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Other symp- to be Rh positive (Rh+) cheap olanzapine 5 mg free shipping symptoms zinc toxicity, and those who do not are toms include slowed brain and head growth order 10mg olanzapine fast delivery symptoms of kidney stones, Rh negative (Rh-) cheap olanzapine 5 mg without prescription treatment molluscum contagiosum. Rh typing is also important during ity of cases are sporadic and result from a new muta- abortion discount 7.5mg olanzapine amex treatment neuroleptic malignant syndrome, miscarriage, pregnancy, and birth, as tion in the girl with Rett syndrome. Organs appear as if in mirror baby that leads to hemolytic disease of the newborn. The patient is felt to muscle is broken down, releasing muscle enzymes have underlying psychological causes for these and electrolytes from inside the muscle cells. Rhabdomyolysis is rel- region, such as chest wall pain, temporomandibular atively uncommon, but it most often occurs as the joint pain, and myofascial pain syndrome pain. Underlying diseases that can also lead to rhabdomyolysis include collagen vascu- rheumatoid arthritis, systemic-onset juvenile lar diseases, such as systemic lupus erythematosus. Treatment includes sur- percent of adults, and a much lower proportion of gery, radiotherapy, chemotherapy, and, most often, a children, who have rheumatoid arthritis. The out- present in patients with other connective-tissue dis- look depends on a number of factors, including the eases, such as systemic lupus erythematosus, and in original location of the tumor. Rheumatoid nod- rheumatic fever An illness that occurs in the ules usually occur at pressure points of the body, wake of a streptococcus infection (strep throat, or most commonly the elbows. Symptoms include fever, pain in the joints, rheumatologist A physician specialist in the nausea, stomach cramps, and vomiting. Rheumatic treatment of rheumatic illnesses, especially forms of fever can cause long-lasting effects in the joints, arthritis. Rheumatic fever may be fol- tology certification, the American College of lowed by Sydenham’s chorea and by symptoms Rheumatology, which can offer board certification characteristic of obsessive-compulsive disorder or a to approved rheumatologists. Pediatric rheumatologists are pediatricians rheumatic heart disease Heart damage caused who have completed an additional 2 to 3 years of spe- by rheumatic fever. Treatment involves prevention of cialized training in pediatric rheumatology and are reinfection with streptococcus and use of medica- usually board certified in pediatric rheumatology. They have special interests in unexplained rash, fever, arthritis, anemia, weakness, weight loss, fatigue, mus- rheumatism An older term used to describe a cle pain, autoimmune disease, and anorexia. Rheumatic conditions have been rheumatology A subspecialty of internal medi- classified as localized (confined to a specific loca- cine that involves the nonsurgical evaluation and tion, such as bursitis and tendonitis), regional (in a treatment of rheumatic diseases and conditions. Rheumatic diseases and condi- rhinitis, acute Inflammation of the nose that tions are characterized by symptoms involving the occurs for only a few days. Typically, acute rhinitis is musculoskeletal system; many also feature immune caused by a virus (a cold). There important roles in protein synthesis and other cell may also be thick bumps on the lower half of the activities. During this type of rhinoplasty, the nasal cartilage and bones are rickets A disease of infants and children that dis- modified, or tissue is added. Rhinoplasty is also per- turbs normal bone formation (ossification), leading formed to repair nasal fractures and other structural to failure to mineralize bone. In these cases, the goal is to restore prein- producing osteomalacia, and permits marked bend- jury appearance or to create a normal appearance. Other features of rick- ets include softness of the infant’s skull rhinorrhea See nose, runny. The 12 pairs of ribs consist of 7 pairs of ribs nutritional rickets has become relatively rare in that attach to the sternum in the front and are known industrialized nations. In developing countries, vita- as true, or sternal, ribs; and 5 pairs of lower ribs that min D–deficiency rickets continues to be a prob- do not connect directly to the sternum and are known lem. The upper 3 false ribs connect to the due to other causes, such as disorders that create costal cartilages of the ribs just above them. The last vitamin D deficiency by interfering with the absorp- 2 false ribs usually have no anchor in front and are tion of vitamin D through the intestines; diseases of known as floating, fluctuating, or vertebral ribs. It may cause pinching of nearby rickets, celiac Rickets caused by failure of the nerves or arteries, in which case it sometimes is intestines to absorb calcium and fat from foods. The basic problem in hypophosphatemic mosome in which the end of each chromosome arm rickets is decreased resorption of phosphate by the has been lost and the broken arms have been tubules in the kidney. The rickets, renal Rickets-like bone malformations medical term for ringworm is tinea. The skin infec- that are caused by prolonged inflammation of the tions are sometimes characterized by round lesions kidneys. See also rickets, vitamin D–resistant See rickets, tinea barbae; tinea capitis; tinea corporis. Rickettsiae cause a series of diseases, including Rocky Mountain spotted fever, typhus, and risk factor Something that increases a person’s trench fever. For example, ciga- host and are transmitted to humans by an insect rette smoking is a risk factor for lung cancer, and (usually arthropod) vector. Features include fever, a dark spot that becomes a small ulcer at the river blindness A disease caused by a parasitic site of the bite, swollen glands (satellite lym- worm (Onchocerca volvulus) that is transmitted by phadenopathy) near the site of the bite, and a biting blackflies that breed in fast-flowing rivers. Treatment is with The adult worms can live for up to 15 years in nod- antibiotics. Treatment is with antibiotics that can small ulcer (eschar) at the site of the tick bite, kill the adult worms in the body. The rooting reflex helps to ensure suc- robotic surgery Surgery performed using a cessful breastfeeding. Robotic surgery is most commonly used that involves using inkblots that show enigmatic and for prostate surgery, hysterectomy, heart valve and highly ambiguous shapes. Ten standardized blots blood vessel repair, pediatric surgery, and urologic are shown, one at a time, to a person, and the per- surgery. The tiny blood ves- and the calcaneus (heel bone) is unusually promi- sels in these areas enlarge (dilate) and become nent. This anomaly usually occurs with other con- more visible through the skin, appearing like tiny genital defects and suggests the presence of a red lines (telangiectasias). Rosacea occurs most often between the ages of 30 and 60, especially in people Rocky Mountain spotted fever An acute febrile with fair skin. Although it tends (feverish) disease that was initially recognized in to occur more in women than in men, it is often the Rocky Mountain states. In most people the symptoms come is caused by Rickettsia rickettsii, transmitted by and go, although it tends to worsen with time. Some patients topical cortisone (steroid) preparations of the right never recover full use of the shoulder joint. Avoiding smoking, food and drink that cause rotavirus A virus that is a leading cause of severe flushing (such as spicy food, hot beverages, and diarrhea and dehydration in young children. The four muscles whose tendons tion of the bowel) following vaccination, but a form the rotator cuff are the subscapularis muscle, newer vaccine was made available in 2006. Patients have an increased risk for minor muscle, which also helps in the outward developing cancer, especially osteosarcoma and turning (external rotation) of the arm. Also known as poikilo- ing the shoulder; overuse in sports, particularly derma congenita and poikiloderma atrophicans those that involve repetitive overhead motions; with cataract. The eggs of der pain of gradual or sudden onset, typically the roundworm usually enter the body through con- located to the front and side of the shoulder and taminated water or food or on fingers placed in the increasing when the shoulder is moved away from mouth after the hands have touched a contaminated the body.
Also known as pleurae cheap 10mg olanzapine with mastercard treatment 5ths disease, which is normally filled with a small Paterson-Kelly syndrome; sideropenic dysphagia buy olanzapine 7.5mg without prescription medications equivalent to asmanex inhaler. A physician can often hear with a stethoscope the friction generated by the rub- pneumatic larynx A device that uses air to pro- bing of the two inflamed layers of pleurae with each duce sound buy olanzapine 10mg with mastercard treatment wasp stings, helping a person whose larynx has breath proven 5mg olanzapine symptoms hepatitis c. Removal of pleu- ral fluid, when present, with a needle and syringe is pneumococcal immunization A vaccine that pre- key in diagnosing the cause of pleurisy and can also vents one of the most common and severe forms of relieve the pain and shortness of breath associated pneumonia, the form that is caused by Streptococcus with pleurisy. Radiation pneu- pneumoconiosis Inflammation and irritation monitis typically occurs after radiation treatments caused by deposition of dust or other particulate for cancer within the chest or breast. Pneumoconiosis usually occurs pneumonitis usually manifests itself 2 weeks to 6 in workers in certain occupations and in people months after completion of radiation therapy. If radiation pneumonitis persists, range from nearly harmless forms to destructive or it can lead to scarring of the lungs, referred to as fatal conditions, such as asbestosis and silicosis. Pneumothorax can occur spontaneously, fol- and life-threatening in premature or malnourished low a fractured rib or other trauma, occur in the infants and in immunosuppressed persons. See also Appendix A, “Prescription between the lungs (mediastinum), which may give Abbreviations. Pneumonia ated with widened capillaries (telangiectasia) in the is frequently but not always due to infection. Symptoms may include fever, chills, cough with spu- poikiloderma congenita See Rothmund- tum production, chest pain, and shortness of Thomson syndrome. For example, a point mutation is the cause lungs due to the sucking in of food particles or flu- of sickle cell disease. Poison treatment depends on the pneumonia, giant cell A deadly but fortunately substance. The lung tissue shows multinucleated giant center set up to inform people about how to cells lining the alveoli (air sacs) of the lungs. Chemicals pro- percent of patients recover, with no residual paraly- duced by this vine cause an immune reaction, pro- sis; about 25 percent are left with mild disabilities, ducing redness, itching, and blistering of the skin. The ideal strategy with polio is clearly to prevent it by immunizing poison oak Skin inflammation that results from against poliovirus. See also poison; Poison malaise, headache, sore throat, and vomiting— control center. Its cause is uncertain, and it does not shown to actually cause polio in extremely rare appear to run in families. Small numbers of virus polio vaccine, killed See polio vaccine, particles enter the blood and go to other sites, inactivated. Another round of virus in the bloodstream leads to invasion polio vaccine, live See polio vaccine, oral. Polio is a minor illness in 80 to 90 percent of clini- cal infections; this is termed the abortive type of polio vaccine, Sabin See polio vaccine, oral. Symptoms are polio vaccine, Salk See polio vaccine, inacti- slight fever, malaise, headache, sore throat, and vated. Symptoms usually pollen Small, light, dry protein particles from appear without prior illness, particularly in older trees, grasses, flowers, and weeds that may be children and adults, 7 to 14 days after exposure. Pollen particles are usually the Symptoms are fever, severe headache, stiff neck and male sex cells of a plant, and they are smaller than back, deep muscle pain, and sometimes areas of the tip of a pin. It lodges in the mucous membranes further progression from this type of illness, which http://www. The gene for the disease is on chromosome poly A short form for polymorphonuclear leuko- 6. Polyarteritis nodosa most commonly problem, also known as polycystic ovarian disease, affects muscles, joints, intestines, nerves, kidneys, that causes women to have symptoms that include and skin. Inflammation of the arteries can lead to irregular or no menstruation, acne, obesity, and inadequate blood supply and permanent damage to excess hair growth. Much of this polyarticular Involving many joints, as opposed risk can be reversed with exercise and weight loss. Medication is generally prescribed to induce regular menstruation, thereby reducing the cancer risk. For polycystic kidney disease An inherited disor- acne and excess hair growth, the diuretic medication der that is characterized by the development of spironolactone (brand name: Aldactazide) can help. Surgical The cysts eventually reduce kidney function, leading procedures involving the removal or destruction of a to kidney failure. Treatment involves managing pain and affected women contain a number of small cysts. Polycythemia can lead to heart failure, stroke, and polycystic kidney disease, adult See polycys- other medical problems when severe. Other features of the disease can leukemia or myelofibrosis, in which the marrow is be cysts in other organs, such as the liver and replaced by scar tissue. Polydipsia occurs in untreated or sive An early-onset disorder that is characterized poorly controlled diabetes mellitus. For example, eye color is polyneuritis, acute idiopathic See Guillain- polygenically controlled because many genes are Barre syndrome. The flat areas of increased skin pigment are called polyhydramnios Too much amniotic fluid. See also sleep polymyositis An autoimmune inflammatory dis- apnea; sleep apnea, central; sleep apnea, ease of muscle that begins when white blood cells obstructive; sleep disorders. Blood testing in a person with polymyositis shows Pompe disease An inherited deficiency of the significantly elevated creatinine phosphokinase lev- enzyme alpha-glucosidase which helps the body els. The diagnosis is further suggested by elec- break down glycogen, a complex carbohydrate that tromyogram testing and confirmed with muscle is converted to glucose for energy. Treatment of polymyositis requires high enzyme, glycogen builds up in the heart and other doses of cortisone-related medications, such as muscles, causing extensive damage. There are sev- prednisone, and immune suppression with medica- eral different forms of Pompe disease which vary in tions, such as methotrexate and cyclophosphamide. Due to popliteal pterygium syndrome An inherited an abnormal aggregation of capillaries, a port-wine condition that is characterized by a web (ptery- stain is a type of hemangioma. See also popliteal pterygium syndrome are cleft palate (with Sturge-Weber syndrome. The opposite of posterior is in an autosomal dominant manner and is due to anterior. See also Appendix B, “Anatomic mutation of the interferon regulatory factor 6 gene. Most porphyrias affect the skin or the nerv- with the chest against the film plate and the X-ray ous system. See patient may suffer rapid heartbeat, mania, muscle also Appendix B, “Anatomic Orientation Terms. Acute attacks are often pre- postherpetic neuralgia See neuralgia, pos- cipitated by the use of certain drugs, such as therpetic. One type of porphyria, acute intermittent occurs together with balanitis, inflammation of the porphyria, may have affected members of the House glans, as balanoposthitis.
Other types of ligases with altered substrate specificities are vanC [D-Ala- D-Ser (serine)] buy olanzapine 10mg low cost medicine 666, vanD (D-Ala- D-Lac) buy olanzapine 10mg with visa symptoms neuropathy, and vanE (D-Ala- D-Ser) purchase 2.5mg olanzapine visa medications ranitidine. These latter species have intrinsic low-level resistance to vancomycin (8 to 16 mg/mL) 10mg olanzapine mastercard medicine to stop diarrhea. Isolates carrying the esp gene seem to be associated with in-hospital spread and possibly with increased virulence. A univariate analysis of patients with and without a urinary tract infection revealed a significant relationship between having a malignancy and a urinary tract infection (131). Similar to adult patients, only about 1 in 10 colonized patients develop infection. Drugs listed included cephalosporins, metronidazole, vancomycin, carbapenems, ticarcillin–clavulanate, and quinolones. Risk factors from Tables 4 and 5 that appear multiple times are use of antacids and enteral feedings. Thus, the focus for control and prevention is on the following: (i) detection of colonized patients by surveillance cultures; (ii) barrier isolation; (iii) hand hygiene; (iv) environmental decontamination; and (v) control of antimicrobial (particularly vancomycin) use. Colonized patients have been detected by screening stool specimens submitted to the clinical microbiology laboratory for Clostridium difficile toxin assay (165). This may have been due to the extensive use of antimicrobial agents in the burn unit where the study was performed. Surveillance cultures can be made more efficient by using a selective culture media to suppress growth of other microorganisms that will likely contaminate the specimens (144,164). This recommendation is further supported by a study that found that rectal and perirectal swabs had approximately the same sensitivity (79%) (167). The guideline also recommends donning clean nonsterile gloves prior to entering the room. The authors state that an easily cleanable nonporous material is the preferred upholstery in hospitals. The effectiveness of decontamination of the environment depends on the method used. In one study, the investigators observed that cleaning environmental surfaces with a cleaning rag sprayed with a quaternary ammonium disinfectant was significantly less effective than dipping the cleaning rag into a bucket of the same disinfectant, drenching all surfaces, allowing the surfaces to remain wet for 10 minutes, and then wiping the surfaces dry with a clean towel (177). Using the method in which the disinfectant was sprayed on the cleaning rag took 2. Based on this study, the bucket method is the preferred method for decontaminating environmental surfaces. In another study investigators examined the elements of environmental cleaning to determine whether changes in cleaning products, cleaning procedures, or performance of cleaning personnel would lead to more effective cleaning of the environment (178). The authors noted that the performance of cleaning personnel was the most important factor in the effective decontamination of the environment. The effectiveness of cleaning personnel performance was related to the number of environmental sites cleaned. After patient contact, hands should be washed with an antiseptic-containing soap or an alcohol hand rub should be applied. Six studies on the use of piperacillin–tazobactam in place of third-generation cephalosporins and ticarcillin–clavulanate have been published (181–186). However, there were several significant differences between the two groups and the authors did not apply multivariable analysis to obtain a clearly un- confounded conclusion of their results. Only one of the latter studies was adequately designed to provide definitive results (185). A novel methicillin-resistance cassette in community-acquired methicillin-resistant Staphylococcus aureus isolates of diverse genetic backgrounds. Intrafamilial spread of highly virulent¨ Staphylococcus aureus strains carrying the gene for Panton-Valentine leukocidin. Community-acquired methicillin-resistant Staphylococcus aureus isolated in Switzerland contains the Panton-Valentine leukocidin or exfoliative toxin genes. Emergence and spread of community-associated methicillin- resistant Staphylococcus aureus in rural Wisconsin, 1989 to 1999. Widespread skin and soft-tissue infections due to two methicillin-resistant Staphylococcus aureus strains harboring the genes for Panton-Valentine Leukocidin. Genetic diversity among community methicillin-resistant Staphylococcus aureus strains causing outpatient infections in Australia. Emergence of methicillin-resistant Staphylococcus aureus with Panton-Valentine leukocidin genes in central Europe. Risk factors and molecular analysis of community methicillin- resistant Staphylococcus aureus carriage. Community-acquired methicillin-resistant Staphylococcus aureus colonization in healthy children attending an outpatient pediatric clinic. Epidemiology and clonality of community-acquired methicillin-resistant Staphylococcus aureus in Minnesota 1996-1998. Global distribution of Panton-Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus, 2006. Epidemic community-associated methicillin-resistant Staphylococcus aureus: recent clonal expansion and diversification. Emergence of and risk factors for methicillin-resistant Staphylococcus aureus of community origin in intensive care nurseries. Modeling the invasion of community-acquired methicillin- resistant Staphylococcus aureus into hospitals. Plasmid-mediated resistance to vancomycin and teicoplanin in Enterococcus faecium. Vancomycin-resistant Enterococcus faecium on a pediatric oncology ward: duration of stool shedding and incidence of clinical infection. Toxin-antitoxin systems are ubiquitous and plasmid-encoded in vancomycin-resistant enterococci. Clonal analysis of methicillin-resistant Staphylococcus aureus strains from intercontinental sources: association of the mec gene with divergent phylogenetic lineages implies dissemination by horizontal transfer and recombination. Severe Staphylococcus aureus infections caused by clonally related community-acquired methicillin-susceptible and methicillin-resistant isolates. Staphylococcal resistance revisited: community-acquired methicillin resistant Staphylococcus aureus—an emerging problem for the management of skin and soft tissue infections. Community-acquired methicillin-resistant Staphylococcus aureus: epidemi- ology and potential virulence factors. Control of endemic methicillin-resistant Staphylococcus aureus: a cost-benefit analysis in an intensive care unit. Staphylococcus aureus rectal carriage and its association with infections in patients in a surgical intensive care unit and a liver transplant unit. Acquisition of methicillin-resistant Staphylococcus aureus in a large intensive care unit. Identification of a variant “Rome clone” of methicillin- resistant Staphylococcus aureus with decreased susceptibility to vancomycin, responsible for an outbreak in an intensive care unit. Eradication of endemic methicillin-resistant Staphylo- coccus aureus infections from a neonatal intensive care unit. Spread of methicillin-resistant Staphylococcus aureus in a neonatal intensive unit associated with understaffing, overcrowding and mixing of patients.
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The top-down approach reaching from single cell hetero- geneity in cell systems and tissues down to the molecular level seems suitable for a human cytomics project to systematically explore the molecular biocomplexity of human organisms order olanzapine 7.5 mg overnight delivery symptoms ruptured ovarian cyst. The analysis of already existing data from scientific studies or routine diagnostic procedures will be of immediate value in clinical medicine generic 7.5mg olanzapine with visa symptoms anxiety, for example as personalized therapy by cytomics (Valet 2005) discount 20 mg olanzapine fast delivery 5 medications. Contributions of Nanobiotechnology to Personalized Medicine Nanotechnology is the creation and utilization of materials olanzapine 7.5 mg discount medicine 5 rights, devices, and systems through the control of matter on the nanometer-length scale, i. It is the popular term for the construction and utilization of functional structures with at least one characteristic dimension measured in nanometers (a nanometer is one billionth of a meter i. Nanobiotechnology is the application of nanotechnology in life sciences and is the subject of a special report (Jain 2015). Role of Nanobiotechnology in Molecular Diagnostics Application of nanobiotechnology in molecular diagnostics is called nanodiagnos- tics and it will improve the sensitivity and extend the present limits of molecular diagnostics (Jain 2005, 2007). Advances in nanotechnology are providing nanofabricated devices that are small, sensitive and inexpensive enough to facilitate direct observa- tion, manipulation and analysis of single biological molecule from single cell. This opens new opportunities and provides powerful tools in the fields such as genomics, proteomics, molecular diagnostics and high throughput screening. It seems quite likely that there will be numerous applications of inorganic nanostructures in biology and medicine as markers. Given the inherent nanoscale of receptors, pores, and other functional components of living cells, the detailed monitoring and analysis of these components will be made possible by the development of a new class of nanoscale probes. Biological tests measuring the presence or activity of selected substances become quicker, more sensitive and more Universal Free E-Book Store 186 8 Non-genomic Factors in the Development of Personalized Medicine flexible when certain nanoscale particles are put to work as tags or labels. Nanomaterials can be assembled into massively parallel arrays at much higher densities than is achievable with current sensor array platforms and in a format compatible with current microfluidic systems. Currently, quantum dot technology is the most widely employed nanotechnology for diagnostic developments. Cantilevers for Personalized Medical Diagnostics An innovative method for the rapid and sensitive detection of disease- and treatment- relevant genes is based on cantilevers. Short complementary nucleic acid segments (sensors) are attached to silicon cantilevers which are 450 nm thick and therefore react with extraordinary sensitivity. Binding of targeted gene transcripts to their matching counterparts on cantilevers results in mechanical bending that can be optically mea- sured. Differential gene expression of the gene 1-8U, a potential biomarker for can- cer progression or viral infections, can be observed in a complex background. The measurements provide results within minutes at the picomolar level without target amplification, and are sensitive to base mismatches. An array of different gene tran- scripts can even be measured in parallel by aligning appropriately coated cantilevers alongside each other like the teeth of a comb. It could be used as a real-time sensor for continuously monitoring various clinical parame- ters or for detecting rapidly replicating pathogens that require prompt diagnosis. These findings qualify the technology as a rapid method to validate biomarkers that reveal disease risk, disease progression or therapy response. This will have applications in genomic analysis, proteomics and molecular diagnostics. Cantilever arrays have potential as a tool to evaluate treatment response efficacy for personalized medical diagnostics. Nanobiotechnology for Therapeutics Design and Monitoring Current therapeutic design involves combinatorial chemistry and system biology- based molecular synthesis and bulk pharmacological assays. Therapeutics delivery is usually non-specific to disease targets and requires excessive dosage. Efficient therapeutic discovery and delivery would require molecular level understanding of Universal Free E-Book Store References 187 the therapeutics-effectors (e. Characterization of nanocarrier-based drug delivery can enable high efficiency of in vivo or topical administration of a small dosage of therapeutics. Multidimensional atomic force microscopy for drug discovery: a versatile tool for defining targets, designing therapeutics and monitoring their efficacy. Genomics and epigenomics: new promises of per- sonalized medicine for cancer patients. Cytomics, the human cytome project and systems biology: top-down resolution of the molecular biocomplexity of organisms by single cell analysis. Personalized exposure assessment: promising approaches for human environmental health research. A circadian gene expression atlas in mammals: implications for biology and medicine. Universal Free E-Book Store Chapter 9 Personalized Biological Therapies Introduction Historically blood transfusion and organ transplantation were the first personalized therapies as they were matched to the individuals. Some cell therapies that use patient’s own cells are considered to be personalized medicines particularly vac- cines prepared from the individual patient’s tumor cells. More recently recombinant human proteins might provide individualization of therapy. The number of biotechnology-based therapeutics introduced in medical practice is increasing along with their use in a personalized manner (Jain 2012). Recombinant Human Proteins There are a large number of therapeutic proteins approved for clinical use and many more are undergoing preclinical studies and clinical trials in humans. Virtually all therapeutic proteins elicit some level of antibody response, which can lead to potentially serious side effects in some cases. Therefore, immunogenicity of therapeutic proteins is a con- cern for clinicians, manufacturers and regulatory agencies. In order to assess immu- nogenicity of these molecules, appropriate detection, quantitation and characterization of antibody responses are necessary. Immune response to therapeu- tic proteins in conventional animal models has not been, except in rare cases, pre- dictive of the response in humans. In recent years there has been a considerable progress in development of computational methods for prediction of epitopes in protein molecules that have the potential to induce an immune response in a recipi- ent. It is expected that computer driven prediction followed by in vitro and/or in vivo testing of any potentially immunogenic epitopes will help in avoiding, or at least minimizing, immune responses to therapeutic proteins. Another approach to protein therapy is in vivo production of proteins by geneti- cally engineered cells where the delivery of proteins can be matched to the needs of the patient and in vivo production and controlled delivery might reduce adverse effects. Therapeutic Monoclonal Antibodies Compared with small-molecule drugs, antibodies are very specific and are less likely to cause toxicity based on factors other than the mechanism of action. Orally available small molecules have many targets but they may also hepatotoxic and are involved in drug-drug interactions. From the point of view of a clean safety profile, antibodies are extremely attractive. Antibodies have for many decades been viewed as ideal molecules for cancer therapy. These will be described in more detail in the section on personal- ized cancer therapy in Chap.
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