Indinavir
Gregory S. Vander Wal, MA
- Doctoral Student, Department of Psychology,
- University of Alabama, Tuscaloosa, AL, USA
For example symptoms you need a root canal indinavir 400mg low cost, a patient may proj ect a parent-like quality onto the doctor and expect that the doctor will provide solutions for all of his problems symptoms jaw cancer indinavir 400 mg fast delivery. Countertransference: A physician unconsciously projects feelings or atti tudes onto the patient medicine 877 discount 400 mg indinavir mastercard. For example medicine school purchase indinavir 400mg without a prescription, a patient who is unable to deal with an internal psychological conflict may unconsciously convert the conflict to somatic symptoms (conversion disorder) medicine 75 yellow 400 mg indinavir sale. They function by keeping conflicts out of the conscious mind medicine 1700s buy indinavir visa, thereby helping to alleviate potential anxiety caused by these conflicts. Immature defense mechanisms are developmentally primitive (seen first dur ing early stages of development) and are characterized by the patient reverting back to childlike behavior in response to psychological stress. Although also unconscious reactions, mature defense mechanisms reflect a more developed understanding of the conflict. A man who has negative feelings about being abandoned by his parents as a child works at an orphanage. Replacing a socially unacceptable desire with an action that is similar, but is socially acceptable. Sublimation A man who has violent thoughts decides to pursue a career as a butcher. A student consciously chooses not to think about upcoming exams until a few days prior to the exams. Suppression Immature Defense Mechanisms Acting out Unacceptable thoughts or feelings are expressed through attention-seeking actions. Transferring an undesirable or unacceptable idea or feeling for one person onto another person. Giving logical reasons for a negative situation in an attempt to convince oneself that the situation is a reasonable one; superficial insight. A woman who has desires to cheat on her husband is convinced that her husband is cheating on her. A man who did not get the job that he wanted told his friends that it was a good thing because it would have been a very stressful position. A woman who unconsciously resents her marriage constantly showers her husband with affection and gifts. A woman has a phobia of spiders but cannot remember the first time she was afraid of them. A patient believes that his primary care physician is a terrible person while his therapist is the most wonderful person in the world. Important examples of specific treatments within these three categories are summarized here and will be mentioned in subsequent sections during the discussion of specific psychiatric disorders. Psychosocial Psychosocial treatments include certain forms of psychotherapy, counsel ing, as well as social and vocational training. Two important psychosocial treatment approaches are psychodynamic therapy and cognitive behavioral therapy. In contrast to psychodynamic therapy, this form of therapy can be shorter in duration and is less centered on the therapeutic relationship between physician and patient. Psychodynamic therapy: A form of psychotherapy that evolved from psy Pharmacologic Psychopharmacotherapy involves the use of psychoactive medications in the treatment of psychiatric disorders. Important categories of psychiatric drugs include anxiolytics, antipsychotics, antidepressants, and mood stabilizers (Table 7-6). Antipsychotics Typical anti psychotics (chlorpromazine, haloperidol) Antagonize dopamine D2 receptors. Parkinsonian symptoms, neuroleptic malignant syndrome, tardive dyskinesia, anticholinergic symptoms. Hypertension, sweating, weight loss, gastrointestinal distress, blurred vision, sexual dysfunction, neuroleptic malignant syndrome. Heart block, bloating, constipation, xerostomia, dizziness, somnolence, urinary retention. Atypical antidepressants (bupropion) Weakly inhibit uptake of serotonin, norepinephrine, and dopamine. Hypertension, tachyarrhythmia, restlessness, loss of appetite, addiction potential. The Mini-Mental State Examination is used to determine the severity of the disor der. Patients are easily distracted, disoriented with respect to time and place, have language disturbances, and can experience illusions and hallucinations. Elderly patients often experience symptoms when "sundowning" (delirium worsening at night). Delirium can be caused by a variety of medical disorders, including infection, trauma, hypoxia, substance withdrawal (eg, alcohol), medications, and toxins (eg, heavy metals). Symptoms of delirium can last for days or weeks, and if left uncorrected, the condition is associated with a high-mortality rate. I vidence that the change in consciousness is secondary to an underlying medical disorder. Pharmacologic therapy: Antipsychotics, benzodiazepines (can also cause delirium; be cautious with their use because they can cause respiratory depression and an increased risk of falls). Limit the amount of sedation given to the patient (to minimize the amount of napping). Dementia Characterized by progressive and usually irreversible impairment of cogni tive function and memory. Unlike delirium, the level of consciousness does not vary throughout the day, and the signs and symptoms of dementia generally appear progres sively. The incidence increases with age, and 20% of people older than age 80 years suffer from severe dementia. Depression is relatively common in elderly patients and should be ruled out in patients with so-called quiet dementia. Causes of dementia include increasing age, Alzheimer disease (5 0-60%), and vascular dementia (1 0-20%). Such causes include hypoxia, hypothyroidism, lead toxicity, Lyme disease, meningitis, neurosyphilis, and medications. Malnutrition can cause vitamin B 1 z or thiamine deficiencies, which can manifest with dementia-like symptoms. J:<olate deficiency is not a malnutrition-related cause of dementia, although emerging evidence suggests that it may be associated with the devel opment of dementia in the elderly. In patients with behavioral or emotional symptoms, low-dose antidepressants or neuroleptics can be used. Antipsychotics can be used for paranoia or hallucinations, and benzodiazepines can be used to treat anxiety and agitation. Amnestic Disorders these disorders lead to memory impairment without impaired conscious ness or other cognitive functions. Like delirium, amnestic disorders are often caused by an underlying medical disorder, including cerebrovascular acci dent, brain trauma or tumor, hypoxia, hypoglycemia, systemic illnesses, sei zures, multiple sclerosis, herpes simplex encephalitis, and substance use (eg, alcohol, medications). Amnestic disorders can be temporary or permanent depending on the underlying cause. It is important to note that patients with psychotic symptoms can have intact reality testing despite ongoing hallucinations. For example, a patient might complain of hearing voices but know that it is his psychotic disorder. It can be caused by psy A chronic psychiatric disorder characterized by episodes of psychosis and abnormal behavior lasting > 6 months. There are several subtypes of schizo phrenia and they are defined by particular associated features (Table 7-8). This psychiatric disorder affects about l% of the population across all ethnic groups and countries studied. Most often, schizophrenia begins to appear in young adult patients; the age of onset generally ranges from 1 5 to 2 5 years in males and 2 5 to 3 5 years in females, with a slight increase in diagnoses for women during the perimenopausal period. Men with schizophrenia are often less responsive to antipsychotic medications than women and show more social and cognitive deficits. Genetic factors likely contribute to the development of schizophrenia, as there is an increased rate of diagnosis seen in monozygotic twins relative to dizygotic twins. Delusions (eg, persecutory), but with better social functioning than other types and best prognosis. Inappropriate emotional responses (eg, emotional blunting), disheveled appearance. One or more psychotic episodes in the past, residual flat affect, withdrawal, odd behavior or thinking, but no severe psychotic symptoms. These patients generally have normal memory and are oriented to person, place, and time. The differences between schizophrenia and type A personality disorders can be subtle and a source of confusion (see Table 7- 1 7). Schizotypal personal ity disorder is considered part of the spectrum of schizophrenic disorders, whereas there is little association between schizophrenia and schizoid per sonality disorder. Also, schizophrenia should not be confused with dissociative identity disorder (multiple personality disorder), which is categorized as a dissociative disorder. Loose associations: Patient repeatedly talks about topics completely unrelated to what she was talking about before. Thought blocking: Patient starts talking about a topic but stops in mid sentence and is unable to continue with what he was saying. Haloperidol decano ate is an example of a long-acting injectable medication that can be useful for noncompliant or poorly compliant psychotic patients. Atypical antipsychotics, such as risperidone and clozapine, are combined dopamine and serotonin receptor antagonists. A continued downward spiral can occur over several years that is associated with frequent treatment noncompliance and recurrent psychotic episodes. Earlier onset of schizophrenia may impair normal brain development and lead to a poorer prognosis. Better prognosis is highly associated with com munity support, low expressed emotion in immediate family, and absence of comorbid substance abuse. Patients presenting with psychosis, delusions, or hallucinations may not meet the diagnostic criteria for schizophrenia, but may in fact be suffering from one of several other psychotic disorders, which include: brief psychotic disorder, schizophreniform disorder, schizoaffective disorder, and substance-induced psychotic disorder (Table 7-9). Normally, people have some control over their mood, but patients with mood disorders lose this control. Uncontrollable, disruptive emotional states cause significant distress as well as impairment in occupa tional and social functioning for patients with mood disorders. How ever, due to disparities in health care availability, patients in lower socioeco nomic classes often come to the attention of health care providers later and may be misdiagnosed as having schizophrenia. The most common and severe mood disorders are bipolar disorder and major depressive disorder. The life time prevalence for major depressive disorder is about two times higher in women, whereas bipolar disorder is about equal across the sexes. Similar symptoms to schizophrenia but lasts < 1 mondl and is often preceded by stressful psychosocial events or factors. Same presentation as brief psychotic disorder but psychotic and residual symptoms last 1 -6 months. Schizophrenia with mood disorder symptoms (see the rest of the section on Mood Disorders). Related to the use of stimulants, hallucinogens, or withdrawal from sedatives; usually visual or tactile hallucinations and delusions. Depression is associated with decreased levels of serotonin, norepineph rine, and possibly dopamine. Note, however, that simply increasing these neurotransmitter levels in the brain does not show therapeutic utility. Cur rent research suggests that improvements in mood associated with increas ing these neurotransmitters pharmacologically or behaviorally result from downstream effects on the cell nucleus and possibly the increased secre tion of trophic factors. Sleep disturbances (eg, hypersomnia or insomnia; early morning awakenings) Loss of Interests (ie, anhedonia) Guilt or feelings of worthlessness Loss of Energy Loss of Concentration Appetite changes/weight changes (usually decreased except in atypical depression) Psychomotor retardation or agitation (ie, abnormally slow or restless) Suicidal ideation the major mood disorders are divided into two broad syndromes: bipolar dis order, which is characterized by the presence of at least one manic or hypo manic episode, and major depressive disorder (Table 7- 1 0). Major depressive disorder is characterized by the occurrence of one or more major depressive episodes. Psychother apy (eg, cognitive behavioral therapy) has also been shown to be effective in some patients. Other associated features may include worse mood in the morning, early morning waking, psychomotor abnormality (agitation or retardation), weight loss or decreased appetite, or excessive or inappropriate guilt. Depressive, manic, or mixed episode occurring within the first 4 weeks after delivery. Not synonymous with subclinical postpartum "blues," which occurs commonly after delivery. Patient displays catatonic features similar to those observed in schizophrenia, including posturing, waxy flexibility, catalepsy, negativism, and mutism. Generally observed in patients at the severe and psychotic end of the spectrum of mood disorders. Depression for at least 2 consecutive years during the same season and periods of depression are followed by nondepressed seasons. Dysthymic disorder: the most effective treatment is insight-oriented psy chotherapy; however, antidepressants can also be used. Seasonal affective disorder: Broad-spectrum light therapy, antidepressants, or psychotherapy. Bipolar Disorder Distractibility Insomnia (decreased need for sleep) Grandiosity Flight of ideas Increased Activity/psychomotor agitation Pressured Speech (nonstop flow of speech) Thoughtlessness/pleasure seeking/ decreased judgment the second major syndrome of disordered mood is bipolar disorder, which is characterized by the occurrence of at least one manic or hypomanic episode.
The spread to the epidural space may be direct through adjacent bone or via transdural veins-the latter occurring in this patient treatment questionnaire buy 400 mg indinavir with visa. Other complications that can be seen with acute sinusitis are pre- and postseptal orbital cellulitis symptoms job disease skin infections generic 400 mg indinavir with mastercard, subperiosteal and orbital abscess formation medicine evolution purchase generic indinavir, cavernous and other dural venous sinus thrombosis medications 4 times a day order indinavir 400mg free shipping, subdural empyema treatment vs cure purchase indinavir uk, meningitis symptoms quit smoking cheap 400mg indinavir visa, and brain abscesses. Reporting Responsibilities Direct communication is strongly recommended for all cases where imaging is done for the suspicion of complications of an acute sinusitis. The impor tance of imaging is to e valuate the e xtent of disease, detect clinically unsuspected complications, and identify possible structural etiology that may have predisposed the patient for such an episode. The coordinated action of the cilia of the columnar epi thelial cell mo ve the sinus contents to ward the natural sinus ostia. Disruption of the ciliary function results in accumulation of sinus secretions and potentially infec tious agents within the sinus. This includes high airf ow and cold air, toxins produced by microorganisms, environmental mediators of the inf ammatory response, mechanical f actors that impede transport of the mucosal blanl<et, primary ciliary dyskine sia and secondary ciliary dysfunction from chronic infec tions, and secondhand smoke exposure. When the natural sinus ostia become obstructed, nor mal mucus drainage is impeded. The obstructed sinus environment becomes hypoxic and causes ciliary dys function and changes in mucus production, all of this fin. Uncomplicated acute bacterial sinusitis should be considered akin to an abscess or empyema since it is essentially a collection of pus under pressure. It is this fundamental situation that creates a potential for the orbital and intracranial compli cations. It lik ely contrib utes to the pathophysiology of bone erosion and direct spread of disease beyond the bony sinus limits as well. Relieving this pressure by draining the causati ve sinus is a strategy aimed at the prevention and treatment for such compli cations. Such drainage also promotes the restoration of normal sinonasal mucociliary drainage by reversing some of the elements causing that dysfunction. She has history of seasonal allergies and was used to recurrent and chronic episodes of sinusitis, but this headache has been bothering her more. The sinus contents b ulge through the sinus ostium, and there is regressive remodeling of the sinus walls (arro wheads). The contents appear dense and likely desiccated with a central area ofhigher density (arr ow). The sinus contents appear of some what greater signal intensity than f uid (white arrow). The edematous mucosa within the sinus again remains relatively thin (arrows) with the polypoid mucosal thick ening in the sphenoeth moidal recess and around the sphenoid ostium causing the primary obstruction somewhat thicker (black arrow). These conditions are most typically encountered in patients with chronic rhinosinusitis and especially those with nasal polyposis. A prior history of either trauma or previous sinus or f acial surgery may also be encoun ti. There should also be confrimatory endoscopic infammation and evidence of rhinosinusitis on imaging. P atients with a history of allergy, occupational or v asomotor rhinitis, nasal polyps, or anatomic obstruction such as septal de viation and concha b ullosa will be predisposed to chronic infec tions. Rhinosinusitis is more common in immunodef cient patients, those with ciliary motility problems such as Karta gener syndrome, and those with mucous blank et problems such as patients with cystic f brosis. Most chronic sinusitis is now thought to be noninfectious in etiology, although infec tion may have incited the process. Common complications of chronic sinusitis are superimposed acute sinusitis and, in children, adenoiditis with secondary serous or purulent oti this media. Dacryoc ystitis and laryngitis may also occur as complications of chronic sinusitis in children. Orbital complications include pre- and postseptal celluli tis, subperiosteal abscess, orbital cellulitis, orbital abscess, and cavernous sinus thrombosis. Intracranial complications include meningitis, epidural abscess, subdural abscess, and brain abscess. Other f actors that decrease the mucociliary clearance, 1ik e additional polyps and anatomic v ariations, can also be addressed in the same setting. Postoperatively, the patient needs to be bet ter managed medically with goals to impr01e mucociliary function and control of infection. This could be achieved by various treatment regimens that include the use of ade quate antibiotic trial, intranasal corticosteroids, and saline irrigations. Sometimes, short courses of oral steroids, decongestants, topical v asoconstrictors, and mucoly tics could be added. In this patient, identifying and treating the nasal aller gy, if a voidance is not possible, is the k ey to achieving long-lasting relief. Also, she will need short-term surv eillance to ensure that the surgical drainage has been successful and that there is no recurrence of the mucocele. In f act, patients with chronic rhinosinusitis and nasal polyposis may ha ve extensive mucoceles involving one or more sinus on either or both sides. The mucoceles can be sources of signif cant consequences, including ocular motility disturbances, proptosis, hypertelorism, compressi ve optic neuropathy, and f acial deformity, depending on the sinus involved. They may also become acutely infected, forming a mucop yocele that can lead to acute orbital and intracranial complications. Reporting Responsibilities Direct communication is recommended for all cases where imaging is done for the suspicion of complications of a chronic rhinosinusitis. They usually have associated nasal inf am mation, and chronic rhinosinusitis is the preferred termi nology. Chronic rhinosinusitis requires tw o or more of the following symptoms: mucopurulent drainage, nasal obstruc- 2. There is continued spread of disease along the posterior superior alveolar branches of the distal maxillary artery and the maxillary artery (arrows) on the affected side compared to the normal structures on the left (white arrow heads). Bone on the right side appears only minimally irre gular (arr o ws) compared to the bone on the unaffected side. This patient also had subtle asymmetry of the nasopharyngeal soft tissues conf rmed to be an e xpression of infltrating fungal disease in the nasopharynx spreading to the parapharyngeal space (arm. Ketoacidosis predisposes to mucormycosis because the acidic, glucose-rich environment favors fungal growth. This aggressive or fulminate fungal disease tends to be angioin may be accompanied by soft tissue and bone necrosis. These vascular pathways allow disease to be on both sides of adjacent bone, sometimes without frankly destro ying bone. The disease can then be recognized by pemscular infltration of the fat bordering these bon y channels as the v essels pass through surrounding fat pads en route to or from their respec tive foramina and canals. The disease may also begin in the lacrimal sac and the nasopharynx and initially be limited to those areas. One of the hallmarks of such in vasive fungal rhinosinusitis is also frank bone erosion, b ut the invasive soft tissue patterns without obvious bone invasion must be kept in mind, as early as possible, when trying to diagnose invasive fungal disease. Complications include e xtension and in volvement of the eye and orbit, cavernous sinus thrombosis, secondary extra axial abscess, meningitis, and brain abscess. Based on the imaging fndings, the risk of invasive fungal disease can be stratif ed for early diagnosis and triage. Moderate- and high-risk patients recei ve nasal endoscopy by the otolaryngology service. Tissue sam pling is obtained, if appropriate, in moderate-risk, and def nitely high-risk, cases. Pyogenic and/or fungal anterior nasal septal abscess may sidered in the search pattern of immunocompromised patients sent for sinonasal evaluation Reporting Responsibilities All cases of moderate or high risk where imaging is done for the suspicion of fungal sinusitis really call for direct, v erbal communication with the treatment team if the study is posi tive or suspicious for an aggressi ve process. This becomes mandatory if there is clear evidence of an orbital or intracra nial complication and ne wly discovered bone erosion since that can be a sign of an aggressive infection or other aggres sive disease process such as cancer. Nasal endoscopy revealed septa/ perforation, signifcant nasal crusting, and few areas of necrosis. Langerhans histiocytosis is typically not a disease ofthe sinuses and nasal ca vity. Spread to those re gions is usually from a contiguous site or a strate gically placed bone lesion. The maxillary sinus is completely opacif ed due to the adhesive changes around its ostium (not shewn). The images suggested chronic cocaine ab use, and this w as e ventually proven to be true. A history ofcocaine use is ob viously helpful b ut often not forthcoming until the pattern and e xtent ofdisease is frmly established. Correlation with history, chest f ndings, and laboratory e vidence ofele vated angio tensin-converting enzyme le vels help to conf rm the diag nosis. The cocaine abuse risk should be reported v erbally for ob vious reasons ofrisk to the patient and others. Reac tive bone changes may become quite prominent in the absence ofactive disease. The nasal bones at their junctions with the frontal bones are driven posteriorly (arr ows) with multiple fragments displaced into the expected position of the fron tal recess (arrowheads). Coronal section shows the fracture fragments driven cephalad as well as posteriorly (arro wheads), resulting in pneumocephalus; the intracranial air conf rms dural tears. While the more superior aspect of this fracture is severely comminuted, the intercanthal region has been left relatively intact (arrows). The medial orbital w alls are spread laterally (white arrowheads), a ref ection of the widening of the intercan- thal distance. There is disruption of the nasal and frontal bones with minimal, if any, comminution. The more simple fractures, if displaced, will typically sho w the nasal bones and frontal process of the maxilla to be tele scoped posteriorly beneath the frontal bone. Comminuted fragments may spread medially into the nasal cavity, superi orly to the anterior cranial fossa, and laterally into the orbit. Shearing of the traversing anterior and posterior ethmoid arteries may cause an orbital hematoma or impress:ire epistaxis. The optic canal is ty pically not directly in volved by hon y injury, b ut edema within the optic canal or free bone fragments may disrupt optic nerve perfusion. Are there associated complications itvolving the eye, optic nerve/sheath complex, or foreign bodies Reporting Responsibilities Evidence of tension orbit, optic nerv e injury, and foreign body or other coincidental fndings like acute epidural hema toma w ould require ur gent v erbal communication directly with the health care provider. In general, the report routinely should catalogue all details suspensory ligaments. Telecanthus requires four fracture sites, including the medial orbital w junction, and the lateral nasal bone. Frontal recess obstruction secondary to trauma could lead of the injury while anticipating possible complications. This would include bony injury; the basic pattern or category of the fracture pattern; and description of indi vidual fractures with respect to their complec. With regard to the orbital injury, the report should con tain details of the e xtent of orbital soft tissue herniation into adjacent sinonasal structures, the presence and location of intraorbital hematomas, and the status of the orbital ap111: with respect to both bone and soft tissue structures. Other compli cations such as entrapment of e xtraocular muscles, injury to nasolacrimal duct, neuro vascular bundles, or medial canthal ligament disruption should be look ed for and reported. The medial w all of the ethmoid complex is much thicker than usual (arrow head), as is the bone of the anteroethmoidal septum region (arrow). The papillary and "fronding" nature of the mass and its e xtension to the ethmoid roof are noted again (white arro ws). Axial T2W images clearly show the frondlike nature of this papillary tumor (arrow) and clearly iden tify the interfuce between the tumor and obstructive sinus contents (arrowhead). The papillary mass flls the nasal cavity and extends into the nasopharynx (arro ws). It does not appear to in vade the nasopharyngeal wall but clearly apposes that mucosa (white arrowheads). T2W image for comparison with other axial images shows the frondlike nature of the tumor (arro w heads) and a possible more solid attachment of the tumor along the lateral nasal ca vity wall (black arro w). The interface with the nasopharyngeal wall is sharp (white arrowheads) and does not suggest invasion. The b ulg ing margin of the obstructed maxillary sinus contents forms an interface with the lateral aspect of the tumor (black arrowheads). The neoplas ment of the disease txtent and all information that is relwant to treatment planning. The attachment to the lateral nasal w all may be discrete com pared to the bulk of the tumor. Spread to the orbit and anterior skull base is unusual lut does occw: Bone erosion is common but may appear more as remodeling, sclerosis, and dehiscence than aggressive erosion. The excision is best approached as an en bloc procedure with a mar entirely benign.
True shunt can be differentiated from V/Q mismatch by giving the hypoxemic patient 1 00% 0 2 treatment 5cm ovarian cyst cheapest indinavir. This increases Pao 2 in the case of V/Q mismatch but not in the case of a shunt medications in carry on luggage indinavir 400 mg cheap, since in the latter treatment hpv buy generic indinavir line, the blood never communicates with the alveolar gas medications at 8 weeks pregnant purchase 400mg indinavir with amex, regardless of its composi tion medicine zebra generic indinavir 400 mg visa. A patient with no shunt should achieve a Pao 2 of at least 400 torr on 1 00% oxygen medicine 75 order indinavir 400 mg with mastercard. Well-perfused areas may be underventilated, whereas underperfused areas may be overventilated. When a large amount of venti lation is "wasted" on underperfused sections of lung, the effect is similar to increasing the dead space: less air is available to exchange gases with the blood, and C0 2 levels in the blood increase. The response of the body to hypercapnia is often to increase alveolar venti lation by hyperventilating and blowing off more C0 2. Thus, C0 2 retention may not occur even if the preceding criteria are met as long as the body is able to compensate. The dorsal respiratory group receives sensory input from peripheral chemoreceptors and lung mech anoreceptors via the vagus and glossopharyngeal nerves. Output travels via the phrenic nerve (C 3-C 5) and the intercostal nerves (T l-T l l) to the diaphragm and the external intercostal muscles, respectively. Ventral respiratory group: Responsible for forced expiration; not active during ordinary passive expiration. Peripheral chemoreceptors in the carotid and aortic bodies: Increased Paco 2 or decreased pH or Pao 2 stimulate these chemoreceptors to increase respiratory rate. In the Hering-Breuer inflation reflex, excessive stretch ing of the lungs during a large inspiratory effort leads to inhibition of the dorsal respiratory group and the apneustic center to promote expiration. The deflation reflex acts during expiration to activate the inspiratory con trol areas. Irritant receptors (nociceptors): Located between airway epithelial cells and stimulated by noxious substances. Juxtacapillary (J) receptors: Located close to the capillaries in the alveolar walls. Joint and muscle receptors: these are activated by limb movement and help to stimulate breathing early in exercise. There are five major categories of lung diseases: obstructive, restrictive, vas cular, malignant, and infectious. Although the range of diseases affecting the lungs is large and perhaps daunting at first, the pathophysiologic processes underlying these diseases can be understood by considering the unique posi tion the respiratory system occupies within the body. In contrast to most organ systems, the respiratory system is constantly chal lenged with foreign matter. The respiratory system is particularly sus ceptible to inflammation and infiltration because of the delicacy of the gas exchange membrane. At the same time, the lungs are the only organs aside from the heart that must bear responsibility for the entire cardiac output. This puts them at risk for vas cular disease as well as hematogenous spread of malignancy. Unfortunately, despite the diverse pathogeneses of respiratory illness, many of the classic symptoms of respiratory disease are particularly nonspecific: short ness of breath, chest pain, cough. Treatment can then be chosen based on the conclusions of this comprehensive problem-solving process. This section defines common physical exam findings as a glossary for subse quent sections on respiratory disease, but discussion of physical exam tech niques is beyond the scope of this text. Simply listening to the lungs of many healthy people is the best way to appreciate the broad range of normal breath sounds. Adventitious breath sounds indicate pathology: Coarse breath sounds (ie, a potpourri of sounds of different fre quencies and intensities) are nonspecific but can indicate lower respiratory tract infections such as bronchiolitis and pneumonia. Care should be taken to distinguish coarse sounds originating in the lung versus transmitted upper airway noise that can be heard over the trachea and mouth. Fine crackles resemble static, a burning fireplace, or Rice Krispies in a bowl of milk and may reflect the opening of collapsed alveoli in atelectasis. Coarse crackles resemble the sound produced by exhaling slowly underwa ter and are associated with airway opening and fluid in the lungs. Diversity of pitch broadly cor relates with the number of airways obstructed (think of the airways as a chorus of elementary school recorders or slide-whistles). Rhonchi are low-pitched, monophonic sounds indicative of air way secretions and obstruction. They resemble the slurping sound produced when one sucks in air through a straw at the bottom of a drink. Stridor is a high-pitched sound heard over the trachea, reflecting tracheal or laryngeal obstruction. Egophony is an auditory phenomenon in which a patient asked to say "E" is heard through the stethoscope to be saying "A. Increased tactile fremitus is felt as a rumbling vibration and is associated with lung consoli dation (eg, pneumonia). Airflow obstruction can originate at any point in the respiratory tree, from the bronchioles to the mainstem bronchi. Emphysema Destruction of alveolar walls leads to loss of elastic recoil within the lung and dilation of the terminal air spaces. The lung compliance curve shifts up and to the left in emphysema and down and to the right in restrictive lung disease. The prolonged expiratory phase seen in emphysema lengthens the overall duration of a single respiratory cycle. Because patients need to ventilate at a high enough rate to remain oxygenated despite the prolonged respiratory cycle, they often begin inhaling their next breath before all of the air from the previous breath is expired. Over the course of several breaths, they breathe at higher and higher volumes (dynamic hyperinflation). Although ventilation and perfusion are both decreased, they are often well matched (alveoli and pulmonary capillaries are destroyed equally), so V/Q mismatch is not severe. Patients require a high minute ventilation to main tain normal levels of Po 2 and Pco 2, so they "puff," working hard to get air in. Although this is the classic presentation, many patients do not fit this description. Leaning forward on extended arms ("tripoding"), using accessory mus cles of respiration. Signs of hyperinflation: Resonance to percussion lower in the back than expected; diminished breath sounds bilaterally. In classic emphy sema (smoking related), paucity of vascular markings (arterial deficiency) in the upper lobes with or without bullae. Arterial blood gas testing: Pao 2 normal or slightly decreased; Paco 2 vari able but is often chronically increased in severe emphysema. During acute exacerbation, Pao 2 may drop and Paco 2 may rise, with a corresponding drop in pH. The pattern of involvement is more irregular and is often localized to the upper parts of the lungs. Lung volume reduction surgery has been found to benefit a small subset of emphysema patients but may not be appropriate for the majority of them. Chronic Bronchitis Defined clinically as a productive cough occurring for at least 3 months per year over at least 2 consecutive years. The increased mucus production and airway wall thickness decreases the cross-sectional area of the lumen, increasing resistance and inhibiting air flow. The obstruction to airflow in chronic bronchitis is in the terminal bronchi oles, which is proximal to the obstruction in emphysema. They are also fre quently obese and can have peripheral edema due to right ventricular fail ure ("bloater"). Chest film: May show increased airway markings (appearing as a "dirty lung"), and there may be evidence of pulmonary hypertension and cor pulmonale. Bicarbonate is elevated by the kidneys in an attempt to compensate for the decreased pH. The Reid index, which is the ratio of bronchial mucous gland depth to the total thickness of the bron chial wall, is abnormally high in chronic bronchitis. Chest physiother apy (percussion, coughing, and postural changes) can loosen and clear airway secretions, and pulmonary rehabilitation is helpful. Supplemen Increased risk of developing pulmonary hypertension secondary to hypox emia and pulmonary vasoconstriction. May evolve to cor pulmonale (right ventricular dilation acutely and right ventricular hypertrophy chronically). Asthma Reversible obstructive disease characterized by hyperreactive and hyper responsive airways that lead to exuberant bronchoconstriction on minimal irri tation. Prevalence is approximately 9% in the United States, although there is variation between races and sexes. Extrinsic and intrinsic subtypes exist, although patients frequently have a combination of both. Common allergens include animal dander (especially cats), pollen, mold, and dust mites. In both types of asthma, airway inflammation leads to bronchial hyper responsiveness. Implicated in this inflammation are eosinophils, lymphocytes, histamine, leukotrienes, and IgE (see Table 1 0- 1 0 for specific mediators). As a result of airway smooth muscle contraction, mucosal edema, and secre tions within the lumen, the airway narrows, thereby increasing resistance and reducing airflow, especially during expiration. Leukotrienes play a role in airway inflammation and are potent bronchoconstrictors. Acute exacerbation manifests with wheezing, dyspnea, tachypnea, coughing, and chest tightness or chest pain. Compared with a person with normal airways, an asthmatic experiences bronchoconstriction at a lower dose of the drug (hyperreactive), along with increased severity of bronchoconstriction (hyperresponsive). Patients with asthma can often monitor their own respiratory status with portable peak flow meters. Arterial blood gas testing: During an attack, Pao 2 is often reduced due to hypoxemia resulting from V/Q mismatch. Paco 2 levels that normalize or b ecome elevated dur ing an asthma attack may indicate worsening airway obstruction or a tiring individual who can no longer maintain a high minute ventilation rate. Pathology: Edema and cellular infiltrates (eosinophils and lymphocytes) seen in the bronchial wall on bronchoscopy. Denuding of the epithelium, hypertrophy and hyperplasia of the smooth muscle layer, and enlargement of mucous glands with an increased number of goblet cells are also seen. Side effects of long-term steroid use include glaucoma, cataracts, weight gain (nuchal hump, moon-shaped facies), sore throat, seizures, mood changes (especially depression), confusion, muscle twitching, shaking, difficulty with sleep, increased osteoporosis, and bulging eyes. Intubation is a last resort because of the difficulty of managing ventilation in the set ting of severe obstruction. Side effects include coughing, tremor, arrhythmia, chest pain, head ache, and hives. Rarely used due to drug interactions and a side effect profile including cardiotoxicity and neurotoxicity. Side effects may include throat irritation, cough, dry mouth, chest tightness, and wheezing. Omalizumab: Monoclonal antibody that binds circulating IgE, reduc ing airway inflammation. A severe attack that is refractory to bronchodilators (status asthmaticus) may require assisted ventilation and can result in death. Bronchiectasis An irreversible dilation of airways caused by inflammatory destruction of air way walls, leading to colonization by bacteria and pooling of secretions. The bacteria and host may form a stable relationship that can be interrupted by Sites of action for l:l-agonists, muscarinic antagonists, theophylline, cromolyn, corticosteroids, and antileukotrienes. Bronchiectasis has multiple causes, including: Infection: May be viral, bacterial, or fungal. Examples include tuberculo sis, pertussis, and allergic bronchopulmonary aspergillosis. A defect in airway clearance of (or protection against) bacterial pathogens can also lead to bronchiectasis. An example is Kartagener syndrome, in which a genetic defect in dynein results in ciliary dysfunction and mani fests as sinusitis, bronchiectasis, and situs inversus. The lungs of these patients are often colonized with Pseudomonas aeruginosa, Staphylococcus aureus, and Haemophilus influenzae; less common organisms include Burkholderia cepacia, which almost exclusively appears in patients with cystic fibrosus. Usage is limited because of narrow therapeutic index (cardiotoxicity, neurotoxicity). Fibrotic lung parenchyma with numerous areas of pneumonia (arrows) and thick inspissated secretions in areas of bronchiectasis (arrowhead) in a pa tient with cystic fibrosis. Chest film: Often nonspecific abnormal findings, including increased markings, crowded vessels, or "ring" shadows corresponding to the dilated airways. Arterial blood gas testing: Usually normal, except in patients with very diffuse disease, who can exhibit hypoxemia and hypercapnia. Bronchopulmonary drainage with physical ther apy helps to clear secretions from the dilated airways.
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Lymphatic metastases are not common if the tumor is confined to the glans or prepuce treatment vitiligo best 400mg indinavir. The tumor disseminates through the lymphatic system and the bloodstream to distant organs in up to 10% of patients medicine 606 buy indinavir discount, most often to the lungs and medicine ads generic indinavir 400mg mastercard, less frequently medications a to z buy indinavir with paypal, to bone and other sites medications elavil side effects indinavir 400 mg without a prescription. The earliest lesion of penile carcinoma is described by patients as a nonhealing sore medications given for adhd generic indinavir 400 mg line, often with an associated foul-smelling discharge. Urinary tract symptoms, such as pain and hematuria, are signs of locally advanced disease. Infection of the tumor is usually present when the patient is examined for symptoms. Biopsy or imprint slides should be done for all patients with a penile mass or with any finding compatible with a precancerous lesion. Liver and bone scans should be obtained only if abnormalities seen on physical examination or blood studies suggest liver or bone involvement. Poor prognostic features include endophytic and high-grade lesions, invasion of the shaft, and involvement of draining lymph nodes, especially at the iliac level or higher. Prevention of penile cancer can be accomplished by routine early circumcision of male babies. Circumcision should be performed in patients with phimosis and penile discharge, inflammation, or induration. Early detection of penile cancer requires regular inspection of the prepuce and glans at physical examination and biopsy of suspected lesions. Surgery is the principal modality of therapy for penile cancer in the United States. Total penectomy is necessary for lesions that invade the body of the penis or are very large. In younger patients with tumor confined to the prepuce, circumcision may be used if close follow-up can be assured; however, the recurrence rate is high. Dissection or routine sampling of the superficial inguinal nodes for patients with low-stage (up to T2), but high-grade, lesions is recommended by some authorities; if the nodes contain tumor, a radical ilioinguinal lymphadenectomy is necessary. Premalignant lesions may respond to topical therapy with fluorouracil or to laser therapy in selected cases. Oncological safety of laparoscopic surgery for urological malignancy: experience with more than 1,000 operations. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase iii trial. Molecular targeting and pharmacogenomics in the management of advanced bladder cancer. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer. International validation of a preoperative nomogram for prostate cancer recurrence after radical prostatectomy. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. Nevoid basal cell carcinoma syndrome (Gorlin syndrome) is a dominantly inherited syndrome of multiple basal cell carcinomas that may be associated with medulloblastoma, meningioma, craniopharyngioma, and some systemic tumors (ovarian tumors, cardiac fibroma, maxillary fibrosarcoma, adrenal cortical adenoma, rhabdomyosarcoma, seminoma). Other features include jaw cysts, palmar and plantar pits, and spine and rib anomalies. The loss of a tumor-suppressor gene on chromosome 9q22 is responsible for this disorder. Neurocutaneous melanosis is a developmental rather than inherited condition of large, hairy, pigmented benign nevi of the skin associated with infiltration of the meninges by melanin-containing cells. Other associated tumors include renal carcinoma, pheochromocytoma, islet cell tumors, endolymphatic sac tumors, and benign renal, pancreatic, and epididymal cysts. Turcot syndrome is a rare autosomal dominant or recessive familial syndrome associated with colon cancer, glioblastoma, and medulloblastoma. Li-Fraumeni syndrome is a clinical syndrome of familial breast cancer, sarcomas, leukemia, and primary brain tumors that is associated with germ line p53 (chromosome 17) mutations. Clinical presentation depends on the location of the tumor and its rate of growth. In general, slow-growing tumors cause little in the way of focal deficits because the brain tissue is slowly compressed and compensatory mechanisms appear to occur. Fast-growing tumors tend to be associated with considerable surrounding cerebral edema; the edema, in addition to the tumor mass, is more likely to cause focal deficits. They are most likely to occur in younger patients with fast-growing tumors and are typically deep, dull, and not intense or throbbing. They are characteristically worse on arising in the morning and are exacerbated by straining or lifting. In 20% of patients >20 years of age, the onset of seizures is caused by a neoplasm. Simple partial seizures commonly consist of transient sensory or motor phenomena of a single limb or side. Complex partial seizures, often of frontal or temporal lobe origin, consist of changes in the level of consciousness or awareness of surroundings, frequently in conjunction with abnormal olfactory or gustatory phenomena. In patients with brain tumors, generalized seizures always have a focal origin even if the focal signature is not evident at seizure onset; evidence of focality is often found on postictal examination of the patient. Large supratentorial masses cause progressive obtundation and can lead to transtentorial herniation, which classically presents with an ipsilateral third cranial nerve palsy and contralateral hemiparesis. Hydrocephalus causes gait ataxia, nausea, vomiting, headache, and decreased alertness. If untreated, hydrocephalus can lead to central herniation, which is not heralded by a third nerve palsy. Supratentorial tumors usually present with focal signs and symptoms, including hemiparesis (frontal lobe), aphasia (left frontal and posterior temporal lobes), hemineglect (parietal lobe), and hemianopsia (temporal, parietal or occipital lobes). Hypothalamic tumors may be associated with disturbance of body temperature regulation, diabetes insipidus, hyperphagia, and, if the optic chiasm is involved, visual-field deficit, typically a bitemporal hemianopia. Brainstem tumors, such as brainstem gliomas, present with multiple cranial nerve deficits, hemiparesis, and ataxia. Nerve-sheath tumors, such as acoustic neuromas, result in deficits of the involved cranial or spinal nerve. As the tumor enlarges, surrounding neural structures may also be compressed, leading to further symptoms. Cerebellar tumors are associated with dysmetria, ataxia, vertigo, nystagmus, headache, and vomiting. Spinal cord tumors present with spastic paraparesis and sensory loss below the level of the tumor as well as disturbances of bowel and bladder function. The hallmark of meningeal disease is neurologic dysfunction at multiple levels of the neuraxis. Contrast studies should always be performed because many tumors show contrast enhancement. It is useful in the preoperative evaluation of highly vascular tumors that require embolization to reduce the blood supply before surgical resection is performed. The differential diagnosis includes a primary tumor of the nervous system, metastasis, stroke, and inflammatory or infectious process. Doing a comprehensive evaluation usually delays the diagnosis and is rarely informative. Such patients should immediately undergo surgical resection and any subsequent testing based on the pathology. This is a reasonable approach because resection is the optimal treatment for either a primary brain tumor or a single brain metastasis. Surgery is required for definitive diagnosis in most cases of suspected primary nervous system tumors and is usually a cornerstone of treatment as well. Exceptions include tumors not requiring surgical extirpation as a component of therapy and that can be diagnosed by characteristic imaging features. The incidence of astrocytoma increases with age, and as the age of the patient increases, the astrocytoma is more likely to be of higher grade. Astrocytomas are most commonly supratentorial but may occur in the cerebellum, brainstem, and spinal cord. Immunohistochemical properties of neurologic malignancies are shown in Appendix C4. Uncommonly, cystic components may be associated with low- or high-grade astrocytomas. Dexamethasone reduces the cerebral edema associated with malignant brain tumors by decreasing vascular permeability through its action on endothelial junctions. Neurologic dysfunction from brain tumors is often due to the surrounding edema rather than to the tumor itself. Therefore, treatment with steroids usually results in considerable clinical improvement. Common steroid-related side effects in brain tumor patients include insomnia, weight gain, hyperglycemia, steroid myopathy, and affective disturbance. Not only is surgery necessary for adequate tissue sampling for pathologic diagnosis, but it can also lead to neurologic improvement from reduction of mass effect. The degree of surgical resection has been shown to correlate with survival, especially for higher-grade lesions. The term gross total resection refers to removal of all or nearly all tumor visualized radiographically. Based on the infiltrative nature of all grades of astrocytoma, however, residual tumor always remains. If resection is not possible, biopsy should be performed for histologic diagnosis. Astrocytoma and Glioblastoma 401 complications of such therapies include steroid dependence and the need for further surgical debulking in one-half of patients for control of radionecrosis. Although efficacy has not been established for patients with anaplastic astrocytoma, many have adopted this regimen for all patients with malignant gliomas. The decision to treat at recurrence and the type of treatment to be administered depends on patient characteristics, such as age and performance status, and on tumor features, such as histologic grade and surgical accessibility. Further surgical debulking may be an option and can improve neurologic function if the patient has a large enhancing mass with extensive edema. The antiangiogenic drug bevacizumab (Avastin) has become the standard at recurrence. It is usually combined with a chemotherapeutic drug such as a nitrosourea, carboplatin, or irinotecan. Optimally, patients should be offered participation in a clinical trial if available. Further irradiation, such as stereotactic radiosurgery, rarely has a role in the treatment of these highly infiltrative neoplasms. Low-grade astrocytomas can recur, often as higher-grade lesions, as long as 20 years after treatment. Tumor recurrence is usually at the primary site, but occasionally astrocytomas can become multifocal or recur at distal sites within the neuraxis. The rate of monitoring is individualized and depends on the grade of the tumor, the performance status of the patient, and the intention for further therapy. Oligodendrogliomas are characterized by loss of heterozygosity of chromosomes 1p and 19q, which correlates with chemosensitivity and improved prognosis. Compared with astrocytoma, oligodendroglioma is more likely to cause seizures and have a higher tendency to calcify and hemorrhage (about 10% of patients). Oligodendrogliomas are most common in the frontal and temporal lobes, particularly in the insular cortex. Treatment is similar to that for astrocytoma and includes dexamethasone for control of symptoms and aggressive surgical resection. Median survival of low-grade oligodendroglioma exceeds 15 years and is about 5 years for the anaplastic oligodendroglioma. They are less invasive, more circumscribed, and much less likely to progress to a more anaplastic state. Pilocytic astrocytoma tends to occur in children and young adults and have a predilection for the cerebellum, hypothalamus, optic chiasm, and thalamus. Radiographically, they are well-demarcated masses that enhance densely and homogeneously and may have cystic components. Subtotally resected tumors may be observed or rarely require immediate focal irradiation. Therefore, these tumors localize to the ventricular system and spinal canal, most often in the fourth ventricle and in the region of the cauda equina. Most are histologically benign, but some, including the anaplastic ependymoma, ependymoblastoma, and myxopapillary ependymoma, can disseminate through the spinal fluid. Ependymomas can be cured by total resection, particularly the filum terminale myxopapillary ependymoma. Chemotherapy plays less of a role in the treatment of ependymomas, but when used, platinum compounds are considered most effective. Brainstem gliomas are astrocytomas that arise in the brainstem, usually the pons, and are more common in children than adults. They can be any grade of astrocytoma, but their outcome is primarily determined by their location, so they are classified separately from the other astrocytomas. Surgical resection is not possible because of the tumor location, and diagnosis is usually based on the typical radiographic and clinical findings. Patients with more localized, discrete tumors, particularly those in the midbrain or medulla, have a longer survival of several years.
Objective regression of manifestations occurs in 60% of patients for a median of 4 months treatment for pink eye indinavir 400mg without a prescription. There is no general agreement on when (or even if) chemotherapy should be started in patients with malignant carcinoid symptoms zika virus buy indinavir on line. Endocrine symptoms may be palliated symptoms nervous breakdown cheap indinavir 400 mg line, but the effect of chemotherapy on survival is not known medicine identifier order indinavir 400mg mastercard. Combination chemotherapy regimens (such as streptozocin and doxorubicin) have not clearly had a more beneficial effect compared with single agents symptoms webmd generic 400 mg indinavir. Cisplatin in combination with etoposide is useful for anaplastic forms of neuroendocrine carcinomas symptoms 7 days pregnant cheap 400 mg indinavir with visa. Hepatic arterial occlusion or embolization, with or without chemotherapy, has been performed for symptomatic hepatic metastases from carcinoid tumors or islet cell carcinomas. Substantial or complete relief from the endocrine syndromes is achieved in about 80% of selected patients, with a median duration of 18 months. It is probably not possible to control the symptoms of carcinoid syndrome completely with aggressive dietary tryptophan restriction and high-dose antiserotonin drugs alone. The drugs have a tumoristatic effect as well and prolong the time to tumor progression. Side effects of both octreotide and lanreotide include abdominal cramping, cholelithiasis, and hyperglycemia. Hypotension, the most life-threatening complication of carcinoid syndrome, is mediated by kinins (and perhaps prostaglandins) and can be precipitated by catecholamines. Pure -adrenergic (methoxamine, norepinephrine) and vasoconstrictive (angiotensin) agents are preferred for treating hypotension in carcinoid syndrome. Adrenergic agents, such as albuterol, do not appear to worsen bronchospasm for carcinoid and may also be used with caution, since they may cause hypotension. Patients with carcinoid syndrome are at high risk for the development of flushing, bronchospasm, and hypotension (carcinoid crisis) during surgery. Stimulation of adrenergic hormone release and use of drugs that induce hypotension (morphine, succinylcholine, and curare) must be minimized. Octreotide should be given intravenously at a rate of 50 mcg/h, starting before anesthesia. These changes develop with far-advanced carcinoid syndrome, which has a poor prognosis independent of the heart lesions. Because of the high surgical risk in these patients, valve replacement may not be warranted. Pellagrous skin lesions may be treated with daily oral vitamin preparations containing 1 to 2 mg of niacin. Thyroid cancer accounts for about 3% of visceral malignancies; there are 45,000 new cases and 1,700 cancer deaths in the United States annually. The lag time between radiation exposure and the onset of thyroid cancer averages 25 years but ranges from 5 to 50 years. Many patients younger than 20 years of age with thyroid cancer have a history of neck irradiation. Between 5% and 10% of patients who have a history of neck irradiation develop thyroid cancer; 25% have an abnormal thyroid by palpation. Thyroid cancers after neck irradiation are often multifocal but have an indolent course and a prognosis similar to that of spontaneous tumors. Neck irradiation also increases the risk for hyperparathyroidism and parotid gland tumors. Thyroid tumors (including papillary and follicular carcinomas), as well as breast neoplasms, also occur frequently in Cowden multiple hamartoma syndrome and in familial adenomatous polyposis (including Gardner syndrome). Several oncogenes and tumor-suppressor genes have been implicated in the pathogenesis of thyroid neoplasms. The more aggressive histologic subtypes of thyroid cancer tend to affect older patients. Histologically, the tumor cells may be arranged in either papillary or follicular patterns; the diagnosis of papillary carcinoma is based on nuclear features, not on the presence or absence of follicles. Psammoma bodies may be present in histologic sections in about 40% of these tumors. Follicular cancers (10% of thyroid cancers) have a peak incidence at 40 to 50 years of age. They tend to invade blood vessels and to metastasize hematogenously to visceral sites, particularly bone. Lymph node metastases are relatively rare, especially compared with papillary cancers. Anaplastic cancers (1% to 2% of thyroid cancers) occur most often in patients older than 60 years of age. Anaplastic thyroid cancers are aggressive cancers, which rapidly invade surrounding local tissues and metastasize to distant organs. Amyloid may be seen on histologic examination and is composed of calcitonin arranged in fibrils. Metastases are mostly found in the neck and mediastinal lymph nodes and may calcify. Other tumors found in the thyroid include lymphomas (1% to 2% of all thyroid cancers), a variety of soft tissue sarcomas, and metastatic cancers from kidney, colon and other primary sites. Thyroid cancer may be found on routine physical examination as a mass in the thyroid or in the midline up to the base of the tongue (thyroglossal duct remnant). Patients with thyroid cancer may have a single palpable nodule; others have a normal, multinodular, or diffusely enlarged thyroid gland. Anaplastic cancer is often manifested by obvious masses infiltrating the skin and soft tissues of the neck or by respiratory distress. Chest radiographs and serum alkaline phosphatase levels may be obtained to look for evidence of metastatic disease in the lung, liver, or bone. Liver and bone scans and selected skeletal radiographs are indicated when the alkaline phosphatase level is elevated. Nonfunctional "cold" nodules are found in 90% of patients with palpable nodules, both benign and malignant, but only about 10% of cold nodules prove to be cancer. Thyroid ultrasonography is useful in determining the size and location of a nodule, diagnosing cystic lesions, detecting nonpalpable nodules or lymphadenopathy, and documenting the presence of features suggestive of malignancy. Purely cystic lesions, found in about 10% of patients with palpable nodules, are reported to be malignant in <1% of cases. Benign and malignant lesions cannot be confidently distinguished by ultrasonography if they contain mixed solid and cystic components or are entirely solid. Normal basal values may require a calcitonin stimulation test using pentagastrin or calcium infusion. Patients with elevated serum calcitonin require neck exploration regardless of findings on physical examination or sonography. Needle aspiration biopsy is invaluable for cytologic diagnosis of thyroid nodules and for preventing unnecessary thyroidectomies. Many authorities recommend needle biopsy as the first step in the evaluation of any thyroid lump. The accuracy of needle biopsy of the thyroid is >90% for benign lesions; the false-negative rate is 5% to 10%. Roughly, if 100 patients with nodules underwent needle biopsy rather than immediate thyroidectomy, and if patients with clearly benign histopathology were excluded from surgery, 1 cancer would be missed, 9 cancers would be appropriately resected, and 10 patients with benign lesions would have undergone unnecessary surgery. Therefore, the needle biopsy saves 80 of 100 patients from unnecessary surgery at the expense of missing one cancer, which is usually indolent and can be detected later. Decreased survival is not noted when compared with age-matched populations until 12 years after the diagnosis. The raw 10-year survival rate is 95% for patients <40 years of age and 75% for patients >40 years of age. Factors that adversely affect prognosis, which both increase the recurrence rate and decrease the survival rate (1) Age > 45 years (2) Size of nodule >4 cm (compared with <2. Follicular adenocarcinoma without vascular invasion has essentially the same survival rate as papillary carcinoma for age-matched populations. Medullary carcinoma without lymph node involvement is nearly always cured with surgery. No uniform opinion exists regarding the management of indolent varieties of thyroid cancer. Total or near-total thyroidectomy is the treatment of choice for all types of thyroid cancer. Overall, subtotal thyroidectomy is associated with double the recurrence rate and a lower survival rate than total thyroidectomy for papillary and follicular cancers. Subtotal thyroidectomy or lobectomy may be sufficient, however, for low-risk patients with small tumors (<1 cm). Medullary cancer of the thyroid is often bilateral, and total thyroidectomy is imperative. Neck nodes that appear to be involved clinically or on sonography should be removed. Routine radical or modified radical neck dissection, however, does not improve the rate of survival or recurrence, except in medullary carcinoma, and is responsible for increasing the rate of major complications. The major complications of thyroidectomy are hypoparathyroidism and vocal cord paralysis; death is rare. Combinations of these problems and other complications occur in 5% to 10% of patients subjected to total thyroidectomy; the incidence is doubled to tripled if neck dissection is added to the procedure. Patients must be monitored for clinical signs of hyperthyroidism and the dose of thyroxine decreased to keep the patient clinically euthyroid. Fears of the leukemogenic potential of 131I have abated because little increase in the incidence of acute leukemia has been found in many long-term studies. The true value of 131I is not known and is difficult to determine because the isotope has been given to patients with thyroid cancer as part of standard practice for many years. Radioactive iodine may not be necessary in all postoperative patients, particularly those with localized, small tumors (<1 cm). In most patients with papillary or follicular cancer, serum levels of thyroglobulin (Tg) correlate with residual thyroid tissue (either normal or neoplastic) and can be used as a tumor marker after all normal thyroid remnants have been ablated. Current evidence suggests that serum thyroglobulin levels >1 to 2 ng/mL in patients receiving replacement thyroxine therapy indicate the presence of residual tumor. Patients with residual tumor may demonstrate a Tg response even when the baseline serum Tg is <1 ng/mL. Thyroid Cancer 419 because the large load of stable iodine will preclude the use of 131I for 1 to 3 months. Relapsing disease develops in about 12% of patients who have no evidence of disease after primary therapy. Chemotherapy for symptomatic, widespread metastatic thyroid cancer that is unresponsive to 131I has not been particularly useful. Hypoparathyroidism complicates total thyroidectomy in 10% to 30% of patients; it is rare after 131I therapy. Hypoparathyroidism is transient in the majority of cases, and serum calcium levels normalize in 1 or 2 weeks. Serum calcium levels and clinical evidence of hypocalcemia are checked daily following surgery for 1 to 2 days. If the serum calcium level is <8 mg/dL, oral calcium citrate (1 g four or five times daily) or calcium carbonate (2. If the patient manifests tetany or the serum calcium is 6 mg/dL, intravenous calcium gluconate or lactate is given (1 g every 4 to 6 hours) and serum calcium levels are monitored more frequently. Patients with persistent hypocalcemia >1 to 2 weeks after thyroidectomy usually require chronic calcium supplements. If hypocalcemia recurs after 2 more weeks of therapy that has been followed by weaning off supplements, vitamin D therapy is necessary as well. Serum calcium measurements are repeated weekly; if <8 mg/dL, the calcitriol is increased in 0. Ergocalciferol or cholecalciferol may also be used; they are much less expensive than calcitriol but may cumulate and cause vitamin D intoxication. Patients who have a history of neck radiation exposure and no palpable abnormalities should be followed by careful annual physical examination and sonography. Radiation-induced thyroid cancer typically has an indolent course and does not necessitate anxiety-provoking management. Familial paraganglioma syndromes due to mutations in succinic dehydrogenase subunits B and D Recent reports indicate that as many as 30% of patients with an apparently sporadic pheochromocytoma may, in fact, harbor a germ line mutation in one of these genes. Screening for these mutations should be performed in patients with bilateral, extra-adrenal, or malignant pheochromocytomas, patients with a family history of one of the syndromes, patients diagnosed with a pheochromocytoma before the age of 20 years, or patients with other phenotypic features of one of the hereditary syndromes. The paraganglia range from the organ of Zuckerkandl at the aortic bifurcation to the carotid bifurcation. Metastases frequently have an indolent growth pattern but are lethal because they often produce cardiovascular complications. Episodes may be triggered by exercise, emotional upset, alcohol ingestion, physical examination in the area of the tumor, or micturition. Vague complaints of anxiety, tremulousness, fever, dyspnea, or angina are often mistaken for psychosomatic illness or thyrotoxicosis. Patients may have cardiovascular collapse after a vague history of arrhythmias and anxiety. Young patients without hypertension but with documented atrial arrhythmia, evidence of an unexplained 1.
