Rhinoviral infections are chiefly limited to the upper respiratory tract but may cause otitis media and sinusitis. Rhinoviral infections may exacerbate asthma, cystic fibrosis, chronic bronchitis, and serious lower respiratory tract illness in infants, elderly persons, and immunocompromised persons. Although infections occur year-round, the greatest incidence occurs in the fall and spring. Of persons exposed to the virus, 70-80% have symptomatic disease.

Rhinoviruses are transmitted to susceptible individuals by direct contact or by aerosol particles infecting both ciliated areas of the nose and nonciliated areas of the nasopharynx. Few cells are actually infected by the virus, and the infection involves only a small portion of the epithelium. Symptoms develop 1-2 days after viral infection, peaking 2-4 days after inoculation, although reports have described symptoms as early as 2 hours after inoculation with primary symptoms 8-16 hours later.

The virus grows in a limited temperature range (33-35°C) and cannot tolerate an acidic environment. Thus, finding the virus outside of the nasopharynx is unlikely because of the acidic environment of the stomach and the increased temperature in both the lower respiratory and gastrointestinal tracts.

Individual patients exhibit a wide variety of signs and symptoms:

• The incubation period is 12-72 hours, averaging 8-16 hours after viral inoculation of the nose. Symptomatic complaints 2 hours after viral inoculation have been described.
• Illness initially begins with a sore throat, which is frequently the most bothersome of the early symptoms. This is followed by nasal discharge, nasal congestion, and sneezing, which intensify over the next 2-3 days.
• Other associated complaints include headache, facial and ear pressure, and loss of smell and taste.
• Thirty percent of infected individuals develop a cough, and 20% develop hoarseness, both of which may persist up to a week, although they seldom become bothersome until nasal symptoms improve.
• Systemic signs and symptoms, such as fever and malaise, are unusual. If they are present, consider an alternative diagnosis.
• Symptoms generally last 7-11 days, although they persist up to 2 weeks in a quarter of patients. Rarely, patients complain of lingering symptoms that last more than 30 days.
• Infants and toddlers may display only nasal discharge. However, Calvo et al recently reported that, among infants younger than 2 years with viral respiratory tract infection requiring hospitalization in Spain, rhinoviral infections are second only to respiratory syncytial virus infections in terms of frequency.  
• School-aged children usually complain of nasal congestion, cough, and runny nose. These symptoms persist for an average of at least 10 days.
• Most patients have obstruction and mucosal abnormalities of sinuses, eustachian tubes, and middle ear, which causes a predisposition to secondary bacterial infection in up to 2% of patients.
• Infection may exacerbate underlying asthma and chronic pulmonary disease.
• People who smoke do not appear to have more frequent rhinoviral infections; however, their infections are more severe and their symptoms of longer duration.

The physical examination findings are typically less severe than those reported by the patient.

• Red nose with dripping nasal discharge may be present.
• Nasal mucous membranes have a glistening glassy appearance without obvious erythema or edema. Yellow or green nasal discharge does not indicate bacterial infection because a large number of white blood cells migrate to the site of viral infection.
• If marked erythema, edema, exudates, or small vesicles are observed in the oropharynx or if conjunctivitis or polyps in the nasal mucosa occur, consider other etiologies, including infection with adenovirus, herpes simplex virus, mononucleosis, diphtheria, coxsackievirus A, or group A streptococci.
• Auscultation of the chest may reveal rhonchi, but the chest is usually clear.

Transmission

• Rhinoviral transmission occurs with close exposure to infected respiratory secretions, including hand-to-hand, self-inoculation of eyes or nose, and, possibly, large- and small-particle aerosolization. The virus has been cultured from the skin after up to 2 hours and after up to 4 days on inanimate objects in ideal conditions. Donors are typically symptomatic with a cold at the time of transmission, and virus is detected on their hands and nasal mucosa.
• One recent study assessed the transfer of virus to surfaces in 15 adults with rhinoviral infection. Each stayed overnight in a hotel room. Afterward, 10 commonly-touched sites in each room were tested for viral contaminants. They found that virus could be recovered from 35% of these sites. Furthermore, they found that virus could be transferred back from inanimate objects to fingertips in many cases. 
• Higher rates occur in humid, crowded conditions, as found in nurseries, daycare centers, and schools, especially during cooler months in temperate regions and the rainy season in tropical regions.
• The likelihood of transmission does not appear to be related to exposure to cold temperatures, fatigue, or sleep deprivation.

Treatment

Rhinoviral infections are predominately mild and self-limited; thus, treatment is generally focused on symptomatic relief and prevention of person-to-person spread and complications. The mainstays of therapy include rest, hydration, antihistamines, and nasal decongestants.

Antibacterial agents are not effective unless bacterial superinfection occurs. Development of effective antiviral medications has been hampered by the short course of these infections. Because peak symptom severity occurs at 24-36 hours after inoculation, antivirals have only a narrow window to positively affect a rhinoviral infection. In addition, the cause of the common cold is not always rhinoviral infection. Therefore, rapid and accurate diagnostic tests would be needed if a specific antiviral therapy were developed.

• Because of the large number of rhinovirus immunotypes and the inaccessibility of the conserved region of the viral capsid (the most likely effective site for targeting a vaccine), no rhinovirus vaccine is on the horizon.
• Because infection is spread by hand-to-hand contact, autoinoculation, and, possibly, aerosol particles, emphasize appropriate hand washing, avoidance of finger-to-eyes or finger-to-nose contact, and use of nasal tissue.
• Heated humidified air has been used for decades for the alleviation of symptoms due to rhinoviral infections but has never been shown to improve objective outcome measures.

Dietary supplements have been touted as possible therapeutic or preventive measures.

• Although large doses of vitamin C have been used for prevention and treatment of colds, controlled trials reveal minimal therapeutic benefit and no preventive qualities.
• Zinc has been found to inhibit rhinovirus replication in vitro, but no proven benefit has been shown in vivo on virus activity or immune modulation.

Drugs used in the symptomatic treatment include nonsteroidal anti-inflammatory drugs (NSAIDs), antihistamines, and anticholinergic nasal solutions. These agents have no preventive activity and appear to have no impact on complications. The combined effect of NSAIDs and antihistamines often relieves nasal obstruction; therefore, decongestion therapy is rarely needed. Oral (pseudoephedrine) and topical (oxymetazoline and phenylephrine) decongestants are commonly used for symptomatic relief.

First-generation antihistamines reduce rhinorrhea by 25-35%, as do topical anticholinergics and ipratropium bromide. Second-generation or nonsedating antihistamines appear to have no effect on common cold symptoms. Corticosteroids may actually increase viral replication and have no impact on cold symptoms.

Skin – Primary lesion of molluscum contagiosum

• Firm, smooth, umbilicated papules, usually 2-6 mm in diameter (range 1-15 mm), may be present in groups or may be widely disseminated on the skin and mucosal surfaces.
• The lesions can be flesh-colored, white, translucent, or even yellow in color.
• The number of lesions varies from 1-20 up to hundreds in some reports.
• Some lesions become confluent to form a plaque.
• Lesions generally are self-limited but can persist for several years.

The common goal of the different treatment methods is the destruction of the lesions. Once the lesion is gone, the infection is gone.  In immunocompetent people, no therapy is indicted with resolution in 6 to 12 months.  In the immunocompromised, aggressive therapy is needed to contain the disease with chemical, cryo, laser, or curettage. 

See the lesion at the arrow.

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. Hepatocellular carcinoma is now the third leading cause of cancer deaths worldwide, with over 500,000 people affected.  The incidence of hepatocellular carcinoma is highest in Asia and Africa, where the endemic high prevalence of hepatitis B and hepatitis C strongly predisposes to the development of chronic liver disease and subsequent development of hepatocellular carcinoma.

Hepatocellular carcinoma is a primary cancer of the liver and occurs predominantly in patients with underlying chronic liver disease and cirrhosis.

The cell of origin is believed to be the hepatic stem cells. 

Tumors progress with local expansion, intrahepatic spread, and distant metastases.

In general, the tumors are discovered either during routine screening or when symptomatic because of their size or location. Tumors may present as a single mass lesion or as diffuse growth, which can be difficult to differentiate from the surrounding cirrhotic liver tissue and the regenerating liver nodules on imaging studies.

The presentation may be caused in part by mass effect that can lead to obstruction of the biliary system or anywhere affecting the liver vasculature.

Without aggressive surgical resection, ablative therapy, or liver transplantation, hepatocellular carcinoma results in liver failure and death.

In the United States, the risk factors have historically included alcoholic cirrhosis, hepatitis B (HBV) infection, hemochromatosis, and now hepatitis C (HCV) infection. However, the obesity epidemic has resulted in a growing population of patients with nonalcoholic fatty liver disease, also referred to as nonalcoholic steatohepatitis. Patients with nonalcoholic fatty liver disease can progress to fibrosis, cirrhosis, and now hepatocellular carcinoma.

Among patients with cirrhosis, current recommendations include cross-sectional imaging studies every 6-12 months and serum alpha-fetoprotein (AFP) measurements.

Liver transplant is still the best treatment!!

Surgical treatment of porcelain gallbladder is based on results from studies performed in 1931 and 1962, which revealed an association between porcelain gallbladder and gallbladder carcinoma.

Porcelain gallbladder is an uncommon condition; recognizing the clinical and imaging characteristics of the disease is important because of the high frequency (22%) of adenocarcinoma in porcelain gallbladder.  

Surgery should not be delayed even if the patient is asymptomatic, because the occurrence of carcinoma in porcelain gallbladder is remarkably high.

Remember. . . a calcified gallbladder on routine x-ray in an asymptomatic patient NEEDS SURGERY!! 

In internal medicine, the main causes for exam purposes are:

1. Anticardiolipin Syndrome
2. Lupus Anticoagulant (Anti-phospholipid)
3. Fibrinogen Disorders
4. Factor 13 deficiency

Symptoms

• Photopsias refer to the perception of flashing lights by the patient. It probably arises from the mechanical stimulation of vitreoretinal traction on the retina. It may be induced by eye movements and appears to be more noticeable in dim illumination.
• Visual field defect: Patients often describe a black curtain (visual field defect).
• Floaters
  • Floaters are opacities in the vitreous that cast a dark shadow according to their form and shape in the patient’s visual field as they float in the vitreous cavity.
  • A ring-shaped floater is the Weiss ring or the remnant of the hyaloid that was attached to the edges of the optic disc.
  • Cobwebs are caused by condensation of the collagen fibers.
  • Small spots usually indicate fresh blood due to the rupture of a retinal vessel during an acute PVD.
• Loss of central vision
  • When the macula becomes detached (ie, extension of subretinal fluid into the macula), the patient experiences a drop in visual acuity.
  • In other cases, a large bullous detachment may obstruct the macula, causing decreased visual acuity despite the fact that the macula is not detached.

The following are risk factors: 

• Abnormal vitreoretinal adhesions
• Prior intraocular surgery, especially cataract extraction
• Certain familial conditions, such as Stickler syndrome, Marfan syndrome, homocystinuria, and Ehlers-Danlos syndrome
• Inflammatory or infectious conditions, such as acute retinal necrosis syndrome, CMV retinitis in AIDS patients, ocular toxoplasmosis, and pars planitis

Eye ischemia is claasified as the following:

• Transient visual obscuration (TVO) – Episodes lasting seconds that are associated with papilledema and increased intracranial pressure
• Amaurosis fugax – Brief, fleeting attack of monocular partial or total blindness that lasts seconds to minutes
• Transient monocular visual loss (TMVL) or transient monocular blindness (TMB) – A more persistent vision loss that lasts minutes or longer
• Transient bilateral visual loss (TBVL) – Episodes affecting one or both eyes or both cerebral hemispheres and causing visual loss
• Ocular infarction – Persistent ischemic damage to the eye, resulting in permanent vision loss

_______________________________________________________________________________

Transient Bilateral Vision Loss

Wray has classified TMVL into 3 different groups based mostly on pathogenesis; they include the following:

• Type 1 is characterized by loss of all or a portion of vision in one eye, lasting seconds to minutes, with full recovery. It is usually secondary to an embolic phenomenon. The attacks have been related to an ICA origin associated with ulceration but not critical narrowing.
• Type 2 includes visual loss due to hemodynamically significant, occlusive, low-flow lesions in the ICAs or ophthalmic arteries. Symptoms are more frequent, less rapid in onset, and longer in duration than type 1 attacks, with gradual vision recovery.
• Type 3 is thought to be due to vasoconstriction or vasospasm.

Angle Closure Glaucoma

The diagnosis is not difficult when the presentation is typical—a painful, red eye with increased intraocular pressure that is accompanied by diaphoresis, nausea, and vomiting. Atypical presentations include chronic angle closure or an acute closure without pain. The presence of a midposition, fixed pupil in an eye with reduced vision can suggest unrecognized angle-closure glaucoma.  Treatment consists of topical miotics and beta-blockers, systemic carbonic anhydrase inhibitors, hyperosmotic agents, and perhaps analgesics and antiemetics. Ophthalmologic consult is warranted.

______________________________________________________________________________________

Medical care for patients with sudden visual loss includes the following:

• Aspirin is believed to be beneficial in patients with no hemodynamically significant disease of the carotid artery (ie, greater than 1 mm residual lumen) or those who are poor surgical candidates.
  • In general, aspirin together with modification of risk factors (eg, decreasing serum cholesterol level, controlling systemic hypertension) reduces the likelihood of myocardial infarction. It is also very effective in reducing the risk of stroke.
• Advise patients with frequent or severe headaches to stop smoking.
• Inferior retinal detachment is treated with the patient sitting up. Superior detachment is treated with the patient lying prone.

In the end, the decision to treat or not treat pharygitis rests with the probability of having a group A beta-hemolytic streptococcal infection, specifically.  Most other causes are self-limiting, and more importantly, do not require antibiotic therapy.  

The Centor criteria have been used in the past as a way to diagnose and treat GAS pharyngitis.  These include the following:

1. Fever
2. Anterior cervical lymphadenopathy
3. Tonsillar exudate
4. Absence of cough

Assess for group A beta-hemolytic streptococcal (GAS) infection if clinically suspected. A suggested algorithm as is follows.

• In general, patients should not be treated without a positive culture or positive rapid antigen detection test result because of increasing antibiotic resistance. Guidelines from the Infectious Diseases Society of America (IDSA) and American Heart Association state that microbiologic confirmation (via a rapid antigen test or culture) is required for the diagnosis of GAS.  
• Perform rapid antigen detection test if GAS is clinically suspected based on history and physical examination. If positive, begin antibiotic therapy. Testing does not usually need to be performed on patients with acute pharyngitis whose clinical and epidemiologic features do not suggest GAS as the etiology (Centor score 0-1).
• Patients who are positive for all 4 Centor criteria can often be treated with antibiotics without antigen testing or cultures.
• Household contacts of patients with GAS infection or scarlet fever should be treated for a full 10 days without testing only if they have symptoms consistent with GAS.
• If clinically doubtful or the above criteria are not met, it is best to await rapid antigen or culture results to initiate antibiotic therapy.

You should recognize Strep pyogenes.

• In classic presentations, patients complain of eyelids sticking together on waking.
• They may describe itching and burning or a gritty foreign-body sensation.
• Pus sliding across the eye may distort vision, though visual acuity is normal.
• Photophobia is minimal.
• Family members with similar complaints typically present with conjunctivitis from an infectious cause.
• A history of a recent upper respiratory infection (URI) typically is associated with a viral cause.

Specific helpful clues in differentiating the causes of conjunctivitis are listed below.

• Bacterial conjunctivitis
  • Preauricular adenopathy sometimes occurs; chemosis (thickened, boggy conjunctiva) is common.
  • Discharge is copious; discharge quality is thick and purulent. Conjunctival injection is moderate or marked.
• Viral conjunctivitis
  • Preauricular adenopathy is common in herpes.
  • Discharge amount is moderate, stringy, or sparse; discharge quality is thin and seropurulent. Conjunctival injection is moderate or marked.
• Chlamydial conjunctivitis tends to be chronic with exacerbation and remission.
  • Preauricular adenopathy is occasional; chemosis is rare.
  • Discharge amount is minimal; discharge quality is seropurulent. Conjunctival injection is moderate.
• Allergic conjunctivitis occurs with pruritus as the hallmark symptom.
  • Preauricular adenopathy is absent; chemosis is common.
  • Discharge amount is moderate, stringy, or sparse; discharge quality is clear. Conjunctival injection is moderate.
• Marginal ulcers (small white ulcers that appear on the cornea at the limbus) may indicate an allergic reaction to staphylococcal antigen.
  • This is a toxin-related complication of staphylococcal species that frequently cause blepharitis.
  • Pain, photophobia, and a foreign-body sensation are common. The ulcers are sterile and respond to topical steroids.
• Bilateral disease typically is infectious or allergic.
• Unilateral disease suggests toxic, chemical, mechanical, or lacrimal origin.

Acute conjunctivitis occurs with almost equal frequency between bacterial and viral causes. Some have noted that viral conjunctivitis occurs more frequently in the summer, and bacterial conjunctivitis occurs more often in the winter and spring.

Treatment with antimicrobials and symptomatic therapy is recommended for all patients initially presenting to the office with simple conjunctivitis.

Numerous topical antimicrobial agents may be used, including topical sulfacetamide, erythromycin, gentamicin, ciprofloxacin, or ofloxacin.

Instill drops every 2 hours. An ointment can be used at night or every 4-6 hours throughout the day.

If a question on the therapy for classic conjunctivitis offers options of:

1. Saline
2. Good hand washing
3. Steroid opthalmologic drops
4. Gentamycin drops

Choose antibiotic therapy (#4) Remember the BEST answer is wanted.

Store this image in your brain.

5-Fluorouracil remains the backbone of chemotherapy regimens for colon cancer, both in the adjuvant and metastatic setting. In the past 10 years, it was established that combination regimens provide improved efficacy and prolonged progression-free survival in patients with metastatic colon cancer.

In addition to 5-fluorouracil, oral fluoropyrimidines such as capecitabine (Xeloda) and tegafur are increasingly used as monotherapy or in combination with oxaliplatin (Eloxatin) and irinotecan (Camptosar).

Adjuvant (postoperative) chemotherapy

The standard therapy for patients with stage III and some patients with stage II colon cancer for the last 2 decades consisted of fluorouracil in combination with adjuncts such as levamisole and leucovorin.  This approach has been tested in several large randomized trials and has been shown to reduce individual 5-year risk of cancer recurrence and death by about 30%.

The role of adjuvant chemotherapy for stage II colon cancer is controversial. A large European trial (QUASAR) demonstrated small but significant benefit (3.6%) in terms of absolute 5-year survival rate for those patients who received 5-fluorouracil/leucovorin versus those in the control group.

Radiation therapy

While radiation therapy remains a standard modality for patients with rectal cancer, the role of radiation therapy is limited in colon cancer. It does not have a role in the adjuvant setting, and in metastatic settings, it is limited to palliative therapy for selected metastatic sites such as bone or brain metastases.

• Tamoxifen use for 5 years reduces risk for at least 10 years in premenopausal women, particularly estrogen receptor (ER) – positive invasive tumors.
  • Women 50 years or younger have few adverse effects with tamoxifen.
  • Vascular/vasomotor adverse effects do not persist post treatment.
• Tamoxifen and raloxifene are equally effective in reducing risk of ER-positive breast cancer in postmenopausal women.
  • Raloxifene is associated with lower rates of thromboembolic disease, benign uterine conditions, and cataracts than tamoxifen.
  • Evidence does not exist regarding whether either agent decreases mortality from breast cancer.
• Recommendations
  • For women with increased risk for breast cancer, offer tamoxifen (20 mg/d for 5 y) to reduce risk of invasive ER-positive breast cancer.
  • In postmenopausal women, raloxifene (60 mg/d for 5 y) may also be considered.
  • Aromatase inhibitors (eg, anastrozole, exemestane, letrozole), fenretinide, or other SERMs are not recommended outside of a clinical trial.

Both genes are believed to be tumor suppressor genes whose products are involved with maintaining DNA integrity and transcriptional regulation.

Mutation rates may vary by ethnic and racial groups.

• For BRCA1 mutations, the highest rates occur among Ashkenazi Jewish women (8.3%)
• followed by Hispanic women (3.5%),
• non-Hispanic white women (2.2%),
• African American women (1.3%), and
• Asian American women (0.5%).

Women who inherit a mutation in the BRCA1 or BRCA2 gene have an estimated 50-80% lifetime risk of developing breast cancer.

Specifically, BRCA1 mutations are seen in 7% of families with multiple breast cancers and 40% of families with breast and ovarian cancer.

BRCA1 mutation carries a lifetime risk of 40% for developing ovarian cancer and are also at a higher risk of colon cancer and prostate cancer.

Breast cancer that develops in BRCA1 mutation carriers are more likely to be high-grade, and ER, PR, and HER-2/neu negative (triple negative) or basal-like subtype.

BRCA2 mutations are identified in 10-20% of families at high risk for breast and ovarian cancers and in only 2.7% of women with early-onset breast cancer.

Women with a BRCA2 mutation have approximately 10% lifetime risk of ovarian cancer.

BRCA2 mutation carriers who develop breast cancer are more likely to have a high grade, ER+/PR+, and HER-2/neu negative cancer (luminal type).

BRCA2 is also a risk factor for male breast cancer.

Other cancers associated with BRCA2 mutations include prostate, pancreatic, fallopian tube, bladder, non-Hodgkin lymphoma, and basal cell carcinoma.

Since 1998, several large trials comparing “newer” classes of agents, including CCBs, ACEIs, an alpha-1 receptor blocker, and an ARB, with the “older” diuretics and/or BBs have been completed. Most of these studies showed the newer classes were neither superior nor inferior to the older ones. One exception was the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) Study, in which CVD events were 13 percent lower (because of differences in stroke but not CHD rates) with the ARB, losartan, than with the BB, atenolol.

There has not been a large outcome trial completed yet comparing an ARB with a diuretic. All of these trials together suggest broadly similar cardiovascular protection from BP-lowering with ACEIs, CCBs, and ARBs, as with thiazide-type diuretics and BBs, although some specific outcomes may differ between the classes. There do not appear to be systematic outcome differences between dihydropyridine and nondihydropyridine CCBs in hypertension morbidity trials. On the basis of other data, short-acting CCBs are not recommended in the management of hypertension.

Rationale for Recommendation of Thiazide-Type Diuretics as Preferred Initial Agent

In trials comparing diuretics with other classes of antihypertensive agents, diuretics have been virtually unsurpassed in preventing the cardiovascular complications of hypertension. In the ALLHAT study, which involved more than 40,000 hypertensive individuals, there were no differences in the primary CHD outcome or mortality between the thiazide-type diuretic, chlorthalidone; the ACEI, lisinopril; or the CCB, amlodipine. Stroke incidence was greater with lisinopril than chlorthalidone therapy, but these differences were present primarily in African Americans who also had less BP lowering with lisinopril than diuretics. The incidence of HF was greater in CCB-treated and ACEI-treated individuals as compared with those receiving the diuretic in both African Americans and Whites. In the Second Australian National Blood Pressure (ANBP2) Study, which compared the effects of an ACEI-based regimen against diuretics-based therapy in 6,000 White hypertensive individuals, cardiovascular outcomes were less in the ACEI group, with the favorable effect apparent only in men.  CVD outcome data comparing ARB  with other agents are limited.

Clinical trial data indicate that diuretics are generally well tolerated. The doses of thiazide-type diuretics used in successful morbidity trials of “low-dose” diuretics were generally the equivalent of 25–50 mg of hydrochlorothiazide or 12.5–25mg of chlorthalidone, although therapy may be initiated at lower doses and titrated to these doses if tolerated. Higher doses have been shown to add little additional antihypertensive efficacy, and are associated with more hypokalemia and other adverse effects.

Uric acid will increase in many patients receiving a diuretic, but the occurrence of gout is uncommon with dosages of 50 mg/day of hydrochlorothiazide or of  25 mg of chlorthalidone. Some reports have described an increased degree of sexual dysfunction when thiazide diuretics (particularly at high doses) are used. In the Treatment of Mild Hypertension Study (TOMHS), participants randomized to chlorthalidone reported a significantly higher incidence of erection problems through 24 months of the study; however, the incidence rate at 48 months was similar to placebo. The VA Cooperative study did not document a significant difference in the occurrence of sexual dysfunction using diuretics when compared with other antihypertensive medications (see section on erectile dysfunction). Adverse metabolic effects may occur with diuretics. In ALLHAT, diabetes incidence after 4 years of therapy was 11.8 percent with chlorthalidone therapy, 9.6 percent with amlodipine, and 8.1 percent with lisinopril. However, those differences did not translate to fewer cardiovascular events for the ACEI or CCB groups.

Those who were already diabetic had fewer cardiovascular events in the diuretic group than with ACEI treatment. Trials of longer than 1 year’s duration using modest doses of diuretics generally have not shown an increase in serum cholesterol in diuretic-treated patients. In ALLHAT, serum cholesterol did not increase from baseline in any group, but it was 1.6 mg/dL lower in the CCB group and 2.2 mg/dL lower in the ACEI group than in diuretic-treated patients. Thiazideinduced hypokalemia could contribute to increased ventricular ectopy and possible sudden death, particularly with high doses of thiazides in the absence of a potassium-sparing agent. In the Systolic Hypertension in the Elderly Program (SHEP) Trial, the positive benefits of diuretic therapy were not apparent when serum potassium levels were below 3.5mmol/L. However, other studies have not demonstrated increased ventricular ectopy as a result of diuretic therapy. Despite potential adverse metabolic effects of diuretics, with laboratory monitoring, thiazide-type diuretics are effective and relatively safe for the management of hypertension.

Thiazide diuretics are less expensive than other antihypertensive drugs, although as members of other classes of drugs have become available in generic form, their cost has been reduced. Despite the various benefits of diuretics, they remain underutilized.

Achieving Blood Pressure Control in Individual Patients

Therapy begins with lifestyle modification, and if BP goal is not achieved, thiazide-type diuretics should be used as initial therapy for most patients, either alone or in combination with one of the other classes (ACEIs, ARBs, BBs, CCBs) that have also been shown to reduce one or more hypertensive complications in randomized controlled outcome trials.

Since most hypertensive patients will require two or more antihypertensive medications to achieve their BP goals, addition of a second drug from a different class should be initiated when use of a single agent in adequate doses fails to achieve the goal. When BP is >20 mmHg above systolic goal or 10 mmHg above diastolic goal, consideration should be given to initiate therapy with two drugs, either as separate prescriptions or in fixed-dose combinations. The initiation of therapy with more than one drug increases the likelihood of achieving BP goal in a more timely fashion. The use of multidrug combinations often produce greater BP reduction at lower doses of the component agents, resulting in fewer side effects.

The use of fixed-dose combinations may be more convenient and simplify the treatment regimen, and may cost less than the individual components prescribed separately. Use of generic drugs should be considered to reduce prescription costs, and the cost of separate prescription of multiple drugs available generically may be less than nongeneric, fixed-dose combinations. The starting dose of most fixed-dose combinations is usually below the doses used in clinical outcome trials, and the doses of these agents should be titrated upward to achieve the BP goal before adding other drugs. However, caution is advised in initiating therapy with multiple agents, particularly in some older persons and in those at risk for orthostatic hypotension, such as diabetics with autonomic dysfunction.

Pressure          = 50-180 mmH2O
Color                = clear
RBC count       = 0-4 x 10^6/L
WBC count      = 0-4 x 10^6/L
Glucose            = >60% of the serum level
Protein             = < 0.45 g/L
Microbiology   = sterile//no growth

Subarachnoid haemorrhage :

Pressure increased, bloody, RBC count increased, WBC = normal/increased, glucose = normal, protein = increased, sterile
 
Acute bacterial meningitis :

Pressure normal/increased, cloudy/turbid, RBC count = normal, WBC = 1000-5000 polymorphs, glucose = decreased, protein = increased, organism present on gram stain/culture

Viral meningitis

Pressure normal, clear, RBC count = normal, WBC = 10-2000 lymphocytes, glucose = normal, protein = normal/increased, sterile/viral DNA or RNA present

Tuberculous meningitis

Pressure normal/increased, clear/cloudy, RBC count = normal, WBC = 50-5000 lymphocytes, glucose = decreased, protein = increased, ZN stain/Auramine stain

Atria & ventricle completely ignoring each other. . .

 When you see this, emergently place temporay pacing in a hospital setting where plans for permanent pacer and cardiovascular consult can be obtained. 

Some P waves are not followed by a QRS.

Second-degree AV block is composed of 2 types: Mobitz I or Wenckebach block, and Mobitz II.

The Mobitz I second-degree AV block is characterized by a progressive prolongation of the PR interval, which results in a progressive shortening of the R-R interval, as shown in the image below.

2nd Degree Mobitz Type 1

Ultimately, the atrial impulse fails to conduct, a QRS complex is not generated, and there is no ventricular contraction.

The Mobitz II 2nd degree AV block is characterized by an unexpected nonconducted atrial impulse, as shown in the image below. Thus, the PR and R-R intervals between conducted beats are constant.

Notice preserved R - R interval

Mobitz I (Wenckebach) block

• No specific therapy is required, unless the patient is symptomatic.
• Patients with suspected myocardial ischemia should be treated with an appropriate anti-ischemic regimen.
• AV nodal blocking agents (including beta-blockade) should be avoided.
• Symptomatic patients should be treated with atropine and transcutaneous pacing. However, atropine should be administered with caution in patients with suspected myocardial ischemia, as ventricular dysrhythmias can occur in this situation.

Mobitz II block

• As with type I block, AV nodal agents should be avoided, and an anti-ischemic regimen should be instituted if ischemia is suspected.
• Transcutaneous pacing pads should be applied to all patients, including asymptomatic patients, as patients with Mobitz II second-degree AV block have a propensity to progress to complete heart block. The transcutaneous pacemaker should be tested to ensure capture. If capture is not able to be achieved, then insertion of a transvenous pacemaker is indicated, even in asymptomatic patients.
• Urgent cardiology consult is indicated for patients who have symptomatic type II block and for those asymptomatic patients who are unable to achieve capture with transcutaneous pacing.

While the conduction is slowed, there are no missed beats. ECG of a patient with first-degree heart block is shown below.

First-degree AV block is more common among African Americans compared with white populations.

The prevalence of first-degree AV block increases with advancing age.

Due to decreased ventricular compliance  (CAD, AS, MR, HCM, Diabetic Cardiomyopathy)

****No S4 during Atrial Fibrillation

The S4 heart sound is associated with any process that increases the stiffness of the ventricle including:

–>hypertrophy of the ventricle

–>long-standing hypertension (causes ventricular hypertrophy)

–>aortic stenosis (causes ventricular hypertrophy)

–>overloading of the ventricle (causes ventricular hypertrophy)

–>fibrosis of the ventricle (eg. post-MI)

–>Congestive Heart Failure

• May be normal in people under 40 years of age and some trained athletes but should disappear before middle age.

• Caused by the oscillation of blood back and forth between the walls of the ventricles initiated by in-rushing blood from the atria.

Due to:

1.Rapid ventricular filling

•   Ventricular decompensation (acutely)
•   Ventricular Septal Defect

2.Severe aortic or mitral regurgitation

3.Poor Left Ventricular Function –Post MI –Dilated Cardiomyopathy  (acutely)

  Ventricular Septal Defect

Persistently split S2 (widened S2) is due to pulmonic stenosis, PE, or RBBB (all cause delayed function of right ventricle.)

A young girl with a split S2 and with RBBB on ECG is Pulmonic Stenosis. Not ASD or VSD.

Normally heard as split during inspiration. The split disappears on expiration.

Heard during the onset of systole

Due to closure of the mitral and tricuspid valve

Loud S1 : pregnancy, anemia, anxiety, thyrotoxicosis, mitral stenosis

Soft S1 : heart failure, mitral regurgitation

 Hypertension is the most common primary diagnosis in America (35 million office visits as the primary diagnosis).5 Current control rates (SBP <140 mmHg and DBP <90 mmHg), though improved, are still far below the Healthy People goal of 50 percent, which was originally set as the year 2000 goal and has since been extended to 2010. In the majority of patients, reducing SBP has been considerably more difficult than lowering DBP. Although effective BP control can be achieved in most patients who are hypertensive, the majority will require two or more antihypertensive drugs. Failure to prescribe lifestyle modifications, adequate antihypertensive drug doses, or appropriate drug combinations may result in inadequate BP control.

 Goals of Therapy

The ultimate public health goal of antihypertensive therapy is to reduce cardiovascular and renal morbidity and mortality. Since most persons with hypertension, especially those >50 years of age, will reach the DBP goal once the SBP goal is achieved, the primary focus should be on attaining the SBP goal.

 Treating SBP and DBP to targets that are <140/90 mmHg is associated with a decrease in CVD complications. In patients with hypertension and diabetes or renal disease, the BP goal is <130/80 mmHg.

Benefits of Lowering Blood Pressure

In clinical trials, antihypertensive therapy has been associated with reductions in (1) stroke incidence, averaging 35–40 percent; (2) myocardial infarction (MI), averaging 20–25 percent; and (3) HF, averaging >50 percent. It is estimated that in patients with stage 1 hypertension (SBP 140–159 mmHg and/or DBP 90–99 mmHg) and additional cardiovascular risk factors, achieving a sustained 12 mmHg reduction in SBP over 10 years will prevent 1 death for every 11 patients treated.

 In the added presence of CVD or target organ damage, only nine patients would require such BP reduction to prevent one death.

 Lifestyle Modifications

Adoption of healthy lifestyles by all persons is critical for the prevention of high BP and is an indispensable part of the management of those with hypertension. Weight loss of as little as 10 lbs (4.5 kg) reduces BP and/or prevents hypertension in a large proportion of overweight persons, although the ideal is to maintain normal body weight. BP is also benefited by adoption of the Dietary Approaches to Stop Hypertension (DASH) eating plan which is a diet rich in fruits, vegetables, and lowfat dairy products with a reduced content of dietary cholesterol as well as saturated and total fat (modification of whole diet). It is rich in potassium and calcium content. Dietary sodium should be reduced to no more than 100 mmol per day (2.4 g of sodium). Everyone who is able should engage in regular aerobic physical activity such as brisk walking at least 30 minutes per day most days of the week. Alcohol intake should be limited to no more than 1 oz (30 mL) of ethanol, the equivalent of two drinks per day in most men and no more than 0.5 oz of ethanol (one drink) per day in women and lighter weight persons. A drink is 12 oz of beer, 5 oz of wine, and 1.5 oz of 80- proof liquor (see table 9). Lifestyle modifications reduce BP, prevent or delay the incidence of hypertension, enhance antihypertensive drug efficacy, and decrease cardiovascular risk. For example, in some individuals, a 1,600 mg sodium DASH eating plan has BP effects similar to single drug therapy. Combinations of two (or more) lifestyle modifications can achieve even better results. For overall cardiovascular risk reduction, patients should be strongly counseled to quit smoking.

 Patient evaluation is made through medical history, physical examination, routine laboratory tests, and other diagnostic procedures. The physical examination should include: an appropriate measurement of BP, with verification in the contralateral arm; an examination of the optic fundi; a calculation of body mass index (BMI) (measurement of waist circumference is also very useful); an auscultation for carotid, abdominal, and femoral bruits; a palpation of the thyroid gland; a thorough examination of the heart and lungs; an examination of the abdomen for enlarged kidneys, masses, distended urinary bladder, and abnormal aortic pulsation; a palpation of the lower extremities for edema and pulses; and neurological assessment.

 Data from epidemiological studies and clinical trials have demonstrated that elevations in resting heart rate and reduced heart-rate variability are associated with higher cardiovascular risk. In the Framingham Heart Study, an average resting heart rate of 83 beats per minute was associated with a substantially higher risk of death from a cardiovascular event than the risk associated with lower heart rate levels. Moreover, reduced heart-rate variability was also associated with an increase in cardiovascular mortality.

No clinical trials have prospectively evaluated the impact of reduced heart rate on cardiovascular outcomes.

Laboratory Tests and Other Diagnostic Procedures

Routine laboratory tests recommended before initiating therapy include a 12-lead electrocardiogram; urinalysis; blood glucose and hematocrit; serum potassium, creatinine (or the corresponding estimated glomerular filtration rate [eGFR]), and calcium; and a lipoprotein profile (after a 9- to 12-hour fast) that includes high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides. Optional tests include measurement of urinary albumin excretion or albumin/creatinine ratio (ACR) except for those with diabetes or kidney disease where annual measurements should be made. More extensive testing for identifiable causes is not generally indicated unless BP control is not achieved or the clinical and routine laboratory evaluation strongly suggests an identifiable secondary cause (i.e., vascular bruits, symptoms of catecholamine excess, or unprovoked hypokalemia). (See Identifiable Causes of Hypertension for a more thorough discussion.) The presence of decreased GFR or albuminuria has prognostic implications as well. Studies reveal a strong relationship between decreases in GFR and increases in cardiovascular morbidity and mortality. Even small decreases in GFR increase cardiovascular risk.67 Serum creatinine may overestimate glomerular filtration. The optimal tests to determine GFR are debated, but calculating GFR from the recent modifications of the Cockcroft and Gault equations is useful.

The presence of albuminuria, including microalbuminuria, even in the setting of normal GFR, is also associated with an increase in cardiovascular risk.  Urinary albumin excretion should be quantitated and monitored on an annual basis in

high-risk groups, such as those with diabetes or renal disease.

Additionally, three emerging risk factors (1) high-sensitivity C-reactive protein (HS-CRP); a marker of inflammation; (2) homocysteine; and (3) elevated heart rate may be considered in some individuals, particularly those with CVD but without other risk-factor abnormalities. Results of an analysis of the Framingham Heart Study cohort demonstrated that those with a LDL value within the range associated with low cardiovascular risk, who also had an elevated HS-CRP value, had a higher cardiovascular event rate as compared to those with low CRP and high LDL cholesterol. Other studies also have shown that elevated CRP is associated with a higher cardiovascular event rate, especially in women. Elevations in homocysteine have also been linked to higher cardiovascular risk; however, the results with this marker are not as robust as those with high HS-CRP.

Identifiable Causes of Hypertension

Additional diagnostic procedures may be indicated to identify causes of hypertension, particularly in patients whose (1) age, history, physical examination, severity of hypertension, or initial laboratory findings suggest such causes; (2) BP responds poorly to drug therapy; (3) BP begins to increase for uncertain reason after being well controlled; and (4) onset of hypertension is sudden. Screening tests for particular forms of identifiable hypertension are shown in table 8.

Pheochromocytoma should be suspected in patients with labile hypertension or with paroxysms of hypertension accompanied by headache, palpitations, pallor, and perspiration. Decreased pressure in the lower extremities or delayed or absent femoral arterial pulses may indicate aortic coarctation; and truncal obesity, glucose intolerance, and purple striae suggest Cushing’s syndrome. Examples of clues from the laboratory tests include unprovoked hypokalemia (primary aldosteronism), hypercalcemia (hyperparathyroidism), and elevated creatinine or abnormal urinalysis (renal parenchymal disease). Appropriate investigations should be conducted when there is a high index of suspicion of an identifiable cause.

The most common parenchymal kidney diseases associated with hypertension are chronic glomerulonephritis, polycystic kidney disease, and hypertensive nephrosclerosis. These can generally be distinguished by the clinical setting and additional testing. For example, a renal ultrasound is useful in diagnosing polycystic kidney disease. Renal artery stenosis and subsequent renovascular hypertension should be suspected in a number of circumstances including: (1) onset of hypertension before age 30, especially in the absence of family history, or onset of significant hypertension after age 55; (2) an abdominal bruit especially if a diastolic component is present; (3) accelerated hypertension; (4) hypertension that had been easy to control but is now resistant; (5) recurrent flash pulmonary edema; (6) renal failure of uncertain etiology especially in the absence of proteinuria or an abnormal urine sediment; and (7) acute renal failure precipitated by therapy with an angiotensin converting enzyme inhibitor (ACEI)

or angiotensin receptor blocker (ARB) under conditions of occult bilateral renal artery stenosis or moderate to severe volume depletion.

In patients with suspected renovascular hypertension, noninvasive screening tests include the ACEI-enhanced renal scan, duplex Doppler flow studies, and magnetic resonance angiography. While renal artery angiography remains the gold standard for identifying the anatomy of the renal artery, it is not recommend for diagnosis alone because of the risk associated with the procedure. At the time of intervention, an arteriogram will be performed using limited contrast to confirm the stenosis and identify the anatomy of the renal artery.

Genetics of Hypertension

The investigation of rare genetic disorders affecting BP has led to the identification of genetic abnormalities associated with several rare forms

of hypertension, including mineralocorticoid-remediable aldosteronism, 11beta-hydroxylase and 17alpha-hydroxylase deficiencies, Liddle’s syndrome, the syndrome of apparent mineralocorticoid excess, and pseudohypoaldosteronism type II. The individual and joint contributions of these genetic mutations to BP levels in the general population, however, are very small. Genetic association studies have identified polymorphisms in several candidate genes (e.g., angiotensinogen, alpha-adducin, beta- and DA-adrenergic receptors, and beta-3 subunit of G proteins), and genetic linkage studies have focused attention on several genomic sites that may harbor other genes contributing to primary hypertension.

However, none of these various genetic abnormalities has been shown, either alone or in joint combination, to be responsible for any applicable portion of hypertension in the general population.

be used.58 Persons should be seated quietly for at least 5 minutes in a chair (rather than on an exam table), with feet on the floor, and arm supported at heart level. Caffeine, exercise, and smoking should be avoided for at least 30 minutes prior to measurement. Measurement of BP in the standing position is indicated periodically, especially in those at risk for postural hypotension, prior to necessary drug dose or adding a drug, and in those who report symptoms consistent with reduced BP upon standing. An appropriately sized cuff (cuff bladder encircling at least 80 percent of the arm) should be used to ensure accuracy. At least two measurements should be made and the average recorded. For manual determinations, palpated radial pulse obliteration pressure should be used to estimate SBP—the cuff should then be inflated 20–30 mmHg above this level for the auscultatory determinations; the cuff deflation rate for auscultatory readings should be 2 mmHg per second. SBP is the point at which the first of two or more Korotkoff sounds is heard (onset of phase 1), and the disappearance of Korotkoff sound (onset of phase 5) is used to define DBP. Clinicians should provide to patients, verbally and in writing, their specific BP numbers and the BP goal of their treatment.

Followup of patients with various stages of hypertension is recommended.

Ambulatory Blood Pressure Monitoring

Ambulatory blood pressure monitoring (ABPM) provides information about BP during daily activities and sleep. BP has a reproducible “circadian” profile, with higher values while awake and mentally and physically active, much lower values during rest and sleep, and early morning increases for 3 or more hours during the transition of sleep to wakefulness. These devices use either a microphone to measure Korotkoff sounds or a cuff that senses arterial waves using oscillometric techniques. Twenty-four hour BP monitoring provides multiple readings during all of a patient’s activities. While office BP values have been used in the numerous studies that have established the risks associated with an elevated BP and the benefits of lowering BP, office measurements have some shortcomings. For example, a white-coat effect (increase in BP primarily in the medical care environment) is noted in as many as 20–35 percent of patients diagnosed with hypertension. Ambulatory BP values are usually lower than clinic readings. Awake hypertensive individuals have an average BP of >135/85 mmHg, and during sleep, >120/75 mmHg. The level of BP measurement using ABPM correlates better than office measurements with target organ injury. ABPM also provides a measure of the percentage of BP readings that are elevated, the overall BP load, and the extent of BP fall during sleep. In most people, BP drops by 10–20 percent during the night; those in whom such reductions are not present appear to be at increased risk for cardiovascular events. In addition, it was reported recently that ABPM patients whose 24-hour BP exceeded 135/85 mmHg were nearly twice as likely to have a cardiovascular event as those with 24-hour mean BPs <135/85 mmHg, irrespective of the level of the office BP.  

 Indications for the use of ABPM are listed in table 5. Medicare reimbursement for ABPM is now provided to assess patients with suspected white-coat hypertension.

Self-Measurement

Self-monitoring of BP at home and work is a practical approach to assess differences between office and out-of-office BP prior to consideration of ABPM. For those whose out-of-office BPs are consistently <130/80 mmHg despite an elevated office BP, and who lack evidence of target organ disease, 24-hour monitoring or drug therapy can be avoided. Self-measurement or ABPM may be particularly helpful in assessing BP in smokers. Smoking raises BP acutely, and the level returns to baseline about 15 minutes after stopping.

Impressive evidence has accumulated to warrant greater attention to the importance of SBP as a major risk factor for CVDs. Changing patterns of BP occur with increasing age. The rise in SBP continues throughout life in contrast to DBP, which rises until approximately age 50, tends to level off over the next decade, and may remain the same or fall later in life (figure 13).

Diastolic hypertension predominates before age 50, either alone or in combination with SBP elevation. The prevalence of systolic hypertension increases with age, and above 50 years of age, systolic hypertension represents the most common form of hypertension. DBP is a more potent cardiovascular risk factor than SBP until age 50; thereafter, SBP is more important

Clinical trials have demonstrated that control of isolated systolic hypertension reduces total mortality, cardiovascular mortality, stroke, and HF events. Both observational studies and clinical trial data suggest that poor SBP control is largely responsible for the unacceptably low rates of overall BP control. In the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) and the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) Trial, DBP control rates exceeded 90 percent, but SBP control rates were considerably less (60–70 percent). Poor SBP control is at least in part related to physician attitudes. A survey of primary care physicians indicated that three-fourths of them failed to initiate antihypertensive therapy in older individuals with SBP of 140–159 mmHg, and most primary care physicians did not pursue control to <140 mmHg. that the diastolic pressure is more important than SBP and thus treat accordingly. Greater emphasis must clearly be placed on managing systolic hypertension. Otherwise, as the United States population becomes older, the toll of uncontrolledSBP will cause increased rates of CVDs and renal diseases.

The prevention and management of hypertension are major public health challenges for the United States. If the rise in BP with age could be prevented

or diminished, much of hypertension, cardiovascular and renal disease, and stroke might be prevented. A number of important causal factors

for hypertension have been identified, including excess body weight; excess dietary sodium intake; reduced physical activity; inadequate intake of fruits, vegetables, and potassium; and excess alcohol intake. The prevalence of these characteristics is high. At least 122 million Americans are overweight or obese. Mean sodium intake is approximately 4,100 mg per day for men and 2,750 mg per day for women, 75 percent of which comes from processed foods. Fewer than 20 percent of Americans engage in regular physical activity, and fewer than 25 percent consume five or more servings of fruits and vegetables daily.

Because the lifetime risk of developing hypertension is very high, a public health strategy, which complements the hypertension treatment strategy, is warranted. To prevent BP levels from rising, primary prevention measures should be introduced to reduce or minimize these causal factors in the population, particularly in individuals with prehypertension. A population approach that decreases the BP level in the general population by even modest amounts has the potential to substantially reduce morbidity and mortality or at least delay the onset of hypertension. For example, it has been estimated that a

5 mmHg reduction of SBP in the population would result in a 14 percent overall reduction in mortality due to stroke, a 9 percent reduction in mortality due to CHD, and a 7 percent decrease in all-cause mortality.

Barriers to prevention include cultural norms; insufficient attention to health education by health care practitioners; lack of reimbursement for health education services; lack of access to places to engage in physical activity; larger servings of food in restaurants; lack of availability of healthy food choices in many schools, worksites, and restaurants; lack of exercise programs in schools; large amounts of sodium added to foods by the food industry and restaurants; and the higher cost of food products that are lower in sodium and calories.10

Overcoming the barriers will require a multipronged approach directed not only to high-risk populations, but also to communities, schools, worksites, and the food industry. The recent recommendations by the American Public Health Association and the NHBPEP Coordinating Committee that the food industry, including manufacturers and restaurants, reduce sodium in the food supply by 50 percent over the next decade is the type of approach which, if implemented, would reduce BP in the population.

Table 3 provides a classification of BP for adults 18 years and older. The classification is based on the average of two or more properly measured, seated, BP readings on each of two or more office visits. Prehypertension is not a disease category. Rather, it is a designation chosen to identify individuals at high risk of developing hypertension, so that both patients and clinicians are alerted to this risk and encouraged to intervene and prevent or delay the disease from developing. Individuals who are prehypertensive are not candidates for drug therapy based on their level of BP and should be firmly and unambiguously advised to practice lifestyle modification in order to reduce their risk of developing hypertension in the future (see Lifestyle Modifications). Moreover, individuals with prehypertension, who also have diabetes or kidney disease, should be considered candidates for appropriate drug therapy if a trial of lifestyle modification fails to reduce their BP to 130/80 mmHg or less.

This classification does not stratify hypertensive individuals by the presence or absence of risk factors or target organ damage in order to make different treatment recommendations, should either or both be present. JNC 7 suggests that all people with hypertension (stages 1 and 2) be treated. The treatment goal for individuals with hypertension and no other compelling conditions is <140/90 mmHg (see Compelling Indications). The goal for individuals with prehypertension and no compelling indications is to lower BP to normal levels with lifestyle changes, and prevent the progressive rise in BP using the recommended lifestyle modifications (see Lifestyle Modifications).

Considerable success has been achieved in the past in meeting the goals of the program. The awareness of hypertension among Americans has improved from a level of 51 percent in the period 1976–1980 to 70 percent in 1999–2000 (table 1).

The percentage of patients with hypertension receiving treatment has increased from 31 percent to 59 percent in the same period, and the percentage of persons with high BP controlled to below 140/90 mmHg has increased from 10 percent to 34 percent. Between 1960 and 1991, median SBP for individuals ages 60–74 declined by approximately 16 mmHg (figure 1). These changes have been associated with highly favorable trends in the morbidity and mortality attributed to hypertension. Since 1972, age-adjusted death rates from stroke and coronary heart disease (CHD) have declined by approximately 60 percent and 50 percent, respectively (figures 2 and 3). These benefits have occurred independent of gender, age, race, or socioeconomic status. Within the last two decades, better treatment of hypertension has been associated with a considerable reduction in the hospital case-fatality rate for heart failure (HF) (figure 4). This information suggests that there have been substantial improvements.

However, these improvements have not been extended to the total population. Current control rates for hypertension in the United States are clearly unacceptable. Approximately 30 percent of adults are still unaware of their hypertension, >40 percent of individuals with hypertension are not on treatment, and two-thirds of hypertensive patients are not being controlled to BP levels <140/90 mmHg (table 1). Furthermore, the decline rates in CHD- and stroke-associated deaths have slowed in the past hypertension prior to developing HF, have continued to increase (figures 5 and 6). Moreover, there is an increasing trend in end-stage renal disease (ESRD) by primary diagnosis. Hypertension is second only to diabetes as the most common antecedent for this condition (figure 7). Undiagnosed, untreated, and uncontrolled hypertension clearly places a substantial strain on the health care delivery system.

Hypertension is an increasingly important medical and public health issue. The prevalence of hypertension increases with advancing age to the point where more than half of people 60–69 years of age and approximately three-fourths of those 70 years of age and older are affected. The age related rise in SBP is primarily responsible for an increase in both incidence and prevalence of hypertension with increasing age.

Whereas the short-term absolute risk for hypertension is conveyed effectively by incidence rates, the long-term risk is best summarized by the lifetime risk statistic, which is the probability of developing hypertension during the decade. In addition, the prevalence and hospitalization rates of HF, wherein the majority of patients have

remaining years of life (either adjusted or unadjusted for competing causes of death). Framingham Heart Study investigators recently reported the lifetime risk of hypertension to be approximately 90 percent for men and women who were nonhypertensive at 55 or 65 years and survived to age 80–85 (figure 8).   Even after adjusting for competing mortality, the remaining lifetime risks of hypertension were 86–90 percent in women and 81–83 percent in men.

The impressive increase of BP to hypertensive levels with age is also illustrated by data indicating that the 4-year rates of progression to hypertension are 50 percent for those 65 years and older with BP in the 130–139/85–89 mmHg range and 26 percent for those with BP between 120–129/80–84 mmHg range.

Data from observational studies involving more than 1 million individuals have indicated that death from both IHD and stroke increases progressively and linearly from levels as low as 115 mmHg SBP and 75 mmHg DBP upward (figures 9 and 10). The increased risks are present in individuals ranging from 40 to 89 years of age. For every 20 mmHg systolic or 10 mmHg diastolic increase in BP, there is a doubling of mortality from both IHD and stroke.

In addition, longitudinal data obtained from the Framingham Heart Study have indicated that BP values between 130–139/85–89 mmHg are associated with a more than twofold increase in relative risk from cardiovascular disease (CVD) as compared with those with BP levels below 120/80 mmHg.

. . . and, on occasion, anemia and thrombocytopenia.

Develops in individuals with long standing RA

Rare in African-Americans

Hypersplenism has been blamed for the syndrome, but not all patients have splenomegaly and splenectomy does not cure all patients.

Excessive margination of granulocytes caused by antibodies to those cells

Complement activation or binding of immune complexes may contribute to neutropenia.

Patients have increased incidence of infections usually associated with neutropenia.

Labs include elevated sedimentation rate, peripheral eosinophilia, hypergammaglobulinemia, and mildly elevated CK (not always).

Histology shows marked thickening and infiltration of the deep fascia with mononuclear cells and eosinophils.

Most patients respond to glucocorticoids.

Associated with ingestion of L-tryptophan (essential amino-acid)

Symptoms include fever and rash, arthralgia and myalgia, cough and dyspnea, and edema.

Accompanied with eosinophilia (>1000 cells/microL).

Peripheral neuropathy, myositis (with lymphocytic and eosinophilic infiltration)

Tryptophan (contaminating L-tryptophan preparations) has been implicated as a cause.