Kristine Madsen MD, MPH

• Associate Professor, Joint Medical Program
• Public Health Nutrition
• Community Health Sciences

https://publichealth.berkeley.edu/people/kristine-madsen/

Other researchers using functional magnetic resonance imaging have recently implicated auditory-limbic interactions to explain the etiology of chronic tinnitus blood pressure medication that doesn't cause cough buy microzide 25 mg overnight delivery. However hypertension and obesity order cheap microzide line, the greatest degree of hyperactivity was noted in two limbic structures arrhythmia with normal heart rate purchase microzide 25mg without a prescription, the nucleus accumbens and the ventromedial prefrontal cortex hypertension young female buy microzide without prescription. Brain changes can also be seen in nonauditory areas blood pressure low pulse high discount microzide 25 mg overnight delivery, including the hippocampus adderall xr hypertension generic 25mg microzide fast delivery, amygdala, and cingulate gyrus. Tinnitus can be acute or chronic in nature, unilateral or bilateral, nonpulsatile or pulsatile: arterial, venous, or nonvascular. The great majority of patients experience tinnitus without significant associated symptoms, but more than one-fourth of persons with tinnitus are distressed by it. I Clinical Manifestations Pathophysiology the mechanism that produces tinnitus remains unclear. Subjective tinnitus is considered to be sensorineurophysiologic in origin, whereas objective tinnitus is thought to arise from vascular, Diagnosis the primary care office is an appropriate place to initiate the management of tinnitus. History Complete medical and psychological history Tinnitus components Sensory Affect Psychomotor Any factors that worsen or relieve symptoms Prior treatment history Complete physical examination Concentrate on the following: Audiologic Neurologic Cardiovascular Metabolic Psychological Laboratory tests Thyroid function tests Vitamin B12 Complete blood count Fasting glucose Lipids, including triglycerides Zinc the evaluation of the patient with tinnitus begins with a thorough patient history, which involves an attempt to determine the etiologic and/or contributing factors causing ear noise. Certain parameters of the sounds heard can help identify potential etiologies and determine the need for further evaluation and treatment as seen in Box 1. In the primary care office, the tinnitus patient should undergo a thorough physical examination with special attention to audiologic (including vertigo), cardiovascular, neurologic, and metabolic systems. A basic otologic examination includes (1) using a stethoscope to identify objective tinnitus, (2) examination of the external canal, (3) basic hearing testing, and (4) specific testing for sensorineural or conductive hearing loss using the Weber and Rinne tests. Thyroid studies, a hematocrit determination, complete blood chemistry, vitamin B12, and lipid profile should be obtained if the patient has any suggestion of a metabolic abnormality. Primary care clinicians can identify many of the parameters that will determine further evaluation and management plans (see Box 1). The management team evaluation continues with diagnostic audiologic testing, including audio testing, speech discrimination testing, and tympanometry. Other audiologic measurements of tinnitus may include pitch masking, loudness masking, minimum masking level, and residual inhibition. Further investigation should be dictated by team discussion of potential etiologic/exacerbating factors for the individual patient. Patients with unilateral or pulsatile tinnitus are more likely to have serious underlying disease, such as vascular middle ear tumors, and should be evaluated by an otolaryngologist and possibly a cardiologist or neurologist. Not all sounds of internal origin perceived by the patient are those defined as tinnitus. Patients can also have ear noise caused by auditory hallucinations, as well as benign "transient noise. In a patient who by appropriate evaluation is considered to be psychotic, and more likely schizophrenic, hearing voices or other sounds may be auditory hallucinations. Stress or sleep deprivation can also cause auditory hallucinations in nonpsychotic patients. In a patient who is not sleep deprived or stressed, or drinking large amounts of caffeine-containing beverages, ear noise is more likely to be tinnitus. Transient noise is defined as a whistling sound accompanied by a sensation of sudden temporary hearing loss. These episodes generally disappear in seconds and occur rarely, whereas tinnitus is generally defined as lasting over 5 minutes and occurring at least twice weekly. They are usually not related to any specific event or activity, often unilateral, and sometimes accompanied by a feeling of ear blockage. There is no cure for tinnitus, although a multidisciplinary approach (tinnitus-targeted therapy) with a medico-audiologic approach can partially alleviate associated symptoms. Eliminate potentially ototoxic medications and/or any precipitating active diseases/disorders (see Risk Factors/ Etiologies above). Administer targeted medication based on contributory medical conditions, severity of distress, tinnitus type (cochlearperipheral or central), and tinnitus components involved (sensory, affective, and/or psychomotor). Use instrumentation such as hearing aids, tinnitus masks, tinnitus retraining including low noise generators, and/or relaxing external sound stimulation with silence avoidance. Provide mental health support, including stress management, biofeedback, reassurance, and relaxation techniques. Level of distress-directs degree of evaluation and management Mild (not bothersome) Moderate (noticeable) Severe (bothersome) 3. Etiology/contributors-directs precision vs general management choices Identifiable Idiopathic 4. Tinnitus origin (pathways)-directs evaluation and management Central (nonauditory system) Peripheral (auditory system) 5. Components of tinnitus sensation-directs priority and types of management strategies Sensory Affective (emotion and behavior) Psychomotor 6. Tinnitus 65 66 No medications have been found to consistently reduce tinnitus symptoms, probably because of the heterogeneity of clinical tinnitus types. The sensory component symptoms among patients with predominantly cochlear-type severe tinnitus (peripheral) can be treated with pentoxifylline (Trental),1 which can enhance the oxygen-carrying capacity of the blood. If response is poor, intratympanic drug therapy with a steroid and/or instrumentation can be considered. Sensory symptoms among patients with predominantly central-type severe tinnitus can be offered trial instrumentation or brain scanning. If scanning is positive, neuroprotection using medications such as gabapentin (Neurontin)1 and clonazepam (Klonopin)1 may be helpful. The affective component of tinnitus can be pharmacologically managed with psychiatric consultation and may also include gabapentin and/or clonazepam (useful for anxiolytic and antiepileptic effects) or some other anxiolytic. The psychomotor component can sometimes be improved with medications such as papaverine1 or clopidogrel (Plavix)1 for cerebrovascular insufficiency and antiseizure drugs for epilepsy. Because anxiolytics and antidepressants can sometimes cause or worsen tinnitus, close follow-up is important for treatment success. Other potentially contributing conditions and/or distressing symptoms should be appropriately treated. Patients with severe tinnitus not responding to initial therapies or who are in significant distress should be referred to audiology, dentistry, neurology, physical therapy, and a mental health expert. Audiologist recommendations about masking devices to cover up the constant ringing may be helpful. Sound generators can be worn in the ear to produce stable signal (white noise) and are most effective alone in patients with normal or near-normal hearing. This therapy can be combined with a hearing aid, which is most effective when done by a professional hearing expert with strict protocols. Surgical cochlear implant in the profoundly hard-of-hearing patient can help with hearing issues but can also cause tinnitus for the first time. Dentists can be helpful by evaluating for temporomandibular joint problems and other habits and recommending dental orthotics and home exercises to reduce clenching and grinding when appropriate. Neurologists can evaluate for vestibular symptoms, pain syndromes, and other cranial disorders. Physical therapists can evaluate the head and neck for biomechanical and posture problems and teach useful exercise techniques. Psychological counseling can improve levels of distress with greater improvement shown in combined cognitive strategies/education interventions. Patients can be taught to pay less attention to symptoms, overcome fear, accept tinnitus as part of life, and keep busy with happy activities. Acceptance and commitment therapy to better understand tinnitus and to look at it more objectively than emotionally may be useful. Careful choices and titrations of anxiolytic, antidepressant, and hypnotic medications reduce some of the affective components of tinnitus. Herbs and dietary supplements are commonly used, but there is no evidence to support their efficacy. Experimental treatments include transcranial magnetic stimulation, low-level laser therapy, phase-out treatment (individualized sound developed to cancel out tinnitus), neuromonics (customized sound therapy), and tinnitus retraining therapy (remove perception from consciousness). The relationship between the auditory and limbic systems may offer a route of management via limbic stimulation and/or external limbic activation associated with emotional stress or depression. Although the causal relationship is unclear, suicide risk must be monitored, especially among persons who were at high suicide risk before they developed tinnitus. Newer theories pointing out the central nervous substrate activation with tinnitus of sensory, affect, and psychomotor centers help explain the complexity and variability of tinnitus comorbidities (Box 2). Shulman A, Goldstein B, Strashun A: Central nervous system neurodegeneration and tinnitus: a clinical experience. They include species of bees (genus Apis, including honey bees and bumblebees), wasps (genus Polistes), yellow jackets (genus Vespula), hornets (genus Dolichovespula), and fire ants (genus Solenopsis). Diagnosis There are two important historical points to ascertain when seeing a patient with an allergic reaction to a stinging insect. Clues about the type of insect can be obtained from the circumstances of the sting. Stings from these insects often occur in fields with flowering plants when a barefoot patient steps or accidently sits on them. Bees have a barbed stinger and attached venom sac, which may be left in place after a sting. These should be removed immediately with a scraping motion; any pinching of the sac may inject additional venom. Yellow jackets are aggressive scavengers and are found wherever food is left in the open. Stings from these insects usually occur in picnic areas or around open garbage containers. Like bees, yellow jackets occasionally leave a stinger in place, so this historical feature is not definitive. However, they tend to build these nests under the eaves and overhangs of our homes, and people stung by wasps are usually entering or exiting their homes. Fire ants are very aggressive in defense of their nests, which are low mounds built above ground with extensive tunnels beneath the surface. In endemic areas (mostly the southeastern United States), they swarm and attack as a group when disturbed. Patients stung by fire ants are usually outdoors and accidently stand in a mound or disturb a mound while working or playing in their yard or garden. They bite only to get a grip and then sting from the abdomen and inject a toxic alkaloid venom. Because they attack as a group, they are usually seen and clearly identified by the patient. The size of the fire ants means their venom is injected less deeply than that of other hymenoptera, which leads to the usual development of a pseudopustule about 24 hours after a sting. These pseudopustules contain necrotic cellular material but are sterile because fire ant venom has antibiotic properties that can kill bacteria and fungi. The pseudopustules should be left alone; opening and draining them only increases the risk of secondary infection. The active venom components produce immediate swelling, redness, and tenderness with fairly intense pain at the site of the sting that slowly resolves over several hours. Sometimes, the immediate reaction progresses, and swelling (>10 cm) continues for 1 to 2 days and extends across several contiguous joints away from the site of the sting. This large local reaction may take 5 to 10 days to fully resolve, and it may be difficult to differentiate this from a secondary infection. Large local reactions peak in 1 to 2 days and then slowly recede, whereas secondary infections continue to get worse. Large local reactions do not cause systemic fever or lymphangitis, which should be treated with antibiotics if they occur. Unfortunately, many of the symptoms are similar to those of anxiety, which also may occur in a concerned patient: feelings of impending doom, a rapid heartbeat, shortness of breath, and nausea. Other symptoms that should not be seen in anxiety include a metallic taste, pruritus, and abdominal or uterine cramping. Signs of anaphylaxis include flushing, urticaria, angioedema, vomiting, diarrhea, bronchospasm, hypotension, and shock. Diagnosis of anaphylaxis requires involvement of 2 organ systems out of cutaneous, pulmonary, gastrointestinal or cardiovascular or a drop in blood pressure after a known allergen exposure. Involvement of the upper airway and cardiopulmonary systems is associated with death, and hymenoptera stings are the cause of about 40 deaths per year in the United States. Documentation of the type of reaction is essential for future risk assessment and determination of whether prophylactic therapy should be offered. The risk for a systemic reaction after hymenoptera sting in the general population is estimated to be 3% to 5%. In patients who have a documented large local reaction to an insect sting or a generalized cutaneous reaction (hives angioedema without other organ 67 system involvement), the risk of systemic reactions increases slightly to about 10%. If a patient has suffered an anaphylactic event after a hymenoptera sting and has specific IgE to that hymenoptera as determined by in vivo (skin testing) or in vitro methods and is then placed on immunotherapy for that insect, the risk of systemic reaction after another sting is only 2% to 3%. Although whole-body extract is not effective therapy for other hymenoptera, it has been shown to be effective for fire ants. Epinephrine autoinjectors are simple devices with instructions clearly printed on them, but mistakes in usage do occur. The most common include "bouncing" the injector off the leg, which ejects the epinephrine onto the leg instead of delivering it intramuscularly, and putting the thumb over the end of the injector, which if the injector is reversed leads to no delivery of epinephrine and thumb trauma. Demonstration pens and videos of proper technique may be obtained from the manufacturers.

Stable angina refers to predictable chest discomfort during various levels of exertional activity that is predictably resolved with rest or administration of sublingual nitroglycerin (Nitrostat) blood pressure medication irbesartan purchase 12.5 mg microzide with visa. The clinical sensation of angina pectoris is caused by stimulation of chemosensitive and mechanosensitive receptors of unmyelinated nerve cells found within cardiac muscle fibers and around the coronary vessels blood pressure chart uk pdf buy microzide 25 mg with amex. Nerve stimulation via the sympathetic ganglia occurs most commonly between the seventh cervical and fourth thoracic portions of the spinal cord heart attack grill locations best purchase for microzide. As plaque is initially deposited within a coronary vessel blood pressure journal template microzide 12.5mg on-line, there may be no significant internal luminal compromise during the early positive remodeling phase heart attack 6 fragger order cheap microzide on line. However blood pressure medication side effects cough order discount microzide on line, at the point at which this compensatory mechanism fails, internal luminal compromise ensues. As long as the coronary artery segment distal to the stenosis retains the ability to vasodilate in response to increasing blood flow demands, coronary homeostasis is maintained. Most patients are aware of the levels of exertion that typically induce angina symptoms. Most describe a pain or heaviness across their middle chest that may or may not radiate to the jaw or left arm. Environmental situations such as cold exposure, emotional stress, or heavy meals can induce angina. The Canadian Cardiovascular Society and the New York Heart Association classification systems are used to define angina severity. The key to the diagnosis in men and women lies in a thorough history, which should always include the quality, location, provoking activities, and duration of pain and factors that relieve the pain. Based on a detailed clinical history, the many diagnoses that can masquerade as angina may be eliminated (Table 1). Whenever feasible, it is more advantageous to obtain an exercise stress test rather than a pharmacologically based study. There are several validated exercise protocols that add additional risk stratification measures to the test results. The predictive value of exercise treadmill stress testing ranges from 40% for single-vessel disease to 90% for three-vessel disease. A baseline left bundle branch block, paced rhythm, poorly controlled atrial arrhythmia, or left ventricular hypertrophy with secondary ischemic changes often renders the test inconclusive when assessing for ischemic changes. Stress test accuracy is markedly improved by the addition of an imaging modality such as echocardiography or nuclear perfusion scanning. The sensitivity and specificity of stress echocardiography and stress nuclear imaging are 85% to 90%. Stress echocardiography is believed to be somewhat more specific, and stress nuclear imaging is thought to be more sensitive. A stress echocardiogram also allows assessment of left ventricular systolic function and valvular function and prediction of right ventricular pressure. Discord has resulted from the publication of recent hypertension guidelines by various medical societies, as well as the 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults Report from the Panel Members Appointed to the Eighth Joint National Committee. It has been shown that cardiovascular risk progressively increases at blood pressures greater than 115/ 75 mm Hg. A meta-analysis of 61 prospective observational trials of hypertension involving 1 million adults with no known vascular disease at baseline revealed several interesting findings. Patient outcomes were related per decade of age to the usual blood pressure at the start of that decade. For example, from ages 40 to 69, for each increase in 20 mm Hg systolic blood pressure, a twofold increase in cardiovascular death rate occurred. These findings were much more pronounced in patients who were between 80 and 89 years old than in the youngest cohort, 40 to 49 years old. Although the relative risk was much higher in the younger group, the absolute risk was greatest among the octogenarians. These increased cardiovascular risks were not confined to subjects with blood pressures greater than 140/90 mm Hg; rather, there was a threshold of risk shown all the way down to 115/ 75 mm Hg. Even small reductions in blood pressure can have a significant positive impact on cardiovascular disease. Blood pressure reductions of 4 mm Hg systolic and 3 mm Hg diastolic were shown to reduce cardiovascular events by 15% in a cohort of 20,888 patients. The Heart Outcomes Prevention Evaluation study asked the question whether all patients with atherosclerosis, regardless of blood pressure, should be treated with an angiotensin-converting enzyme inhibitor. The mean blood pressure was 139/79 mm Hg, suggesting that a significant portion of the 9297 participants had a baseline blood pressure higher than this value. Compared with placebo, the treatment group had a 22% reduction in the primary outcome composite of myocardial infarction, stroke, or cardiovascular death. A small substudy using 24-hour ambulatory blood pressure monitoring showed blood pressure differences of 11 mm Hg systolic and 4 mm Hg diastolic in the treatment group compared with the placebo group, which may explain the cardiovascular event reductions reported. The blood pressure goal for treatment of hypertension in patients with established ischemic heart disease should be <130/80 mm Hg. One must be careful with aggressive diastolic blood pressure management, as some studies have shown a J-shaped curve relationship between diastolic blood pressures and coronary events. Observational evidence suggests that regardless of how cholesterol is lowered, a reduction in atherosclerotic cardiovascular disease will result. Initial treatment of hypertension in patients with ischemic heart disease should always include lifestyle management. Appropriate weight loss with a goal of achieving a body mass index <25 kg/m2 can improve hypertension control. The trial, which enrolled 20,536 patients aged 40 to 80 years, showed a 24% reduction in major cardiovascular events, a 25% reduction in stroke, and a 13% reduction in overall mortality with statin therapy. Patients with a recent acute ischemic syndrome were enrolled in the Pravastatin or Atorvastatin Evaluation and Infection Therapy trial, known as Thrombolysis in Myocardial Infarction 22, which compared 80 mg atorvastatin (Lipitor) with 40 mg of pravastatin (Pravachol). The Treating to New Targets trial was the first to compare a more intensely treated group with a less intensely treated group using the same agent. The design of this 10,000-patient study eliminated concerns that outcome differences were induced by dissimilar statin preparations. In other patient populations that require moderate-intensity statin therapy, there are several statin choices. Metabolic Syndrome the combined presence of insulin resistance, hypertension, dyslipidemia, and abdominal obesity define metabolic syndrome. There is debate about whether this is a true syndrome or simply a clustering of cardiovascular risk factors in a particular individual. The approach to treatment for this syndrome is no different from that for the individual components. Smoking Cigarette smoking is probably the most important of the identified modifiable cardiovascular risk factors. The pathophysiological process that leads to atherosclerosis from smoking stems from induced platelet dysfunction, endothelial dysfunction, smooth muscle cell proliferation, and attenuated high-density lipoprotein-cholesterol levels. The Mediterranean diet has been shown to positively affect cardiovascular disease, and conversely, a diet high in saturated fats has been shown to negatively influence multiple cardiac risk factors. Patients should be encouraged to incorporate high proportions of fruits and vegetables into their diet, along with olive oil and regular servings of fish coupled with a reduced amount of red meats. Other Lifestyle Changes Exercise should be encouraged in patients with stable angina, once all appropriate invasive and noninvasive tests have been completed and a stable medical regimen has been established. Endorphins released during exercise are thought to be mood enhancers, as well as effective muscle relaxants. For these reasons, appropriate exercise programs for patients with stable angina have far-reaching positive benefits. Major depression affects approximately 25% of people recovering from a myocardial infarction, and another 40% suffer from mild depression. In any given year, one of every three long-term acute ischemic syndrome survivors will develop depression. Patients identified with depression were twice as likely to experience recurrent cardiovascular events. Physical inactivity was associated with a 44% greater rate of cardiovascular events. Patients with symptoms of depression were less likely to follow dietary, exercise, and medication recommendations. Nitrates Nitrates provide an exogenous source of nitric oxide, which serves to relax smooth muscle and inhibit platelet aggregation. Nitrates exert their antianginal effect by reducing myocardial oxygen demand through coronary and systemic vasodilatation. Nitrates are strong venodilators, and in higher doses they can also induce arterial dilatation. Coronary artery dilatation of stenotic vessels and intracoronary collaterals directly increases myocardial oxygen delivery. Through these mechanisms, nitrates have been shown to prevent recurrent episodes of angina and to increase exercise tolerance. There are several nitrate preparations; they differ mainly in route of administration, onset of action, and effective half-life. A study comparing atenolol with placebo showed that all doses from 25 through 200 mg/day were effective in reducing angina, but only the two highest doses led to an increase in exercise tolerance. Certain -blockers have intrinsic sympathomimetic activity, including pindolol (Visken)1 and acebutolol (Sectral). When -blockers are used to treat angina, a goal resting heart rate should be between 55 and 60 beats/minute. Caution should be used in patients with resting bradycardia and in those with known reactive airway disease. Atenolol is renally excreted and should be used with caution in the elderly and in those with known renal dysfunction. Calcium Channel Blockers Calcium channel blockers are classified as either dihydropyridines or nondihydropyridines. The former group includes amlodipine (Norvasc), felodipine (Plendil),1 nifedipine (Procardia), and nicardipine (Cardene); the latter includes diltiazem (Cardizem) and verapamil (Calan). There are differences among the two subclasses in regard to chronotropic, dromotropic, and inotropic effects. Calcium channel blockers positively alter myocardial oxygen supply and demand, mainly through direct arterial vasodilatation. The nondihydropyridines also exhibit negative chronotropic and inotropic effects, thus further lowering myocardial oxygen demands. One of the early quick-release preparations of a dihydropyridine calcium channel blocker, nifedipine, was reported to potentially induce myocardial infarction when used to treat angina. This was most likely due to a rapid drop in afterload leading to reflex adrenergic activation. Although amlodipine and felodipine are tolerated in patients with left ventricular systolic dysfunction, other calcium channel blockers should be avoided in this patient subset. Ranolazine (Ranexa) Ranolazine (Ranexa) is a new and unique antianginal drug approved for the treatment of stable angina. It is a sustained-release preparation that has been approved for patients who remain symptomatic while on standard angina pharmacotherapy. Its mechanism of action may be through reduction of fatty acid oxidation or effects on sodium shifts and intracellular calcium levels. Dosing is 500 or 1000 mg twice daily, and the major route of metabolism is the cytochrome P-450 system. Because of receptor upregulation, acute -blocker withdrawal may lead to a transient supersensitivity to catecholamines and subsequent angina or even myocardial infarction. Some -blockers are receptor specific, and some exert an effect over all three receptors. However, at higher doses, even -selective agents have cross-reactivity for all -receptors. Several cardioselective -blockers, including atenolol (Tenormin) and metoprolol (Lopressor), have been shown to be effective Medication Combinations Many patients with chronic stable angina require more than one antianginal medication to control their symptoms. Further medications may be added and individualized to each patient based on their degree of angina and overall clinical response. Angina Pectoris 91 should be used cautiously with -blockers, especially in patients with preexisting conduction system disease. Nitrates do not have a side-effect profile that raises concerns when they are used with -blockers or with calcium channel blockers. Antiplatelet medications have been shown to consistently decrease morbidity and mortality in a wide array of cardiovascular disease patients. In this patient population, aspirin therapy resulted in a 26% reduction in myocardial infarction; the number of patients needed to treat to prevent a myocardial infarction was 83. Consensus guidelines recommend indefinite oral aspirin for the secondary prevention of cardiovascular events in all angina patients. Clopidogrel (Plavix)1 is an effective alternative to aspirin for the treatment of stable cardiovascular disease in those patients with a true aspirin allergy. However, there are no compelling data to indicate that clopidogrel (or newer agents, such as prasugrel [Effient]1 and ticagrelor [Brilinta]1) are superior to aspirin in this particular patient population. In patients with unstable angina, dual antiplatelet therapy with aspirin and clopidogrel is recommended. Invasive Assessment the decision to pursue an invasive treatment approach differs significantly in patients with chronic stable angina and in those with acute coronary syndromes. Within both groups, accurate risk stratification is the key consideration in choosing who will benefit from coronary angiography and subsequent percutaneous coronary intervention. An invasive strategy in unstable angina patients has been shown to reduce recurrent acute coronary syndrome events consistently in many trials. In patients with unstable angina, there are significant gender differences in outcomes related to the use of invasive therapy. Both men and women with elevated biomarkers from myocardial necrosis have comparable reductions in rates of death, myocardial infarction, and rehospitalization with invasive treatment strategies.

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Nerve entrapment syndromes such as the carpal tunnel syndrome occur in nearly half of patients hypertension food order microzide 25mg mastercard. Cardiovascular System Arterial hypertension is found in 30% of patients hypertension journals discount microzide 12.5mg with amex, and when associated with diabetes arrhythmia quiz ecg purchase microzide no prescription, it contributes to the increased mortality rate of the disease blood pressure medication cialis discount microzide 12.5mg on line. Hyperaldosteronism with low renin levels and the resulting sodium retention play an important role in the pathogenesis of hypertension blood pressure medication every other day purchase discount microzide on line, but other contributors such as an increased sympathetic tone are also present quercetin and blood pressure medication microzide 25mg fast delivery. Echocardiographic findings include left ventricular and septal hypertrophy with varying Clinical Manifestations Acromegaly develops insidiously over many years. An 8- to 10-year delay in diagnosis has been estimated from the beginning of the first symptom. Symptomatic cardiac disease develops in 15% of patients and is usually due to coronary artery disease, heart failure, and arrhythmias. Although the existence of an acromegalic cardiomyopathy is still controversial, there are patients without hypertension and with angiographically normal coronaries, who develop severe congestive heart failure, in whom histologic evidence of subendocardial, subepicardial, and myocardial fibrosis and necrosis has been documented. Respiratory Abnormalities the majority of patients with acromegaly are affected by loud snoring. A significant fraction of these have sleep apnea (with both central and obstructive components) with significant drops in oxygen saturation, which can be complicated by arrhythmias, daytime somnolence, and chronic fatigue. Although successful treatment of acromegaly, be it by surgical, pharmacological, or radiotherapeutical interventions, results in significant improvements in metabolic control, the prevalence of diabetes remains higher than in the general population. Abnormalities in Lipid Metabolism the classic lipid profile consists of diminished total cholesterol, along with elevated triglyceride concentrations. Bone and Calcium Metabolism Acromegaly is associated with hypercalciuria and hyperphosphatemia. High serum 25-hydroxyvitamin D3 and urinary levels of hydroxyproline can be found, reflecting a state of increased bone turnover. Cortical bone mineral density is elevated, whereas trabecular bone mass is diminished. Neoplasia Retrospective studies suggested that colonic adenomatous polyps and adenocarcinoma were more frequent in acromegalic patients than in the general population. Prospective studies have demonstrated that the risk, albeit smaller than previously thought, is real and probably justifies screening colonoscopy in these patients. Patients with uncontrolled acromegaly have a higher risk of recurrence of premalignant polyps and a higher mortality rate from colon cancer compared with subjects with biochemically controlled disease and the general population. Recently, an increased incidence of well-differentiated thyroid carcinoma has been documented. Associated Endocrine Abnormalities A euthyroid goiter is often found but seldom requires specific treatment. Hypopituitarism occurs variably, depending on the size and extension of the tumor and whether the patient has undergone surgery or radiation therapy. Hypogonadotropic hypogonadism is the most common pituitary deficiency, occurring in 20% of patients. A decreased libido is a common presenting complaint in both male and female patients with acromegaly; women often have menstrual and ovulatory disturbances and men complain of impotence. Acromegaly can also develop in patients with the McCune-Albright syndrome (polyostotic fibrous dysplasia, caf e au lait spots, and endocrinopathies such as sexual precocity and autonomous thyroid nodules), and occurs in the context of the Carney complex. Mortality Life expectancy in patients with acromegaly is decreased by about 10 to 15 years, and the standardized mortality ratio is 1. Most patients die of cardiovascular causes, followed by cerebrovascular events, respiratory abnormalities, and neoplastic diseases. Other factors associated with an increased mortality include advanced age and the presence of hypertension and diabetes. Treatment the decision as to what therapeutic modality should be used has to take into account medical issues (cardiopulmonary comorbidities, size, and extension of the tumor) as well as the local characteristics of the treating center. The latter refers to the availability of pituitary surgeons and radiotherapeutic technologies as well as the economic feasibility of pharmacologic therapy. Pharmacologic Therapy Somatostatin analogues are the most commonly used medical treatment for acromegaly. More recent trials performed in unselected populations reveal that the real success rate lies between 25% and 35%. Side effects of somatostatin analogues, including nausea, abdominal pain, alopecia, and biliary sludge, occur in 20% of subjects. Transient elevations of liver aminotransferases can occur, although this seldom requires drug discontinuation. Few patients respond marginally to difficult-to-tolerate large doses of bromocriptine. Newer dopamine agonists, such as cabergoline,1 are better tolerated and achieve biochemical control in 20% to 30% of patients. Combination treatment with cabergoline 1 and octreotide appears to be promising in cases resistant to somatostatin analogues. Radiation Therapy Both external-beam radiotherapy and radiosurgery are indicated in patients with persistent disease and a demonstrable tumor remnant who are either intolerant or resistant to pharmacologic treatment. Biochemical success occurs in 20% to 60% and requires many years to become apparent. Hypopituitarism, involving at least two axes, develops in more than 50% of patients within 10 years. Serious adverse effects such as brain necrosis and optic nerve damage seldom occur with the currently used techniques that minimize radiation to the normal surrounding tissues. Novel pharmacologic therapies are being developed, some of which will likely become useful particularly in patients who do not respond to current somatostatin analogues. Dopastatin5 is a recently developed chimeric compound that behaves both as an analog and as a dopamine agonist; clinical trials had to be discontinued at early stages due to lack of efficacy. Oral octreotide, known as octreolin,5 is a new preparation of octreotide acetate attached to a transient permeability enhancer, which selectively allows the translocation of the somatostatin analog through the paracellular tight junctions. Infiltration in the context of malignancy is often due to a known plurimetastatic cancer; other infiltrative diseases are rare. In some patients with glucocorticoid receptor hypersensitivity, even smaller doses of glucocorticoid other than oral (topical, injected, or inhaled) can also suppress the hypothalamo-pituitary-adrenal axis. Other causes, such as autoimmune lymphocytic hypophysitis, are most frequent peripartum, either in the third trimester or postpartum. Sheehan syndrome is rare and characterized by pituitary apoplexy secondary to shock due to severe blood loss during parturition. Doses are usually 15 to 20 mg divided into two or three daily doses, with the highest dose in the morning. Symptoms start as subtle and nonspecific in some patients but may evolve rapidly in adrenal crisis. Hyponatremia and hyperkalemia (as a result of mineralocorticoid deficiency) are often present. Laboratory abnormalities are less common, but hypoglycemia is occasionally seen, especially with concomitant growth hormone deficiency. More than 90% of Addison disease in the developed world is secondary to autoimmune adrenalitis, and it is more common in women. Risk Factors Primary Adrenocortical Insufficiency A personal or family history of autoimmune disease. Cosyntropin testing should not be used in cases of short-term secondary insufficiency, such as after recent pituitary surgery, because adrenal atrophy must have occurred for the adrenal response to cosyntropin to be blunted. One must consider the total serum cortisol as affected by its binding protein, which is elevated by high estrogen levels and could be low in hypoalbuminemia. If the clinical picture is not concordant with the investigation, an endocrinology consult should be sought. Enlarged adrenal glands with highdensity areas or calcification on computed tomography can suggest granulomatous disease or neoplasm. Acute hematoma or fluid collections around the adrenals during an acute adrenal crisis can indicate adrenal hemorrhage. Treatment Glucocorticoid replacement is recommended with oral hydrocortisone two or three times daily. Oncedaily, modified-release hydrocortisone is available in Europe and may better mimic the physiological circadian rhythm of cortisol, but it is not yet available in the United States. Patients should be instructed to increase this dosage according to physiologic stress, as doses should be doubled or tripled for 3 or more days in case of fever or intercurrent systemic illness. For surgery, parenteral glucocorticoid doses should be administered according to the level of surgical stress, such as 25 mg for minor stress. Patients should wear a medical alert bracelet or necklace and should be dispensed hydrocortisone or dexamethasone injection with instructions for home self-administration in case of vomiting and inability to take oral doses. If symptoms do not improve within hours after injection, patients should seek an urgent medical evaluation. Iatrogenic Cushing syndrome can develop if the dose of glucocorticoid replacement is supraphysiologic over the long term. Iatrogenic/Medication Chronic steroid therapy, most often oral or parenteral, but could also be inhaled, topical, or injected Chronic opioid therapy Pituitary Injury Post-transsphenoidal or transcranial surgery Radiation to the sella Infarction. Aggressive hydration with a saline solute will help increase the intravascular volume, and high-dose glucocorticoids have some mineralocorticoid activity; thus mineralocorticoids are not required in the treatment of acute adrenal crisis. The controversial entity of suboptimal cortisol response during acute stress may be associated with worse outcome, but no consensus exists for its diagnosis and treatment. Development of hypertension, edema, or hypokalemia could mandate a dose reduction. Monitoring of mineralocorticoid status should include volume status, electrolytes, blood pressure, and occasionally serum renin levels. Lower success rates and higher incidence of relapse are recorded in less-experienced centers. Somatostatin analogues and various chemotherapeutic regimens have been used in the treatment of metastatic tumors. Macroadenomas are rare and often invasive, with extension outside of the sella turcica. Other tumors causing the syndrome are bronchial, thymic, and pancreatic carcinoids; medullary thyroid carcinoma; pheochromocytoma; or other rare neuroendocrine tumors, especially in pediatric patients. They are divided into two groups of disorders, macronodular and micronodular hyperplasias, on the basis of the size of the associated nodules. In macronodular disorders, the greatest diameter of each nodule exceeds 1 cm; in the micronodular group, nodules are less than 1 cm. We use two additional basic characteristics in this classification of bilateral adrenocortical hyperplasias: presence of tumor pigment and status (hyperplasia or atrophy) of the surrounding cortex. Pigment in adrenocortical lesions is rarely melanin; most of the pigmentation in adrenocortical adenomas and bilateral adrenocortical hyperplasias that produce cortisol is lipofuscin. The accumulation of lipofuscin-like material results from the progressive oxidation of unsaturated fatty acids by oxygen-derived free radicals in lysosomes. Lipofuscin pigmentation appears macroscopically as light brown to occasionally dark brown or even black discoloration of the tumor or hyperplastic tissue. Truncal obesity is the most common clinical sign and is usually the initial manifestation in most patients. Other symptoms include central fat deposition, supraclavicular fat accumulation, buffalo hump, plethora, rounded face, purple striae, thin skin, proximal muscle weakness, hypertension, impaired glucose metabolism, gonadal dysfunction, and hirsutism (see Table 3). Osteoporosis, mood disorders, emotional lability and cognitive deficits are commonly observed. Diagnosis Confirmation of the Diagnosis the initial evaluation should always include a careful clinical history and physical examination. On an outpatient basis, this is typically done through the urinary free cortisol test. We typically recommend collections over two or three consecutive days so that we avoid errors due to over- or undercollection that are not uncommon with single 24-hour studies. The results of the test need to be corrected for body surface area, as long as total creatinine excretion is normal. A 1-mg overnight dexamethasone test is less useful and more expensive, but it provides a good alternative for patients in whom urinary collection is impossible or unreliable.

Heart Block Heart block refers to block or delay of electrical propagation between the atria and ventricles blood pressure zantac generic microzide 25mg line. Pacemaker therapy is an effective treatment prehypertension risk factors discount 12.5mg microzide otc, but it is associated with significant short- and long-term complications pulse pressure 38 generic microzide 25 mg. This underscores the importance of recognizing preventable and reversible causes of heart block for accurate targeting of permanent pacing blood pressure reading 400 purchase generic microzide from india. Risk stratification of patients with heart block hypertension word parts purchase discount microzide on-line, assessment of the benefits and risks of the therapeutic options heart attack 80 blockage discount 25mg microzide fast delivery, and patient education and guidance are largely in the domain of heart rhythm specialists. However, heart block may be encountered unexpectedly in any patient during any clinical encounter. A basic understanding of heart block may be useful to initiate emergency treatment and to recognize patients who warrant further evaluation or specialist referral. The prevalence and incidence of heart block are difficult to establish because they are strongly dependent on the demographic and clinical characteristics of the population sample. Higher degrees of heart block can be expected to be less common but similarly associated with age and underlying cardiovascular disease. In a study of the Framingham population, the prevalence of firstdegree heart block was 1. However, the vast majority with risk factors never develop symptomatic heart block and have not been shown to benefit from intense monitoring or prophylactic pacemaker placement. In addition, specialized conduction cells exhibit automaticity (impulse formation). Although normally latent because normal activation inhibits spontaneous discharge, when the normal impulse is blocked, discharges from these subsidiary physiological pacemakers provide vital heart rate support. Block of electrical activation can occur due to failure of any step in the process, for example, lack of metabolic energy, electrolyte imbalance, inflammatory disruption of the membrane, block of ion channels by drugs, or interference with gap junction function due to infiltration of fibrous tissue (Table 1). Because of the extensive redundancy and interconnectivity and because of the capacity to compensate for injury by electrical and anatomic remodeling, there may be extensive damage before signs or symptoms of heart block occur. Regions of the heart where there are fewer alternative paths for electrical activation, such as proximal portions of the His-Purkinje system where all conducting fibers are confined to a relatively small area, are more vulnerable to complete block. Subsidiary pacemakers sometimes fail to provide adequate rate support when heart block occurs because of preexisting injury. If the patient survives an episode of heart block, there is a possibility for recovery due to remodeling. Although there are many potential causes of heart block, the pathophysiology is not known for the vast majority of cases because there are no tests that allow detailed structural or functional examination in patients. By the time of death, morphologic examination may reveal only nonspecific changes such as fibrosis. Because most etiologies cannot be verified, the clinician must remain open to alternative explanations and accept the likelihood of multiple contributors. Some patients, usually young, otherwise healthy individuals, present with prolonged asystole due to heart block but have no other detectable abnormalities and have excellent outcomes in the absence of intervention beyond counseling. This suggests that autonomic influences alone can cause prolonged heart block and suppression of subsidiary pacemakers. Electrical activation is initiated by pacemaker cells of the sinus node regulated by the autonomic nervous system. Unlike conduction in common electrical circuits in which electrons flow along a conductor according to the voltage gradient, electrical activity in cardiac cells propagates from segment to segment of the cell membrane in cardiac myocytes (myocardial cells) and in specialized cardiac conduction cells. Energy-requiring ion pumps maintain an electrochemical gradient across the insulating cell membrane. Electrical activity opens voltage-sensitive ion channels causing regenerative electrical activity as ions shift along their electrochemical gradient. Electrical activity in a single cell excites several adjacent cells via gap junctions. This cascade effect makes it possible for a single cell impulse to spread rapidly throughout the myocardium to enhance synchronous contraction. However, the identification of such patients is important because most can be managed without pacemakers. Prevention Because various arrhythmias and other cardiac and noncardiac disorders may be responsible for similar symptoms, it is important to identify the cause. Absence of arrhythmias at the time of symptoms is also helpful in excluding heart block as the cause. Significant disease of the His bundle may be electrocardiographically silent, but more often concomitant distal disease is evident in the form of fascicular or bundle branch block or a nonspecific intraventricular conduction delay. In a patient with syncope, the presence of bifascicular block raises the possibility of transient third-degree block as the mechanism and of progression to permanent complete block. Most patients with conduction disorders are not symptomatic and do not progress to complete block. Nevertheless, conduction disturbances of the His-Purkinje system should not be assumed to be responsible for syncope or cardiac arrest because they are relatively common in patients with cardiovascular disorders that cause syncope or cardiac arrest due to other mechanisms. Conduction disturbances can cause dyssynchronous contraction and result in adverse remodeling. This pattern is considered a harbinger of complete block and warrants continuous monitoring and evaluation for permanent pacemaker implantation. Unsustained polymorphic ventricular tachycardia is an ominous sign in any context and may result from a variety of cardiac, metabolic, and autonomic abnormalities. Multiple tracings of suspicious events should be obtained in multiple leads when possible. Some instances can be prevented by treatment of inflammatory disorders that cause heart block, such as Lyme disease or cardiac sarcoid. Other individuals who should be identified are those with conditions that place them, their relatives, or their unborn children at risk for heart block. This includes patients and family members with genetic disorders associated with heart block. Neonatal lupus syndrome is a rare disorder with a high mortality rate and risk of permanent complete heart block in survivors. Members of this group may benefit from counseling and anticipatory evaluation and treatment of offspring. It should be recognized that with current methods the vast majority of heart block events cannot be predicted or prevented, and the vast majority of persons with risk factors never develop symptomatic heart block. Differential Diagnosis 115 Clinical Manifestations Most of the symptoms experienced by patients with heart block are common and nonspecific, including syncope, lightheadedness, fatigue, and dyspnea. Asystole or profound bradycardia may cause syncope, death, or other manifestations of hypoperfusion. For the patient with documented heart block, the clinician selects therapy based, in part, on whether the arrhythmia is permanent or likely to recur. Other indirect sources such as coronary angiography, magnetic resonance imaging, nuclear imaging, and myocardial biopsy, as well as a large number of specific laboratory tests, are often helpful for identifying disorders that may be causative or associated with heart block and that may affect the choice of treatment. Another common context is the patient with symptoms for whom the objective is to verify or exclude heart block as the mechanism by correlating the cardiac rhythm with symptoms. Holter monitoring is useful for patients who have very frequent events (at least 1 every 24 hours), and they are useful for capturing asymptomatic rhythm disturbances. External recorders are applied for a month or longer and are very helpful to associate rhythm abnormalities with symptoms and to rule out a rhythm disorder as the cause of symptoms in patients with at least one event per month. Patients with infrequent events may be candidates for implantable loop recorders, which monitor for greater than a year. Modern monitors will provide a permanent record of arrhythmias on activation by the patient or by a detection algorithm. Unfortunately, the sensitivity is low and a negative test does not imply a low risk of future episodes. Therapy the object of the evaluation and management for heart block is to prevent death and morbidity by (1) heart rate support in patients with poorly tolerated bradycardia; (2) monitoring and standby heart rate support in patients at high risk for asystole or severe bradycardia; (3) identifying and treating reversible causes of heart block; (4) identifying patients at high risk for sudden death, syncope, or recurrent symptoms; and (5) selecting and implanting the appropriate rate support system as soon as safety permits. Advanced cardiac life-support guidelines apply to the patient who is unresponsive or severely compromised by heart block. Therefore evaluation and treatment of other disorders should continue while efforts to obtain the appropriate heart rate are underway. Basic laboratory tests (electrolytes, metabolic panel, cardiac biomarkers, thyroid function, blood count, and coagulation studies) and basic imaging (chest x-ray and echocardiography) are usually appropriate. The patient should then be stratified for the appropriate level of care: (1) the unstable patient who requires ongoing evaluation and treatment in an intensive care setting, (2) the stable patient at high risk for asystole or complications who needs temporary transvenous pacing or other invasive procedures, (3) the patient at moderate risk who requires continuous monitoring and standby noninvasive heart rate support measures, (4) the patient at low risk who requires rapid but not immediate access to heart rate support measures that hospital monitoring provides, and (5) the patient at low risk who can be evaluated and managed as an outpatient. Additional testing and procedures may be necessary to determine the etiology of heart block and to determine whether there is a significant risk of future adverse events. Determination of the need for long-term heart rate support, as well as other issues that may affect implantable device selection. The reasons for the selected therapy, including the rationale for any deviation from established guidelines, should be documented and provided to the patient. This will reduce future confusion or misunderstanding about the original rationale for implantation that can affect management of patients with device complications, recalls (safety alerts), and those with a compelling need for device upgrade or explantation. The incidence of heart block in patients with myocardial infarction based on creatine phosphokinase as the marker of necrosis is approximately 10%. Although the incidence is probably lower using more sensitive markers such as troponin, heart block is still likely to be associated with increased in-hospital mortality due to larger infarct size. Therefore overcorrection of heart rate and blood pressure should be avoided and ischemia should be relieved by reperfusion as soon as possible. Studies in the prethrombolytic era did not demonstrate a benefit in mortality with prophylactic temporary transvenous pacing, and complications were frequent. The risks of transvenous insertion may be higher in patients requiring administration of thrombolytics and other anticoagulants. Catheter-based revascularization methods should be given strong consideration because of established effectiveness, the possible avoidance of thrombolytic drugs, and because transvenous temporary pacing, if needed, is readily and safely accomplished during the procedure. Suggestions for standby temporary pacing (Table 3) should take into consideration the risks of transvenous pacing based on local circumstances (experience, fluoroscopic guidance, insertion site, use of anticoagulants, etc. Most conduction disturbances associated with myocardial ischemia or infarction resolve quickly but can persist for days or weeks. The need for permanent pacemaker implantation as a consequence of myocardial infarction is rare, and prophylactic pacemaker implantation in high-risk subsets has not been shown to reduce mortality. Selection of the correct therapeutic approach balances the risks and benefits of therapy against the risks of heart block for both immediate and long-term management. Catecholamines (dobutamine, dopamine, epinephrine, isoproterenol [Isuprel]) are useful for emergency, temporary, and standby heart rate support. To avoid underdoses or overdoses at the time of sudden symptomatic heart block, the optimal dose can be established in advance by test doses starting at low infusion rates. Vagal activity inhibits sympathetic activity; therefore, reduction of vagal tone by atropine disinhibits sympathetic activity and may account for the unpredictable effects of atropine on heart rate. Elevations in heart rate after atropine can persist for hours and cannot be readily reversed. The effective refractory period shortens in most tissue but this effect varies with dose and specific tissue type. This can result in unwanted hypotension in some circumstances but it is also less likely to cause a reflex increase in vagal tone than drugs that cause vasoconstriction. It is recommended for asystolic cardiac arrest in part because it increases myocardial and cerebral flow. However, the increase of systemic vascular resistance may be detrimental by augmenting metabolic acidosis and decreasing cardiac performance in patients with poor left ventricular function. Transcutaneous pacing provides noninvasive heart rate support, as well as immediate access to countershock, but it is often so painful that most patients require sedation. For these reasons its principal uses are for short-term pacing during cardiopulmonary resuscitation and standby pacing in patients at risk for bradyarrhythmias. Therefore users should be ready to continue 1 mechanical cardiopulmonary support and seek alternative methods. If used in standby applications, ventricular capture should be verified in advance. Transvenous insertion of an electrode catheter is the method of choice for most patients who require temporary pacing. This approach is reliable and safe when performed by competent staff with strict aseptic technique, fluoroscopic guidance, and appropriate catheters. Monitoring Patients with high-grade or symptomatic heart block require close monitoring until the process is reversed by treatment or a pacemaker is implanted. All patients who receive pacemakers require lifelong follow-up by a trained team of physicians, nurses, and ancillary personnel using standard procedures guided by practice guidelines and manufacturer recommendations. Catecholamines used to increase heart rate may precipitate tachyarrhythmias by electrophysiological effects mediated by adrenergic receptors or by myocardial ischemia, and they may worsen hemodynamic status. Ischemia and receptor-mediated electrophysiologic effects occur immediately after administration; changes in gene expression of ion channels begin as early as several hours; and long-term changes such as myocardial hypertrophy, apoptosis, and fibrosis occur within 24 hours and may progress over much longer periods. This suggests that the duration and dose of catecholamine infusions should be minimized. Complications of temporary transvenous pacing include inadequate pacing or sensing thresholds, vascular complications, pneumothorax, myocardial perforation, infection, and dislodgment. Permanent pacemakers are highly effective, safe, and cost-effective with few contraindications. Although the complications are rarely life threatening, they should be carefully considered and acknowledged. In patients with pacemaker-related endocarditis, the in-hospital mortality rate is reported to be over 7% with a 20-month mortality rate over 25%. About 10% of pacemakers will become infected or develop some other type of failure that may require extraction. In a recent series the rate of major complications associated with extraction was 1. Abandoned leads block venous access and extractions are associated with significant risks.