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While the emergent treatment that may cause hemorrhagic cystitis and is started buy 45mg pioglitazone amex, a sample is drawn for an arterial cardiomyopathy? What pattern is most (A) Azathioprine likely to be indicated by the arterial blood gas (B) Cyclosporine values? Which of the following is an antidote for agent that has been shown to help patients with iron overdose? Which of the following is true regarding provide the best relief from episodic attacks of infliximab? A 56-year-old woman with severe rheuma- toid arthritis returns to see her rheumatologist buy 45 mg pioglitazone amex. Which of the following is useful in an acute She had been referred to a gastroenterologist, gout attack? At this point, what would be reasona- (E) Celecoxib ble for the rheumatologist to prescribe? He is G1–S transition referred to a gastroenterologist, who performs (E) It inhibits proliferation of promyelocytes esophogastroduodenoscopy with biopsy that Comprehensive Examination 329 demonstrates ulcers with the presence of 51. Use of which of the follow- and she still complains of bloody diarrhea, ing regimens would provide the most effective fever, and weight loss. The gastroen- and omeprazole terologist could consider using which of the fol- (B) Pepto Bismol, metronidazole, tetracycline, lowing agents? An 83-year-old man with multiple medical of theophylline include problems develops worsening constipation dur- (A) Seizures ing his hospitalization for lower extremity cellu- (B) Arrhythmias litis. Which of the following is an appropri- (D) Nausea and vomiting ate choice and why? A 62-year-old male alcoholic being treated (B) An osmotic agent, such as senna, which is for non-insulin-dependent diabetes mellitus administered rectally comes to the emergency department with a (C) A stool softener such as lactulose adminis- 1-hour history of nausea, vomiting, headache, tered rectally hypotension, and profuse sweating. What is the (D) A stool softener such as methylcellulose most likely causative agent? A 35-year-old intravenous drug abuser in a methadone maintenance program is admitted 54. An 81-year-old man with a history of to the hospital for a work-up of suspected pul- coronary artery disease and a recent diagnosis monary tuberculosis. While in the hospital, he of hypothyroidism presents to the emergency complains of diarrhea and cramping. After stool department with an acute myocardial studies return with a negative result, you decide infarction. Which of the following would be an appro- acute exacerbation of lupus erythematosus priate treatment to begin in a patient with complains of pain on eating. It is likely that the acquisition of antibiotic he smells like alcohol and he is flush, warm, resistance in gram-negative bacilli such as and uncomfortable. A 30-year-old patient is undergoing chemo- therapy for Hodgkin disease and develops a 61. Which of the following can occur in an adult fever, prompting an admission by his oncolo- patient treated with chloramphenicol? He is found to have a severely decreased (A) Gray baby syndrome white blood cell count, and therapy is started (B) Bone marrow suppression with several antibiotics for febrile neutropenia. A 32-year-old man complains of a persis- (B) Clavulanic acid tent, dry cough for several days with a mild fever (C) Sulbactam and fatigue. The family physician suspects a (D) Cycloserine diagnosis of ‘‘walking pneumonia’’ on clinical (E) Cilastatin grounds, presumably due to Mycoplasma pneu- moniae. What would be a good antibiotic to (D) Chloramphenicol administer prophylactically before the surgery? A 23-year-old woman, who is 23 weeks (C) Difficulty hearing pregnant, develops a bladder infection due to (D) Diarrhea Pseudomonas spp. A thin blood (D) Piperacillin smear shows malarial organisms within red (E) Ciprofloxacin blood cells. The nurse calls you to (C) Doxycycline evaluate the patient as he returned from a visit (D) Primaquine from his ‘‘buddy’’ outside. Which of the following might be considered the emergency room 3 weeks ago with com- for treatment of acute myelocytic anemia plaints of swelling, warmth, and pain in her (M3 variant)? She was diagnosed with cellulitis and sent (A) Cisplatin home on a 10-day course of an oral first-genera- (B) Lomustine tion cephalosporin. She returns with severe di- (C) Tretinoin arrhea, and Clostridium difficile is suspected. She is to receive (B) Rituximab both radiation and chemotherapy, with cyclo- (C) Imatinib phosphamide as part of her chemotherapy. A 54-year-old woman is undergoing an ex- (E) Daunorubicin perimental high-dose regimen with adriamycin and cyclophosphamide for breast cancer.

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Immunotherapy of Cancer Cancer immunology deals with the study of natural interplay between oncogenesis order 15 mg pioglitazone with amex, inflammation and immune surveillance of the body as well discount pioglitazone 30 mg online. Immune mechanisms may contribute to the efficacy of some currently used chemotherapeutic agents that may involve recognition of tumor-associated antigens or controlling growth of can- cer stem cells. Immunological biomarkers may be used to determine prognosis of cancer and predict the efficacy of anticancer action. Functional antibodies target molecules carried on the outside of a cancer cell membrane known as antigens. These cell surface proteins are decorated with sugar chains in distinctive arrangements that can be used as targets for Universal Free E-Book Store 238 10 Personalized Therapy of Cancer therapeutic monoclonal antibodies. Antigens can act as biochemical signatures or markers that distinguish a cancer cell from a normal cell, and one person’s cancer from another’s. Generally, a number of biochemical and proteomic approaches are taken for the identification of the target antigen. In addition, a number of valida- tion studies for the antibody are performed including testing for recognition of human cancer, as well as specificity studies. The antibodies are studied in animal models of human cancer to determine its effectiveness in vivo. If the antibodies are found to be safe and effective then they become candidate for clinical study. More significantly, it showed almost com- plete suppression of tumor growth in a prophylactic breast cancer xenograft model while the antibody was being administered. Ongoing research is aimed at identifying and validating the antibody target, and showing antibody safety and specificity. The long-term aim of targeted antibody therapy is to match multiple antibodies to different antigens on each patient’s cancer cell, delivering multiple cancer killing messages simultaneously. Personalized therapy will improve on targeted therapy by further reducing the risks of failed treatment and improving the likelihood of cure. Genentech’s anticancer drug Herceptin may be considered the first targeted anti- body therapy in that it is only appropriate for use in patients who over-express the Her2-Neu antigen on the surface of their breast cancer cells. Emerging evidence from clinical and preclinical studies suggests that tumor dormancy is a critical step in the development of both primary cancer and advanced-stage disease. A review has shown that (i) naturally occurring tumor dormancy precedes occurrence of pri- mary cancer; and (ii) conventional cancer therapies result in treatment-induced tumor dormancy, which in turn could lead to distant recurrence of cancer or perma- nent tumor dormancy, depending on immunogenic status of dormancy (Manjili 2014). Given that cellular dormancy is an evolutionary conserved survival mecha- nism in biologic systems, any stress or cytotoxic therapy could trigger cellular dor- mancy. Therefore, a successful cancer therapy is likely to be achieved by establishing permanent tumor dormancy and preventing distant recurrence of cancer or by elimi- nating dormant tumor cells. This could be accomplished by cancer immunotherapy because of the establishment of long-term memory responses. Mechanisms involved in metastatic cancer dormancy−cellular dormancy, angio- genic dormancy, and immune-mediated dormancy−can restrain disseminated cancer cells, thereby promoting their permanent dormancy (Romero et al. Furthermore, immune dormancy promotes cancer cell growth arrest and angiogenic control. Immunotherapeutic interventions in metastatic dormancy may help to control or eradicate cancer. Thus immune-mediated metastasis dormancy provides an opportunity for targeting cancer by immunotherapy. Personalized vaccines may be antigen-specific or tumor-derived, but patient-specific vaccines may be a combined approach. Most of the personalized cancer vaccines are cell-based and these were the earliest forms of personalized medicine (Jain 2010). Antigen-Specific Vaccines Antigen-specific approach may generate an antigen-specific response even when the tumor antigens are not known. Currently the scope of cancer immunization is limited because most of the vaccines have targeted antigens that are restricted to a subset of patients. Functional genomics and proteomics will enable molecular characterization of whole transcriptomes and proteomes of cancer cells, thereby also identifying potential new targets for cancer immunotherapy. Based on funda- mental immunological knowledge, the most promising approach would be patient-tailored. Active Immunotherapy Based on Antigen Specific to the Tumor Active immunotherapy is focused on overcoming the limitations of the immune system and directing it to mount an attack against cancer cells. Activating the immune system begins with the selection and modification of a tumor antigen spe- cific to the cancer (e. The lead product in this category is sipuleucel-T (Provenge™, Dendreon Corporation), which targets prostatic acid phosphatase. A proprietary technique is then used to isolate antigen presenting cells taken from a cancer patient, which are combined with the modified antigen using Antigen Delivery Cassette™. The acti- vated cells are then re-administered to the patient to stimulate T-cells to recognize and attack cancer cells that contain prostatic acid phosphatase. In clinical studies, patients typically received 3 infusions over a 1-month period as a complete course of therapy. Integrated results of two randomized trials demonstrate a survival benefit for prostate cancer patients treated with sipuleucel-T with a modest toxicity profile (Higano et al.

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This procedure is very important because all inferential statistics involve computing something like a z-score for our sample data order 45 mg pioglitazone fast delivery. We’ll elaborate on this procedure in later chapters but discount pioglitazone 45mg otc, for now, simply understand how to compute a z-score for a sample mean and then apply the standard normal curve model. The problem is the same as when we examined individ- ual raw scores: Without a frame of reference, we don’t know whether a particular sample mean is high, low, or in-between. Previously, a z-score compared a particular raw score to the other scores that occur in this situa- tion. Now we’ll compare our sample mean to the other sample means that occur in this situation. Therefore, the first step is to take a small detour and create a distribu- tion showing these other means. To evaluate our sample mean, we first create a distribution showing all other pos- sible means we might have obtained. So that we can see all possible sample means that might occur the stat- istician would sample the population an infinite number of times: She would randomly select a sample with the same size N as ours (25), compute the sample mean, replace the scores in the hat, draw another 25 scores, compute the mean, and so on. At other times, a sample would contain too many low scores and not enough high scores, so the mean would be below 500 to some degree. Therefore, over Using z-Scores to Describe Sample Means 125 the long run, the statistician would obtain many different sample means. To see them all, she would create a frequency polygon, which is called the sampling distribution of means. The sampling distribution of means is the frequency distribution of all possi- ble sample means that occur when an infinite number of samples of the same size N are randomly selected from one raw score population. This is similar to a distribution of raw scores, except that here each score on the X axis is a sample mean. To the right of are the sample means the statistician obtained that are greater than 500, and to the left of are the sample means that were less than 500. This is because most scores in the population are close to 500, so most of the time the statistician will get a sample containing scores that are close to 500, so the sample mean will be close to 500. Less frequently, the statistician will obtain a strange sample containing mainly scores that are farther below or above 500, producing means that are farther below or above 500. Once in a great while, some very unusual samples will be drawn, resulting in sam- ple means that deviate greatly from 500. The story about the bored statistician is useful because it helps you to understand what a sampling distribution is. The central limit theorem is a statistical principle that defines the mean, the standard deviation, and the shape of a sampling distribution. From the central limit theorem, we know that the sampling distribution of means always (1) forms an approximately normal distribution, (2) has a equal to the of the underlying raw score population from which the sampling distribution was created, and (3), as you’ll see shortly, has a standard deviation that is mathematically related to the standard deviation of the raw score population. The importance of the central limit theorem is that with it we can describe the sam- pling distribution from any variable without actually having to infinitely sample the population of raw scores. Then we’ll know the important characteristics of the sampling distribution of means. Remember that we took a small detour, but the original problem was to evaluate our Prunepit mean of 520. To do so, we simply determine where a mean of 520 falls on the X axis of the sampling distribution in Figure 6. But if 520 lies toward the tail of the distribution, far from 500, then it is a more infrequent and unusual sample mean (the statistician seldom found such a mean). The sampling distribution is a normal distribution, and you already know how to determine the location of any “score” on a normal distribution: We use—you guessed it—z-scores. That is, we determine how far the sample mean is from the mean of the sampling distribution when measured using the standard deviation of the distribution. This will tell us the sample mean’s relative standing among all possible means that occur in this situation. To calculate the z-score for a sample mean, we need one more piece of information: the standard deviation of the sampling distribution. The Standard Error of the Mean The standard deviation of the sampling distribution of means is called the standard error of the mean. That is, in some sampling distributions, the sample means may be very different from one another and, “on average,” deviate greatly from the average sample mean. For the moment, we’ll discuss the true standard error of the mean, as if we had actually computed it using the entire sampling distribution. The σ indicates that we are describing a population, but the subscript X indicates that we are describing a population of sample means—what we call the sampling dis- tribution of means. The central limit theorem tells us that σX can be found using the following formula: The formula for the true standard error of the mean is σX σX 5 1N Using z-Scores to Describe Sample Means 127 Notice that the formula involves σX, the true standard deviation of the underlying raw score population, and N, our sample size.

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The ability of the breast to infections generic pioglitazone 45 mg otc, a disabling cough buy pioglitazone 30mg visa, shortness of breath, produce milk diminishes soon after childbirth with- and coughing up blood. The breathing The process of respiration, during bronchioles connect to the alveoli (air sacs). Breech birth is bronchitis, acute An infection of the bronchi of more likely to cause injury to the mother or the recent origin, typically characterized by cough, infant than head-first birth. In many cases a baby in chest discomfort, and production of mucus (spu- the breech position can be turned before delivery by tum). Brenner tumors are usually benign, but in and obstruction generally resulting in daily cough. The inflammation stimulates production of mucus, which can cause further blockage of the airways. For example, disease in infants who received mechanical respira- heart tissue that has formed over a coronary artery, tory support with high oxygenation in the neonatal sometimes physically pinching the artery, is referred period. For example, the right upper Rickettsia prowazekii, the agent that causes epi- lobe of the lung has apical, anterior, and posterior demic typhus, remains viable for many years. Bronchospasm causes the injure teeth and cause local pain in the mouth or breathing difficulties seen in asthma. B-type natriuretic peptide A 32-amino-acid bronchus A large air tube that begins at the end polypeptide secreted by the ventricles of the heart in of the trachea and branches into the lungs. The sup- response to excessive stretching of heart muscle porting walls of the bronchus are made up in part of cells. Buboes particularly occur in the groin and by other conditions that affect the normal function armpit (the axillae). These swollen glands are seen of the eye muscles, such as nodules from rheuma- in a number of infectious diseases, including gon- toid arthritis or rare tumors in the eye muscle. Brucellosis An infectious disease characterized by rising and lowering (undulant) fever, sweating, bubonic plague An infectious disease that is muscle and joint pains, and weakness. Brucellosis caused by the bacterium Yersinia pestis and is trans- is caused by the bacterium Brucella, which can be mitted to humans from infected rats by the oriental transmitted in unpasteurized milk from cattle, rat flea. It is named for the characteristic feature of sheep, and goats; cheese made from this unpasteur- buboes (painfully enlarged lymph nodes) in the ized milk; and contact with diseased animals. Bubonic plague can lead to gangrene (tissue death) of the fingers, toes, and bruise Injury of the soft tissues that results in nose. In the skin it can be seen as a reddish- buccal mucosa The inner lining of the cheeks purple discoloration that does not blanch when and lips. When a bruise fades, it becomes green and brown, as the body metabolizes the blood cells in bulbourethral gland A pea-sized gland in the the skin. It is best treated with local application of a male located behind and to the side of the urethra cold pack immediately after injury. Most com- monly, a bruit is caused by abnormal narrowing of bulimia An eating disorder characterized by an artery. Listening for a bruit in the neck with a periods of extreme overeating, often interrupted by stethoscope is a simple way to screen for narrowing periods of anorexia. Bulimia is usually accompa- (stenosis) of the carotid artery, which can be a nied by self-induced vomiting or other forms of result of cholesterol plaque accumulation. Bulimia can be life-threatening Brushfield spot A little white spot on the surface due to dehydration, and it can cause permanent of the iris. Brushfield spots are arranged in a ring, damage to the bowels, liver, kidney, teeth, and heart. It is mal children but are far more frequent in those with believed to be closely related to obsessive-compul- Down syndrome. Treatment may include cognitive behavior therapy, dietary and health education, and bruxism Grinding and gnashing of the teeth. Also known as bulimia Bruxism is due to clenching of the teeth other than nervosa. See also anorexia nervosa; body dysmor- in chewing and is associated with forceful lateral or phic disorder; obsessive-compulsive disorder. The pain of a second- bullous Characterized by blistering, such as a degree burn is usually somewhat more intense than second-degree burn. The skin inflammation associated with antibodies in the base- is white and without sensation. It is diagnosed by damage may extend beyond the skin and into under- skin biopsy showing the abnormal antibodies lying tissue. Unless skin grafts are feasible, cortisone creams but sometimes requires high loss of the affected limb, permanent disfigurement, doses of cortisone (steroids) or other medicines and even death are likely in such severe cases. Burning mouth syndrome tends to develop tissues, as well as from the body’s inflammatory in “supertasters”—people with an unusually large response to the injury. A purplish, flat bruise that density of taste buds, each surrounded by pain occurs when blood leaks out into the top layers of fibers—and in postmenopausal women, who may skin is referred to as an ecchymosis.