Property:Explanation
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Hodgkin’s disease is a curable malignancy, however, patients are at an increased risk of developing secondary malignancies such as solid tumours, leukaemia and non Hodgkin’s lymphoma even after 20 years of follow up. Lung and breast cancers are the most common among solid tumors.<br>
Other late complications of radiation and chemotherapy treatment for Hodgkin’s disease are cardiac involvement and hypothyroidism.<br><br/>
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Mild to moderate asymptomatic hypercalcemia does not require any immediate treatment. Any symptomatic moderate hypercalcmia (>12-14 mEq/L) or severe hyercalcemia (>14 mEq/L) should be treated.
Intravenous hydration is always the first step. 4-6 L of IV fluids (0.9% NS) should be given over the first 24 hours. Hydration helps by increasing the calcium excretion by kidneys, also hypercalcemia leads to dehydration so volume resuscitation is required. However, comorbidities like CHF should be kept in mind with aggressive hydration. Loop diuretics like furosemide should be added only after volume expansion is adequately reached. Severe and acutely raised calcium levels, or hypercalcemia of malignancy require treatment with hydration, bisphonates and calcitonin.<br/>
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Chlamydia and gonorrhea infection are very often coexist, differentiation between them clinically is difficult. Treatment should be directed to both of them.<br/>
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Immune reconstitution inflammatory syndrome (IRIS) is a paradoxical worsening of preexisting infections in HIV positive patients that occur days to weeks after highly active antiretroviral therapy (HAART) begin. The rapid improvement of the immune system initiates inflammatory reactions in the sites of preexisting infections. IRIS is typically self -limited syndrome, the best management is to continue HAART and antibiotics treatment of the underlying infections.<br/>
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Exposure to body fluids of HIV-positive patient should be followed within hours by antiretroviral prophylaxis. Regimen include two nucleoside reverse transcriptase inhibitor (zidovudine and lamivudine ) for four weeks, some experts suggest adding protease inhibitor (e.g. indinavir ) if viral resistance to the post exposure prophylaxis is suspected<br/>
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Ampicilline-associated maculopapular rash in patients with infectious mononucleosis is a well know phenomenon. It is caused by the circulating IgG and IgM targeting penicillin derivatives causing this immune vasculitic rash<br/>
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The patient high risk behavior put him at risk of having HIV. The CSF findings are characteristic for cryptococcal meningitis , which is managed by amphotericin B and flucytosine.<br/>
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According to the current CDC recommendation, CSF should be examined before the start of treatment in case of patients diagnosed with syphilis of unknown duration, or late latent syphilis. Patients with CD4 < 350 mm3, and RPR titer greater than 1:32 considered high risk patients for neurosyphilis. Neurosyphilis can present early with CSF changes without neurological manifestations.<br/>
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HIV infected patient with latent syphilis of unknown duration, or late syphilis should be treated with benzathin penicillin G IM weekly for three weeks<br/>
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Jarich-Herxheimer reaction is an acute febrile reaction develops within 24hours after the initiation of any syphilis treatment. Fever is usually accompanied with headache, malaise, chills, and myalgias. The etiology is not clear. No effective prevention is available. The patient should be informed with this possible condition, and advised to contact his clinician in severe cases.<br/>
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HIV infection suspicion should be high in any young patient with non specific symptoms, and unintentional l loss of weight. New onset seborrheic dermatitis is commonly seen in HIV infected patients. The patient should be screened for HIV infection, and possible risk factors, which include detailed sexually history and any IV drugs use.<br/>
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Progressive multifocal leukoencephalopathy (PML) is an opportunistic infection seen in immunocompromised patients. It is caused by JC virus, a human polyomavirus.
PML predominantly involves the cortical white matter, but the brainstem and cerebellum may also be involved. The lesion typically doesn’t produce mass effect, and has a gradual onset of the symptoms.
The most common presenting symptoms are hemipariesis and disturbances in speech, vision, and gait.
An immunocompromised patient with focal neurological deficits should raise the suspicion for PML, and diagnosis is best confirmed with MRI.
Classic MRI findings of PML consist of multiple demyelinating, non enhancing lesions with no mass effect.
There is no effective treatment for PML, and the mean duration of survival from the time of diagnosis is six months.<br/>
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Ductal carcinoma in situ (DCIS) is a non-invasive breast cancer that causes a wide clinical spectrum of disease. It is often considered to be an intermediate step before progression to invasive breast cancer. DCIS is characterized by the presence of malignant epithelial cell proliferation bounded by the basement membrane of the breast ducts with no invasion to the basal myoepithelial layer. Accordingly, the presence of well-defined breast ducts is required for the diagnosis of DCIS. Based on the grade of the breast lesion, DCIS may be classified as low-grade, intermediate, or high-grade. DCIS is frequently detected by mammography. Management ranges from local excision, lumpectomy, breast-conserving surgery, to partial or total mastectomy with or without radiation, chemotherapy, or hormonal therapy.
DCIS contains several subtypes that are classified based on the architecture of the proliferation:<br>
1- Comedo<br>
2- Cribriform<br>
3- Papillary <br>
4- Micropapillary<br>
5- Solid<br>
However, patients usually present with lesions that involve more than 1 subtype or are said to have ''mixed'' lesions.
Comedocarcinoma of the breast is characterized by the presence of cancerous cells surrounded by central necrosis. It is considered a more malignant form of DCIS compared to other subtypes, but is still an in-between state of in-situ cancer and an invasive cancer.<br/>
'''Educational Objective:''' Comedocarcinoma of the breast is characterized by the presence of central necrosis.<br/>
'''References:''' Pinder SE. Ductal carcinoma in situ (DCIS) pathological features, differential diagnosis, prognostic factors, and specimen evaluation. Mod Pathol. 2010;23:S8-S13.<br>Richie RC, Swanson JO. Breast cancer: a review of the literature. J Insur Med. 2003;35:85-101.<br>Virnig BA, Tuttle TM, Shamliyan T, Kane RL. Ductal carcinoma in situ of the breast: a systematic review of incidence, treatment, and outcomes. J Natl Cancer Inst. 2010;102(3):170-8<br>First Aid 2014 page 585
Granulosa cell tumor of the ovary is a rare estradiol-secreting sex cord stroma tumor. It may present among young children with a clinical presentation of precious puberty, or among adult women of reproductive age with a typical clinical presentation of menstrual irregularities, abnormal uterine bleeding (AUB), predisposition of endometrial hyperplasia, and endometrial cancer. Accordingly, granulosa cell tumors are classified into 2 subtypes: juvenile and adult. While most of granulosa cell tumors are unilateral, a bilateral presentation is observed in less than 5% of patients. The typical presentation includes signs of isosexual precocious pseudopuberty, such as premature breast development, presence of pubic hair, and vaginal bleeding, along with a palpable lower abdominal or pelvic mass on physical exam. Ruptured granulosa cell tumor is a complication of the disease, and patients classically present with acute abdominal pain and ascites.
Two important features of granulosa cell tumors include a long natural history of the tumor and a tendency to recur many years after the initial diagnosis. Diagnosis requires imaging, such as abdominopelvic CT scan. Management is first by surgery for resection, debulking, confirmation of histological diagnosis, and staging. Chemoradiation are also required in advanced disease. The stage of the disease is the most important prognostic factor of the disease, and is associated with the risk of recurrence.
Theca cells are still important in the mechanism of estradiol-secretion in granulosa cell tumors. Theca cells are required for the production of the estradiol precursor, androstenedione. Because more than 30% of granulosa cell tumors lack theca cells, these tumors are non-secretory, making estradiol secretion a non-reliable element for either diagnosis or follow-up.
Grossly, granulosa cell tumor appears as a white-gray solid mass with a possible hemorrhagic, fibrotic, multilocular, or cystic appearance. Five morphological patterns have been described: <br>
1- Multilocular cystic <br>
2- Thick-walled unilocular cystic<br>
3- Thin-walled unilocular cystic<br>
4- Homogeneously solid<br>
5- Heterogeneously solid
Microscopically, granulosa cell tumors may be moderately or well-differentiated. The histological appearance may be microfollicular, trabecular, solid tubular, diffuse, water-silk, or mixed. Call-Exner bodies, which are follicular structures containing acidophilic material, are characteristic.<br/>
'''Educational Objective:''' Granulosa cell tumor is an estrogen-secreting sex cord stroma tumor characterized by the clinical presentation of precocious puberty among young females and the presence of Call-Exner bodies on microscopy.<br/>
'''References:''' Mava Y, Chinda JY, Alhaji MA, Naggada HA. Childhood ovarian juvenile granulosa cell tumor: a case report and review of literature. Niger J Paed. 2012;39(4):199-201.<br>Koukourakis GV, Kouloulias VE, Koukourakis MJ, et al. Granulosa cell tumor of the ovary: tumor review. Integr Cancer Ther. 2008;7(3):204-15.<br>First Aid 2014 page 583
The patient is presenting with gynecomastia. Use of several medications are associated with gynecomastia. Knowing these medications is important for the USMLE. The following is a list of medications and conditions that are associated with gynecomastia: <br>
1- Medications: Spironolactone, digitalis, cimetidine, ketoconazole, dopamine, anti-psychotic drugs<br>
2- Substances: Alcohol, heroin, marijuana <br>
3- Diseases: Klinefelter syndrome, cirrhosis, testicular tumors<br>
4- Physiological conditions: Puberty, old age, estogen<br/>
'''Educational Objective:''' Gynecomastia is an adverse effect of cimetidine.<br/>
'''References:''' First Aid 2014 page 586 +
Ondansetron is a 5-hydroxytryptamine (5-HT3) receptor antagonist or a serotonin receptor antagonist. It has a powerful central antiemetic activity that is very effective against nausea and vomiting associated with chemotherapy and is usually given prophylactically. However, it might also be administered in other conditions, such as severe hyperemesis gravidarum among pregnant women.
It is generally well-tolerated by patients. The most common adverse effects of ondansetron are: headache, constipation or diarrhea, sedation, and small increases in liver function tests that are usually self-limited. Ondansetron is almost totally eliminated by the liver with minimal amounts retrieved intact in the urine. Generally, its half life is 3-4 hours, but might vary according to age. Half-life is shorter among children and more prolonged among older patients.<br/>
'''Educational Objective:''' Ondansetron, a 5-HT3 or serotonin receptor antagonist, is indicated for prophylaxis against chemotherapy-associated nausea and vomiting.<br/>
'''References:''' Kohler DR, Goldspiel BR. Ondansetron: a serotonin receptor (5-HT3) antagonist for antineoplastic chemotherapy-induced nausea and vomiting. DICP. 1991;25(4):367-80.<br>First Aid 2014 page 372 +
The use of lisinopril, an ACE-inhibitor, inhibits the renin-angiotensin system from producing aldosterone. Since ACE is inhibited, aldosterone will not be secreted from the adrenal gland.
The adult adrenal gland contains an adrenal cortex and an adrenal medulla. The cortex contains 3 distinct layers that are arranged in order (from superficial to deep) in the following order: <br>
1- Glomerulosa<br>
2- Fasciculata<br>
3- Reticularis
Each layer in the adrenal cortex is involved in the secretion of specific compounds. The zona glomerulosa mainly secretes aldosterone, the zona fasciculata mainly secretes cortisol, and the zona reticularis mainly secretes sex hormones. On the other hand, the medulla is the main secretory zone of catecholamines.<br/>
'''Educational Objective:''' Aldosterone is mainly secreted from the zona glomerulosa.<br/>
'''References:''' First Aid 2014 page 306 +
Cortisol upregulates β-adrenergic receptors to increase the sensitivity to norepinephrine, and thus increase blood pressure. The mechanism by which cortisol or glucocorticoids achieve such permissive effect is by coupling the β-adrenergic receptors and the G-protein receptors to stimulate adenylate cyclase, which is sensitive to catecholamines, leading to cAMP accumulation. As such, it it believed that the target for cortisol to achieve its action is the β-adrenergic receptor. Following the administration of cortisol, the activity of β-adrenergic receptors increases to as much as 3 times its baseline value. Thyroid hormones are another example of permissive hormones that allow activity of other hormones that act through the cAMP pathway.<br/>
'''Educational Objective:''' Cortisol and glucocorticoids are permissive hormones that regulate the action of other hormones that act through cAMP pathway by targeting the adrenergic receptors.<br/>
'''References:''' Hadcock JR, Malbon CC. Regulation of beta-adrenergic receptors by "permissive" hormones: glucocorticoids increase steady-state levels of receptor mRNA. Proc Natl. Acad. Sci. USA. 1988;85:8415-8419.<br>First Aid 2014 page 313 +
Platelet-derived growth factor (PDGF) is a compound found in platelet alpha-granules and other numerous cell types. It exerts its effects via an autocrine or paracrine fashion. PDGF helps growth and proliferation of smooth muscle cells and fibroblasts. It has been hypothesized that PDGF's proliferative function may contribute to proliferative pathological processes, such as cancers and atherosclerosis. PDGF, similar to other growth factors and insulin, achieves its hormonal effects by the intrinsic tyrosine kinase signaling pathway. PDGF contains extracellular ligang-binding domains that are associated with intracellular domains. Following ligand binding, the receptor dimerizes, with each subunit binding to one receptor molecule. Dimerization then causes activation of the enzyme protein kinase on the receptor via phosphorylation mechanisms.<br/>
'''Educational Objective:''' Growth factors, such as PDGF, and insulin achieve their hormonal activity by the intrinsic tyrosine kinase signaling pathway.<br/>
'''References:''' Heldin CH, Westermark B. Platelet-derived growth factor: mechanism of action and possible in vivo function. Cell Regulation. 1990;1:555-566.<br>
First Aid 2014 page 315 +
Neutrophils are key components of the innate immune response. They are the first cells to respond to bacterial infections, areas of inflammation, and wound sites. To achieve adequate chemotaxis, which is defined as migration to sites of inflammation, intracellular signaling pathways, which are spacially and temporally regulated, help the neutrophil identify gradients of chemoattractants, such as LBT4, before it undergoes polarization and physical migration. Endogenous and exogenous chemoattractants allow the neutrophil to alter its morphological appearance to achieve polarization that aids in orientation during migration. Chemotaxis is thus an important feature of neutrophil activity. The pathway shown in the image is the arachidonic acid pathway that involves 2 main enzymes: Lipoxygenase which forms hydroperoxides to yield leukotrienes, and cyclooxygenase (COX), which forms endoperoxides. The 2 enzymes have significant roles in unrelated domains. In the pathway, LTB4 is an important neutrophil chemotactic agent.<br/>
'''Educational Objective:''' LTB4 is an important neutrophil chemotactic agent.<br/>
'''References:''' Nuzzi PA, Lokuta MA, Huttenlocher A. Analysis of neutrophil chemotaxis. Methods Mol Biol. 2007;370:23-36.<br>
First Aid 2014 page 224 and 439 +