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By: John Walter Krakauer, M.A., M.D.

  • Director, the Center for the Study of Motor Learning and Brain Repair
  • Professor of Neurology

https://www.hopkinsmedicine.org/profiles/results/directory/profile/9121870/john-krakauer

Dental referral for identified caries more than 14 days Aphthous Ulcers (Canker Sores) Herpes Labialis (Cold Sore symptoms zyrtec overdose order on line domperidone, Fever Blister) • Definition: Shallow medicine vials 10mg domperidone mastercard, painful mouth ulceration medications known to cause seizures purchase domperidone, and Herpes Simplex S to medications hypertension order 10mg domperidone fast delivery matitis prone to recurrence, two types: minor and major • Definition 1. Ulceration and infiammation of oral mucosa • Etiology/Incidence from the herpes virus 1. Appearance: well defined lesion, appears as an • Etiology/Incidence ulcer with yellow/white necrotic base with sur 1. Virus acquired from individual who has mouth rounding erythema sore or herpetic whitlow on a finger or to e; 3. Illness starts 5 to 10 days after exposure or hema to logic disorders, infectious agents 3. Onset often in adolescence (20%) and recurrent after primary acute episode; reactivated from 5. Initial symp to ms include fever, chills, irri • Signs and Symp to ms tability, tender submandibular adenopathy, 1. Burning or tingling before appearance of ulcerative exanthem of the gingiva and lesion mucous membranes of the mouth 2. Recurrent herpes simplex limited to a few • Differential Diagnosis lesions on the lips. Small vesicles erode to ulcers on buccal base; commonly found on mucocutaneous mucosa, hard palate, to nsils, and to ngue border of lips 2. Primary gingivos to matitis—vesicles on oral lesions on arms, legs, palms, soles mucosa, gingiva, to ngue, and lips; ulcer forma 3. Lesions on but to cks are not usually vesicular tion following vesicle stage which bleed easily; diffuse erythema to us, edema to us gingiva, • Diagnostic Tests/Findings: Unnecessary especially the interdental papillae 3. Cervical adenopathy with gingivos to matitis • Management/Treatment: See Herpangina 4. May spread to perioral skin Herpangina • Diagnostic Tests/Findings: None • Definition: Acute viral illness presenting with • Management/Treatment ulceration and infiammation of oral mucosa 1. Pain management—acetaminophen or ibu • Etiology/Incidence profen; to pical relief with occlusive gels. Coxsackievirus, group A (most common) infant oral anesthetic agents; 1:1 mixture of 2. Coxsackie B viruses and echoviruses (less diphenhydramine combined with antacid common) preparations consisting of magnesium and 3. Resolves spontaneously in 3 to 5 days oral mucosa (severe cases add 2% viscous lido caine sparingly) • Signs and Symp to ms 3. Spontaneous recovery within 2 weeks, rarely cant oral discomfort, drooling complications; dehydration is a concern in primary herpes • Differential Diagnosis 1. Pharyngitis/ to nsillitis mucosa; papulovesicular exanthem on hands, feet, legs, and occasionally the but to cks • Physical Findings: Small vesicles or punched out ulcers, especially on soft palate and to nsillar • Etiology/Incidence pillars; anterior structures. Coxsackievirus A16 (most common), A5, and mucosa, and hard palate) are typically not affected A10 2. Enterovirus 71—frequently more severe illness • Diagnostic Tests/Findings: Unnecessary (aseptic meningitis, encephalitis, and paralytic disease) • Management/Treatment 3. Topical relief with 1:1 mixture of diphenhy • Signs and Symp to ms dramine combined with antacid preparations 1. Dysphagia vide a protective coating for the oral mucosa (severe cases add 2% viscous lidocaine; use • Differential Diagnosis sparingly) 1. Sudden or gradual onset of symp to ms mation, to nsillitis is more appropriate term to use 2. Causes vary by geographic location, season, iting, abdominal pain, and malaise age; most common in 5 to 15-year-olds 5. Virus is probable cause in conjunction may be present with nasal congestion and rhinorrhea c. Neisseria gonorrhoeae—in sexually active both viral and strep infections adolescents or sexually abused children 3. Corynebacterium haemolyticum and consistent with viral sore throats Corynebacterium diphtheriae—character 4. Cervical nodes usually enlarged with possible istic presence of grey pseudomembranous tenderness exudate on pharynx and to nsils which bleeds with attempts at removal; quite rare • Diagnostic Tests/Findings in U. Trauma from to bacco smoke, heat, alcohol tive (older latex agglutination assays were b. Treat if positive; throat culture to confirm respira to ry secretions, shared silverware negative test 6. Peri to nsillar or retropharyngeal abscess or infections, but not entirely reliable cellulitis 3. Acute rheumatic fever in untreated group A beta hemolytic strep to coccal pharyngi • Management/Treatment tis—prevented if treatment started within 1. Viral pharyngitis/ to nsillitis—symp to matic/ 9 days of initial complaints of sore throat supportive care d. Analgesics for fever/pain (acetaminophen, strains are nephri to genic; manifests in 1 to ibuprofen) Throat 111 c. Encourage fiuids for maintaining • Signs and Symp to ms: Generally lasts one week; dry hydration cough with rhinorrhea, may persist up to 3 weeks 2. Irritability, restlessness, fever (100° to 250 mg every eight hours for 10 days (500 102°F) mg bid in adults and children weighing 60 b. Sore throat, sneezing, cough, chills losporin for those with penicillin allergy c. Occasional headache, malaise (cephalosporins can be substituted if nonanaphylactic reaction • Differential Diagnosis c. Diphtheria—hospitalization and treat cents, or overuse of medicated nasal spray ment with erythromycin or penicillin G • Physical Findings Acute Nasopharyngitis (Common Cold) 1. Infiamed, moist nasal mucosa and oropharynx • Definition: Acute viral infection of upper respi 3. Chest clear ra to ry tract with potential involvement of nasal passages, sinuses, Eustachian tubes, middle ears, • Diagnostic Tests/Findings conjunctiva, and nasopharynx 1. If suspicious of differential diagnosis, consider • Etiology/Incidence additional tests such as throat culture, chest or 1. Analgesics for sore throat, muscle aches and noviruses, enterovirus, infiuenza viruses, fever 101°F Mycoplasma pneumoniae 2. Saline nose drops with nasal bulb syringe secretions and easily spread through self b. Antihistamines and decongestants not (clothing, environmental surfaces) routinely recommended 3. Antibiotics are not indicated in viral 8 infections/year with a peak incidence during infections first 2 years 3. Increased susceptibility associated with consider secondary infection active/passive smoke exposure 4. Good hygiene and cleaning of clothes, climates—peaks in early fall, late January, and to ys, and play areas early April b. In older children—usually superinfection from penetrating injury to posterior wall of • Etiology/Incidence oropharynx 1. Can occur at any age; more common in pre children under 6 years of age with a peak inci adolescent or adolescent age groups dence age 3 4. Complication of untreated peri to nsillar abscess—lateral pharyngeal abscess leading to • Signs and Symp to ms possible airway obstruction; aggressive early 1. Unilateral enlargement of to nsil(s), bulg hyperextension ing medially with anterior pillar prominence 2. Trismus can occur, making visualization of the pharynx dificult • Diagnostic Tests/Findings 1. Lateral neck radiography—retropharyngeal • Diagnostic Tests space wider than C4 vertebral body or 6 mm 1. Strep to coccus pyogenes and Staphylococ increasing in size despite treatment, refer for cus aureus account for approximately 80% biopsy of cases b. Secondary to local infections of the ear, nose, mation and swelling of the supraglottic and throat (most common) structures leading to life threatening upper airway 3. Prevalent among preschool children obstruction • Signs and Symp to ms • Etiology/Incidence 1. Pathogens—group A beta-hemolytic strep to impinges on airway cocci, pneumococci, Haemophilus infiuenzae • Differential Diagnosis 3. Bilateral cervical adenitis—mononucleosis, infiuenzae with use of Hib vaccine by 99% in tularemia, diphtheria children under 5 years, but can still occur even 2. Subacute or chronic adenitis—cat scratch with a complete set of vaccines (Rafei, 2006) fever, nonspecific viral infections 3.

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Genetic engineering has prepared these substances artificially medicine queen mary order domperidone toronto, and they are used as thrombolytic agents (agents that dissolve blood clots) treatment ringworm purchase domperidone with mastercard. The solution undisturbed for a few minutes will allow may be used for direct intravenous adminis dissipation of any large bubbles mueller sports medicine generic domperidone 10 mg free shipping. Before Each kit contains a two single-use reteplase diluting or administering the product treatment strep throat trusted 10 mg domperidone, it is vials of 10. Alteplase is this thrombolytic agent is marketed with a stable for up to 8 hours in these solutions at needleless administration set that can be used room temperature, and either polyvinyl chlo to deliver the medication with just one dose in ride bags or glass bottles are acceptable. Doses are calculated on Recombinant Reteplase (Retavase) the basis of body weight. It is administered as a 10 + 10 U rates) and safety (intracranial hemorrhage, double-bolus injection. Each 10-mL bolus is major bleeding episodes) as an accelerated administered intravenously over 2 minutes. These substitu containing heparin, the health professional tions have provided a prolonged half-life that should flush the line with 0. To be effective, tenecteplase, like the other clot busters, must be used within the first hours of a heart attack. Tyrosine Kinase inhibi to r the Philadelphia (Ph) chromosome, a trun cated chromosome 22, was the first consis tent chromosomal abnormality identified in human malignancy (27). Improved chromo some banding techniques demonstrated that this chromosome was the result of a recipro cal translocation between the long arms of chromosomes 9 and 22. The molecular con sequences cause the fusion of the c-Abl onco gene (chromosome 9) and the Bcr sequence (chromosome 22) in to the Bcr-Abl gene. Ultimately, this activates several other multiple signaling pathways that affect cell Figure 19. Because all of these events tinib while transplantation is being evalu (cell growth, adhesion, proliferation) depend ated. The accelerated phase or blast crisis kinase activity are central for transformation. The patient should be instructed to take this med Imatinib Mesylate (Gleevec) ication with food and a large glass of water Imatinib mesylate demonstrates potent because of mild gastrointestinal effects. Other common adverse effects Chapter 19 • produCts of BioteChnology 709 include edema, muscle cramps, hemorrhage, other immunocompromised patients, and and musculoskeletal pain. The dosage regimen cated for immunization of persons of all of nilotinib is 400 mg orally every 12 hours, ages against infection caused by all types and the capsule dosage form should be swal of hepatitis B virus. Similarly, recommended for infants and younger chil patients receiving concurrent therapy with dren. This avenue avoids the of bacterial meningitis and leading cause use of live viruses and minimizes the risk of of serious systemic bacterial disease among causing the disease the vaccine was intended children worldwide. The chemotherapy regi meningitidis, to produce an antigen that is men is implemented 4 to 24 hours after the postulated to convert the T-independent first dose of rasburicase. The pro istered as an intravenous infusion over tein carries both its own antigenic deter 30 minutes. Consequently, water from the mucus der for injection containing 10 mg purified of the lung gets absorbed in to the cell, and Haemophilus B capsular polysaccharide and the mucus dries out, resulting in thick, tena 24 mg tetanus to xoid/5 mL. This is avail cious mucus that accumulates in the small able in single-dose vials with 7. This leads to a domino diphtheria and tetanus to xoids and pertussis effect of chronic infection and inflammation, vaccine as diluents or with 0. This drug offers uric acid in to an inactive and soluble metab hope for breaking the cycle of chronic lung olite, allan to in. Rasburicase is active only at infection and inflammation associated with the end of the purine catabolic pathway. Chapter 19 • produCts of BioteChnology 711 that are delivered via nebulizer should be administered to patients sequentially, not mixed to gether. To date, no literature sug gests the optimal sequence for all of these drugs to be administered. The ampuls have an 18-month expiration date when s to red in the refrigera to r at 2°C to 8 °C and should be protected from strong light. The patient or caregiver should discard the solu tion if it is cloudy or discolored and should be to ld to make sure that the product is within Figure 19. Their compressor problems include variable tissue penetra • Durable Sidestream nebulizer with tion (because of the size of the molecules) Mobilaire compressor and to xicity related to the stimulation of an • Durable Sidestream nebulizer with Porta immune or allergic reaction. Neb compressor A distinct advantage of these biotechno Patients who are unable to inhale or logic proteins over proteins from natural exhale orally throughout the entire nebuliza sources is enhanced purity. The their presence has been confirmed only after portable jet nebulizers simply may not be disastrous results. Products derived from capable of generating enough force or appro recombinant technology will not have coex priate particle size to ensure optimal delivery tracted contaminants. Research is also directed to ward the dis To make administration efficient, it may be covery of new methods of delivery for these tempting to coadminister other compounds agents. A challenge is to deliver regula to ry relatively low to xicity and the versatility of proteins. One strategy that is bearing fruit is preparation techniques and bilayer constitu nanotechnology defined as the study, manip ents. Depending on their size, charge, and ulation, and manufacture of ultrasmall struc bilayer rigidity, among other characteristics, tures made of as few as one molecule. Sometimes, of cancer, diabetes, pain relief, asthma, and their residence in the systemic circulation can allergy, among others (29). Nanotechnology be for hours and even days if they are stable involves the control of matter in the 1 to and not recognized as foreign bodies by the 100-nm dimension range. Doxil is doxorubicin produced within micro To date, nanoparticle-based drug deliv scopic pegylated lipid spheres that are grafted ery has demonstrated distinct advantages. The pegylated drug For example, the solubility of poorly water delivery platform is an example of a polymer– soluble drugs is improved; by reducing drug conjugate. The pegylated liposomal immunogenicity, a prolongation of a drug’s shell protects the inner compartment. A systemic circulation is shown; the release single lipid bilayer membrane composed of of the drug is sustained, and consequently, hydrogenated soy phosphatidylcholine and administration frequency is reduced. Further, cholesterol separates this internal aqueous drugs are delivered in a target manner that is compartment from the external medium. It is theorized that the primary products are liposomal drugs the long residence times and stability of and polymer–drug conjugates. This provides a protective of some combination of phosphatidylcho layer and suppresses recognition by opso line, cholesterol, phosphatidylglycerol, other nins. An opsonin is any molecule that acts as glycolipids, and/or phospholipids (30,31). The previously mentioned pegylated composed of several phospholipid layers doxorubicin and pegfilgrastim are prime surrounding an aqueous core, with the outer examples of this strategy. The polyethylene shell capable of providing direction to specific coating reduces mononuclear phagocyte sys target cells. Usually, liposomes tem uptake and provides long plasma resi concentrate the drug in cells of the reticuloen dence times and plasma stability. There is also a growing knowledge base undesired substances on to the membrane of and research about signaling transduction nanoparticles that decrease renal clearance pathways. This has led to the creation of of the relatively small drug molecules, thus antibodies that target recep to rs, enzymes, or effecting a prolonged half-life. Other hydrophilic poly more diagnostic products for in-home test mers that are grafted to liposomes and dem ing. If the liposome is to o big, it will tigations or for product marketing approvals; not be able to extravasate through defects in these functions were executed by the appro the capillary endothelium. Nor was this office small, the liposome may have an inadequate intended to perform labora to ry research or amount of drug encapsulated to be effective. Instead, it was created to serve a central delivery include phospholipid micelles, plu coordinating, problem-solving, and advisory ronic micelles, poly(l-amino acid) micelles, role within the Office of the Commissioner. It was to advise and assist the commis smaller and smaller agents will require larger, sioner and other central officials about multidisciplinary teams from numerous scientific issues related to biotechnology disciplines including medicine, pharmacy, policy, direction, and long-range goals. It provided leadership and direction on the printed information sheet should also be scientific and regula to ry issues related to provided when the product requires recon biotechnology through an agency-wide stitution. It is desirable to perform the first coordinating group, the Biotechnology injection under the supervision of an appro Coordinating Committee, to promote com priately qualified health care professional to munication and consistency on biotechnol ensure that the patient understands the tech ogy matters across organizational lines.

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Biological Agents: Smallpox Introduction: Smallpox is caused by infection with Variola virus medicine net buy domperidone toronto. Naturally occurring smallpox has been globally eradicated since the last case occurred in Somalia in 1977 medicine vs dentistry purchase domperidone overnight delivery. The categorization of smallpox virus as a viable weapon stems from the fear that belligerent groups may possess clandestine s to medicine daughter order 10mg domperidone overnight delivery cks medicine shoppe locations buy cheap domperidone on line. Moreover, fear exists that other closely related orthopoxviruses (such as monkeypox or cowpox) might be genetically manipulated to produce variola-like disease. Subjective: Symp to ms Begin abruptly with malaise, fever, rigors, headache, backache, and vomiting. Objective: Signs Using Basic Tools: Characteristic rash appears 2-3 days after the onset of symp to ms; all lesions progress synchronously from macules to papules to pustules, and are concentrated on the hands, face and trunk; fever and mental status changes; complications include viral “sepsis”, hepatic insufficiency, encephalopathy, skin hemorrhage. Assessment: Differential Diagnosis chickenpox (lesions in various stages of progression and not concentrated on the trunk), monkeypox, enteroviral exanthems (such as hand-foot-mouth disease). Caregivers should employ airborne and contact precautions when dealing 6-59 6-60 with patients. At a minimum, mask either the casualty or the health-care team and close contacts. Those immunized within the first several days after exposure may be protected against the development of smallpox. Quarantine contacts for 17 days (incubation period) to ensure they will not be secondary cases. Biological Agents: Tularemia Introduction: Tularemia is caused by infection with Francisella tularensis, a gram-negative coccobacillary organism. Although several forms are known, the pneumonic or typhoidal forms of the disease would likely occur after intentional aerosol delivery. Subjective: Symp to ms Fever, malaise, fatigue, cough, shortness of breath and abdominal pain. Objective: Signs Using Basic Tools: Fever, tachycardia, tachypnea, dyspnea, cyanosis, diaphoresis, rales, hypotension, and abdominal tenderness and pneumonia and sepsis later. Assessment: Differential Diagnosis other forms of pneumonia (both conventional etiologies and other potential biological weapons: plague, staphylococcal entero to xins); sepsis caused by other gram-negative bacteria, typhoid fever, anthrax. Patient Education General: Tularemia is not typically contagious; caregivers need only employ standard precautions when dealing with patients. Prevention: Start asymp to matic persons thought to have been exposed to tularemia via aerosol on oral doxycycline (100 mg every 12 hours). Try other fluoroquinolones or tetracycline if doxycycline or ciprofloxacin is unavailable. They share a propensity to cause bleeding but otherwise vary considerably in their clinical manifestations and severity. Subjective: Symp to ms Fever, malaise, myalgias, headache, pho to phobia, vomiting, diarrhea, abdominal pain, cough and dizziness. Other symp to ms: hematuria, hypotension, shock, edema, hepatic tenderness (hepatic failure), pharyngitis, hyperesthesias. Using Advanced Tools: Lab: Blood culture to rule out meningococcemia and typhoid fever. Assessment: Differential diagnosis any cause of a bleeding, diathesis or disseminated intravascular coagulation (both conventional causes as well as plague): dengue (which can cause hemorrhagic fever but is not transmissible by aerosol), malaria, typhoid fever, meningococcemia, rickettsial diseases, lep to spirosis, shigellosis, fulminant hepatitis, leukemia, lupus, hemolytic-uremic syndrome, and thrombocy to penic purpuras. Most of these conditions are discussed in this book and can be differentiated based on differences in presentation and labora to ry findings. Plan: Treatment Primary: Supportive (oxygen, intravenous fluids, and antipyretics). At a minimum, this entails wearing gloves when to uching the patient and disinfecting medical equipment (such as stethoscopes) between patient encounters. Follow-up Actions Evacuation/Consultant Criteria: Consult early with preventive medicine experts. Quarantine contacts for 21 days (incubation period) to ensure they will not be secondary cases. Shorten the quarantine period to reflect the appropriate incubation period when a definitive diagnosis is available. Lumbar punctures may be necessary to rule out meningitis in patients with meningeal signs and/or altered mental status. Prodrome: (within hours of exposure) nausea, vomiting, diarrhea, fatigue, weakness, fever and headache; time to onset, duration and severity of these symp to ms varies with radiation dose received. Relatively symp to m-free latent phase, lasting 2-6 weeks depending on dose received. Clinical symp to ms in the affected major organ system (hema to poietic, gastrointestinal, neurovascular). Assessment: Differential Diagnosis radiogenic vomiting may be confused with psychogenic vomiting that often results from stress and fear reactions. Patient Education General: A patient who receives a minimal dose should be reassured and returned to duty. A patient with any lymphocyte depletion within the first 24 hours should be evacuated as quickly as possible for definitive care of subsequent infectious and gastrointestinal complications. Prevention and Hygiene: Definitive surgical management of associated wounds and trauma must be completed within 36 hours in a patient with significant radiologic injury so as to avoid infection and increased morbidity associated with poor wound healing. Wound Care: As above, definitive wound care within 36 hours of injury is mandated. Follow-up Actions Evacuation/Consultation Criteria: Evacuate a patient with suspected significant radiologic injury as soon as possible. Those casualties who answer the question appropriately have an intact airway, are breathing and are conscious. The medic should then focus his attention on those casualties who are unconscious or in obvious distress. Meanwhile, the medic can direct the lightly injured casualties or non-medical team members to assist in controlling the bleeding of those patients with active hemorrhage, thus addressing the circulation step. During combat, moving the patient to a safe location takes priority over the Primary and Secondary Survey unless a rapid maneuver can be performed for an obvious life-threatening injury, i. Airway: A conscious spontaneously breathing patient requires no immediate airway intervention. If the patient is semi-conscious or unconscious, the flaccid to ngue is the most common source of airway obstruction. The chin lift or jaw thrust maneuver should be attempted and should readily relieve any obstruction created by the to ngue. Once the airway is opened or if further difficulty is encountered, a nasopharyngeal or oropharyngeal airway should be inserted. The nasopharyngeal airway is better to lerated in the semi-conscious patient and the patient with an intact gag reflex. If the above measures fail to provide an adequate airway or if the patient is unconscious, unresponsive and apneic, orotracheal intubation should be considered. Orotracheal intubation done on a trauma patient with an intact gag reflex without the use of pharmacological sedation and paralysis will be difficult and may cause additional complications such as vomiting, airway trauma and increased intracranial pressure, and thus should be avoided except as a last resort. Other adjuncts to airway management can and should be used if available and if the medic is skilled in their use. If the patient has obvious maxillofacial trauma with signs of airway compromise or if orotracheal intubation fails, then a surgical cricothyroido to my may be a necessary and lifesaving maneuver (see Procedure: Cricothyroido to my). The most common mistake when performing a surgical airway is delaying to o long before starting the procedure. Civilian models of trauma care include cervical spine control and immobilization with airway management. Few if any battlefield casualties with penetrating trauma will have associated injury to the cervical spine unless they have combined blunt injuries from vehicle or aircraft crashes, falls or crush injuries, or penetrating injury to the spinal cord. Meticulous attention to presumed cervical spine injury on the battlefield is not war ranted if penetrating trauma is the obvious mechanism. Furthermore, the medic or the casualty may sustain additional injury if evacuation from the battlefield, and/or treatment of other injuries such as hemorrhage is delayed while the cervical spine is immobilized.

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