By L. Xardas. University of Saint Mary.
Three oral formulations are available: standard tablets (100 extra super levitra 100mg otc, 500 quality 100 mg extra super levitra, and 1000 mcg) cheap extra super levitra 100 mg otc, sublingual tablets (500 purchase extra super levitra 100mg amex, 1000, 2500, 5000, and 6000 mcg), and lozenges (50, 100, 250, and 500 mcg). Parenteral administration is indicated for patients with impaired B12 absorption —although most of these people can be treated with oral cyanocobalamin instead. If there is a positive response after this time, continue to administer 100 mcg every other day for 7 doses, then decrease to every 3 to 4 days for another 2 to 3 weeks. After anemia has been corrected, doses of 100 mcg are administered monthly for life. Efficacy of intranasal cyanocobalamin has not been determined for patients with nasal congestion, allergic rhinitis, or upper respiratory infections. Accordingly, until more is known, patients with these disorders should not use this formulation until symptoms subside. Hot foods or liquids can increase nasal secretions, which might flush cyanocobalamin gel from the nose. Accordingly, hot foods should not be eaten within 1 hour before or 1 hour after administering the drug. Intranasal cyanocobalamin is available in a metered-dose formulation called Nascobal, which delivers 500 mcg/actuation. Guidelines for Treating Vitamin B Deficiency 12 Route of B Administration12 As discussed previously, oral therapy can be used for most patients, including those with conditions that impair B12 absorption. The major exception is patients with severe neurologic deficits caused by B12 deficiency. Treatment of Moderate B Deficiency12 The primary manifestations of moderate B12 deficiency are megaloblasts in the bone marrow and macrocytes in peripheral blood. Moderate deficiency does not cause leukopenia, thrombocytopenia, or neurologic complications. Moderate deficiency can be managed with vitamin B12 alone; no other measures are required. Treatment of Severe B Deficiency12 Severe deficiency produces multiple effects, all of which must be attended to. Unlike mild deficiency, in which erythrocytes are the only blood cells affected, severe deficiency disrupts production of all blood cells. Loss of erythrocytes leads to hypoxia, cerebrovascular insufficiency, and heart failure. Loss of leukocytes encourages infection, and loss of thrombocytes promotes bleeding. After treatment with vitamin B12 plus folic acid, recovery from anemia occurs quickly. Within 1 to 2 days, megaloblasts disappear from the bone marrow; within 3 to 5 days, reticulocyte counts become elevated; by day 10, the hematocrit begins to rise; and within 14 to 21 days, the hematocrit becomes normal. Recovery from neurologic damage is slow and depends on how long the damage had been present. When deficits have been present for only 2 to 3 months, recovery is relatively fast. When deficits have been present for many months or for years, recovery is slow: Months may pass before any improvement is apparent, and complete recovery may never occur. Long-Term Treatment For patients who lack intrinsic factor or who suffer from some other permanent cause of vitamin B12 malabsorption, lifelong treatment is required. However, large daily oral doses can be just as effective, as can weekly intranasal doses. During prolonged therapy, treatment should be periodically assessed: plasma levels of vitamin B12 should be measured every 3 to 6 months, blood samples should be examined for the return of macrocytes, and blood counts should be performed. Potential Hazard of Folic Acid Treatment with folic acid can exacerbate the neurologic consequences of B12 deficiency. Recall that folic acid, by itself, can reverse the hematologic effects of B12 deficiency—but will not alleviate neurologic deficits. So, by correcting the most obvious manifestation of B12 deficiency (anemia), folic acid can mask the fact that deficiency of B12 still exists. As a result, use of folic acid can lead to undertreatment with B itself12 and can thereby permit neurologic damage to progress. Clearly, folic acid is not a substitute for vitamin B12, and vitamin B12 deficiency should never be treated with folic acid alone. Whenever folic acid is employed during treatment of vitamin B12 deficiency, extra care must be taken to ensure that B12 dosage is adequate. Folic Acid Deficiency In one respect, folic acid deficiency is identical to vitamin B12 deficiency: in both states, megaloblastic anemia is the most conspicuous pathology. However, in other important ways, folic acid deficiency and vitamin B12 deficiency are dissimilar (Table 45. Consequently, when a patient presents with megaloblastic anemia, it is essential to determine whether the cause is deficiency of folic acid, vitamin B12, or both. Under normal conditions, activation occurs through a pathway that employs vitamin B12 (see Fig. However, when large amounts of folate are ingested, some can be activated through an alternate pathway—one that does not employ vitamin B12. Fate in the Body Folic acid is absorbed in the early segment of the small intestine and then transported to the liver and other tissues, where it is either used or stored. That is, folate from the liver is excreted into the intestine, after which it is reabsorbed and then returned to the liver through the hepatic-portal circulation. In contrast to vitamin B12, folic acid is not conserved rigidly: every day, significant amounts are excreted. As a result, if intake of folic acid were to cease, signs of deficiency would develop rapidly (within weeks if body stores were already low). Good sources include peas, lentils, oranges, whole-wheat products, asparagus, beets, broccoli, and spinach. Folic Acid Deficiency: Causes, Consequences, and Diagnosis Causes Folic acid deficiency has two principal causes: (1) poor diet (especially in patients who abuse alcohol), and (2) malabsorption secondary to intestinal disease. Alcoholism Alcoholism, either acute or chronic, may be the most common cause of folate deficiency. Deficiency results for two reasons: (1) insufficient folic acid in the diet and (2) derangement of enterohepatic recirculation secondary to alcohol- induced injury to the liver. Fortunately, with improved diet and reduced alcohol consumption, alcohol-related folate deficiency will often reverse. Sprue Sprue is an intestinal malabsorption syndrome that decreases folic acid uptake. Because sprue does not block folate absorption entirely, deficiency can be corrected by giving large doses of folic acid orally. Consequences With the important exception that folic acid deficiency does not injure the nervous system, the effects of folate deficiency are identical to those of vitamin B12 deficiency. As with B12 deficiency, the most prominent consequence of folate deficiency is megaloblastic anemia. Because we already noted that many of the consequences of vitamin B12 deficiency result from depriving cells of active folic acid, the similarities between folate deficiency and vitamin B12 deficiency should be no surprise. The Developing Fetus Folic acid deficiency very early in pregnancy can cause neural tube defects (e. Accordingly, it is imperative that all women of reproductive age ensure adequate folate levels before pregnancy occurs. Preventive Services Task Force now recommends that all women who may become pregnant consume 400 to 800 mcg of supplemental folic acid each day—in addition to the folate they get from food. Other Consequences As discussed in Chapter 65, folic acid deficiency may increase the risk for colorectal cancer and atherosclerosis. One form is inactive as administered (but undergoes activation after being absorbed). Both forms have several generic names: the inactive form is referred to as folacin, folate, pteroylglutamic acid, or folic acid; the active form is referred to as leucovorin calcium, folinic acid, or citrovorum factor. Indications Folic acid has three uses: (1) treatment of megaloblastic anemia resulting from folic acid deficiency; (2) prophylaxis of folate deficiency, especially during pregnancy and lactation; and (3) initial treatment of severe megaloblastic anemia resulting from vitamin B12 deficiency. However, as noted in Chapter 65, even moderately large doses (1000 mcg/day), when taken long term, may increase the risk for some cancers, including colorectal cancer and cancer of the prostate. Dosage For treatment of folate-deficient megaloblastic anemia in adults, the usual oral dosage is 1000 to 2000 mcg/day. For prophylaxis during pregnancy and lactation, doses up to 1000 mcg/day may be used.
Liothyronine (T ) 3 Liothyronine [Cytomel] is a synthetic preparation of triiodothyronine order extra super levitra 100 mg without a prescription, a naturally occurring thyroid hormone buy extra super levitra 100 mg with visa. Because liothyronine is the active form of levothyroxine extra super levitra 100mg on line, the3 effects of the two drugs are identical discount extra super levitra 100 mg amex. Contrasts With Levothyroxine Liothyronine differs from levothyroxine in three important ways: (1) liothyronine has a shorter half-life and shorter duration of action, (2) liothyronine has a more rapid onset, and (3) liothyronine is more expensive. Because of its high price and relatively brief duration of action, liothyronine is less desirable than levothyroxine for long-term use. However, because its effects develop quickly, liothyronine may be superior to levothyroxine in situations that require speedy results, especially myxedema coma. Evaluation As with levothyroxine, the dosage of liothyronine is adjusted on the basis of clinical evaluation and laboratory data. Because of its short half-life, oral liothyronine is taken twice daily, in contrast to levothyroxine, which is taken once daily. Other Thyroid Preparations Liotrix Liotrix [Thyrolar] is a mixture of synthetic T plus synthetic T in a 4 : 1 fixed4 3 ratio. However, because levothyroxine alone3 produces the same ratio of T to T, liotrix offers no advantage over4 3 levothyroxine for most indications. Thyroid (Desiccated) Thyroid [Armour Thyroid, others] consists of desiccated animal thyroid glands. For practical purposes, thyroid is obsolete: use is limited to patients who have been taking the preparation for years. These agents can be used long term to treat hyperthyroidism or short term as preparation for subtotal thyroidectomy or therapy with radioactive iodine. Mechanism of Action Therapeutic effects result from blocking synthesis of thyroid hormones. First, methimazole prevents the oxidation of iodide, thereby inhibiting incorporation of iodine into tyrosine. Both effects result from inhibiting peroxidase, the enzyme that catalyzes both reactions. Please note that, although methimazole prevents thyroid hormone synthesis, it does not destroy existing stores of thyroid hormone. Hence, after therapy has begun, it may take 3 to 12 weeks to produce a euthyroid state. Therapeutic Uses Methimazole has four applications in hyperthyroidism: • It can be used as the sole form of therapy for Graves disease. Adverse Effects Methimazole is generally well tolerated but should be avoided by women who are pregnant or breastfeeding. The reaction is rare (about 3 cases per 10,000 patients) and usually develops during the first 2 months of therapy. Sore throat and fever may be the earliest indications, and patients should be instructed to report these immediately. Because agranulocytosis often develops rapidly, periodic blood counts cannot guarantee early detection. Treatment with granulocyte colony-stimulating factor (filgrastim [Neupogen]) may accelerate recovery. When given in high doses, methimazole can convert the patient from a hyperthyroid state to a hypothyroid state. Methimazole can cause neonatal hypothyroidism, goiter, and even congenital hypothyroidism. Methimazole therapy does not affect thyroid function or intellectual development in breastfed infants with doses up to 20 mg daily. Preparations, Dosage, and Administration Methimazole is supplied in tablets (5, 10, 15, and 20 mg) for oral dosing. When methimazole is discontinued, some 30% to 40% of patients remain euthyroid, indicating remission. Nonetheless, severe adverse effects can occur, especially liver injury and agranulocytosis. Treatment of Graves Disease High doses (100–300 mg 3 times a day) are used initially. Children/adolescents Thyroid hormone preparations are used in children and adolescents. Breastfeeding Thyroid hormone preparations and antithyroid medications are generally safe in breastfeeding women women. Thyroid hormone preparations and antithyroid medications can be used successfully to treat thyroid dysfunction in the older adult. Radioactive Iodine Physical Properties 131 Iodine-131 ( I) is a radioactive isotope of stable iodine that emits a combination 131 of beta particles and gamma rays. Hence, after 56 days (seven half-lives), less than 1% of 131 the radioactivity in a dose of I remains. Use in Graves Disease 131 I can be used to destroy thyroid tissue in patients with hyperthyroidism. The objective is to produce clinical remission without causing complete destruction of the gland. Unfortunately, delayed hypothyroidism, due to excessive thyroid damage, is a frequent complication. Effect on the Thyroid 131 Like stable iodine, I is concentrated in the thyroid gland. Destruction of thyroid tissue is produced primarily by emission of beta particles. About 66% of 131 patients with Graves disease are cured with a single exposure to I. First, the effect of treatment is delayed, taking several months to become maximal. Second, and more important, treatment is associated with a significant incidence of delayed hypothyroidism. Hypothyroidism results from excessive dosage and occurs in up 131 to 90% of patients within the first year after I exposure. Who Should Be Treated and Who Should Not 131 I is indicated for adults with hyperthyroidism, as well as patients who have not responded adequately to antithyroid drugs or to subtotal thyroidectomy. Also, there is 131 concern that administration of I to young patients may carry a slight risk for 131 cancer. It should be noted, however, that there is no evidence that the use of I in Graves disease has ever caused cancer of the thyroid or any other tissue. Exposure of the fetus to I after the first trimester may damage the immature thyroid, and exposure to radiation at any point in fetal life carries a risk for generalized developmental 131 harm. Dosage 131 Dosage of I is determined by thyroid size and by the rate of thyroidal iodine uptake. However, because most forms of thyroid cancer do not accumulate iodine, only a small percentage of patients 131 are candidates for I therapy. Because high amounts of radioactivity are involved, body wastes must be disposed of properly. Diagnostic Use 131 I is employed to diagnose a variety of thyroid disorders, including 131 hyperthyroidism, hypothyroidism, and goiter. After I administration, the 131 thyroid is scanned for uptake of radioactivity; the amount and location of I uptake reveal the extent of thyroid activity. Doses for diagnosis are minuscule (less than 1 microcurie for children and less than 10 microcuries for adults). Please note that, although 131 123 I can be used for diagnosis, the preferred isotope is I. Nonradioactive Iodine: Lugol Solution Description Lugol solution, also known as strong iodine solution, is a mixture containing 5% elemental iodine and 10% potassium iodide. Mechanism of Action When present in high concentrations, iodide has a paradoxical suppressant effect on the thyroid. Second, high concentrations of iodide inhibit thyroid hormone synthesis by suppressing both the iodination of tyrosine and the coupling of iodinated tyrosine residues. Third, high concentrations of iodine inhibit release of thyroid hormone into the blood. Therapeutic Use Strong iodine solution can be given to hyperthyroid individuals to suppress thyroid function in preparation for thyroidectomy.
Decreasing trend in lactate levels may indicate that tissue oxygenation is being restored purchase 100mg extra super levitra. Similarly buy 100mg extra super levitra free shipping, base excess on the arterial blood gas should normalize if oxygen delivery to the tissues is improving buy 100 mg extra super levitra with visa. This is achieved through optimization of preload generic 100mg extra super levitra, cardiac contractU� ity, afterload, and oxygen�carrying capacity. While fluid resuscitation and blood transfsions can improve preload and oxygen-carrying capacity, in severe cases ad ditional pharmacologic support may be required to improve cardiac contractility and afterload. A vasopressor can improve perfsion pressure and maintain blood flow to the tissues. The Surviving Sepsis Campaign recommends norepinephrine (Levophed) or dopamine at the lowest dose necessary to maintain tissue perfusion. The assessment of the adequacy of tissue perfsion can be determined using blood pressure, Cvo, urine output, normalization of blood2 lactate concentrations, and normalization of base excess on arterial blood gas. Some patients with septic shock do not respond to vasopressors due to relative vasopressin deficiency and would benefit from the addition of vasopressin at a constant infsion rate of 0. Dobutamine is a �-agonist that increases cardiac contractility and therefore increases cardiac output. Dobutamine is given when the Cvo is low2 or when myocardial dysfnction is suspected based on elevated filling pressures or low cardiac output. By increasing cardiac output, oxygen delivery to the tissues may be improved in these individuals. The Role of Glucocorticoid Therapy in Septic Shock Some critically ill patients have a relative adrenal insuficiency and may beneft from glucocorticoid supplementation. The randomized controlled French multi center trial involving septic patients with persistent hypotension after appropriate fluid and vasopressor therapy demonstrated improvements in shock reversal and a reduction in mortality when patients received corticosteroids. It is not necessary to prove that a patient has adrenal insuficiency with cortisol stimulation testing prior to giving supplementation. He is tender in the right upper quadrant and has a leukocytosis 3 of 19,000/mm • Which of the following is the best next step in his treatment? Which ofthe following is the most appropriate set of therapeutic endpoint in the treatment of sepsis? Central venous oxygen >70%, urine output > 10 mL/kg/h, central venous pressure 8 to 12 mm Hg D. Additionally his clinical presen tation is consistent with infectious cholangitis. Early goal-directed therapy with thegoal of restoring tissue oxygen delivery improves survival from sepsis, so thefirst step in the treatment of this patient should be fluid resuscitation. Diagnosing the source of his infection should be done as well but a right upper quadrant ultrasound is not the initial step in his treatment. The goals of therapy for early goal-directed treatment of sepsis refect the need to restore oxygen delivery to the tissues. Temperature is not an endpoint used to measure the adequacy of tissue oxygenation. Normal central venous oxygen saturation ( >70%) similarly implies adequate oxygen delivery to the end organs. In septic patients, institution ofearly antibiotic therapy, within 1 hour ofdiag nosis, is very important. While cultures should be obtained, it is not necessary to prove that infection exists or to identif the infecting organism before start ing therapy. It is better to start broad-spectrum antimicrobials initially and then tailor them when culture data is available or stop them entirely if no source is identifed. Surviving Sepsis Campaign: International guidelines for man agement of severe sepsis and septic shock: 2008. He was diagnosed with pneumonia confrmed by chest x-ray, and his laboratory tests identifed neutropenia. He received cyclosporine to prevent rejection of his graf, and he is no longer dependent on hemodialysis since his transplant. Blood, urine, and sputum specimens were taken fo r Gram stain, routine culture, acid fa st stain and culture, fu ngus smears and cultures, and cytol ogy. Despite the empiricantimicrobial therapy, he continues to appear ill and has a tem perature of l01. Adjust antimicrobials based on culture reports and clinical response (improvement or lack of improvement). To know the immune dysfnction in sepsis and the proinfammatory and anti infammatory states. To know the potential methods for monitoring the immune status of a critically ill patient. The patient is immunosuppressed to assist survival of his renal transplantation, and his persistent neutropenia is due to his therapy (cyclosporine). His antibiotic regimen should also be reassessed and possibly changed to cover the earlier-noted bacterial organisms, realizing the possibility of treatment failure with the vancomycin, ceftazidime, and levofoxacin. This resistance is usually plasmid mediated (eg, Klebsiella pneu moniae, Pseudomonas aeruginosa, Escherichia coli, Enterobacter sp. Therapy-induced immunosuppression may be caused by a variety of drugs and treatments. These include corticosteroids, azathioprine, methotrexate, mycophe nolate mofetil, cyclophosphamide, infiximab, rituximab, an increasing number of chemotherapeutic agents, and irradiation or radiation therapy, to list a few. These infections may arise from microorganisms called "opportunistic infections" (01) that do not normally cause infectious diseases. Infections are usually more severe in immunosuppressed patients, and have a greater potential to result fatally. The best methods to pro tect these patients are to avoid unnecessary or overly aggressive immunosuppressive therapy as much as possible, avoid exposure to infectious agents, and reconstitute the immune system when possible. Other preventive strategies include appropriate immunizations, prophylactic antimicrobials, and following isolation and handwash ing policies. Travel and immigration has fu rthercomplicated this venuewith the "globalization of infections. Attention to hand washing and the proper use of gloves, facial masks, and clothing is essential. The proper application of hand hygiene is critical in the prevention of these infections, but compliance among health-care workers is below 40%. Health-care associated infections are the most common adverse events resulting from hospitalization. Approximately 5% to 10% of hospi talized patients in the developed world acquire such infections. An immunocompromised host may have alterations in phagocytic, cellular, or humoral immunity that increase the risk of infectious complications or provide an opportunistic process from a therapy-induced lympho proliferative disorder or cancer. Additionally, patients may also become immunocompromised if they have an alteration or breach of their skin or mucosal defense barriers that permits microor ganisms to initiate a local or a systemic infection (eg, indwelling vascular catheters, Foley catheters, endotracheal tubes, and erosions of the mucosa or skin). Specific organisms must be considered in the setting of immunosuppression based on the type of defect(s) present. Specic Organisms Although the causes of fever in immunocompromised hosts are numerous and often never elucidated, some guidance to therapy is given by knowing the specific immunologic defect or defects present in the patient (Table 20-2). The duration of immune defense alteration has an extremely important effect on the types of infectious complications that are likely to occur. The number of septic patients is increasing every year, and the mortality rate from sepsis remains high. Clinically, sepsis initially presents as a hyperinflammatory response to the immune system to attenuate the inflammation, and then progresses to an im mune system down-regulation, which can result in prolonged immune dysfnction. Host Response The host response to infection is complex and varies depending on type of infec tion, the infective dose (bacterial load), and host genetic factors. Microbial inva sion of a healthy patient activates both the acquired and innate immune systems. Endogenous mediators released during the anti-microbial response ampli f this response.
Fit zp a t r ic k ’s Co lo r At la s & Syn o p s is o f Clin ic a l De r m a t o lo g y purchase extra super levitra 100mg mastercard. H is pulses are normal in the left femoral artery and popliteal artery order extra super levitra 100mg on-line, and no palpable pulses are found in the left foot best 100mg extra super levitra. Lo cal d eb r id em en t buy cheap extra super levitra 100 mg online, wo u n d car e, syst em ic an t ib io t ics, an d h yp er b ar ic oxygen therapy C. Local debridement, wound care, and if no improvement left below the knee amputation E. W hich of t he following is most likely t o h elp in t he det ect ion of osteomyelitis? You not ed t hat the infect ed area init ially had improved aft er a 2-week course of vancomycin t herapy. Which of t he follow- ing is t he best ant imicrobial t herapy for t his pat ient at this t ime? In principle, ch r on ic woun ds that do n ot h eal sh ou ld t r igger us t o invest igat e for possible ischemia, infect ion, and poor nut rit ional st ate. T h e P E D I S cla s s ifi ca t i o n o f u lce r e va lu a t io n a s s es s e s fo r Perfusion, Ext ent of wound (wound size), Dept h, Infection, and Sensat ion. Most new diabetic foot ulcers do not have polymicrobial involvement unless the patient has received prior antimicrobial therapies. Charcot neuroarthropathy is associated with increased tissue blood flow and bony dest ruct ion. Ischemia is not a cont ribut ing factor and t he process may occur without osteomyelitis. A gallium scan can be useful to help identify osteomyelitis in this patient wit h open wounds of t he foot and ankle. This diabetic patient is presenting with late stage diabetic foot infection that is associated with septic shock. For patients with diabetic foot infections that are less severe, it is often helpful to t ry to preserve the foot ; however, at t his t ime t he pat ient is exhibit ing severe systemic signs t hat are sugges- tive of an ongoing life-threatening process. Amputat ion and systemic broad- spect rum ant ibiot ics t herapy are t he best t reat ment for this pat ient. Fo r this 5 6 - year - o ld m an wit h p r io r h ist o r y of an t ib io t ics t r eat m en t t ar get - ing Gram-posit ive organisms and now has recurrence of foul-smelling drain- age associated with the wound; this presentat ion following the sequence of prior t reatment is highly suggestive of a polymicrobial infection at this t ime. Anaerobic organisms are less likely to develop in diabet ic foot infect ions unless also with arterial insufficiency and tissue ischemia. Increasing t he dosage of vancomycin is not likely to improve t he infect ion unless t he peak and t rough levels of t he drug are low. Th e t yp ical appearance is an upward bend to the second to fifth toes at the meta- tarsal-proximal phalangeal joint and a downward bend of the distal portion of the toes producing the typical “clawed toes. This is associated with angulation of the first -t o e t o wa rd the o the r t o e s. Th e p ro ce ss o ccu rs m o st ly in wo m e n a n d is co n t rib u t e d b y we a rin g t ig h t, p o in t e d, a n d co n fin in g sh o e s. Diabetic foot ulcer-review on pathophysiology, classification and microbial etiology. Th e p a t ie n t re la t e s t h a the se sym p t o m s h a ve b e e n p re s- ent over the p ast 12 months and have worsened slightly. He currently has p ain and tightness in both calves that develop a ter walking more than one block, but the symptoms always resolve a ter several minutes o rest. The emoral pulses are nor- mal bilaterally; however, his popliteal, dorsalis pedis, and posterior tibial pulses are absent bilaterally. Risk factors for the condition: N on-modifiable r isk fact ors in clu de age, sex, an d et hnicit y. Modifiable risk fact ors include smoking, diabet es mellitus, hypert en- sion, renal insufficiency, and dyslipidemia. Next step: Assessment of disability, patient counseling to discuss natural his- tory of the disease process, treatment options, and risks/ benefits of invasive intervent ions. Best initial treatment: Lifestyle modification with smoking cessation, exercise program, and pharmacological treatment at reducing cardiovascular risks. Be able to recognize the indications for lower extremity revascularization and benefits and limit ations of open surgical and endovascular treatment approaches. Learn the noninvasive modalities available for the evaluation and follow-up of patients with claudication. Co n s i d e r a t i o n s This patient’s presentation is very typical for individuals with lower extremity arte- rial occlusive disease: a h ist or y of p ain in the lower extrem it y mu scles that d evelop s wit h exert ion and improves with rest. Pain in t he legs with exert ion can occur as t he result of a number of different disease processes other than arterial insufficiency, wit h different ial diagnoses that include bones and join abnormalit ies, and cent ral and peripheral neurologic causes. To help different iate arterial insufficiency from the other causes, it is important to obtain additional details regarding his symp- toms (Table 50– 1). Since arterial insufficiency pain is produced by inadequate blood flow to meet the metabolic demands associated with exercise, a patient with arterial insufficiency usually report s symptoms that are reproduced each and every time that he exerts the same work load. As for the location of the pain, symptoms produced by insufficient blood flow sh ould consist ent ly manifest in the muscle groups below t he location of the arterial obstruction or the flow-disturbing lesion(s). In this patient wit h bilateral calf claudicat ion, the locat ions of t he arterial occlusions are most likely in the superficial femoral art eries. In order to confirm t hat the symptoms are due to poor blood flow an d n ot an ot h er cau se su ch as p er iph er al n eu r op at h y, the p u lse exam in at ion, ankle/ brachial index, and noninvasive imaging studies are helpful for confirmat ion of arterial insufficiency. Our priorities in managing this patient are: (1) to identify, treat, and prevent pro- gression of the syst emic man ifest at ion s of at h er osclerot ic disease; (2) t o impr ove fu n ct ion al st at u s of the pat ient. For this man wit h su sp ect ed femor al-p oplit eal occlusive disease and claudication, invasive treatments such as angioplasty/ stent- ing and bypass procedures are generally not indicated because t he majorit y of t hese patients will not progress to a limb-threatening situation. With invasive interven- tions, patients’ symptoms may improve, but there is an associated risk of failure, that may contribute to limb loss. In addition, diabetic patient need to be inst ruct ed on proper foot care and should be closely monit ored and aggressively treated for skin conditions and ulcers on their feet. The drawback of segmental pressure measurement is falsely high pressures are seen in diabetic patients secondary to calcified ar t er ies. Exer cise t est in g is u sefu l wh en the h ist or y, ph ysical exam in at ion, and pressure readings are ambiguous. Art eriography is the most invasive of t he imaging modalities used, but it is considered the “gold standard. The pat ient evaluat ion should always begin wit h h ist ory focusing on his/ her atherosclerotic disease risk factors and comorbidities, the patients’activ- it y levels, sympt omat ology, incit ing fact ors, durat ion of pain, locat ion of pain, and alleviat ing factors. Claudicat ion associated with insufficient arterial flow is generally manifested in t he largest muscle groups just below t he level of t he flow disturbing lesion(s). For example, patients with aorto-iliac occlusive disease may complain of pain in the upp er t h igh s an d but t ock r egion s wit h walkin g. In male patients with this problem, impotence may result from occlusive disease in the internal iliac arteries. The combinat ion of buttock and thigh claudication, impo- tence, an d diminished femoral pulses is referred to as Leriche syndrome. Pat ient s wit h superficial femoral artery occlusive disease most often manifest wit h calf clau dicat ion. In addit ion, t h ese pat ient s oft en have rest pain, which is described as pain locat ed predominat ely in the foot and t oes at rest, and rest pain is improved or relieved with dependent positioning of the extremit y. O n physical examination, patients with rest pain have chronic ischemic changes of the feet and lower legs including at roph ic and shiny skin and loss of leg hairs. Arte- rial occlusive disease can often be considered as inflow disease (above the inguinal ligament) or outflow disease (below the inguinal ligament). The durability and success of treatments for outflow diseases is further reduced for interventions performed to treat occlusive disease in the below-the-knee arteries such as the distal popliteal and tibial arteries. Diffe re n t ia l Dia g n o sis N ot all pat ient s present ing wit h effort -related lower ext remit y pain have vasculo- gen ic clau d icat ion. In som e cases, n eu r ogen ic cau ses n eed t o be d iffer en t iat ed from vascu lo gen ic clau d icat io n ( see Tab le 5 0 – 1 ). N eu r o gen ic clau d icat io n can o ccu r in associat ion wit h spinal st enosis, which can also produce excruciat ing lower ext remit ies pain during exert ion or wit h posit ional changes; however, t h ere are subt le differences that should be appreciat ed. Becau se this is a fu n ct ion of wor k load an d blood supply, the sympt oms are reproducible wit h t he same amount of work load each and every time. Physical findings such as skin temperature, capillary refill, and peripheral pulses are critical to help differentiate patients with neurogenic causes from those from vascu lar cau ses. In addition, patients need to be counseled regarding the import ance of life st yle modificat ions.
At the end of the menstrual cycle order extra super levitra 100mg online, a decline in estrogen levels can bring on menstruation buy cheap extra super levitra 100 mg line. However generic extra super levitra 100mg mastercard, it is the fall in progesterone levels at the end of the cycle that normally causes breakdown of the endometrium and resultant menstrual bleeding order 100mg extra super levitra fast delivery. However, final transformation of the breast for milk production requires the combined influence of estrogen, progesterone, and human placental lactogen. Under normal conditions, bone undergoes continuous remodeling, a process in which bone mineral is resorbed and deposited in equal amounts. The principal effect of estrogens on the process is to block bone resorption, although estrogens may also promote mineral deposition. During puberty, the long bones grow rapidly under the combined influence of growth hormone, adrenal androgens, and low levels of ovarian estrogens. When estrogen levels grow high enough, they promote epiphyseal closure and thereby bring linear growth to a stop. Cardiovascular Effects Cardiovascular disease is much less common in premenopausal women. For example, estrogen receptors in the vascular smooth muscle respond to activation by decreasing vasoconstriction. Activation of estrogen receptors in vessel endothelium results in the production of nitric oxide, which results in vasodilation and increased perfusion. Estrogens suppress coagulation by increasing the activity of factors that promote breakdown of fibrin, a protein that reinforces blood clots. The net effect—increased or decreased coagulation—may be determined by a hereditary defect in one of these targets. They also have a role in neuronal growth and repair through stimulation of nerve growth factors. Estrogen-induced synaptic changes, coupled with estrogen-promoted increases in synaptic serotonin, dopamine, and norepinephrine, are thought to preserve cognitive function, enhance short-term memory, and regulate mood. Cerebral perfusion is also enhanced by the release of nitric acid and the resulting vasodilation. In conditions that lead to insulin resistance due to impaired transport, estrogen has been shown to increase insulin sensitivity to promote glucose uptake. Estrogens also have a role in insulin secretion and are believed to protect pancreatic islet beta cells from certain types of injury. Physiologic Alterations Accompanying Menopause Menopause may occur as the result of surgery (i. Natural menopause typically begins at about age 51 to 52 years, with 95% of women entering menopause between the ages of 45 and 55 years. During the initial phase, the menstrual cycle becomes irregular, anovulatory cycles may occur, and periods of amenorrhea may alternate with menses. Production of ovarian estrogens decreases gradually, coming to a complete stop several years after menstruation has ceased. Prominent symptoms experienced by the patient include vasomotor symptoms, sleep disturbances, and urogenital atrophy. Vasomotor Symptoms Vasomotor symptoms (hot flashes and night sweats) develop in about 70% of postmenopausal women. Episodes are characterized by sudden skin flushing, sweating, and a sensation of uncomfortable warmth. In most women, hot flashes abate within several months to a few years; in others, they may persist for a decade or more. Urogenital Atrophy Of all structures in the body, the urethra and vagina have the highest concentrations of estrogen receptors. Activation of these receptors maintains the functional integrity of the urethra and vaginal epithelium. Hence, when estrogen levels decline during menopause, these structures undergo degenerative change. In addition, alterations in vaginal secretions result in decreased acidity, which can allow the growth of pathogenic bacteria, resulting in vaginal infections. Mental Changes Many women report cognitive changes such as difficulty in problem solving and short-term memory loss around the time when menopause begins. These, also, tended to occur during the time of transition and often compounded sleep disturbances. Bone Loss In the absence of estrogen, bone resorption accelerates, leading to a 12% loss of bone density shortly after menopause. Osteoporosis is characterized by bone demineralization, altered bone architecture, and reduced bone strength. Compression fractures of the vertebrae are common and can decrease height and produce a hump. In osteoporotic women, fractures of the hip and wrist can result from minimal trauma. These are thought to have a role in the increase in cardiovascular disease that increases after menopause. Menopausal Hormone Therapy Hormone therapy in postmenopausal women is the most common noncontraceptive use of estrogens. When estrogen is used for this purpose, it is usually accompanied by the use of progestins. For this reason, we will cover hormone therapy after the discussion of progestins. Female Hypogonadism In the absence of ovarian estrogens, pubertal transformation will not take place. Causes of estrogen deficiency include primary ovarian failure, hypopituitarism, bilateral oophorectomy (removal of both ovaries), and Turner syndrome (a genetic disorder that impairs gonadal function). In girls with estrogen insufficiency, puberty can be induced by giving exogenous estrogens. This treatment promotes breast development, maturation of the reproductive organs, and development of pubic and axillary hair. To simulate normal patterns of estrogen secretion, the regimen should consist of continuous low-dose therapy (for about a year) followed by cyclic administration of estrogen in higher doses. Treatment is limited to patients at least 14 or 15 years old who want contraception. Cancer Palliation Estrogens are sometimes used for palliative therapy in management of advanced prostate cancer in men and in a select type of metastatic breast cancer in both men and women. Adverse Effects The principal concerns with estrogen therapy are the potential for endometrial hyperplasia, endometrial cancer, breast cancer, and cardiovascular thromboembolic events. Of these, the potential for endometrial hyperplasia and endometrial cancer can be resolved by prescribing a progestin, if indicated. Jaundice may develop in women with preexisting liver dysfunction, especially those who experienced cholestatic jaundice of pregnancy. Fortunately, nausea diminishes with continued use and is rarely so severe as to necessitate treatment cessation. They should not be prescribed to women who are pregnant or who have vaginal bleeding without a known cause. Patients with a history of liver disease, estrogen- dependent tumors, or breast cancer (except when indicated for management) also should not take estrogens. Inducers of these isoenzymes may lower estrogen levels, whereas drugs that are inhibitors may raise estrogen levels. Additionally, they may decrease the effectiveness of some antidiabetic drugs and thyroid preparations. Estrogens can also interact with anticoagulants and other drugs that affect clotting. Preparations and Routes of Administration Estrogen is available in conjugated and esterified forms. Esterified estrogens are plant based; conjugated estrogens are natural preparations derived from the urine of pregnant horses. Until mid-2016 synthetic conjugated estrogens A [Cenestin] and B [Enjuvia] were available; however, the manufacturer has withdrawn them from the market. At the time of this writing, there is no generic substitution for these synthetic conjugated estrogens. The most active estrogenic compound—estradiol—is available alone and in combination with progestins.
If t he pat ient has an acut e or subacut e onset of confusion or has a fluc- tuating level of consciousness effective 100 mg extra super levitra, the most likely diagnosis is a delirium r esu lt in g from infect ion extra super levitra 100mg discount, int oxicat ion generic 100 mg extra super levitra mastercard, or adverse medicat ion effect s extra super levitra 100mg with mastercard, or met abolic derangement s such as hyponat remia, hypercalcemia, or hypoglycemia. If cognitive decline occurs with prominent mood disturbance, then one consid- erat ion is depression or pseudodementia. Distinguishing which occurred first is often difficult because many elderly patients with cognitive decline and a declining level of independent funct ion ing suffer from a react ive depression. H ist ory pro- vid ed b y in volved fam ily m em b er s r egar d in g the on set of sym p t om s or h ist or y of prior depression or other psychiatric illness may help establish the diagnosis, and an empiric t rial of ant idepressant s may be considered. If the patient has a history of irregular stepwise decline in functioning, especially if the pat ient h as h ad apparent st roke sympt oms or t ransient isch emic event s or h as a known cardiovascular disease or at rial fibrillat ion, t hen vascular, or multi-infarct, dementia is the most likely diagnosis. T his t ype of vascular dement ia is the second most common cause of dementia in the United States, composin g 10% t o 20% of dementias. This con d it ion is oft en r efer r ed t o as Binswanger disease or subcor t ica l arteriosclerotic leukoencephalopathy. Other common causes of dementia include cognitive decline as a result of long- st anding alcoholism or dementia associated with parkinsonism. Bot h of t h ese underlying conditions may be discovered by the appropriate history or physical findings (eg, rest ing tremor with bradykinesia and masked faces of parkinsonism). Other dementia syndromes include behavioral changes with intact navigation in frontotemportal dementia, or r apid pr ogression of dement ia wit h muscu lar r igidit y and myoclonus in Creutzfeld-Jakob disease. A variety of primary central ner- vo u s syst em ( C N S ) d iseases can lead t o d em en t ia o r o t h er co gn it ive d ysfu n ct io n, including H unt ington disease, mult iple sclerosis, neoplast ic diseases such as primary or metastatic brain tumors (although they are much more likely to produce seizures or focal deficits rather than dementia), or leptomeningeal spread of various cancers. Normal pressure hydrocephalus is a potentially reversible form of dementia in wh ich the cerebral vent ricles slowly enlarge as a result of disturbances t o cerebral spinal fluid resorpt ion. The classic triad is dementia, gait disturbance, and urinary or bowel incontinence. Relief of h ydr oceph alu s t h rough placement of a vent r icu- loperit oneal shunt may reverse the cognit ive decline. D escript ions of the primary neurologic diseases associated with cognitive dysfunction are listed in Table 37– 2. Once likely diagnoses have been established by history and physical examina- tion, investigation should be undertaken to look for treatable or reversible causes. The choice of laboratory or imaging tests is not straightforward because of the numerous, yet uncommon, causes of reversible dementia, so testing is generally low yield. Test s that may be considered for the evaluat ion of dement ia are list ed in Table 37– 1. The clinical course is characterized by progressive decline of cognitive functions (memory, orientation, attention, and concentration) and the development of psy- ch ological an d beh avioral sympt oms (wan der ing, aggression, an xiet y, depr ession, and psychosis; Table 37– 3). Donepezil, rivastigmine, and galantamine are ch oli n est er a se i n h i bi - tors that are effective in improving co gnitive function and global clinical state. Risperidone reduces psychot ic symptoms and aggression in patient s with dementia. Other issues include wakefulness, nightwalking and wandering, aggression, incont inence, and depression. T h e Alzh eim er Associat ion is a nat ional organizat ion developed to give support t o family members and can be cont act ed t h r ou gh it s web sit e at www. W hich of the following agents is most likely to help with the cognitive function? H is wife noted that 6 months ago his function deteriorated noticeably, and 2 months ago another level of deterioration was noted. Which of the following is most likely to reveal the etiology of his functional decline? H e has difficulty making it to the bathroom in time and com- plains of feeling as though “he is walking like he was drunk. C or t ical at r o p h y wit h at r o p h y of m ed ial t em p or al st r u ct u r es C. Cholinesterase inhibitors help with the cognitive function in Alzheimer disease and may slow the progression. The stepwise decline in function is typical for multi-infarct dementia, diagnosed by viewing multiple areas of the brain infarct. The classic triad for normal pressure hydrocephalus is dementia, inconti- nence, and gait disturbance; one treatment is shunting the cerebrospinal fluid. Alzheimer disease has no pathognomonic structural imaging criteria, but may include cortical atrophy and mesial temporal atrophy, whereas normal pressure hydrocephalus has enlarged brain ventricles without sig- nificant brain atrophy. She has had a fairly severe headache for the last 3 weeks (she rates it as an 8 on a scale of 1-10). She describes the pain as constant, occasionally throb b ing b ut mostly a dull ache, and localized to the right side of her head. She thinks the pain is worse at night, especially when she lies with that side of her head on the pillow. She has had headaches before, but they were mostly occipital and frontal, which she attributed to “stress,”and they were relieved with acetaminophen. Her medical history is significant for hypertension, which is controlled with hydrochlorothiazide, and “arthritis” of her neck, shoulders, and hips for which she takes ibuprofen when she feels stiff and achy. Her visual acuity is normal, visual fie ld s a re in t a ct, a n d h e r fu n d u sco p ic e xa m in a t io n is sig n ifica n t fo r a rt e rio la r n a r- rowin g b ut n o p ap ille d e m a or h e m orrh ag e. Sh e h as m od e rate te n d e rn e ss ove r the right side of her head but no obvious scalp lesions. Her chest is clear, and her heart rhythm is regular, with normal S and S but an S gallop. She has no joint swelling or deformity but is tender to palpation over her shoulders, hips, and thighs. Her medical history is significant for hypertension and “arthritis”of her neck, shoulders, and hips, for which she takes ibuprofen. She has moderate tender- ness over the right side of her head but no obvious scalp lesions. Be familiar with the clinical features that help to distinguish a benign headache from on e r epresent in g a ser iou s u n d erlyin g illn ess. Know the clinical features of migraine and cluster headaches and of subarach- noid hemorrhage. Co n s i d e r a t i o n s Although headaches are a very common complaint, this patient has features that are of greater concern: older age of onset, abrupt onset and severe intensity, and dissimilarity to previous milder headaches. She is very concerned about the headaches and is worried that they indicate a brain tumor. Medium- and large-sized vessels, especially the superficial temporal artery, are affected. It periodically afflicts 90% of adults, and almost 25% have recurrent severe head- aches. As with many common symptoms, a broad range of conditions, from trivial to life-threatening, might be responsible. The majority of patients presenting with headache have tension-type, migraine, or cluster; h owever, fewer t h an 1 in 20 h ave significant underlying pat hology. Because headache sympt oms usually are accom- panied by a paucity of associated findings, including those on laboratory examina- tion, the clinician must depend largely on a thorough history with a general and focu sed n eurologic examin at ion as the in it ial workup. Carefu l h ist or y an d ph ysical examinat ion, keeping in mind t he “red flags” of headaches (see Table 38– 1), will serve t he clinician well. D ifferent iat ing serious underlying causes of headache from more benign causes may be difficult. One of the most catastrophic secondary causes of headache is subarachnoid hemorrhage, usually secondary t o a ruptured int racerebral ( berry) aneurysm. Up to 4% of patients presenting to an emergency center with severe headache, or the classic “worst ever headache,” have a subarachnoid bleed. The initial hemor- rhage may be fatal, may result in severe neurologic impairment, or may produce only minor symptoms such as headache. This study will be positive in more than 90% of cases on the first day, with decreasing sensitivity over the next several days. Giant cell arteritis, or temporal arteritis, is a ch r on ic vascu lit is of lar ge- an d medium-size vessels, usually involving t he cranial branches of t he arteries arising from the aor t ic ar ch. The presence of three or more criteria yields more than 90% sensitivity and specificity for the diagnosis.
Becau se en domet r ial carcin oma is the most common female gen it al t ract malignancy and is very treatable when detected at an early stage generic 100 mg extra super levitra overnight delivery, the benefit of using multiple techniques to further examine the cervix and endometrium at a microscopic level should not be delayed buy extra super levitra 100 mg visa. D elaying furt her invest igat ion by repeating a Pap smear in 3 months may allow progression of any sort of malignancy the patient might have order extra super levitra 100 mg free shipping. An abnormal Pap smear is not very specific order 100 mg extra super levitra otc, so wait ing t o repeat t he test and again obt aining abnormal result s would st ill not specify wh et h er or not t he pat ient has cancer or anot her pathologic process. Vaginal sampling would not give us information as to the patient’s likelihood of having an endometrial or cervical malignancy. In addit ion, vaginal cancer is not nearly as common as endomet rial or cervical can cer an d vaginal sampling would n ot be cost -effect ive if t h ere are n o symp - toms associated with vaginal carcinoma. Hormone-replacement therapy (estrogen) would either worsen the situation if it were endometrial cancer. Unopposed estrogens increase the proliferation of endometrial cells and the likelih ood of developing endomet rial hyperplasia and event ually, endome- trial carcinoma. Persistent postmenopausal bleeding, especially in a woman with risk fac- tors for endometrial cancer, must be evaluated. Hysteroscopy would be very cost -effect ive in this pat ient, wh o pr esent s wit h per sist ent p ost m en opau sal bleeding with many risk factors. H ysteroscopy is one of the best methods for assessing the uterine cavity since it allows for direct visualization and guided biopsy of the uterine cavity. Continued observation and reassurance would not be indicated since there is a high suspicion that this patient may be pre- senting with endomet rial cancer. Any delay in treatment may allow progres- sion of the cancer, making it more difficult to t reat, and reassurance would be misleading. Unopposed estrogen-replacement therapy would not be indi- cat ed for this pat ient wh o already h as so many r isk fact or s an d sympt oms for endomet rial cancer. Endomet rial ablat ion may be beneficial in st opping bleeding in patients with menorrhagia who no longer wish to bear children, but it is not a method for diagnosing or treating endometrial carcinoma. Endometrial ablation in this patient would delay the diagnosis and treatment of endometrial cancer. Surgery is a fundamental aspect of the treatment and staging of endometrial carcinoma. R adiot h er apy is u sed as an adjun ct ive t reat ment wh en the sur ger y performed for staging shows high suspicion of spread. Progestin therapy is effective in sh edding t he endomet rial lining, but not at inh ibit ing cellular proliferat ion or treating endometrial cancer. Less com- monly, women who are below 40 are affected, and almost always with a long history of anovulation (unopposed estrogen). Ascites typically is present with ovarian cancer and not as often with endometrial cancer. G alact or rh ea cau ses h ypot h alamic dysfun ct ion an d a h ypoest r ogen ic st at e. Pelvic irradiat ion is associated wit h ut erine sarcomas and not endome- trial cancer. Management of abnormal cervical cancer screen- ing test results and cervical cancer precursors. The role of transvaginal ultrasonography in the evaluation of postmenopausal bleeding. The p e lvic e xam in at ion re ve als n orm al e xte rn al fe m ale g e n it alia. Th e sp e culum examination reveals a 3-cm exophytic lesion on the anterior lip of the cervix. The speculum examinat ion reveals a 3-cm exophyt ic lesion on the anterior lip of the cervix. Most likely diagnosis: Cervical cancer with metastases to the right pelvic sidewall. Understand that a cervical biopsy and not a Pap smear (which is a screening test) is the best diagnostic procedure when a cervical lesion is seen. Co n s i d e r a t i o n s This 50-year-old woman presents with postcoital spotting. Abnormal vaginal bleeding is the most common presenting symptom of invasive cervical cancer, and in sexually act ive women, post coit al spott ing is common. T his pat ient’s age is close to the mean age of presentation of cervical cancer, 51 years. She also complains of a malodorous vaginal discharge t hat is because of t he large, necrot ic tumor. N ot a- bly, the woman has right flank tenderness, which is very suspicious for metastatic obstruction of the ureter, leading to hydronephrosis; her leg swelling is also consis- tent with involvement with the pelvic sidewall. A cervical biopsy and not Pap smear is t he best diagnost ic test to evaluat e a cervical mass. A Pap smear is a screening test and appropriate for a woman with a normal-appearing cervix. Risk factors for cer vical can cer in this woman in clu d e mu lt ipar it y, cigar et t e smokin g, an d h ist or y of a sexually t ransmitt ed disease (syphilis). An abn or mal Pap smear is u su ally evaluat ed by colposcopy wit h biopsies, in which t he cervix is soaked wit h 3% or 5% acet ic acid solut ion. The colposcope is a binocular magnifying device t hat allows visu al exam in at ion of the cer vix. The majority of cervical dysplasia and cancers arise near the squamocolumnar junction of the cervix. Typically, cervical intraepithelial lesions will t urn wh it e wit h the addit ion of acet ic acid, the so-called “acet owh it e ch an ge. An example of mild vascular pat- tern is punctuations (vessels seen end-on) versus atypical vessels (such as corkscrew and hairpin vessels). A biopsy of t he worst -appearing area should be t aken during colposcopy for h ist ologic diagn osis. H en ce, the n ext st ep t o evalu at e an abn or mal Pap smear is colposcopic examinations with directed biopsies. When a woman presents with a cervical mass, biopsy of the mass, not a Pap smear, is appropriate. Because the Pap smear is a screening test, used for asymptomatic women, it is not the best t est for a visible lesion. T h e Papanicolaou smear t est h as a false-negat ive rat e and may give false reassurance. Cervi- cal can cer is st aged clin ically, mean in g u sin g ph ysical examin at ion, imagin g t est s, or nonsurgical procedures (Table 58– 2). Early cervical cancer (generally less than 4 cm in diameter and contained within the cervix) may be treated equally well wit h surgery (radical hysterectomy) or radiat ion t herapy. H owever, advanced cervical cancer is best treated with radiotherapy, consisting of brachytherapy (implants) with teletherapy (whole pelvis radiation) along with chemotherapy, usually platinum-based ( ci s-platinum), to sensitize the tissue to the radiotherapy. I d eally, the vaccin e sh o u ld b e ad m in ist er ed at an age p r io r t o sexu al act ivit y. Cervical cancer often spreads t hrough t he cardinal ligament s toward t he pelvic sidewalls. In fact, bilateral ureteral obstruction leading to uremia is the most common cause of death due to this disease. I n gen er al, ab n o r m al P ap sm ea r s a s a scr een - ing t est require colposcopy and biopsy t o determine the full extent of the dysplasia. Cervical cytology is generally begun at age 21 years regardless of the age of onset of sexual intercourse (see Table 58–3). For patients with three consecutive cervical cytology tests that are negat ive for int raepithelial lesions and malignancy at age 30, the interval of screening can be extended to every 3 years. Screening can be stopped at age 65 to 70 after three negative cytology screening tests and no abnormal tests in the past 10 years. Finally, rout ine cervical cytology is not recommended in women who have had a t ot al hyst erect omy for benign indicat ions, and no hist ory of cervical dysplasia. Once colposcopic-directed biopsies have delineated the extent of the dysplasia, appropriate therapy may be used. T his may include observat ion in younger pat ient s and/ or mild disease, cryot herapy (freezing of t he cervix), or excisional procedures such as loop elect rosurgical excision procedure for more significant dysplasia. Em e r g i n g Co n c e p t s Cervical cancer is typically treated with either radical hysterectomy if early (small tumor) invasive cancer is found or radiation therapy if advanced disease is found. However, in younger women who desire children, radical trachelectomy (removal of the cervix and upper vagina while leaving the uterus) can be performed.