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Which of the following is the determining factor in the decision regarding whether or not to pursue curative therapy in this patient? It is small and distant from the mediastinum purchase 400 mg levitra plus fast delivery, and he has no positive lymph nodes or metastases (T1N0M0) buy levitra plus 400mg visa. Although he still smokes, he is willing to consider quitting, and smoking is not an absolute contraindication to cura- tive surgery. His stable angina is also not a contraindication to surgery. However, his FEV1 of less than 800 ml is below the lower limit for safe resection of the tumor. He would not have enough reserve lung capacity to survive the surgery. For this reason, therapy should be aimed at palliation. In general, the extent of involvement described by the TNM system correlates with prognosis. In addition to cancer prognosis, tolerability of therapy is crucial to decisions regarding palliation or goal of cure because aggressive therapy may be harm- ful to patients, as in this case. The patient in Question 10 wants your advice about the treatment options for his cancer. Clinical trials relevant to his condition are available. He is very well educated and wants to know which ones he should participate in. You tell him that there are several phase III trials available, and he asks what a phase III trial studies. Which of the following is investigated in a phase III trial? The maximum tolerated dose of an antineoplastic agent B. Efficacy of treatment as measured by changes in the size of tumors and time to progression C. Efficacy of treatment as measured by survival rates and quality of life D. Efficacy of a new active agent compared with that of the best available therapy Key Concept/Objective: To understand the phases of treatment trials 12 ONCOLOGY 7 Phase I clinical trials identify the maximum tolerated dose of a new drug. Phase II clinical trials assess efficacy by use of change in tumor size, quality of life, disease-progression parameters, and survival. Phase III clinical trials compare a new chemotherapeutic agent with the best available therapy. A 43-year-old woman presents with a 2 cm breast mass. Excision biopsy and node dissection reveal an aggressive carcinoma with 6 of 10 axillary nodes positive. The patient is concerned about combination therapy and wishes to have single-agent therapy. You explain that combination chemotherapy is desirable because it does which of the following? Increases cure rates by decreasing the risk of cross-resistance C. Decreases resistance-conferring mutations by allowing larger doses of each agent to be given E. Decreases the risk of gastrointestinal side effects Key Concept/Objective: To understand the rationale for combination chemotherapy The Goldie-Coldman model predicts drug resistance by use of cell number and the spon- taneous cancer cell mutation rate. Even a tumor that is too small to be detected clinically has a significant chance of containing a cell with a resistance-conferring mutation. Although combination chemotherapy allows for reduction of the dosage of any one agent, it does not inherently reduce side effects or the risk of mutation-induced secondary malig- nancy or eliminate the need for radiation therapy (which reduces the risk of local recur- rence). Finally, combination therapy does not allow for higher dosages. If anything, com- bination chemotherapy necessitates lower dosages of agents that have common toxicities. Combination chemotherapy attempts to address possible cross-resistance by employing different mechanisms, and nonoverlapping toxicities allow for effective dosing. A 55-year-old man returns to the office 2 months into treatment for metastatic prostate cancer. His treat- ment includes prostatectomy, nilutamide, and radiation. He now reports tender, enlarged breasts, whitish nipple discharge, nausea, and diarrhea. He has no ill contacts and has recently returned from a trip to Arizona. He also reports that he has stopped drinking alcohol because it makes him feel ill. Examination results are as follows: temperature is 99. Breast examination confirms gynecomastia and galactorrhea.
AGENTS THAT RESTORE THE NORMAL STRUCTURE OF THE DERMAL AND SUBCUTANEOUS TISSUE Retinol (vitamin A) and the retinoids have been evaluated for their effectiveness in the treatment of cellulite generic levitra plus 400 mg otc. Topical retinoic acid and related vitamin A derivatives have been used to stimulate circulation best levitra plus 400 mg, decrease the size of adipocytes, and increase collagen deposi- tion in the dermis (9,35). Based on the capacity of all-trans-retinoic acid (tretinoin) to pro- mote the synthesis of glycosaminoglycans in normal skin and increase the deposition of collagen in the photodamaged dermis, Kligman et al. The premise for its use in cellulite treatment is that topical retinol can be used to increase the thickness and ﬁrmness of the dermis, disguising the effect of the superﬁcial fat histologically present immediately beneath it. The use of retinol was pro- posed instead of tretinoin due to its better tolerability and the evidence that retinol is meta- bolized to retinoic acid in the skin. Of the 19 patients, twelve demonstrated greater clinical improvement on the actively treated side on clinical evaluation and laser Doppler velocimetry. In a rando- mized, placebo-controlled study combining the use of retinol with gentle massage, skin elas- ticity was increased by 10. The main retinol-related change consisted of a two- to ﬁvefold increase in the number of factor XIIIa þ dendrocytes both in the dermis and in the ﬁbrous strands of the hypodermis. This is all indicative of increased skin ﬁrmness and smoothened appearance of the surface. In addition, some topical ingredients such as vitamin C may help by stabilizing collagen and/or stimulating collagen deposition (3,4,9). Bladderwrack (Fucus vesiculosus) is a brown marine algae that contains sulfated polysaccharides, iodine compounds, and alginic acid. It is reported to produce contraction of the dermal connective tissue through the increased expression of integrin molecules (19). Increasing dermal density is the likely mechanism by which this agent improves cellulite. AGENTS THAT PREVENT OR DESTROY FREE-RADICAL FORMATION Vitamins such as ascorbic acid and vitamin E may work as antioxidants, protecting dermal and subcutaneous cell membranes from free-radical toxicity. Also, vitamins may improve microcirculation, the impairment of which may be an etiological factor in cellulite formation. COMBINATION AGENTS It is likely that the future of topical cellulite therapy will consist of agents that contain mul- tiple active ingredients. In addition to providing different mechanisms of action directed toward the same goal of reducing cellulite, the different constituents may work synergis- tically to yield results better than those obtained when each component is used alone. Unfortunately, there are very few good studies in the literature that document the use of these combination products. This product com- bines retinol with a microencapsulated time-release mechanism to treat cellulite. The com- pound contains caffeine to stimulate the lipolysis and prevent fat accumulation, esculoside to improve local microcirculation, Asiatic centella as an anti-inﬂammatory agent, and l-carnitine to stimulate free fatty acid transport and breakdown. Efﬁcacy parameters included cellulite appearance before and after treatment, histology, cutaneous ﬂowmetry, and skin mechanical characteristics. As mentioned, retinol has been shown to increase der- mal thickness. The product also contains ruscogenine, which inhibits elastase activity, allowing recovery of extracellular matrix integrity that contributes to the thickening of the dermis and the masking of cellulite. In a recent multicenter, randomized, placebo-controlled trial involving the testing of a combination anticellulite cream, subjects applied cream on a nightly basis with occlusion on the posterolateral region of one of the thighs. Overall, 62% (21/34) noticed an improve- ment in their cellulite, with 62% (13/21) reporting greater improvement in the thigh that was treated with the active product. The average measured decrease in thigh circumference was 1. Upon review of the pre- and poststudy photographs, dermatologist evaluators found thighs treated with active product to show greater improvement than thighs treated with placebo in 68% of subjects. This product contained several active ingredients includ- ing caffeine, green tea extract, black pepper seed extract, citrus extract, ginger root extract, cinnamon bark extract, and capsicum annum resin (41). A novel agent named ‘‘Bio-actif’’ consists of a compound containing neuropeptide Y and peptide YY (38). These agents are known to participate in the metabolism of fat with lipogenic effects on adipocytes. Bio-actif is a topical gel of these neuropeptides, combined with green tea, ivy, aloe vera, wheat protein, and other agents, and has shown to decrease fat herniation responsible for the appearance of cellulite. EXTERNAL AIDS TO TOPICAL THERAPY Supplemental techniques such as massage and fomentation have been shown to assist in topical medication delivery into the skin and further reduce the appearance of cellulite (36). Goldman describes the use of a synthetic bioceramic-coated neoprene TOPICAL MANAGEMENT OF CELLULITE & 167 garment to stimulate lymphatic and vascular ﬂow that assisted in improving cellulite (4). Figure 1 Bioceramic-coated neoprene shorts, worn after topical application of an anticellulite product to the posterior and lateral regions of the thighs to provide greater penetration into the skin by occlusion. Recently, a double-blinded, randomized, placebo-controlled trial examined the effect of this garment for the treatment of cellulite (39). In this study, 17 subjects were evaluated for cellulite reduction using an anticellulite cream and occlusive garment on only one thigh. Four weeks later, 76% of subjects noticed an improvement in their cellulite, with 54% reporting greater improvement in the thigh that was subjected to garment occlusion. The evaluators who were dermatologists found an overall improve- ment in cellulite in 65% of treated legs with occlusion and 59% of treated legs without occlusion.
Depending on the drug category and the clinical manifestations generic 400 mg levitra plus with mastercard, specific pharmacologic treatment may be indicated cheap levitra plus 400mg with visa. Overdoses with stimulants typically produce tachycardia, cardiac arrhythmias, and potentially life-threatening elevations in blood pressure and body temperature; seizures may also occur. Treatment includes administration of intravenous fluids; administration of intra- venous benzodiazepines for seizures; use of cooling blankets to control hyperthermia; and administration of intravenous phentolamine or nitroprusside for blood pressure control. High doses of opioids produce life-threatening decreases in respiratory rate, heart rate, and blood pressure; pulmonary edema or coma are possible. Patients who have overdosed on benzodiazepines are treated with general supportive measures and an intravenous infusion of the antagonist flumazenil. A 49-year-old man who has a documented history of multiple substance abuse is brought to the emer- gency department after being "found down. After speaking with his family, it becomes evident that he is in a drug withdrawal state. Which of the following statements regarding withdrawal states from drugs of abuse is false? Stimulant withdrawal only requires general support; the patient will experience somnolence, hunger, an inability to concentrate, and mood swings 8 BOARD REVIEW B. Depressant withdrawal resembles alcohol withdrawal and comprises insomnia, anxiety, and an increase in most vital signs C. Opioid withdrawal is characterized by enhanced pain throughout the body, diarrhea, runny nose, cough, and a generalized flulike feeling D. The time course of the withdrawal syndrome depends mostly on the half-life of the drug involved. Patients undergoing withdrawal from stimulants require only general support. The most promi- nent acute difficulties include sleepiness; hunger; difficulty focusing attention; and mood swings, with prominent feelings of sadness and frustration. A withdrawal syn- drome may occur after the prolonged consumption of high doses of illicit opioids, such as heroin, or of any prescription narcotic analgesic. Opioid withdrawal is characterized by enhanced pain throughout the body, diarrhea, runny nose, cough, and a generalized flulike feeling. In addition to the usual supportive social-model approach, opioid with- drawal states can be treated by readministering an opioid such as methadone. An alter- native approach focuses on providing symptomatic relief with decongestants and antidiarrheal medications such as loperamide. Relief of some autonomic symptoms can be provided with an alpha blocker such as clonidine. The withdrawal syndrome asso- ciated with depressant drugs, such as benzodiazepines or barbiturates, resembles alco- hol withdrawal and comprises insomnia, anxiety, and an increase in most vital signs. About 1% to 3% of patients experience a grand mal convulsion or delirium; this com- plication most often occurs in patients who concomitantly use more than one drug of abuse or who use high doses of depressants or in patients with medical disorders. The treatment for withdrawal from a depressant drug (other than alcohol) usually involves readministering the specific drug involved in the dependence and tapering it over about 5 days or 3 weeks, depending on the half-life of the drug. He reports that he has no other medical history but has experienced these symptoms previously. He has a pulse of 120 beats/min, and his blood pres- sure is 152/97 mm Hg. Drug use anytime within the past 2 weeks can lead to a positive serum drug screen B. These symptoms may be a result of cocaine withdrawal C. These symptoms may be a result of cocaine dependence D. This patient has a risk factor for cocaine addiction Key Concept/Objective: To understand the characteristics of cocaine addiction Addiction can be understood as a chronic medical illness. Addiction has identifiable risk factors, including genetic factors. The most well-established risk factors for addic- tion are family history and male sex. Serum and urine tests are useful when they are positive, but they are of limited utility when they are negative because of the short duration of detectability of cocaine (6 to 8 hours) and cocaine metabolites (2 to 4 days). Cocaine does not produce compensatory adaptations in brain regions that control somatic functions and therefore does not produce dependence. Dependence and, there- fore, withdrawal are not produced by highly addictive compounds such as cocaine. A 45-year-old woman presents with complaints of back pain. She requests "something strong" for pain and states that various NSAIDs and nonnarcotic pain medications do not help her when she has pain. A review of her medical record shows a pattern of various musculoskeletal complaints, for which she has been given opiate-derivative pain medications on several occasions. For this patient, which of the following statements is false? Opiates function by blocking norepinephrine reuptake D. Pharmacologic therapy is available for treatment of opiate addiction Key Concept/Objective: To understand opiate abuse All addictive drugs share the property of activating a subcortical brain circuit that nor- mally functions to motivate the pursuit of goals with positive survival value, such as obtaining food and sexual partners. This circuit extends from the ventral tegmental area (VTA) of the midbrain to the nucleus accumbens (NAc), which is the ventral portion of the striatum and uses dopamine as its neurotransmitter.
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