to the accumulation of substances that would normally be degraded by the lysozomal enzymes. Typical manifestations of inclusion cell disease are coarse facial features, restricted joint movement, and clouded corneas among very young children, all of which result from the aggregation of substances that would otherwise normally be degraded in the lysosomes. I-cell disease is usually deadly in early childhood.<br/>
'''Educational Objective:''' Clinical features of inclusion cell disease (I-cell disease) are coarse facial features, clouded corneas, and restricted joint movement, all of which result from the aggregation of substances in the cytoplasm that would otherwise be normally degraded in the lysosomes.<br/>
'''References:''' Tiede S, Storch S, Lübke T, et al. Mucolipidosis II is caused by mutations in GNPTA encoding the alpha/beta GlcNAc-1-phosphotransferase. Nat Med. 2005;11(10):1109-12.<br>
First Aid 2015 page 73
First Aid 2014 page 77 +
Adenosine deaminase deficiency, the likely culprit in this patient, is an important cause of severe combined immunodeficiency (SCID). SCID is a syndrome encompassing a group of rare congenital disorders characterized by B cell and T cell deficiency. All forms of SCID are inherited, most common of which is X-linked. X-linked SCID is caused by a deficiency of IL-2 receptor gamma leading to a failure in the development and differentiation of T and B cells. Adenosine deaminase deficiency is the second most common cause of SCID. Adenosine deaminase is coded for by a gene on chromosome 20 and is essential for the breakdown of purines. Loss of this enzyme leads to the accumulation of dATP causing feedback inhibit the activity of ribonucleotide reductase. As ribonucleotide reductase is essential for dNTP synthesis, DNA replication would cease and lymphocyte proliferation is subsequently inhibited. Accordingly, patients with SCID present early in childhood with failure to thrive and recurrent infections by viruses, bacteria and fungi. Work-up may reveal thymic aplasia and loss of germinal centers on lymph node biopsy. Currently, the only curative treatment for SCID is bone marrow transplantation despite several controversial attempts at introducing gene therapy as an alternative (mainly due to the high incidence of leukemias).<br/>
'''Educational Objective:''' Adenosine deaminase deficiency is a common cause of severe combined immunodeficiency (SCID).<br/>
'''References:''' Weinberg K, Parkman R. Severe combined immunodeficiency due to a specific defect in the production of interleukin-2. N Engl J Med. 1990;322(24):1718-23.<br>
Parkman R, Gelfand EW, Rosen FS, Sanderson A, Hirschhorn R. Severe combined immunodeficiency and adenosine deaminase deficiency. N Engl J Med. 1975;292(14):714-9.<br>
First Aid 2014 page 68. +
Acetylation of core histones, such as H2A, H2B, H3, and H4, plays a major role in the regulation of transcription in eukaryotic cells. The acetylation of lysine residues at the tails of histones neutralizes its positively charge and decreases its affinity for DNA. Consequently, the alteration of nucleosomal conformation facilitates the transcription at the level of chromatin templates.<br/>
'''Educational Objective:''' Histone acetylation is crucial in the regulation of eukaryotic transcriptional activity.<br/>
'''References:''' Struhl K. Histone acetylation and transcriptional regulatory mechanisms. Genes Dev. 1998;12:599-606. +
Telomeres are specific regions located at the end of each chromatid that function to protect the end of the chromosome from degradation or from fusion with other chromosomes. The regulation mechanisms of both the telomere length and replication are significant for the integrity of the genome. Telomeres have a role in cell senescence and the replicative potential of cells. The length of telomeres is regulated by telomerase and by the replication fork itself. If telomerases are absent, the lengths of telomeres are shortened with every replication until the length reaches the lower limit, the replicative senescence (the Hayflick limit), is induced. Additionally, G-rich overhanging regions at the end of telomeres are susceptible to oxidative damage, whose cumulative effects is associated with the biological age of somatic cells.<br/>
'''Educational Objective:''' Telomeres are important for the replicative potential of cells and for identifying the biological age of somatic cells.<br/>
'''References:''' Salpea KD, Humphries SE. Telomere length in atherosclerosis and diabetes. Atherosclerosis. 2010; 209(1):35-38.
Waga S, Stillman B. The DNA replication fork in eukaryotic cells. Annu. Rev. Biochem. 1998; 67:721-51. +
The patient in this scenario is most likely diagnosed with sickle cell disease. Patients with sickle cell disease often require hydroxyurea, which provides symptomatic relief by increasing HbF levels. HbF has high affinity for oxygen and may aid in the delivery of oxygen to peripheral tissues in patients with SCD. Hydroxyurea is a chemotherapeutic agent that hinders ribonucleotide reductase ability to decrease DNA synthesis during S-phase. It is typically used to treat cancers, such as melanoma and CML. Common side effects of hydroxyurea include GI symptoms, bone marrow suppression, and an increased risk of developing leukemias.<br/>
'''Educational Objective:''' Hydroxyurea often administered to patients with sickle cell disease in order to increase HbF levels.<br/>
'''References:''' First Aid 2014 page 67 +
The patient in this scenario likely suffered an injury to his spinal accessory nerve secondary to neck trauma. The spinal accessory nerve is the eleventh cranial nerve that arises mostly from the spinal cord. Only a small portion of the spinal accessory nerve originates from the nucleus ambiguus and eventually joins the vagus nerve. The spinal portion arises from a column of nuclei in the ventral medulla. The nerve supplies both the sternocleidomastoid (SCM) and trapezius muscles. The sternocleidomastoid muscles originate from the sternum and clavicle and inserts on the mastoid process. The SCM rotates the head contralaterally and flexes the neck ipsilaterally. Patients with accessory nerve injury classically present with shoulder pain, weakness with sustained shoulder abduction, and difficulty shrugging shoulder. Signs in the SCM include weakness with ipsilateral neck flexion and contralateral head rotation.<br/>
'''Educational Objective:''' The spinal accessory nerve (CN XI) supplies the sternocleidomastoid (SCM) muscles responsible for ipsilateral neck flexion and contralateral head rotation, and the trapezius muscles responsible for shoulder elevation.<br/>
'''References:''' Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 64.<br>
First Aid 2014 page 472 +
The Patient Self-Determination Act of 1990 states that hospitals, nursing homes, health maintenance organizations, and hospices that participate in Medicare and Medicaid should inquire about advance directive and should incorporate advance directive into patients' medical records. Also, Patients should have the adequate amount of information about advance directive.
Written advance directives are either a living will or a durable power of an attorney for healthcare. When unconscious patients with no advance directives are hospitalized, the patient's surrogate is his decision-maker for life-sustaining medical interventions. Surrogates should make decisions that conform to what the patient would want, based on written or oral advance care planning. If advance care planning is not available, the patient's desires may be assumed on the basis of the patient's social values, previous decisions, and beliefs, or on the basis of the patient's best interest if these values are not agreed upon. the following order of priority for health care surrogates must be taken into account:<br>
1- Patient's guardian<br>
2- Patient's spouse<br>
3- Patient's adult son or daughter<br>
4- Patient's parent<br>
5- Patient's adult brother or sister<br>
6- Patient's adult grandchild or adult relative who is familiar with the patient and has shown care and concern for the patient <br>
7- Patient's close friend<br>
8- Patient's guardian of the estate<br>
At all times, physicians must be careful to make sure that the patient's surrogate makes decisions that are consistent with the patient's own values and his best interest. In case of conflict or difficult situations, hospital ethics committees may be useful to help patient families reach reasonable conclusions. In this scenario, the patient cannot make his own decisions, so the patient's wife is considered his health care surrogate. The physician must ensure that the spouse's decisions must conform to the patient's values and beliefs based on previous decisions made by the patient and his own set of values and beliefs. In the scenario above, other family members argue that the patient's wife might not have the patient's best interest in mind. Accordingly, the physician in charge may use the help of a hospital ethics committee to aid the family in reaching a conclusion.<br/>
'''Educational Objective:''' A patient's spouse is considered the health care surrogate for adult patients who do not have any advance directive. In case of conflict or difficult situations, hospital ethics committees may be useful to help patient families reach reasonable conclusions.<br/>
'''References:''' Snyder L. American College of Physicians Ethics Manual: sixth edition. Ann Intern Med. 2012;156(1 Pt 2):73-104.<br>First Aid 2014 page 60
The patient in this scenario likely has major depressive disorder, which is considered a risk factor for suicide. Generally, patients who present to the primary care office with feelings of hopelessness and guilt must be screened for a history of psychiatric disorders, depression, substance abuse, and most importantly, previous suicide attempts. These are often predictors for future suicide attempts (among other psychiatric risk factors). Asking a patient about suicidal thoughts likely will not augment their suicidal mentality, but rather will provide relief by offering space for discussion about their ideations.
Inquiring about suicidal ideations requires a special approach, given that some patients with medical and psychiatric disorders might not directly admit their intent to commit suicide. For example, it can be beneficial to introduce the topic, prior to directly asking whether the patient is considering suicide.
Patients who demonstrate risk factors for suicide or show signs of suicidal intent, such as saying they are are worthless, hopeless, feel like a burden, or would rather by dead, should be screened for suicidal tendencies and further questioned about their planned method of suicide.<br/>
'''Educational Objective:''' Patients with symptoms of major depression should be asked about suicidal ideations.<br/>
'''References:''' Gliatto MF, Rai AK. Evaluation and treatment of patients with suicidal ideation. Am Fam Physician. 1999;59(6):1500-1506. +
DNA ligase is the enzyme responsible for the formation of phosphodiester bonds at single-strands in double-stranded DNA. DNA ligase is important in 2 major steps: First in the discontinuous replication of DNA and joining of Okazaki fragments, and second in the radiation-induced DNA single-stranded breaks and their consequent repair. DNA ligase requires ATP. Its activity increases dramatically in replicating cells, such as cells in liver regeneration. There are 2 DNA ligases: DNA ligase I and DNA ligase II, both of which are present in the nucleus and in the cytoplasm, but less likely in the mitochondria.<br/>
'''Educational Objective:''' DNA ligase is responsible for catalyzing the formation of phosphodiester bonds in discontinuous DNA, the Okazaki fragments, and in radiation-induced single-stranded DNA breaks.<br/>
'''References:''' Soderhall S. DNA ligases during rat liver regeneration. Nature.1976; 260;640-642. +
While dizygotic twins always form from 2 separately fertilized eggs, monozygotic twins form from 1 fertilized egg that later splits into 2 zygotes during early pregnancy. The time post-fertilization by which the fertilized egg cleaves is important for determining the number of chorions and amnions.
<br>0-4 days: Dichorionic diamniotic twin pregnancy
<br>4-8 days: Monochorionic diamniotic twin pregnancy
<br>8-12 days: Monochorionic monoamniotic twin pregnancy
<br> > 13 days: Monochorionic monoamniotic conjoined twin pregnancy<br/>
'''Educational Objective:''' Monochorionic diamniotic twin pregnancy occurs when the fertilized egg cleaves at 4-8 days post-fertilization.<br/>
'''References:''' First Aid 2014 page 555 +
The patient is most likely presenting with epidural hematoma following the motor vehicle collision due to a fracture of the temporal bone that leads to rupture of the middle meningeal artery, a branch of the maxillary artery. Based on the CT scan findings, there is a biconvex blood collection that appears hyperdense. It does not cross the suture lines, but may cross the falx and the tentorium. Embryologically, the maxillary artery is derived from the 1st aortic arch.<br/>
'''Educational Objective:''' The middle meningeal artery, ruptured in epidural hematomas, is a branch of the maxillary artery. The maxillary artery is derived from the first 1st aortic arch.<br/>
'''References:''' First Aid 2014 page 462 +
Anti-mullerian hormoner (AMH) or mullerian inhibitory factor (MIF) is secreted by the immature Sertoli cells. In the neonatal period, AMH levels are elevated and are not inhibited by the action of testosterone, as Sertoli cells lack any receptors for androgens in the neonatal period. Conversely, when males reach puberty, AMH levels are significantly decreased, due to the pubertal development of the Sertoli cells. Remarkably, the decrease in AMH levels are seen before the rise of serum testosterone levels is seen in male subjects at puberty. This observation led to the discovery that intratesticular testosterone is the real inhibitor of AMH at puberty. This physiological process is absent in patients with androgen-insensitivity, whereby AMH levels remain elevated by the function of FSH without any inhibitory effects of androgens.<br/>
'''Educational Objective:''' Intratesticular testosterone inhibits AMH (or MIF) in the pubertal period, but not in the neonatal period. Treatment with FSH increases AMH, whereas treatment with exogenous testosterone decreases AMH due to the inhibition of endogenous intratesticular testosterone.<br/>
'''References:''' Al-Attar L, Noel K, Dutertre M, et al. Hormonal and cellular regulation of Sertoli cell anti-Mullerian hormone production in the postnatal mouse. J Clin Invest. 1997; 100(6):1335-1343. +
The Hepatitis E virus is a positive-sense single stranded RNA virus transmitted via fecal-oral route. Usually, it is a clinically benign disease that is often contracted in childhood and usually follows an asymptomatic or mildly symptomatic clinical course. Mortality rates are typically low, with the exception being among patients with severe liver failure. Among pregnant women infected with hepatitis E, mortality rates can be as high as 20%, particularly among women who contract the virus during their third trimester.<br/>
'''Educational Objective:''' Hepatitis E is associated with an increased rate of mortality among pregnant women.<br/>
'''References:''' Kumar A, Beniwal M, Kar P, et al. Hepatitis E in pregnancy. Int J Gynaecol Obstet. 2004;85(3):240-4.<br>
First Aid 2014 page 165 +
Facultatively anaerobic organisms are capable of surviving independent of the presence or absence of oxygen. They produce energy by aerobic respiration in the presence of oxygen, but are capable of using fermentation as a source of energy production in anaerobic situations. Examples of facultatively anaerobic organisms include ''Staphylococcus spp.'' and ''Escherichia coli''. ''E. coli'' is a gram-negative, facultative anaerobic rod-shaped organism that can produce energy using a variety of substrates. In anaerobic conditions, it uses mixed-acid fermentation producing ethanol, lactate, acetate, succinate, and carbon dioxide.
* Obligate aerobes that depend on oxygen for energy production include: ''Nocardia'', ''Pseudomonas aeruginosa'', ''Legionella spp.'', and ''Mycobacterium tuberculosis''.
* Obligate anaerobes that cannot tolerate oxygen as a result of oxidative damage include: ''Actinomyces'', Bacteroides'', and ''Clostridium''.<br/>
'''Educational Objective:''' Facultatively anaerobic organisms such as ''Escherichia coli'' and 'Staphylococcus spp.'' can survive independent of the presence or absence of oxygen.<br/>
'''References:''' Baron S, editor. Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Section 1, Bacteriology. Available from: http://www.ncbi.nlm.nih.gov/books/NBK7994/ +
Bupivacaine is a local anaesthetic used in nerve blocks, epidurals, and intrathecal anesthesia. It acts by binding to neuronal sodium channels and blocking sodium influx. This leads to a block of depolarization. Although bupivacaine is relatively safe with proper handling, when injected accidentally into the bloodstream, it is associated with significant cardiotoxicity. By the same mechanism, it blocks sodium channels in the cardiac muscle fibers often leading to significant bradycardia, hypotension and eventual cardiac arrest. Several reports have shown serious cardiotoxicity with difficult resuscitation especially in pregnant women. Several measures have been introduced to decrease toxicity from anesthetic drugs including better teaching and monitoring of students as well as technical steps such as aspiration, incremental injection, dose control, the use of test doses, and ultrasound guidance.<br/>
'''Educational Objective:''' Bupivacaine can cause significant cardiotoxicity if injected intravascularly by blocking cardiac sodium channels.<br/>
'''References:''' Mulroy MF. Systemic toxicity and cardiotoxicity from local anesthetics: incidence and preventive measures. Reg Anesth Pain Med. 2002;27(6):556-61. +
Rodenticides, or rat poisons are a variety of agents used to exterminate rodents. The most commonly used rodenticides are anticoagulants typically of the coumarin class notably warfarin, coumatetralyl, difenacoum, and brodifacoum. They are also known as superwarfarins due to their substituted phenyl groups replacing the terminal methyl groups, that make these agents approximately 100 times more potent than regular coumarins. These agents act as they would for therapeutic purposes by inhibiting the gamma-carboxylation of coagulation factors that requires vitamin K. Coumarins inhibit the enzyme epoxide reductase that forms the active vitamin K needed for carboxylation. Blood levels of factors II, VII, IX and X drop to dangerously low levels after ingestion of large doses of rat poison usually leading to massive GI bleeding that may manifest as hematemesis. Treatment for early ingestion includes immediate gastric lavage. For late cases presenting with massive bleeding, treatment is typically with fresh frozen plasma and vitamin K administration.<br/>
'''Educational Objective:''' The most common types of rat poison are anticoagulants from the coumarin family that inhibit epoxide reductase and lead to a decrease in clotting factors.<br/>
'''References:''' Spahr JE, Maul JS, Rodgers GM. Superwarfarin poisoning: a report of two cases and review of the literature. Am J Hematol. 2007;82(7):656-60. +
Menopause is caused by decreased production of estrogen and progesterone from oocytes in females and usually between the age of 48 to 52 years. It is diagnosed by elevated levels of gonadotropins (FSH and LH) . Decreased estrogen in menopause may lead to Osteoporosis, Hot flashes, vaginal dryness, and increased LDL levels, Decreased HDL levels. Until the onset of menopause women are considered to be at lower risk for coronary artery disease than men because of the protective effect of estrogen. But Hormone replacement therapy can never be given to prevent risk of Coronary artery disease. Studies say hormone replacement therapy may decrease the levels of low density lipoproteins but cannot decrease the risk of coronary artery disease.
'''Educational Objective''': After menopause the protective effect of estrogen over coronary artery disease risk in females Is lost. While administration of estrogen to post-menopausal women decreases LDL, it does not decrease the risk of coronary artery disease
'''References''': Page 50, 482 Master the Boards Step 2 CK Second edition, Page 445 Master the boards Step 3 2009 edition<br/>
'''Educational Objective:''' <br/>
'''References:''' +
Takotsubo cardiomyopathy is mostly seen in post menopausal women after a stressful event like earthquake, lightening strike, sudden bad news etc. It leads to ballooning of apex of the left ventricle and alters its contraction ability. Electrocardiogram often shows changes consistent with an anterior wall MI including ST segment elevation.Cardiac enzymes such as troponin may be elevated as well. In contrast to ischemic myocardial infarctions, angiography will demonstrate patent coronary arteries which do not show vasospasm even on ergonovine provocative test. These patients are best managed with Beta blockers and angiotensin converting enzyme inhibitors.
'''Educational Objective''' : Takotsubo cardiomyopathy (also known as broken heart syndrome) is mostly seen in post menopausal women after a stressful event like earthquake, lightening strike, sudden bad news etc. It leads to ballooning of apex of the left ventricle and alters its contraction ability. Electrocardiogram may show ST segment elevation and troponin might be elevated. But Coronary arteries are normal and do not show vasospasm even upon ergonovine provocative test.
'''References''' : Page 52 , 54 6Master the boards Step 2 CK second edition, Page 169 Master the boards step 3 2009 edition<br/>
'''Educational Objective:''' <br/>
'''References:''' +