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It acts by acylating a bacterial transpeptidase enzyme that is vital to cholesterol in dried shrimp order prazosin 1 mg otc cell-wall synthesis within the bacterium; by structurally disrupting the cell wall how much cholesterol in eggs benedict 2 mg prazosin fast delivery, penicillin leads to cholesterol fasting cheap 2mg prazosin with visa death of the bacterial cells. Bonds to receptor sites are also formed by antiparasitic agents that inactivate the thiol enzymes of a parasite through bonding of a heavy metal. Ionic bonds are ubiquitous and, since they act across long distances, play an important role in the actions of ionizable drugs. The interaction between a negatively charged carboxylate and a positively charged ammonium is a prototypic example of an ionic interaction. The use of charged groups within a drug molecule can be used to influence the pharmacokinetic properties of the molecule. Also, charged groups can be used to preclude a drug molecule from traversing the bloodbrain barrier. Dipole moments are bond moments resulting from charge differences and the distance between charges within a molecule; they are vectorial quantities and are expressed in Debye units (about 1020 esum, or electrostatic units per meter). Linear group moments (as in p-dichlorobenzene) can cancel one another out; nonlinear ones. A carbonyl (C=O) functional group, for example, constitutes a dipole since the carbon is electropositive and the oxygen is electronegative. The energy of dipoledipole interactions can be calculated from the following expression: E= 2µ1 µ2 cos 1 cos 2 Dr 3 (2. Thus, this interaction occurs over a fairly long range, declining only with the third power of the distance between the dipole charges. Iondipole interactions are even more powerful, with energies that can reach 100150 kJ/mol. The energy of such an interaction can be calculated from E = eµ cos /D(r 2 - d 2) (2. Because the bond energy in this interaction declines only with the square of the distance between the charged entities, it is consequently very important in establishing the initial interaction between two ligands. A classic example of a dipoleion interaction is that of hydrated ions which, in the process of hydration, become different from the same ions in a crystal lattice. Surprisingly, hydrogen bonds are probably less important in intermolecular bonding between two structures. There is no advantage in exchanging hydrogen bonding with water molecules for hydrogen bonding with another molecule unless additional, stronger bonding brings the two molecules into sufficient proximity. Hydrogen bonds are strongly directional, and linear hydrogen bonds are energetically preferred to angular bonds. Hydrogen bonds are also somewhat weak, having energies ranging from 7 to 40 kJ/mol. Acceptor molecules are p-electron-deficient systems such as purines and pyrimidines or aromatics with electron-withdrawing substituents. However, although the interaction: between induced dipoles sets up a temporary local attraction between the two atoms, this noncovalent interaction decreases very rapidly, in proportion to 1/R6, where R is the distance separating the two molecules. While individual van der Waals bonds make a very low energy contribution to a system, a large number of van der Waals forces can add up to a sizable amount of energy. The concept of these indirect forces, first introduced by Kauzman in the field of protein chemistry, also explains the low solubility of hydrocarbons in water. Because the nonpolar molecules of a hydrocarbon are not solvated in water, owing to their inability to form hydrogen bonds with water molecules, the latter become more ordered around the hydrocarbon molecule, forming a molecular level interface that is comparable to a gasliquid boundary. The resulting increase in solvent structure leads to a higher degree of order in the system than exists in bulk water, and therefore a loss of entropy. When the hydrocarbon structures-whether two protein side chains or hexane molecules dispersed in water-come together, they will "squeeze out" the ordered water molecules that lie between them (figure 2. Since the displaced water is no longer part of a boundary domain, it reverts to a less ordered structure, which results in an entropy gain. By displacing part of the hydrate envelope, the two alkyl side chains occupy the same water "cavity" while many of the water molecules (represented by circles) become randomized. As discussed in chapter 1, a drug molecule is a collection of geometrically arranged functional groups displayed on a molecular framework. These functional groups establish interactions with the drug receptor by one or more of the various binding forces discussed above. When designing a drug, the designer wishes to have an energetically favorable and geometrically optimal interaction with the receptor site. This may be achieved in two strategies: (i) by having multiple points of contact between the drug molecule and the receptor. If the drug molecule has only two functional groups capable of binding to a receptor, then the interaction lacks specificity; such a drug could interact with too many putative receptors and would probably demonstrate unwanted toxicities. On the other hand, if the drug molecule has too many functional groups capable of interaction with a receptor, the molecule tends to be too polar and is thus too poorly absorbed and too rapidly excreted. Therefore, when designing a drug, an average of 35 points of contact between the drug and the receptor tends to be optimal; this corresponds to the drug molecule containing 35 functional groups capable of establishing binding interactions with the receptor macromolecule. If the drug is to cross the bloodbrain barrier, then fewer contact points may be required; if the drug is to stay confined to the gastrointestinal tract and not absorbed, then more contact points may be tolerated. The second strategy concerns the selection of functional groups capable of enabling the most energetically desirable interaction with the receptor site. As stated, polar groups tend to give the most energetically favorable binding interactions. However, desirable though they may be, too many polar groups make the drug molecule too hydrophilic, causing poor absorption, rapid excretion, and poor distribution. Usually, a mixture of varying functional groups with varying properties is desirable. If the drug is to cross the bloodbrain barrier, incorporating lipophilic groups (such as aromatic rings capable of both lipophilic interactions and charge transfer interactions) into the drug molecule satisfies the twofold role of adding a point of contact between the drug and the receptor and of increasing the lipophilicity of the drug so that it can diffuse into the brain. The drug designer must select functional groups from the following interaction types to be incorporated into the drug molecule: ionic interactions. Initially, these groups are selected to enable an optimal pharmacodynamic interaction with the drug receptor macromolecule. However, these functional groups may also be selected to influence the pharmacokinetic and pharmaceutical properties of the drug molecule. Highly polar functional groups will facilitate renal excretion; lipophilic functional groups will promote passive diffusion across the bloodbrain barrier. To aid in this discussion, some classical pharmacological binding terms are briefly defined. The traditional doseresponse curve is central to these discussions, and a representative example is given in figure 2. An agonist is a substance that interacts with a specific cellular constituent, the receptor, and elicits an observable biological response.
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Conductive hearing loss with a normal ear canal and intact tympanic membrane suggests ossicular pathology cholesterol medication calculator order prazosin 2 mg fast delivery. Fixation of the stapes from otosclerosis is a common cause of low-frequency conductive hearing loss; onset is between the late teens to high cholesterol definition wikipedia generic 2 mg prazosin with amex the forties cholesterol medication in powder form cheap prazosin 2mg with mastercard. While small perforations often heal spontaneously, larger defects usually require surgical tympanoplasty (90% effective). Sudden unilateral hearing loss ґ ` may represent a viral infection of the inner ear or a cerebrovascular accident. In early stages, symmetric high frequency hearing loss is typical; with progression, the hearing loss involves all frequencies. Hearing aids provide limited rehabilitation; cochlear implants are treatment of choice for severe cases. For unresponsive cases, labyrinthectomy and vestibular nerve section abolish rotatory vertigo. Vestibular schwannomas present with asymmetric hearing impairment, tinnitus, imbalance (rarely vertigo); cranial neuropathy (trigeminal or facial nerve) may accompany larger tumors. It may have a buzzing, roaring, or ringing quality and may be pulsatile (synchronous with the heartbeat). Digital hearing aids can be individually programmed, and multiple and directional microphones at the ear level may be helpful in noisy surroundings. If the hearing aid provides inadequate rehabilitation, cochlear implants can be effective. Hearing aids are also helpful in tinnitus suppression, as are tinnitus maskers, devices that present a sound to the affected ear that is more pleasant to listen to than the tinnitus. Prevention Conductive hearing losses may be prevented by prompt antibiotic therapy for acute otitis media and by ventilation of the middle ear with tympanostomy tubes in middle-ear effusions lasting l2 weeks. Loss of vestibular function and deafness due to aminoglycoside antibiotics can largely be prevented by monitoring of serum peak and trough levels. Ten million Americans have noise-induced hearing loss, and 20 million are exposed to hazardous noise in their employment. Symptoms include rhinorrhea, nasal congestion, cough, sore throat, hoarseness, malaise, sneezing, and fever. Sinuses become infected when sinus ostia are obstructed or when ciliary clearance is impaired. Nosocomial cases, which are associated with nasotracheal intubation, are commonly caused by Staphylococcus aureus and gram-negative bacilli and are often polymicrobial and highly resistant to antibiotics. Clinical Features Common manifestations of acute sinusitis include nasal drainage, congestion, facial pain or pressure, headache, thick purulent nasal discharge, and tooth pain. Life-threatening complications include meningitis, epidural abscess, and brain abscess. Diagnosis It is difficult to distinguish viral from bacterial sinusitis clinically. Pts without improvement or with severe disease at presentation should be given antibiotics. Extensive debridement is usually needed for invasive fungal sinusitis in immunocompromised pts. Adjunctive treatments include intranasal administration of glucocorticoids, sinus irrigation, and surgical evaluation. Unilateral disease with a mycetoma within the sinus (fungus Table 60-1 Guidelines for the Diagnosis and Treatment of Selected Upper Respiratory Tract Infections in Adultsa Treatment Recommendations Syndrome, Diagnostic Criteria Acute sinusitis Moderate symptoms. Some organizations support treating adults with these symptoms and signs without the need for rapid streptococcal antigen testing. Acute localized otitis externa, furunculosis in the outer third of the ear canal, is usually due to S. Pts have severe pain, erythema and swelling of the canal, and white clumpy discharge from the ear. Malignant or necrotizing otitis externa is an aggressive, potentially lifethreatening disease occurring primarily in elderly diabetic or immunocompromised pts. On exam, granulation tissue in the posteroinferior wall of the canal, near the junction of bone and cartilage, is seen. External Ear Infections · Auricular cellulitis: Tenderness, erythema, and swelling of the external ear, 3. Other findings include otalgia, otorrhea, decreased hearing, fever, and irritability. However, pts with mild to moderate disease will do well if treated with analgesia and anti-inflammatory agents initially, with antibiotics reserved for pts who do not improve in 2 3 days. Other bacterial causes include streptococci of groups C and G, Neisseria gonorrhoeae, Corynebacterium diphtheriae, and anaerobic bacteria. Most experts recommend that children have a throat culture performed if rapid testing is negative, but this course is not recommended for adults because of the low incidence of disease. Acute Pharyngitis · Viral: Respiratory viruses typically cause mild disease associated with non- Oral Infections Oral-labial herpesvirus infections and oral thrush caused by Candida are discussed in Chaps. Pts are hoarse, exhibit reduced vocal pitch or aphonia, and have coryzal symptoms. Examination may reveal respiratory distress, inspiratory stridor, and chest wall retractions. Laboratory or diagnostic procedures are then used, when appropriate, to clarify the diagnosis. Linear [contact dermatitis such as poison ivy, lesions that appear at sites of local skin trauma (Koebner phenomenon)]; annular- "ring-shaped" lesion with an active border and central clearing (erythema chronicum migrans, erythema annulare centrificum, tinea corporis); iris or target lesion- two or three concentric circles of differing hue (erythema multiforme); circinate- circular lesion (urticaria, herald patch of pityriasis rosea); nummular- "coin-shaped" (nummular eczema); guttate- droplike (guttate psoriasis); morbilliform- "measles-like" with small confluent papules coalescing into unusual shapes (measles, drug eruption); reticulated- "netlike" (livedo reticularis); herpetiform- grouped vesicles, papules, or erosions (herpes simplex). Macule- a flat circumscribed lesion of a different color, allowing for differentiation from surrounding skin; patch- macule 2 cm in diameter; papule- elevated, circumscribed lesion of any color 1 cm in diameter, with the major portion of lesion projecting above surrounding skin; nodule- palpable lesion similar to a papule but 1 cm in diameter; plaque- an elevated, flattopped lesion 1 cm in diameter; vesicle- sharply marginated elevated lesion 1 cm in diameter filled with clear fluid; bulla- vesicular lesion 1 cm in diameter; pustule- a well-marginated focal accumulation of inflammatory cells within skin; wheal- a transient elevated lesion due to accumulation of fluid in upper dermis; cyst- lesion consisting of liquid or semisolid material contained within limits of cyst wall (true cyst). Scale- a flaky accumulation of excess keratin that is partially adherent to skin; crust- a circumscribed collection of inflammatory cells and dried serum on skin surface; excoriation- linear, angular erosions caused by scratching; erosion- a circumscribed, usually depressed, moist lesion resulting from loss of overlying epidermis; ulcer- a deeper erosion involving epidermis plus underlying papillary dermis; may leave a scar on healing; atrophy: (1) epidermal- thinning of skin with loss of normal skin surface markings, (2) dermal- depression of skin surface due to loss of underlying collagen or dermal ground substance; lichenification- thickening of skin with accentuation of normal skin surface markings most commonly due to chronic rubbing; scar- collection of fibrous tissue replacing normal dermal constituents. Evolution of the lesion- site of onset, manner in which eruption progressed or spread, duration, periods of resolution or improvement in chronic eruptions Symptoms associated with the eruption- itching, burning, pain, numbness; what has relieved symptoms; time of day when symptoms are most severe Current or recent medications- both prescription and over-the-counter Associated systemic symptoms. Scale is collected from advancing edge of a scaling lesion by gently scraping with side of a microscope slide. Positive preparations show translucent, septate branching hyphae among keratinocytes. Classic lesion is a well-marginated, erythematous plaque with silvery-white surface scale. Initially, there is a single 2- to 6-cm annular salmon-colored patch (herald patch) with a peripheral rim of scale, followed in days to weeks by a generalized eruption involving the trunk and proximal extremities. Individual lesions are similar to but smaller than the herald patch and are arranged in symmetric fashion with long axis of each individual lesion along skin lines of cleavage. Course is variable, but most pts have spontaneous remissions 6 24 months after onset of disease. Lesions are most commonly on flexures, with prominent involvement of antecubital and popliteal fossae; generalized erythroderma in severe cases.
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In these situations foods raise good cholesterol naturally discount prazosin 2mg with visa, the physician can assume consent for any necessary stabilizing treatment cholesterol range age chart generic 2 mg prazosin mastercard. In the rare case of a guardian or parent refusing to cholesterol elevated purchase prazosin american express consent to life-saving treatment needed to stabilize a child, physicians should generally provide necessary treatment and obtain a court order after the fact. Note that age by itself does not necessarily preclude the ability to consent, as there are conditions that allow minors to make their own medical decisions. These conditions vary from state to state, but often include the ability to consent without parental knowledge to treatment for sexually transmitted illnesses, pregnancy, drug and alcohol dependency, rape, and mental health concerns. Emancipated minors, individuals who the law recognizes as adults despite their age, also can consent or refuse treatment without parental involvement. Circumstances that allow minors to apply for legal emancipation vary, but often include active duty in the armed forces, marriage, pregnancy, and parenthood. Patients who "elope" should be discussed among involved care providers, including nursing and ancillary staff, to determine if the patient reasonably appeared to have the capacity to withdraw consent and leave. Patients who do not, such as the patient above, must be searched for and retrieved as soon as possible. Unfortunately, unless these orders are explicit, it often remains unclear as to what exactly the patient would want for conditions less severe than cardiac arrest. If the patient displays signs of impending respiratory failure, should they be intubated? If they are hypotensive from unstable ventricular tachycardia, should they be cardioverted? What constitutes "actual knowledge" may be debated in individual cases, but generally refers to situations in which a physician has personally seen the advance directive even though it is not currently present. Informed refusal Patients with decision-making capacity may withdraw consent for treatment at any time. When a patient withdraws consent, the physician must again determine his or her capacity to do so. Patients with impaired decisionmaking capacity cannot provide an informed refusal, and the physician has a duty to provide stabilizing treatment. Occasionally, patients do not understand the various treatment options or the potential for deterioration of their condition. In California, for example, patients who are suicidal, homicidal, or gravely disabled may be detained up to 72 hours for psychiatric evaluation. During this period, these patients may receive treatment necessary to stabilize a condition brought on by a suicide attempt, and they may be restrained by physical or chemical means necessary to protect themselves or others. The procedure for involuntarily detaining a patient is complex, and physicians should become thoroughly familiar with the laws in their area, carefully document the events that required detainment, and the methods of restraint implemented. Privacy and confidentiality Another common legal issue arising during patient care involves privacy and confidentiality issues. While the medical records are typically owned by the hospital, the information within them is considered property of the patient. In general, medical information cannot be shared with a third party without the consent of the patient unless such information is necessary for medical treatment. This includes releasing information to other family members, insurance companies, and employers. Exceptions to this exist, as all states have mandatory reporting of victims of violence and of certain health conditions. Emergency physicians must be careful to obtain consent from patients prior to speaking with other family members, friends, or employers. Patients unable to consent due to medical conditions represent a special case that the courts have yet to fully explore. Generally, physicians should proceed with the assumption of what a reasonable person in a similar situation would want with regard to confidentiality. For example, refusing to update a spouse on the status of a criticallyinjured patient because the patient is unable to give consent for the release of medical information seems unreasonable. While the courts have yet to determine many issues in this area, they typically allow discretion when a physician acts in the best interest of an incapacitated patient. Similarly, certain medical information, such as drug or alcohol tests in the hands of civil authorities, may result in serious consequences to some patients. Legal aspects of emergency care the criminal justice system Emergency physicians often interact with police, detectives, district attorneys, and criminal defense attorneys. Interacting with the criminal justice system is an inevitable part of emergency medicine, and Table 44. Those in custody retain their rights to refuse medical treatment (barring altered mental status). Most police agencies prefer to obtain their own blood or urine specimens for legal reasons. Legal issues and practice suggestions Physicians must report children and certain at-risk adults (elderly, cognitively-impaired, etc. Many states require physicians to report victims of domestic violence or animal attacks. Physician must either comply with subpoena or contact the party issuing the subpoena (usually prosecutor or defense attorney) and make alternative arrangements. Do not cut through bullet holes in clothing, destroy or discard personal belongings, or place chest tubes through gunshot or stab wounds. Refrain from describing wounds as "entry" or "exit" or speculating on bullet trajectory unless specifically trained to do so. In the medical record, use the term "alleged" because the physician has no direct knowledge of the events. Consider transferring to specialized sexual assault referral center if available after appropriate contacts have been made and safe transport is arranged. Physician evaluates trauma patient prior to evidence collection (victim of gunshot wound, etc. These patients may have suffered significant injury or death due to delays in finding emergency care. The parties usually rely on expert witness testimony to establish or refute these elements. This often results in highly technical testimony that can be confusing to jury members. Additionally, the information on which these experts draw their conclusions comes primarily from the medical record, which may be illegible, incomprehensible, or incomplete. This frequently results in not only disagreements over issues of judgment, but also debates over issues of fact. For example, the plaintiff argues that peripheral pulses were not checked while the defense claims they were.
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Conclusions include the following: As initial monotherapy for adults with newly diagnosed or untreated partial-onset seizures: Carbamazepine cholesterol in butter or eggs buy prazosin with visa, levetiracetam cholesterol levels vary proven prazosin 2mg, phenytoin total cholesterol chart by age best 1mg prazosin, and zonisamide are established as efficacious/effective. Gabapentin, lamotrigine, oxcarbazepine, phenobarbital, topiramate, and vigabatrin are possibly efficacious/effective. As initial monotherapy for children with newly diagnosed or untreated partial-onset seizures: Oxcarbazepine is established as efficacious/effective. Carbamazepine, phenobarbital, phenytoin, topiramate, valproate, and vigabatrin are possibly efficacious/effective. Clobazam, carbamazepine, lamotrigine, and zonisamide are potentially efficacious/effective. As initial monotherapy for elderly adults with newly diagnosed or untreated partial-onset seizures: Gabapentin and lamotrigine are established as efficacious/effective. Carbamazepine, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, topiramate, and valproate are possibly efficacious/effective. For children with newly diagnosed or untreated generalized-onset tonic-clonic seizures: Carbamazepine, phenobarbital, phenytoin, topiramate, and valproate are possibly efficacious/effective. Carbamazepine and phenytoin may precipitate or aggravate generalized-onset tonic-clonic seizures. As initial monotherapy for children with newly diagnosed or untreated absence seizures: Ethosuximide and valproate are established as efficacious/effective. Carbamazepine, oxcarbazepine, phenobarbital, phenytoin, tiagabine, and vigabatrin may precipitate or aggravate absence seizures (based on scattered reports). Gabapentin, levetiracetam, oxcarbazepine, and sulthiame (not available in the United States) are potentially efficacious/effective. Carbamazepine, gabapentin, oxcarbazepine, phenytoin, tiagabine, and vigabatrin may precipitate or aggravate absence, myoclonic, and in some cases generalized tonic-clonic seizures. There is a lack of well-designed randomized trials in epilepsy, particularly for generalized seizures and in the pediatric population. The review included the use of carbamazepine, phenytoin, valproate, phenobarbital, oxcarbazepine, lamotrigine, gabapentin, topiramate, levetiracetam, and zonisamide for the treatment of partial onset seizures (simple partial, complex partial or secondarily generalized) or generalized tonic-clonic seizures with or without other generalized seizure types. This network meta-analysis showed that for the primary outcome, the time to withdrawal of allocated treatment: For individuals with partial seizures: (i) Levetiracetam performed better than carbamazepine and lamotrigine. For individuals with generalized onset seizures, valproate performed better than carbamazepine, topiramate and phenobarbital. For both partial and generalized onset seizures, phenobarbital seems to perform worse than all other treatments. For the secondary outcome, time to first seizure: For individuals with partial seizures, phenobarbital and phenytoin seem to perform better than most other drugs; and carbamazepine performed better than valproate, gabapentin, and lamotrigine. For individuals with generalized seizures, phenytoin seems to work better than most other drugs. There were few notable differences between the newer drugs (oxcarbazepine, topiramate, gabapentin, levetiracetam, and zonisamide) for either partial seizures or generalized seizures. Few notable differences were shown for either partial or generalized seizure types for the secondary outcomes of time to 6-month or 12-month remission of seizures. Overall, direct evidence and network meta-analysis estimates were numerically similar, and effect sizes had overlapping confidence intervals. Data for individuals with generalized seizures are still limited and additional randomized trials are needed. The relative efficacy among valproate, lamotrigine, phenytoin, carbamazepine, ethosuximide, topiramate, levetiracetam, and phenobarbital as monotherapy for generalized (n = 7 studies) or absence seizures (n = 3 studies) was evaluated in a systematic review and network meta-analysis (Campos et al 2018). For absence seizures, ethosuximide and valproate were found to have a higher probability of seizure freedom compared to lamotrigine. A meta-analysis estimated the comparative efficacy of achieving seizure freedom with 22 antiepileptic drugs and placebo in children and adolescents (Rosati et al 2018). For the treatment of newly diagnosed focal epilepsy (n = 4 studies), point estimates suggested superiority of carbamazepine and lamotrigine; however, this was not statistically significant. For refractory focal epilepsy (n = 9 studies), levetiracetam and perampanel were more effective than placebo in mixed comparisons. Ethosuximide and valproic acid were more effective than lamotrigine for absence seizures. The authors concluded that better designed comparative studies with appropriate length of follow-up, well-defined outcomes, and reliable inclusion criteria are needed to validate these results. Approximately 20% to 40% of patients with epilepsy can be considered refractory to drug treatment, referred to as drugresistant epilepsy. Treatment of drug-resistant epilepsy may include additional anticonvulsant drug trials, epilepsy surgery, vagal nerve stimulation, and dietary changes (the ketogenic diet) (Sirven 2017). Examples of combinations for which there is some evidence of efficacy include valproate plus lamotrigine for partial-onset and generalized seizures, valproate plus ethosuximide for absence seizures, and lamotrigine plus topiramate for various seizure types; however, even this evidence is fairly limited. Two-drug therapy should be attempted before considering addition of a third drug, and higher numbers of drugs should be avoided as they are associated with a very low likelihood of additional seizure reduction (Kwan et al 2011). The efficacy outcomes studied were 50% responder rate and state of seizure freedom. The primary outcome was seizure freedom, which was defined as a 100% seizure reduction in the maintenance or double-blind treatment period of the trial. Based on results of 54 studies that evaluated the efficacy outcome, the most effective agents included tiagabine, brivaracetam, and valproic acid, and the least effective agents included rufinamide, lamotrigine, and zonisamide. Products with favorable safety included levetiracetam, brivaracetam, and perampanel, while those with the least favorable safety included retigabine, oxcarbazepine, and rufinamide. The authors stated that agents with the best outcomes in terms of efficacy and safety included levetiracetam, vigabatrin, valproic acid, and brivaracetam. Its approval for these 2 indications was based on 3 placebo-controlled trials in patients refractory to other treatments. Epidiolex, along with use of other agents, demonstrated a significant reduction in seizure frequency compared to placebo. Two multicenter placebo-controlled studies evaluated the addition of stiripentol to clobazam and valproate therapy in patients 3 years to less than 18 years of age with Dravet syndrome. Responder rates (seizure frequency reduced by 50%) with respect to generalized tonic-clonic seizures were significantly lower with stiripentol compared to placebo (Diacomit prescribing information 2018). American Academy of Neurology and American Epilepsy Society (French et al 2004A, Kanner et al, 2018A). The 2004 publication summarizes the efficacy, tolerability, and safety of gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide for the treatment of children and adults with newly diagnosed partial and generalized epilepsies. Lamotrigine can be included in the options for children with newly diagnosed absence seizures. The 2018 recommendations include the following: As monotherapy in adult patients with new-onset focal epilepsy or unclassified generalized tonic-clonic seizures: Lamotrigine use should be considered to decrease seizure frequency. Lamotrigine use should be considered and gabapentin use may be considered to decrease seizure frequency in patients aged 60 years. Levetiracetam use and zonisamide use may be considered to decrease seizure frequency.
- Immunodeficiency with short limb dwarfism
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A normal resting echocardiogram cholesterol jimmy moore purchase 2 mg prazosin, however cholesterol medication during pregnancy buy prazosin 1 mg on-line, gives no information about cardiac reserve cholesterol test eating cheap 2mg prazosin visa. Although this lady has bilateral pleural effusions which could explain her tachypnoea, she also has a history of chronic obstructive airways disease. Pulmonary function tests will give an indication of the severity of her underlying lung disease as well as the degree of reversibility with bronchodilators. Morbid obesity is associated with a higher than normal incidence of difficult airway, which will need a full assessment and possibly further investigations. She would benefit from pre-optimisation with invasive monitoring, fluids (including blood) and possibly inotropes before theatre. Obese woman with fractured neck of femur 323 Choose your technique and back it up. One gave a spinal anaesthetic and the other a general anaesthetic after pre-operative optimisation with invasive monitoring. Allogeneic red blood cell transfusions: efficacy, risks, alternatives and indications British Journal of Anaesthesia, 95, 3342. The important anaesthetic considerations are that this is an urgent paediatric case in which the child has symptomatic asthma, possible left lower lobe collapse/consolidation and requires a rapid sequence induction. Testicular torsion this results from rotation of the testis with interference of the blood supply and is usually associated with some abnormality. Venous compression from the torsion leads to congestion and eventual venous infarction unless corrected. Acute epididymo-orchitis Testicular trauma Strangulated inguinal hernia Idiopathic scrotal oedema It is often impossible to differentiate between the first two diagnoses. The torsion is corrected and the testicle fixed with anchoring sutures at the upper and lower poles. The other testicle is always explored and fixed in a similar fashion as this can occur bilaterally. The history will elicit the duration of asthma symptoms, precipitating factors, frequency of attacks, increasing need for treatment and hospital admissions. On examination the respiratory rate, ability to speak, pulse rate and peak flow rate should be noted. This child has significant asthma given the history of previous hospital admissions and a recent cough. He has widespread wheeze, a raised white cell count (which may be secondary to his surgical condition or from a chest infection) and left lower lobe collapse/consolidation on his chest X-ray. His respiratory rate, peak expiratory flow rate and response to bronchodilators need to be measured. The chest X-ray shows blunting of the left costophrenic angle and loss of the left hemi-diaphragm behind the heart. X-ray features of left lower lobe collapse Triangular opacity behind the heart (sail sign) Loss of medial part of hemidiaphragm 6. What are the other important issues in the pre-operative preparation of this child? The important pre-operative considerations in addition to assessment of respiratory function are: Asthmatic child with torsion 327 the pre-operative visit which should focus on the parental anxieties as well as those of the patient. This boy has been vomiting and therefore fluid and electrolyte status is important. An intravenous cannula should be in situ with appropriate fluid therapy commenced. In addition to this, pre-operative questions such as previous anaesthesia, allergies and loose dentition should be asked. The patient and parents should be informed of the proposed method of induction and post-operative analgesic regimen. Pre-medication may include bronchodilators and topical local anaesthetic cream if required. Dehydration is treated by calculating the fluid deficit from reduced intake and insensible losses (vomiting, respiratory losses, sweating) and replacing the fluid and electrolytes needed. The hourly maintenance requirements should be calculated and added into the equation. Following pre-oxygenation for 3 minutes, a rapid sequence induction is performed with thiopentone 150 mg and suxamethonium 60 mg. Anaesthesia is maintained with a volatile agent in oxygen and nitrous oxide or air. A non-depolarising neuromuscular 328 Asthmatic child with torsion blocking agent is added when the suxamethonium induced block is wearing off. A caudal epidural block can then be performed with the patient in the left lateral position and paracetamol suppositories inserted. The boy should have core temperature measured with a nasal or rectal probe and should be actively warmed with a warm air blower. At the end of surgery, neuromuscular blockade is reversed and the patient extubated awake in the left lateral position. Paediatric formulae: Weight in kg (Age + 4) x 2 Tracheal tube internal diameter (mm) Age/4 + 4. Paracetamol suppositories (initial dose of up to 40 mg/kg, then 15 mg/kg 6-hourly thereafter) are also used as co-analgesics with opioids. Perhaps the best form of post-operative analgesia is from a local anaesthetic block, in this case a caudal epidural. The sacral hiatus is identified, flanked by the sacral cornua, and a Asthmatic child with torsion 329 needle is introduced through the skin and sacrococcygeal membrane. It should inject with little resistance and there should be no subcutaneous swelling. The complication of dural puncture is more likely in children as the spinal cord ends at L3 but the dura ends at S34. He has had three admissions to hospital in the last year for chest pain and he becomes short of breath after walking 30 yards. This is an elective case, and because his symptoms are poorly controlled at present, he needs investigation and treatment of his cardiorespiratory problems before he is anaesthetised. Further history regarding his episodes of chest pain would be very important in this case. If his pain was due to angina, he should be referred to a physician to improve his condition prior to elective surgery. An echocardiogram would show any wall motion abnormalities that might indicate previous myocardial infarction. If the ejection fraction is normal, however, this does not necessarily imply good cardiac reserve. Arterial blood gas analysis on air would be helpful to further delineate his respiratory function and as a baseline with which to compare post-operative results. This is distinguished on the basis of the history, examination and investigations.
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Red Blood Cell Transfusion Indicated for symptomatic anemia unresponsive to cholesterol lowering foods and spices prazosin 1mg with mastercard specific therapy or requiring urgent correction cholesterol eggs high buy generic prazosin 2 mg on-line. Platelet Transfusion Prophylactic transfusions usually reserved for platelet count 10 optimal cholesterol levels nz purchase 2mg prazosin amex,000/ L (20,000/ L in acute leukemia). One unit elevates the count by about 10,000/ L if no platelet antibodies are present as a result of prior transfusions. Leukapheresis is increasingly being used to harvest hematopoietic stem cells from the peripheral blood of cancer pts; such cells are then used to promote hematopoietic reconstitution after high-dose myeloablative therapy. Plateletpheresis Used in some pts with thrombocytosis associated with myeloproliferative disorders with bleeding and/or thrombotic complications. Resource management and quality-of-care assessments can be facilitated by the use of illness-severity scales. Mechanical Ventilatory Support Principles of advanced cardiac life support should be adhered to during initial resuscitative efforts. Any compromise of respiration should prompt consideration of endotracheal intubation and mechanical ventilatory support. Mechanical ventilation may decrease respiratory work, improve arterial oxygenation with improved tissue oxygen delivery, and reduce acidosis. Reduction in arterial pressure after institution of mechanical ventilation is common due to reduced venous return from positive thoracic pressure, reduced endogenous catecholamine output, and concurrent administration of sedative agents. Respiratory Failure Four common types of respiratory failure are observed, reflecting different pathophysiologic derangements. Type I or Acute Hypoxemic Respiratory Failure Occurs due to alveolar flooding with edema (cardiac or noncardiac), pneumonia, or hemorrhage. Current ventilator strategy requires the use of low tidal volumes (4 6 mL/kg ideal body weight) to avoid ventilatorinduced lung injury. Treat the underlying cause and provide mechanical support with mask or endotracheal ventilation. Less commonly, neuromuscular blocking agents are required to facilitate ventilation when there is extreme dyssynchrony that cannot be corrected with manipulation of the ventilator settings. Weaning from Mechanical Ventilation Daily screening of patients who are stable while receiving mechanical support facilitates recognition of patients ready to be liberated from the ventilator. If there is no tachypnea, tachycardia, hypotension, or hypoxia, a trial of extubation is commonly performed. Multiorgan System Failure Defined as dysfunction or failure of two or more organs in patients with critical illness. In addition to pulse oximetry, frequent arterial blood-gas analysis can reveal evolving acid-base disturbances. Modern ventilators have sophisticated alarms that reveal excessive pressure requirements, insufficient ventilation, or overbreathing. Intraarterial pressure monitoring and, at times, pulmonary artery pressure measurement can reveal changes in cardiac output or oxygen delivery. Prevention of Complications Critically ill patients are prone to a number of complications, including the following: and may occur at the site of central venous catheters · Gastrointestinal bleeding- most often in patients with bleeding diatheses or respiratory failure, necessitating acid neutralization in such patients · Renal failure- a tendency exacerbated by nephrotoxic medications and dye studies. Evidence suggests that strict glucose control [glucose mg/dL)] improves mortality in critically ill patients. Pathophysiology Respiratory failure occurs when one or more components of the respiratory system fails. Many processes will involve more than one of these components of the respiratory system, but assessment of each compartment can provide a basis for differential diagnosis. Clinical Evaluation Initial inspection should assess upper airway patency and signs of distress such as nasal flaring, intercostal retractions, diaphoresis, level of consciousness. Use of sternocleidomastoid muscles and pulsus paradoxus in a patient who is wheezing suggest severe asthma. Because of the potential for rapid, possibly fatal, deterioration, therapy may need to be initiated without a definite diagnosis. In ventilated patients obstruction can be deduced by inspection of the flow:time curve as displayed on most current ventilators. If hypercarbia and acidosis coexist, mechanical ventilation should be strongly considered. Management depends on determining its cause, alleviating triggering and potentiating factors, and providing rapid relief whenever possible. These second-order neurons form crossed ascending pathways that reach the thalamus and are projected to somatosensory cortex. Pain transmission is regulated at the dorsal horn level by descending bulbospinal pathways that contain serotonin, norepinephrine, and several neuropeptides. Anticonvulsants (gabapentin, carbamazepine) may be effective for aberrant pain sensations arising from peripheral nerve injury. Evaluation Pain may be of somatic (skin, joints, muscles), visceral, or neuropathic (injury to nerves, spinal cord pathways, or thalamus) origin. Neuropathic pain definitions: neuralgia: pain in the distribution of a single nerve, as in trigeminal neuralgia; dysesthesia: spontaneous, unpleasant, abnormal sensations; hyperalgesia and hyperesthesia: exaggerated responses to nociceptive or touch stimulus, respectively; allodynia: perception of light mechanical stimuli as painful, as when vibration evokes painful sensation. Causalgia is continuous severe burning pain with indistinct boundaries and accompanying sympathetic nervous system dysfunction (sweating; vascular, skin, and hair changes- sympathetic dystrophy) that occurs after injury to a peripheral nerve. Chronic Pain the problem is often difficult to diagnose, and pts may appear emotionally distraught. Psychological evaluation and behaviorally based treatment paradigms are frequently helpful, particularly in a multidisciplinary pain management center. Some pts may require referral to a pain clinic; for others, pharmacologic management alone can provide significant help. The tricyclic antidepressants are useful in management of chronic pain from many causes, including headache, diabetic neuropathy, postherpetic neuralgia, atypical facial pain, chronic low back pain, and post-stroke pain. The combination of the anticonvulsant gabapentin and an antidepressant such as nortriptyline may be effective for chronic neuropathic pain. The long-term use of opioids is accepted for pain due to malignant disease but is controversial for chronic pain of nonmalignant origin. When other approaches fail, long-acting opioid compounds such as levorphanol, methadone, sustained-release morphine, or transdermal fentanyl may be considered for these pts (Table 8-2). Here, we review more invasive diagnostic and therapeutic procedures performed by internists- thoracentesis, lumbar puncture, and paracentesis. Indications for this procedure include diagnostic evaluation of pleural fluid, removal of pleural fluid for symptomatic relief, and instillation of sclerosing agents in pts with recurrent, usually malignant pleural effusions. The pt should sit on the edge of the bed, leaning forward with the arms abducted onto a pillow on a bedside stand. Pts undergoing thoracentesis frequently have severe dyspnea, and it is important to assess if they can maintain this positioning for at least 10 min. Percussion of dullness is utilized to ascertain the extent of the pleural effusion with the site of entry being the first or second highest interspace in this area. The entry site for the thoracentesis is at the superior aspect of the rib, thus avoiding the intercostal nerve, artery, and vein, which run along the inferior aspect of the rib. The skin is then prepped and draped in a sterile fashion with the operator observing sterile technique at all times. A small-gauge needle is used to anesthetize the skin and a larger-gauge needle is used to anesthetize down to the superior aspect of the rib.
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Dyspnea is a symptom associated with many disorders cholesterol medication with the least side effects prazosin 1 mg low price, from nonurgent to bad cholesterol levels nz buy prazosin online life-threatening cholesterol levels 60 year old cheap prazosin 2 mg with visa. Like the perception of pain, dyspnea is subjective and its severity does not necessarily correlate with the seriousness of the underlying pathology. Approximately twothirds of these patients have an underlying cardiac or pulmonary disorder. Specific data on the general prevalence of dyspnea is not available, although in the Framingham study, 627% of the adult population reported experiencing dyspnea. Pathophysiology In general, breathing is a well-synchronized, unconscious, quiet and effortless process. Although the exact mechanism responsible for dyspnea is unknown, abnormalities or alterations of gas exchange, pulmonary circulation, cardiovascular function, respiratory mechanics, or the oxygen (O2) carrying capacity of blood may result in dyspnea. Respirations are regulated by various afferent input from mechanoreceptors in the lungs, airways and respiratory muscles, as well as chemoreceptors in the blood. Here, the rate of ventilation is adjusted to maintain blood gas and acidbase homeostasis. Feedback from mechanoreceptors regarding the mechanical status and function of the ventilatory pump and respiratory muscles leads to adjustment of the level and pattern of breathing. The efferent nerve pathway to the muscles of respiration starts in the brainstem (medulla/pons), crosses over and then travels in the contralateral spinal cord to reach the spinal motor neurons. Respirations are also subject to voluntary control through input from the cerebral cortex to the respiratory centers in the medulla/pons. Of all the vital signs, respiratory rate is the only vital sign which can be influenced by voluntary control, although to a limited extent. During "normal" respiration, the main work of breathing is done by the diaphragm and intercostal muscles. When a patient experiences respiratory distress, contraction of the intercostal muscles becomes more forceful and visible to the observer. When there is increased work of breathing or respiratory distress, other muscles are recruited in an effort to maintain the movement of air in the lungs. Similarly, "abdominal breathing" or "see-saw" respirations occur when the abdominal muscles are recruited. History If dyspnea is not due to an immediate life-threat, the history and physical examination can proceed in an orderly fashion. Immediate resuscitation must occur if the shortness of breath is from respiratory failure, shock with inadequate tissue perfusion, or hypoxia at a cellular level. The history is critical in the evaluation of dyspnea in Primary Complaints 485 order to differentiate life-threatening from benign causes, and in determining its etiology. Asthma is the most likely diagnosis in a child or nonsmoking adult who experiences chronic symptoms of shortness of breath which wax and wane, especially if wheezing is present. A patient with "chronic" shortness of breath (for months or years) may present with an acute exacerbation of dyspnea. Orthopnea is dyspnea that is worse with lying down and better with sitting or standing. Orthopnea is also one of the earliest findings in patients with diaphragmatic weakness from neuromuscular disorders. Palpitations or an irregular heartbeat felt by the patient generally signifies a cardiac etiology for the dyspnea, particularly if new. A dyspneic patient who complains that "my heart was beating fast," "slow," "skipped a beat," or "beating funny" suggests a dysrhythmia. Dyspnea with symptoms such as drooling, hoarseness, aphonia, and "muffled voice" suggest upper airway problems, specifically airway obstruction, such as epiglottitis or foreign body. Hemoptysis may occur with pulmonary or upper airway tumors/malignancies, pulmonary infections, tuberculosis, and vasculitis. Vomiting can lead to electrolyte abnormalities, which may result in dyspnea, or can be due to diabetic ketoacidosis, with dyspnea secondary to a compensatory respiratory alkalosis from metabolic abnormalities. Injury or illness to either phrenic nerve can cause paralysis of the diaphragmatic muscles. Oncology patients, patients on immunosuppressive agents, or patients with autoimmune disorders are especially prone to dyspnea. This may be due to infection or severe anemia secondary to bone marrow suppression. Medicines can have dangerous side effects and can be a clue to any underlying diseases. Allergies should be noted in case patients need therapy for their dyspnea, or if a particular medication is causing the dyspnea. An intoxicated patient with shortness of breath, cough, and fever may have aspiration pneumonia. Patients inhaling illegal drugs may get a pneumonitis from the adulterants used to "cut" the drugs. A dyspneic patient exposed to a fire may have smoke inhalation or a hypersensitivity reaction from burning chemicals or toxins. Recent surgery (especially abdominal or pelvic surgery), atrial fibrillation, pregnancy, malignancy, and prolonged immobility are predisposing factors (Table 33. A previous history of any neurologic or muscular disorders may provide a clue to the etiology of dyspnea, as patients with such conditions may experience respiratory muscle weakness and develop respiratory failure. Physical examination Physical examination may be instrumental in diagnosing the etiology of dyspnea, as well as in determining which patients are critically ill and need immediate therapy (even resuscitation). A patient who is sitting upright and leaning forward on the hands (the "tripod" position) is urgently attempting to maintain an open airway and improve ventilation. Pursing of the lips, intercostal retractions, or the use of accessory muscles are other methods to facilitate air entry into the lungs. A patient who can speak in full sentences does not have significant respiratory distress; a patient who can speak only a few words has moderate respiratory distress. A patient who is too short of breath to even answer with a few words is experiencing severe respiratory distress. For example, an asthmatic in respiratory distress will initially increase their respiratory rate in order to improve their oxygenation and ventilation. When they begin to tire from the additional work of breathing, their respiratory rate starts to drop. They may fall into the normal range of respiratory rates during this period of decompensation before they become bradypneic and have a respiratory arrest. All patients complaining of shortness of breath should have pulse oximetry measured. Although pulse oximetry has a few technical limitations, a pulse oximetry 90% indicates hypoxia and requires immediate evaluation (Table 33. Although a fever is typically found in patients with respiratory infections, they may have a normal temperature or hypothermia. Increased respiratory effort and rate, especially if prolonged, may contribute to dehydration due to increased insensible losses from the airway and lungs. Tachycardia usually accompanies respiratory distress, although exceptions may occur in patients taking beta- or calcium channel blockers.
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Females who inherit the defective gene generally do not manifest symptoms-they become carriers of the defective genes blood cholesterol level definition 2mg prazosin with mastercard, and their children have a 50% chance of inheriting the disease cholesterol of 260 prazosin 2 mg mastercard. In 1992 scientists discovered the defect in the gene that causes myotonic dystrophy cholesterol webmd 1mg prazosin with mastercard. National Library of Medicine, National Center for Biotechnology Information, 2004 HbS is responsible for the premature destruction of red blood cells, or hemolysis. In addition, it causes the red cells to become deformed, actually taking on a sickle shape, particularly in parts of the body where the amount of oxygen is relatively low. These abnormally shaped cells cannot travel smoothly through the smaller blood vessels and capillaries. This blockage produces anoxia (lack of oxygen), which in turn causes more sickling and more damage. Genetic research offers hope of finding effective treatments, and even cures, for these diseases. Research teams have identified the crucial proteins produced by these genes, such as dystrophin, beta sarcoglycan, gamma sarcoglycan, and adhalin. One experimental treatment approach involves substituting a protein of comparable size, such as utrophin for dystrophin, to compensate for the loss of dystrophin. Muscle cells, unlike other cells in the body, fuse together to become giant cells. New delivery methods called vectors are also being tested, such as implanting a healthy gene into a virus that has been stripped of all of its harmful properties and then injecting the modified virus into a patient. As a result of the defect, the affected individual is unable to convert phenylalanine into tyrosine. When it occurs during pregnancy, it may jeopardize the health and viability of the unborn child. It also shows how when red blood cells with HbS are oxygen-deprived they become sickle shaped and may cause blockages that result in tissue death. In sickle-cell anemia, a point mutation causes the amino acid glutamine (Glu) to be replaced by valine (Val) in the chains of HbA, resulting in the abnormal HbS. B Under certain conditions, such as low oxygen levels, red blood cells with HbS distort into sickled shapes. C these sickled cells can block small blood vessels producing microvascular occlusions which may cause necrosis (death) of the tissue. National Library of Medicine, National Center for Biotechnology Information. A severe crisis or several acute crises can permanently damage various organs of the body. A sickle-cell crisis, however, occurs more often during infections and after an accident or an injury. In addition, patients experience occasional sickle-cell crises-attacks of pain in the bones and abdomen. Blood 68 Genetic Disorders Both the sickle-cell trait and the disease exist almost exclusively in people of African, Native American, and Hispanic descent and in those from parts of Italy, Greece, Middle Eastern countries, and India. People of African descent are advised to seek genetic counseling and testing for the trait before starting a family. Crises accompanied by extreme pain are the most common problems and can usually be treated with painkillers. Maintaining healthy eating and behavior and prompt treatment for any type of infection or injury is important. Special precautions are often necessary before any type of surgery, and for major surgery some patients receive transfusions to boost their levels of hemoglobin (the oxygen-bearing, iron-containing protein in red blood cells). In early 1995 a medication that prevented the cells from clogging vessels and cutting off oxygen was approved by the Food and Drug Administration. In 1995 a multicenter study showed that among adults with three or more painful crises per year, hydroxyurea lowered the median number of crises requiring hospitalization by 58%. It is caused by the absence of an important enzyme called hexosaminidase A (hex-A). According to the National Tay-Sachs and Allied Diseases Association (2007. Genetic testing has enabled researchers and clinicians to detect inherited traits, diagnose heritable conditions, determine and quantify the likelihood that a heritable disease will develop, and identify genetic susceptibility to familial disorders. Many of the strides made in genetic diagnostics are direct results of the Human Genome Project, an international thirteen-year effort begun in 1990 by the U. Department of Energy and the National Institutes of Health, which mapped and sequenced the human genome in its entirety. The increasing availability of genetic testing has been one of the most immediate applications of this groundbreaking research. Genetic tests have diverse purposes, including screening for and diagnosis of genetic disease in newborns, children, and adults; the identification of future health risks; the prediction of drug responses; and the assessment of risks to future children. There is a difference between genetic tests performed to screen for disease and testing conducted to establish a Genetics and Genetic Engineering diagnosis. Diagnostic tests are intended to definitively determine whether a patient has a particular problem. They are generally complex tests and commonly require sophisticated analysis and interpretation. They may be expensive and are generally performed only on people believed to be at risk, such as patients who already have symptoms of a specific disease. In contrast, screening is performed on healthy, asymptomatic (showing no symptoms of disease) people and often to the entire relevant population. A good screening test is relatively inexpensive, easy to use and interpret, and helps identify which individuals in the population are at higher risk of developing a specific disease. By definition, screening tests identify people who need further testing or those who should take special preventive measures or precautions. For example, people who are found to be especially susceptible to genetic conditions with specific environmental triggers are advised to avoid the environmental factors linked to developing the disease. Examples of genetic tests used to screen relevant populations include those that screen people of Ashkenazi Jewish heritage (the East European Jewish population primarily from Germany, Poland, and Russia, as opposed to the Sephardic Jewish population primarily from Spain, parts of France, Italy, and North Africa) for Tay-Sachs disease, African-Americans for sickle-cell disease, and the fetuses of expectant mothers over age thirty-five for Down syndrome. A reliable test is consistent and measures the same way each time it is 71 used with the same patients in the same circumstances. For example, a well-calibrated balance scale is a reliable instrument for measuring body weight. It is the degree to which the test correctly identifies the presence of disease, blood level, or other quality or characteristic it is intended to detect. Mathematically speaking, it is the percentage of people with the disease who test positive for the disease. Ideally, diagnostic and screening tests should be highly sensitive and highly specific, thereby accurately classifying all people tested as either positive or negative. In practice, however, sensitivity and specificity are frequently inversely related-most tests with high levels of sensitivity have low specificity, and the reverse is also true.