Articles on Medical Diseases and Conditions

Month: July 2009

Nontuberculous Mycobacteria

There are other mycobacteria besides Mycobacterium tuberculosis, some of which are frequently pathogenic for humans and some of which rarely cause human infection. The nontuberculous mycobacteria were originally called “atypical mycobacteria.” The first useful classification was that of Runyon, who subdivided the nontuberculous mycobacteria into four groups, depending on growth speed and colony characteristics (Table 14-2). These groups have some clinical value as rough guides to the type of organism present while awaiting more definitive identification and speciation. It is desirable to place the organisms in the correct species, since some members (species) of any of the Runyon groups may not be pathogenic very often or may differ in degree of pathogenicity. Mycobacterium intracellulare or Mycobacterium avium-intracellulare complex (formerly known as the Battey Mycobacterium), a member of Runyon group III, and Mycobacterium kansasii, from Runyon group I, together cause the majority of significant nontuberculous mycobacterial infections in about equal proportions. These produce a disease similar to pulmonary tuberculosis (although often milder or more indolent) that is much more frequent in adults. M. avium-intracellulare infections are very frequent in persons with acquired immunodeficiency syndrome (AIDS) or AIDS-related conditions. The mycobacterial infection frequently becomes bacteremic or disseminated due to compromise of the immune system by HIV-1 causing AIDS. Runyon group II organisms are more frequent in children and clinically tend to cause cervical lymphadenopathy. Diagnosis of the nontuberculous mycobacteria is essentially the same as for M. tuberculosis. Skin tests (old tuberculin or PPD) for M. tuberculosis will also cross-react with the nontuberculous mycobacteria. In general, the nontuberculous mycobacteria tend to produce less reaction to standard tuberculin skin tests than M. tuberculosis. In fact, several studies claim that the majority of positive intermediate-strength tuberculin skin test results that produce a reaction of less than 10 mm diameter are due to nontuberculous mycobacterial infection rather than TB. Skin test antigens are available for each of the nontuberculous mycobacterial groups, although some reports challenge the specificity of these preparations. The main clinical importance of these nontuberculous organisms is resistance that many have toward one or more of the standard antituberculous chemotherapeutic agents.

Table 14-2 Classification of the atypical mycobacteria

Several reports have linked one of the non-MTB organisms, M. paratuberculosis, to Crohn’s disease (regional ileitis).

July 24, 2009
Tuberculosis and Mycobacterial Disease

Tuberculosis is caused by Mycobacterium tuberculosis (MTB), a rod-shaped bacterium that requires special media for culture and that has the peculiarity of “acid-fastness” (resistance to decolorization by strong acidic decolorizing chemicals such as acid alcohol after being stained by certain stains such as carbol fuchsin). Tuberculosis is still very important and common despite advances in drug therapy. It has been reported that about 25% of persons exposed to MTB will become infected; and of those infected, about 10% will develop clinical disease (range, 5%-40%). The disease usually begins in the chest due to inhalation of airborne infectious material. This material is carried to some localized area of the lung alveoli and provokes a host response of granulomatous inflammation around the material (the “Ghon complex”). It is thought that in many cases there is also a silent hematogenous spread of the organisms. In most cases the host is able to contain and eventually destroy the organisms in the chest and those reaching other locations. Those in the lungs seem better able to survive than those deposited elsewhere. In some cases the organisms remain dormant, and the infection can be reactivated at a later date; in some cases the initial infection spreads; and in some cases reinfection takes place. If infection in the lungs progresses to clinical disease, the most important symptoms are cough, fever, and hemoptysis. (The most important diseases to rule out are lung carcinoma and bronchiectasis.) The kidney is involved in a small percentage of advanced cases, with the main symptom being hematuria (Chapter 12). A small number of patients develop widespread extrapulmonary disease, known as miliary tuberculosis. The laboratory findings in tuberculosis depend to some extent on the stage and severity of the disease.

Chest x-ray films

Chest x-ray films often provide the first suggestion of tuberculosis and are a valuable parameter of severity, activity, and response to therapy. Depending on the situation, there are a variety of possible roentgenographic findings. These may include one or more of the following:

1. Enlargement of hilar lymph nodes.
2. Localized pulmonary infiltrates. These occur characteristically in an upper apical location or, less commonly, in the superior segment of the lower lobes. Cavitation of lesions may occur.
3. Miliary spread (small punctate lesions widely distributed). This pattern is not common and may be missed on routine chest x-ray films.
4. Unilateral pleural effusion. The most common causes are tuberculosis, carcinoma, and congestive heart failure. Tuberculosis has been reported to cause 60%-80% of so-called idiopathic pleural effusions, although this percentage varies greatly depending on the patient’s geographic location and other factors.

Sputum smear

Sputum smears provide a rapid presumptive diagnosis in pulmonary tuberculosis. The smear is usually stained by one of the acid-fast (acid-fast bacillus, or AFB) procedures (usually the Ziehleelsen or Kinyoun methods). Fluorescent Auramine-o staining methods are available, faster, and somewhat more sensitive. Smears require about 5 Ч 103 organisms/ml of specimen for microscopic detection. The more advanced the infection, the more likely it is to yield a positive smear. Therefore, the rate of positive findings is low in early, minimal, or healing tuberculosis. Also, the smear may be normal in a substantial minority of advanced cases. Culture is more reliable for detection of tuberculosis and also is necessary for confirmation of the diagnosis, for differentiation of MTB from the “atypical” mycobacteria, and for sensitivity studies of antituberculous drugs. According to the literature, false negative smears (smear negative but culture positive) have been reported in an average of 50% of cases (literature range, 16%-70%). Some of these false negative results may be due to laboratory technique problems and differences in smear staining methods. A high centrifugation speed when concentrating the specimen is said to increase the yield of positive smears. False positive smears (positive smear but negative culture) have been reported, averaging about 1%-5% of positive smears (literature range, 0.5%-55%). Some of these were apparently due to contamination of water used in the smear-staining procedure by saprophytic mycobacteria. Control slides are necessary to prevent this. Some authorities believe that only 1-2 acid-fast organisms/300 oil immersion fields should be considered negative (although indicative of need for further specimens). Smears may sometimes be positive for up to 2 months when cultures are negative if the patient is on antituberculous drug therapy (this would not be considered a genuine false positive, since the drugs inhibit mycobacterial growth or the organisms may be nonviable). After 2 months, persistence of positive smears raises the question of treatment failure. Temporary persistence of positive smears with negative cultures is more likely to occur in severe cavitary disease (in one series, this occurred in 20% of cases). Sputum specimens should be collected (for culture and smear of the concentrated specimen) once daily for at least 3 days. If the smear is definitively positive, further smears are not necessary. Also, a definitively positive smear means high probability that culture of the specimens already collected will obtain positive results, and it is not necessary to collect more than three specimens or to proceed to more complicated diagnostic procedures. If smears are negative, one must consider the possibility that the culture may also be negative, and conventional cultures on standard solid media average 20 days to produce growth from MTB smear-positive specimens and about 27 days from MTB smear-negative specimens (overall range, 2–8 weeks).

Culture

Sputum culture is preferred for pulmonary tuberculosis (gastric aspiration may be done if adequate sputum specimens cannot be obtained); urine culture is preferred for renal involvement; and bone marrow culture is preferred in miliary tuberculosis. Reports indicate that an early morning specimen, either of sputum or urine, produces almost as many positive results as a 24-hour specimen and has much less problem with contamination. Special mycobacteria culture media are needed. The necessity for adequate sputum culture specimens, regardless of the concentrated smear findings, should be reemphasized. Several reports indicate that aerosol techniques produce a significantly greater yield of positive cultures than ordinary sputum collection. The aerosol mixture irritates the bronchial tree and stimulates sputum production. At any rate, it is necessary to get a “deep cough” specimen; saliva alone, although not completely useless, is much less likely to reveal infection and is much more likely to be contaminated. If sputum cultures are negative or if the patient is unable to produce an adequate sputum sample, gastric aspiration may be used. Gastric contents are suitable only for culture; nontuberculous acid-fast organisms may be found normally in the stomach and cannot be distinguished from M. tuberculosis on AFB smear. If renal tuberculosis is suspected, urine culture should be done (Chapter 12). However, renal tuberculosis is uncommon; and even with urine specimens obtained on 3 consecutive days, only about 30% of cases are positive.

Cultures should be grown in high carbon dioxide atmosphere, since this is reported to increase the number of positive cultures by at least 10%. Inoculation on several varieties of media increases the number of positive results by 5%-10%. The 4% sodium hydroxide traditionally used to digest and decontaminate sputum before concentration also kills some mycobacteria. Use of weaker digestion agents increases culture yield, but troublesome overgrowth by other bacteria may also increase.

Culture should be done on all tissue specimens when tuberculosis is suspected. Acid-fast stains on tissue slides reveal tuberculosis organisms in only 30%-40% of cases that are positive by culture. Several newer methods such as BACTEC (which uses liquid media and a machine that detects metabolic products of bacterial growth) have been able to decrease detection time for MTB smear-positive specimens to 8 days and time for MTB smearegative specimens to 14 days (overall range, 1-3 weeks). The system is about 93% sensitive compared to conventional multimedia culture. Once culture growth occurs, the organism must be identified. Conventional methods require biochemical and growth tests to be performed that may take 3-6 weeks to complete. The BACTEC system has a nucleic acid phosphate method that can identify MTB (only) in 3-5 days. Commercial DNA probes are available that can identify MTB and certain non-MTB mycobacteria in 1 day. Gas-liquid chromatography and high-performance liquid chromatography have also been used. Antibiotic sensitivity studies are recommended when a mycobacterial organism is isolated, since multiresistant MTB is increasing in various areas and non-MTB mycobacteria have often been multiresistant. Conventional culture methods take 21 days; BACTEC takes about 5 days.

Data on sputum culture sensitivity using conventional AFB media is difficult to find since culture is usually considered the gold standard of AFB detection. Sputum culture appear to average about 75% sensitivity (range, 69%-82%). Sensitivity using BACTEC averages about 85% (range, 72%-95%).

Nucleic acid probe

Nucleic acid (DNA) probe methods are now becoming available that permit direct nonsmear detection of mycobacteria in clinical specimens. The first such test available (Gen-Probe, Inc.) is reported in two studies to be 83%-85% sensitive compared with culture using sputum specimens. However, it has been reported that antituberculous drugs can interfere with the probe; this study found sensitivity in nontreated patients to be over 90% (when comparing probe to culture, culture only detects about 75%-80% of cases). Ten percent of specimens were positive by probe but negative by culture, which may represent additional true positives that could not be confirmed. A DNA probe is also available specifically for M. tuberculosis. Same-day results can be obtained. Disadvantages of this first-generation method are need for considerable technologist time and certain special equipment. Compared with culture, the general Mycobacterium screen probe will not differentiate M. tuberculosis from other mycobacteria, whereas the specific M. tuberculosis probe will not detect the other mycobacteria. Neither probe would provide therapeutic drug sensitivity information. The major drawback regarding its use as replacement for the acid-fast smear is the relatively high cost of the probe method, very high if only one specimen at a time is processed. DNA probes with PCR amplification have been reported (e.g., Roche Diagnostics) that are said to have a sensitivity of 3-30 organisms/ml (compared to at least 5 Ч 103 organisms/ml required for a positive acid-fast smear). Nevertheless, one study involving 7 prestigious worldwide reference laboratories who were sent sputum or saliva specimens to which various quantities of BCG (M. Bovis) mycobacteria were added, showed false positive PCR rates of 3%-77%. In specimens containing 102 organisms, sensitivity ranged from 0%-55%; in specimens containing 103 organisms, 2%-90%; and in specimens containing 101 organisms, 20%-98%.

Skin test (Mantoux test)

This test is performed with an intradermal injection of purified protein derivative (PPD) or old tuberculin (Table 14-1). A positive result is represented by an area of induration having a specified diameter by 48 hours. The diameter used to be 10 mm but was redefined in 1990 to require different diameters depending on the person’s risk group (see box). In addition, a distinction was made between “reaction” (diameter or width of induration without record of previous test result) and “conversion” (increase in reaction width within 2 years from last previous reaction width). For all persons younger than 35 years of age whose previous reaction was negative, an increase in PPD induration of 10 mm or more in diameter within a period of 2 years would be considered a conversion and presumptive suspicion for occult tuberculosis (TB), whereas the change would have to be at least 15 mm for persons 35 years of age or more (that is, for nonrisk persons above or below age 35 who have had a PPD within 2 years, conversion criteria would replace reaction size criteria).

Table 14-1 Comparison of tuberculosis skin tests*

A positive skin test is a manifestation of hypersensitivity to the tubercle bacillus. This reaction usually develops about 6 weeks after infection, although it may take several months. A positive reaction means previous contact and infection with TB; the positive reaction does not itself indicate whether the disease is currently active or inactive. However, in children under 3 years of age it usually means active TB infection. Apparently, once positive, the reaction persists for many years or for life, although there is evidence that a significant number of persons revert to negative reactions if the infection is completely cured early enough. In a few cases of infection the test never becomes positive. The Mantoux test may revert to negative or fail to become positive in the following circumstances:

1. In about 20% of seriously ill patients, due to malnutrition (severe protein deficiency).
2. In newborns and occasionally in old age.
3. In some persons with viral infections, or within 1 month after receiving live virus vaccination.
4. In 50% or more of patients with miliary tuberculosis.
5. In a high percentage of patients with overwhelming pulmonary tuberculosis.
6. In a considerable number of patients who are on steroid therapy or immunosuppressive therapy.
7. In many persons who also have sarcoidosis or Hodgkin’s disease.
8. In some persons with chronic lymphocytic leukemia or malignant lymphoma.
9. In some patients with chronic renal failure or severe illness of various types.
10. In some persons with old infection (“waning” of reactivity).
11. When there is artifact due to improper skin test technique (e.g, subcutaneous rather than intradermal injection).

In cachectic patients and those with protein malnutrition, treatment with an adequate protein diet can restore Mantoux test reactivity to most patients after about 2 weeks. In patients after age 50 with M. tuberculosis infection, especially those with old previous infection, the PPD skin test sometimes may slowly decrease in reactivity and eventually become negative. (How often this occurs is controversial; the best estimate seems to be 8%-10%, but studies range from 0.1%-21%, possibly influenced by the elapsed time period since infection and time intervals between testing.) If another skin test is performed, the new skin test itself stimulates body reaction and may restore reactivity (“booster phenomenon”). This phenomenon could simulate a new infection if previous infection were not known, since the next time a skin test is performed the physician would see only conversion of a negative to a positive reaction. Restoration of skin reactivity can take place in only 1 week, so that retesting 1 week after the first negative reaction can usually show whether or not there is potential for the booster reaction. (The 1-week interval would in most cases not be long enough for true conversion in persons with their first infection.) Repeated skin tests will not cause a nonexposed person to develop a positive reaction. Some investigators recommend skin testing with antigens used to demonstrate the presence of skin test anergy (e.g., Candida or Trichophyton antigen) if the Mantoux test is repeatedly negative in a person with substantial suspicion of mycobacterial infection.

The standard procedure for skin testing is to begin with an intermediate strength PPD (or the equivalent). If the person has serious infection, some clinics recommend starting with a first-strength dose to avoid necrosis at the injection site. A significant minority of patients with tuberculosis (9%-17%) fail to react to intermediate strength PPD; a second-strength dose is then indicated.

Miliary tuberculosis

Miliary TB is clinically active TB that is widely disseminated in the body by hematogenous spread. Clinical symptoms are often nonspecific, such as fever, weakness, and malaise. There frequently is an associated condition, such as alcoholism, intravenous (IV) drug abuse, or malignancy, that decreases immunologic defenses. About 20% have a negative tuberculin skin test reaction. About 35% do not show a miliary pattern on chest x-ray film. If routine clinical and culture methods fail, biopsy of bone marrow or liver may be useful. Liver biopsy has a fairly good positive yield (up to 80%), considering that a needle biopsy specimen is such a tiny random sample of a huge organ. However, it is usually difficult to demonstrate acid-fast organisms on liver biopsy even when tubercles are found, and without organisms the diagnosis is not absolutely certain. Bone marrow aspiration is probably the best procedure in such cases. Bone marrow yields much better results for mycobacterial culture than for demonstration of tubercles. Routine marrow (Wright-stained) smears are worthless for histologic diagnosis in TB. Aspirated material may be allowed to clot in the syringe, then formalin-fixed and processed as a regular biopsy specimen for histologic study. Before clotting, some of the aspirate is inoculated into a suitable TB culture medium. It should be emphasized that bone marrow aspiration or liver biopsy is not indicated in pulmonary tuberculosis (since this disease is relatively localized), only in miliary TB.

PPD Reaction Size Considered “Positive” (Intracutaneous 5 TU* Mantoux Test at 48 Hours)
5 MM OR MORE
Human immunodeficiency virus
(HIV) infection or risk factors for HIV
Close recent contact with active TB case
Persons with chest x-ray consistent with healed TB
10 MM OR MORE
Foreign-born persons from countries with high TB prevalence in Asia, Africa, and Latin America
Intravenous (IV) drug users
Medically underserved low-income population groups (including Native Americans, Hispanics, and African Americans)
Residents of long-term care facilities (nursing homes, mental institutions)
Medical conditions that increase risk for TB (silicosis, gastrectomy, undernourished, diabetes mellitus, high-dose corticosteroids or immunosuppression RX, leukemia or lymphoma, other malignancies
Employees of long-term care facilities, schools, child-care facilities, health care facilities
15 MM OR MORE
All others not listed above
* TU, tuberculin units.

Renal tuberculosis

Renal TB is almost always bilateral and presumably results from nonhealing infection produced during the transient bacteremia of the lung primary stage. There is usually a latent period of many years before clinical infection becomes evident. The estimated incidence of eventual active renal infection is about 2%-5%, but this probably represents incidence in high-risk groups. About 25% (range, 20%-75%) of patients are said to have a normal chest x-ray film. About 14% (range, 12%-15%) of patients are reported to have a negative PPD skin test result. Even the intravenous pyelogram results (IVP) are normal in about 25% (range, 14%-39%) of cases. Most patients do not have systemic symptoms, such as fever. The erythrocyte sedimentation rate was elevated in 23% of patients in one report. Only 20%-56% have urinary tract symptoms. Gross hematuria is the classic finding in renal TB but is present in only about 20% of patients. Pyuria (with negative urine culture) and microscopic hematuria are more frequent, occurring in about 65%-85% of cases. Some patients have a positive urine culture with some ordinary pathogen in addition to renal TB. Urine culture for TB was mentioned previously; 30%-80% of patients have positive cultures when three 24-hour or early morning specimens are collected (true culture sensitivity is probably less than 80%, since the diagnosis could easily be missed with negative cultures).

July 24, 2009
Anaerobic Bacteria

The three major sources of anaerobic organisms are the dental and mouth area, the lower intestinal tract (ileum and colon), and the female external genital tract (vagina and vulva area). Anaerobes comprise about 95% of the bacterial flora of the colon and outnumber aerobes in the mouth and vagina. From the mouth the organisms can reach the lungs and brain; from the vagina they may involve the remainder of the female genital tract; diseases of the lower intestinal tract may release anaerobes into the abdominal cavity; and all of these locations may be the source of organisms found in the bloodstream. In addition, anaerobic bacteria are frequently associated with chronic infection, such as bronchiectasis, abscess, or chronic osteomyelitis. Infections with anaerobes frequently are mixed infections that also contain aerobes. The types of infection most frequently associated with anaerobes are listed in the box below.

Types of Infection Most Frequently Associated With Anaerobes (Alone or as a Mixed Infection)
Dental or mouth area infection
Chronic sinus infection
Bite wounds
Bronchiectasis and aspiration pneumonia
Gynecologic intraabdominal and extra abdominal infection
Abscess of any area other than skin; including brain, abdominal and thoracic cavities, and any organ
Infections associated with the intestinal tract, especially the colon (diverticulitis, appendicitis, bowel perforation, etc.)
Deep tissue infection or necrosis
Biliary tract infection
Chronic osteomyelitis

Anaerobic infections usually center on three groups of organisms: Clostridia species, Bacteroides species, and the anaerobic streptococci.

Clostridia

These gram-positive anaerobic rods include several important organisms. Clostridium perfringens (Clostridium welchii) is the usual cause of gas gangrene. It is a normal inhabitant of the GI tract and reportedly can be isolated from the skin in about 20% of patients and from the vagina and female genitalia in about 5%. Therefore, just as with S. aureus, a culture report of C. perfringens isolated from an external wound does not necessarily mean that the organism is producing clinical infection. When isolated from abdominal or biliary tract infections, C. perfringens most often is part of a polymicrobial infection and, although serious, is not quite as alarming as isolation from a deep tissue wound. Clostridium perfringens occasionally is a cause of “food poisoning” (discussed later).

Clostridium tetani causes tetanus. The organism can be found in the human GI tract but is more common in animals. Spores are widely distributed in soil. Clinical disease is produced by release of bacterial exotoxin after local infection in a manner analogous to diphtheria. Puncture-type wounds are notorious for high risk of C. tetani infection. The incubation time is 3-14 days in most patients, a few cases being reported as early as 24 hours after exposure. Cultures for C. tetani are said to be positive in less than 50% of patients. Clostridium difficile is the most frequent proven cause of antibiotic-associated diarrhea. In the 1950s and early 1960s, broad-spectrum oral antibiotics were frequently used, and S. aureus was thought to be the major cause of antibiotic-associated enteritis. Beginning in the late 1960s parenteral antibiotics became much more common in hospitals, and C. difficile was eventually proven to be the major etiology. Clostridium difficile enteritis usually occurs during or after therapy with antibiotics, although some patients have not received antibiotics. One report indicated a possible association with diarrhea induced by cancer chemotherapeutic agents. The condition may consist only of varying degrees of diarrhea, may progress to inflammation of portions of the colon mucosa, and in the more severe form (known as pseudomembraneouscolitis) there is inflammation and partial destruction of varying areas of the colon mucosa, with formation of a pseudomembrane of fibrin, necrotic cells, and segmented neutrophils on the surface of the remnants of the affected mucosa. Some patients develop intestinal perforation and sepsis.

Diagnosis of C. difficile colitis is not always easy. Only about 25%-30% (range, 20%-33%) of diarrhea occurring with antibiotic therapy is due to C. difficile, with most of the remainder not associated with currently known infectious agents. Sigmoidoscopy or colonoscopy can be done to document pseudomembrane formation, but this procedure runs the risk of perforation; and even in pseudomembraneous enterocolitis (PMC), pseudomembranes can be demonstrated in only about 50% (range, 40%-80%) of patients. The patient stools in PMC typically contain WBCs and often contain red blood cells, but gross blood is uncommon. However, WBCs on Gram stain actually are present in only about 45%-50% of cases. For several years, culture was the usual means of diagnosis. Today, this is not often done. C. difficile can be cultured, with reliable results, only on special media, so diagnosis usually is made through detection of C. difficile cytotoxin. Stool specimens must be frozen and sent to a reference laboratory with dry ice. The specimen container must be sealed tightly since the carbon dioxide from the dry ice can inactivate the toxin. Another problem is the fact that C. difficile can be found in the stool of some clinically healthy persons, including 30%-40% (range, 11%-63%) of clinically healthy neonates, 10%-15% of children, 3% (range, 0%-10%) of adults, 20% (range, 11%-36%) of hospitalized persons without diarrhea and not taking antibiotics, and about 30% (range, 20%-46%) of patients taking antibiotics but without diarrhea. Even in patients with endoscopy-proven PMC, stool culture is positive for C. difficile in only about 90% (range, 75%-95%) of cases. Most laboratories today rely more on tests to detect C. difficile toxin, which has been shown to correlate much better with C. difficile clinical infection than does stool culture. There are several C. difficile toxins, of which the best characterized are called toxins A and B. Toxin B is a cytotoxin that must be detected by a tissue culture system with an incubation period of 48 hours. In endoscopy-proven PMC, toxin B sensitivity is reported to be about 90% (range, 64%-100%). Results may be positive in some patients with positive C. difficile cultures who are clinically normal, especially in infants. An enzyme immunoassay kit is commercially available that detects both toxin B and toxin A (Cytoclone A+B). Sensitivity reported to date is about 85%-90% (range, 76%-99%). Toxin A is an enterotoxin that originally was assayed with a biologic system, the rabbit ileal loop test. Several EIA tests are commercially available for toxin A, with reported sensitivity of about 85% (range, 65%-97%). There is a simple latex agglutination kit available (CDT or Culturette CDT) that can provide same-day results. This kit was originally thought to detect toxin A but subsequently was found to be detecting an enzyme (glutamate dehydrogenase) from C. difficile. The test detects non-toxin-producing as well as toxin-producing C. difficile and cross-reacts with Clostridium sporogenes and a few strains of other clostridia. Nevertheless, in various studies this test frequently gave results equivalent to those of the cytotoxicity test (about 75%-90%; range, 38%-97% positive in patients with proven PMC, with roughly 90% specificity). Another company has a similar test (Meritec-CD). In one comparison between CDT and Meritec-CD, Meritec-CD showed about 10% less sensitivity.

Clostridium botulinus produces botulism. Botulism is a severe food poisoning due to ingestion of preformed botulinal endotoxin (a powerful neurotoxin) contained in the contaminated food, rather than actual infection of the patient by the organism. C. botulinum spores are widespread, but they can germinate only in anaerobic conditions at a fairly high pH (>4.6). These conditions are met in canned foods that have not been sufficiently heated during the canning process. Therefore, C. botulinum is usually associated with canned food, especially home canned. Vegetables are the most frequently involved home-canned food, but any variety of canned food may become contaminated. Fortunately, the disease is not common. Although the endotoxin is preformed, symptoms most often appear 12-36 hours after ingestion (in adult patients) and commonly include nausea, vomiting, and abdominal cramps (about 50% of patients), constipation (75%), cranial nerve signs of dysphagia, dysarthria, and dry mouth (80%-90%), upper or lower extremity weakness (70%), and diplopia or other eye abnormalities (90%). There is no fever or diarrhea. Differential diagnosis in adults includes Guillain-Barrй syndrome, drug reaction (especially phenothiazines), myasthenia gravis, cerebrovascular accident, chemical poisoning (mercury, arsenic, etc.), diphtheria, and tick bite paralysis (Landry’s ascending paralysis). Botulism may also occur in infants, usually between ages 3 and 26 weeks (median age 10 weeks). The classic syndrome is onset of constipation followed by 4-5 days of progressive feeding difficulty, ptosis, muscle hypotonia, and possibly respiratory distress. Mildly affected infants may have varying degrees of “failure to thrive” with feeding difficulty and mild muscle weakness, whereas severely affected infants may have severe respiratory distress. Some cases of sudden infant death syndrome (SIDS) have been ascribed to infant botulism, whereas some infants and older children (investigated during studies initiated by botulism cases) were found to harbor C. botulinum organisms without symptoms. Honey was incriminated in some cases as the source of infection but was not used in the majority of cases.

Standard laboratory tests, including those on the CSF, are usually normal in botulism. Electromyography (EMG) may be helpful in differentiating adult botulism from certain other neurologic diseases, but the typical EMG findings are neither specific nor always present. The diagnosis is confirmed by stool culture and demonstration of C. botulinum toxin, neither of which can be done in the ordinary laboratory. In addition, food suspected of contamination should always be tested. Patient vomitus and gastric contents have also been tested. The basic specimens in adult botulism are stool (25 gm or more) and serum (at least 5 ml). For diagnosis of infant botulism a stool specimen is required; but infant serum rarely contains C. botulinum toxin and therefore infant serum specimens are not necessary. The specimens should be kept refrigerated, since the toxin is heat labile, and sent to a reference laboratory with a coolant (for short distances) or dry ice (for more than 1-day transit). There are several C. botulinum serotypes, but most cases are caused by types A and B, with type A predominating.

Bacteroides

Bacteroides are the most frequent organisms found in anaerobic infections. They comprise several species of gramegative rods normally found in the mouth, the intestine, and the female genital tract. Isolation of these organisms often raises the question of their significance or pathogenicity. It seems well established that bacteroides occasionally cause serious infection, which frequently results in abscess or gangrene. The most commonly associated clinical situations include septic abortion, aspiration pneumonia, focal lesions of the GI tract (e.g., carcinoma or appendicitis), and pelvic abscess in the female.

Anaerobic streptococci

Anaerobic streptococci are frequently associated with Bacteroides infection but may themselves produce disease. They are normally present in the mouth and GI tract. Septic abortion and superinfection of lesions in the perirectal area seem to be the most commonly associated factors. Anaerobic streptococci are also part of the fusiform bacteria-spirochetal synergistic disease known as Vincent’s angina.

Laboratory diagnosis of anaerobic infections

Anaerobic specimens cannot be processed by the laboratory as easily as those from aerobic infections. Anaerobic bacteria in general do not grow as readily as common aerobic bacteria, and prereduced media or other special media are often needed. Achieving and maintaining anaerobic culture conditions are not a simple matter. However, by far the greatest problem is the specimen received by the laboratory. If the specimen is not properly maintained in an anaerobic environment en route to the laboratory, the best and most elaborate facilities will be of little help. For abscesses or any fluid material, the preferred collection technique is to aspirate the material with a sterile syringe and needle, then expel the residual air from the needle by pushing the syringe plunger slightly, and then immediately cap the needle point with a sterile cork or other solid sterile material. The syringe must be transported immediately to the laboratory. If there is no liquid content, a swab that forms part of one of the special commercially available anaerobic transport systems should be used. Directions for creating the anaerobic environment should be followed exactly. A less satisfactory procedure is to inoculate a tube of thioglycollate medium immediately after the specimen is obtained and immediately recap the tube.

July 24, 2009
Gram-Positive Rods

Listeria monocytogenes

Listeria monocytogenes is a short gram-positive rod. Although most gram-positive rods of medi- cal importance are anaerobes, Listeria is an aerobic (rather than anaerobic) organism. It is found widely in soil, sewage, and various animals, as well as in the feces of about 15% (range, 2%-60%) of asymptomatic adults. Infection in children and adults is most often from contaminated food (salads, soft cheese and blue-veined cheeses but not hard cheese or cottage cheese, or unpasteurized milk). Listeria survives at refrigerator temperatures and can contaminate refrigerators so that leftovers, “cold cuts,” or cold processed-meat products would have to be adequately heated before serving. In newborns, infection may occur from the mother’s vagina. Most cases are found in neonates, in pregnancy, the elderly, and immunocompromised persons. Infection is especially associated with renal transplants, leukemia or lymphoma, and pregnancy. The most common infection at nearly all ages is meningitis (about 55%-80% of Listeria cases). Next most common (about 25% of cases) is bacteremia (which is the type of Listeria infection found in pregnancy). Listeria occasionally has been reported to cause stillbirth and may produce septicemia in newborns (especially in premature infants). Culture of the mother’s lochia has been suggested as an aid in diagnosis, as well as blood cultures from the infant. On Gram stain the organism may be mistaken for diphtheroids, streptococci, or improperly stained H. influenzae. Listeria may cause meningitis in early infancy, usually after the first week of life. In Listeria meningitis, CSF Gram stain is said to be negative in about one half of the patients and misinterpreted in some of the others, most often being mistaken for contaminant “diphtheroids.” About one third of patients have predominance of lymphocytes or mononuclears rather than neutrophils. CSF glucose is said to be normal in 50% or more of patients. CSF culture is the most reliable method of diagnosis. DNA probe methods have recently been described.

July 24, 2009
Medications for Angina or Heart Attack

If you experience angina, medications are certain to be a part of your treatment. Because angina is an indication that your heart needs more oxygen (usually because of a blocked coronary artery), treatment includes drugs that either reduce your heart’s oxygen requirements or increase blood ?ow to your heart so that it gets more oxygen. The goal of treatment with medications is to prevent or ease the discomfort of this symptom.
If you have a heart attack, you may be given medications (throm- bolytic agents) at the hospital to dissolve blood clots that may have formed in an artery already clogged with plaque. This step limits the extent of damage to heart muscle and may save tissue before it is beyond repair.

Nitroglycerin

If you have angina, your doctor is likely to prescribe nitroglycerin, which is a vasodilator, meaning that it expands blood vessels to increase blood supply. Used properly, it relieves angina in as little as 2 minutes by reduc- ing the return of (depleted) blood to the heart and thereby easing its workload, and by relaxing the coronary arteries to allow more oxygen- rich blood to reach your heart. It’s important to remember that angina alone does not mean that you are having a heart
attack or that heart muscle is being damaged it is a temporary decrease in blood to the heart because of restricted supply and increased demand. Nitroglycerin provides a “quick ?x” that allows you to be more active and free of pain.
Nitroglycerin is inexpensive and not at all habit-forming. You can take it several times a day without harm. It works best if you take it at the very earliest sensation of discomfort. Better yet, doctors advise people with stable angina to learn to recognize the conditions (exertion, excitement, or deep emotion) that are likely to lead to the pain and take nitroglycerin preventively. Many people experience angina in predictable circum- stances, such as walking outdoors on a cold, windy, or humid day; carrying parcels or heavy items and hurrying; getting exercise after a heavy meal; working under deadline pressure; speaking in public; engaging in sexual activity; or feeling angry, worried, or tense. Being able to “head off ” angina or keep an episode short is an excellent way to take control of your heart condition.

If your doctor prescribes nitroglycerin, ask for directions about how to take it (see box) and talk to him or her about any concerns you have about using it. If you feel uncertain about it, ask to take a nitroglycerin tablet in your doctor’s presence. You will probably feel a slight tingling sensation under your tongue, your face may ?ush, or you may have a sensation of fullness in your head as the medication works in your blood vessels, but more troublesome side effects (light-headedness or headache) are rare. Once you are accustomed to taking nitroglycerin freely, you can derive the full bene?t of the relief it provides.

Beta-blockers

Beta-blockers (or beta-adrenergic blocking agents) are a group of drugs that reduce the heart’s workload and decrease its need for oxygen. They are commonly prescribed for angina, high blood pressure (see page 62), irregular heartbeat, cardiomyopathy (disease of the heart muscle), and heart failure. (They are also used to treat non-heart-related conditions such as migraine headaches and glaucoma.)
A beta-blocker works by interfering with the body’s natural response to stress. When your body is responding to stress, it releases hormones called catecholamines (norepinephrine and epinephrine) that stimulate an increase in heart rate, heart muscle contraction, and blood pressure. A beta-blocker diminishes the effects of the catecholamines, thereby modifying the heart’s response to stress. Numerous beta-blockers are available that act selectively on different aspects of the action of catecholamines.
If your doctor prescribes beta-blockers for angina, the effects of the drug will enable your heart to work longer during exercise or other stress before the angina occurs. You will need to take the beta-blockers daily, in addition to other drugs such as nitroglycerin. Even if you have no symptoms, doctors will often prescribe beta-blockers, since studies have shown they can reduce the risk of a second heart attack.
If you experience a heart attack, your body will produce high levels of catecholamines that cause your heart to work harder. Doctors may give you a beta-blocker to ease your heart’s activity and limit the injury done to heart tissue. After the heart attack, beta-blockers can help pre- vent another one from occurring. You may take the drugs inde?nitely to reduce your risk of another heart attack.
Although beta-blockers are a well-established remedy for heart con- ditions, some people who take them experience muscle fatigue after exercise, light-headedness, or fainting. If you have a lung condition such as asthma, beta-blockers can cause a spasm of the bronchial muscles and thus interfere with passage of air into the lungs, resulting in shortness of breath or wheezing. Some people with diabetes may have light- headedness if the drug interferes with their recognition of when their blood sugar levels are too low. If you experience any side effects from beta-blockers, notify your doctor immediately. A different beta-blocker or an adjustment in the dosage may resolve the problem. However, do not stop taking the drug suddenly, and try not to miss any doses because that could worsen any cardiac symptoms. If you are taking other medi- cines or herbal remedies, be sure to tell your doctor to avoid a harmful drug interaction.
The following are some commonly prescribed beta-blockers, listed by their generic names: acebutolol, atenolol, betaxolol, bisoprolol, carvedilol, metoprolol, nadolol, pindolol, propranolol, sotalol, and timolol.

Calcium Channel Blockers

A group of drugs called calcium channel blockers, or calcium antagonists, relax the arteries and increase the supply of blood to the heart, while reducing its workload by decreasing blood pressure, heart rate, and muscular contraction. Chemically, calcium channel blockers work by preventing an essential step in the process of muscle contraction the movement of calcium into muscle cells in the heart and blood vessels. As a result, the heart and blood vessels relax. Calcium channel blockers may be prescribed for high blood pressure or angina and may also be used to prevent migraine headaches. Calcium channel blockers are also very effective for the treatment of coronary spasm and the variant angina it causes.
There are many calcium channel blockers, including both short-acting and longer-acting types. Calcium channel blockers are often used in com- bination with beta-blockers. Possible side effects vary with different types of the drug, but some people experience headache; tenderness, swelling, or bleeding of the gums; drowsiness; constipation; or a slow pulse rate (less than 50 beats per minute). Talk to your doctor immediately about any side effects, but do not stop taking the medication abruptly.
The following are some frequently prescribed calcium channel blockers, listed by their generic names: amlodipine, bipridil, diltiazem, felodipine, isradipine, nicardipine, nifedipine, nisoldipine, and verapamil.

ACE Inhibitors

ACE (angiotensin-converting enzyme) inhibitors are a group of drugs widely prescribed to treat high blood pressure and are now also given to many people after a heart attack to improve heart function. After a heart attack, some heart muscle is damaged and weakened, and it may con- tinue to weaken over time. By lessening the workload of the heart and arteries, ACE inhibitors slow down this weakening.
As antihypertensives (drugs that lower blood pressure), ACE inhibitors reduce the workload on the heart caused by hypertension, and help prevent damage to the blood vessels of the heart, brain, and kidneys. Controlling high blood pressure reduces the likelihood of stroke, heart failure, kidney failure, and heart attack.
ACE inhibitors appear to work by blocking an enzyme (protein) in the body that helps produce angiotensin, a substance that makes the blood vessels contract. By inhibiting this process, the drugs relax blood vessels, the vessels expand, blood pressure goes down, and the workload for the heart decreases.
If your doctor prescribes ACE inhibitors after a heart attack, you will probably take the drugs for the rest of your life. These drugs also control blood pressure and preserve kidney function in people with diabetes.

ACE inhibitors tend to increase the level of potassium in your blood, so it is particularly important that you remind your doctor if you are taking potassium, salt substitutes (which often contain potassium), or low-salt milk (which can increase potassium levels). Talk to your doctor about any other medications you are taking, and check with him or her before using any over-the-counter medications or supplements.
Some people taking ACE inhibitors experience side effects including dizziness, light-headedness, or fainting; skin rash; fever; or joint pain. If you experience any of these effects or others, check with your doctor as soon as possible. A high potassium level often has no symptoms or very nonspeci?c symptoms such as nausea, weakness, malaise (feeling list- less), palpitations, irregular heartbeat, or a slow or weak pulse. Tell your doctor if you experience these symptoms. However, high potassium levels usually cause few symptoms until they are dangerously high, so your doctor may periodically monitor the potassium level in your bloodstream.
The following are commonly prescribed ACE inhibitors, listed by their generic names: benazepril, captopril, enalapril, enalaprilat, fosino- pril, lisinopril, perindopril, quinopril, ramipril, and trandolapril.
Angiotensin-2 receptor blockers (ARBs) may be prescribed. ARBs differ from ACE inhibitors in that ARBs inhibit the effect of angio- tensin, rather than blocking it in the ?rst place .

July 24, 2009
Outcomes of a Heart Attack

Lack of blood ?ow to the heart (myocardial ischemia) usually causes symptoms such as angina, a sensation of pressure in the chest; shortness of breath; or light-headedness. Ischemia may lead to a heart attack (myocardial infarction), as some part of the heart is deprived of blood for a period long enough for the heart muscle tissue to die. It is impor- tant to recognize these symptoms and seek medical help urgently, espe- cially if you have any risk factors for coronary artery disease. Prompt medical help, in which the blocked arteries can be opened quickly with medications or a procedure such as angioplasty (which compresses the plaque on the artery walls), can minimize damage to heart tissue.
Insuf?cient blood supply can also cause cardiac arrest—when the heart stops abruptly. Cardiac arrest most often occurs when a person’s heart rhythms are disturbed. The electrical impulses that control heart rhythms become either too fast (tachycardia), chaotic (?brillation), or in rarer cases, extremely slow (bradycardia). A person in cardiac arrest is in extreme danger. To reverse cardiac arrest, the person’s circulation should be maintained by cardiopulmonary resuscitation (CPR), and the heartbeat must be restored with an electrical shock (defibrillation). Brain death begins in just 4 to 6 minutes after a person’s heart stops.
In some people the main effects of a heart attack are seen in the pericardium, the layer of protective tissue around the heart (see “Pericardi- tis,” ).
The worst possible outcome of a heart attack is sudden cardiac death. Any form of heart disease can cause sudden death. But in most victims (about 90 percent) two or more major arteries are blocked by plaque, and the heart also shows scars from previous attacks. Sudden cardiac death can occur without a warning sign.

Ischemic Cardiomyopathy

Cardiomyopathy is a term for disease of the heart muscle that results from a condition that impairs the muscle tone of the heart and reduces its ability to pump blood. One form of the disease, called

ischemic cardiomyopathy, starts as a result of damage from blockage in a coronary artery supplying a portion of the muscular walls of the heart. This damage leads to the inef?cient pumping that is characteris- tic of cardiomyopathy. Frequently, cardiomyopathy is diagnosed by an echocardiogram (see page 132). The echocardiogram measures the ejection fraction, which is the amount of blood pumped with each heartbeat. In people with cardiomyopathy, this number is low, meaning that not enough blood is being pumped. Often the heart will dilate (widen) to compensate, so people with cardiomyopathy often have an enlarged heart.
Treatment for ischemic cardiomyopathy focuses on restoring the heart’s pumping ability with medications and opening the blocked arter- ies to improve blood supply to the heart. Other types of cardiomyopathy include a viral cardiomyopathy, in which the heart is damaged by a virus, and toxic cardiomyopathy, in which the heart is damaged by some out- side agent—for example, alcohol. If the heart has been severely and irreparably damaged by the disease, doctors may recommend a heart transplant .

Pericarditis

Pericarditis is an inflammation of the pericardium, the membrane surrounding your heart. The pericardium actually has two layers, one of which is attached to the heart’s muscular walls and the other which lines the cavity of the chest in which the heart is located. Fluid between the two layers enables the heart to move as it beats, yet stay in position. When pericarditis inflames the membrane, the amount of fluid increases and the heart’s movement (particularly its ability to ?ll with blood) can become restricted. About 10 percent of people who have had a heart attack develop pericarditis, as a result of the death of tissue. Peri- carditis occurs more often in men than in women. Infection, often due to a virus, is a common cause of pericarditis, especially in young adults. In many cases the causes of pericarditis may be unknown. Other causes of pericarditis include cancer or radiation therapy for cancer, injury to the chest, prior chest surgery, autoimmune disease, kidney failure, or use of medications that suppress the immune system.
The most common symptom of pericarditis is a sharp, stabbing pain in the center or the left side of the chest, and it sometimes radiates to the neck or shoulder. It can easily be mistaken for a symptom of a heart attack. Your doctor can begin to diagnose pericarditis by listening to your description of the pain and how it began. He or she can also listen with a stethoscope for characteristic rubbing sounds in your chest, which sometimes can be heard when the in?amed layers of the pericardium rub against each other as the heart beats. A chest X-ray may show an accumulation of ?uid around your heart, which can be con?rmed by an echocardiogram . An electrocardiogram can show changes that indicate pericarditis. Occasionally, periocardiocentesis—a pro- cedure in which a sample of ?uid is withdrawn and analyzed—is needed to help determine the cause of the pericarditis.
Pericarditis is usually treated with pain relievers and anti-in?ammatory medications such as aspirin or ibuprofen. When the condition is the result of a heart attack, pericardi- tis usually responds well to treatment and you are likely to recover in 1 to 3 weeks.
However, if the condition causes an accumulation of ?uid around your heart that is seriously restricting your heart’s ?lling ability (a rare but life-threatening disorder called cardiac tamponade), your doctor may perform pericardiocentesis (either with a needle or as minor sur- gery) to remove the excess ?uid. Examination of the extracted ?uid can help determine the cause of the cardiac tamponade. Repeated accumu- lations of ?uid may require surgery.
Complications of pericarditis are rare, but the infection can cause arrhythmias or even a heart block (when the electrical impulses triggering heart rhythm fail to perform).
Constrictive pericarditis can also develop, in which the in?ammation causes the pericardium to thicken and develop scar tissue (adhesions) between the pericardium and the heart. The pericardium becomes in?exible, and heart failure can result. In such cases, surgical removal of part or all of the pericardium is the only remedy.
There are other complications after a heart attack, depending on where the damage is located in the heart and how severe it is. The heartbeat may slow markedly, requiring a pacemaker. Arrhythmias or heart failure may also occur.

Considering Your Options

If testing shows that you have blockages in your coronary arteries, if you have angina, or if you have a heart attack, your physician may recom- mend treating your condition with lifestyle changes, medications, or procedures such as angioplasty or bypass surgery. In making a treat- ment recommendation, he or she will consider the overall pumping strength and electrical sta- bility of your heart, as shown by testing, and also the severity of your symptoms. Deciding which treatment or combination of treatments is best for you is complex, but you and your doctor may discuss these strategies:
• Lifestyle changes. Lifestyle changes such as eating a healthy diet, getting regular exercise, and quitting smoking are proven to be beneficial in reducing the risk of heart attack, improving angina, or slowing the progression of disease after a heart attack. These factors are essential to support any other treatments you may receive. Your doctor will provide you with information and support, but only you can follow through.
• Medications. Medications such as beta- blockers, calcium channel blockers, ACE inhibitors, or statins (cholesterol-lowering drugs) can improve your heart’s function and treat contributing factors such as high blood pressure and high cholesterol. They may relieve symptoms such as angina and may play an important role in controlling inflammation and preventing the plaque ruptures that lead to some heart attacks. They also may be prescribed after surgery to support your heart during recovery.
• Angioplasty. If one or more of your arter- ies is substantially blocked, angioplasty will clear the blockage and restore blood flow. If you are having a heart attack, angioplasty at the time of the heart attack may help minimize heart damage. It is a considerably less invasive, less risky, and less expensive procedure than bypass. But some arteries are not suitable for angio- plasty because they are too small. Other blockages are too dense or too large to pen- etrate with angioplasty. During angioplasty, a stent may be placed in an artery in an attempt to keep it from closing up .
• Bypass. Bypass grafting is the best approach for some people with severe angina or extensive blockages. Your doctor may recommend bypass surgery if your left main coronary artery, which supplies the left ventricle (the major pumping chamber), is significantly blocked, because any problem with angio- plasty could cause serious damage to the heart muscle; if you have several major coronary arteries blocked; or if you have had previous angioplasty procedures. Bypass also may be necessary if you have another condition such as heart failure or diabetes.

July 24, 2009
Other Gram-Negative Organisms

Pseudomonas

These gramegative rods are not classified with the Enterobacteriaceae, although they may be found normally in the GI tract. The most important is Pseudomonas aeruginosa. Pseudomonas is less common in community-acquired infection than with most of the major Enterobacteriaceae but becomes more frequent in hospital-acquired infections (about 10% of nosocomial infections). The conditions for which it is best known are urinary tract infection, septicemia, pneumonia (especially in patients with cystic fibrosis), extensive burn infection, malignant otitis externa, and infection associated with ocular contact lenses or physical therapy whirlpool tubs. P. aeruginosa is also known for its resistance to many antibiotics and for its high mortality rate.

In the environment, Pseudomonas organisms live in water or on moist surfaces. In human disease, Pseudomonas has many attributes similar to “opportunistic fungi” in that infection is rare in healthy persons; and even in hospitalized persons, colonization is more common than infection. Infection is most often superimposed on serious underlying diseases such as hematologic or nonhematologic malignancy (especially during chemotherapy), severe burns, wounds, and foreign bodies (tracheostomy, catheter), or in immunocompromised patients. P. aeruginosa is resistant to many of the standard antibiotics and therefore may become a secondary invader after antibiotic therapy for the original infection. This is most frequent in urinary tract infections. Pseudomonas may be found normally on the skin (as well as in the GI tract) and thus is a very important and frequent problem in severe burns. Pseudomonas septicemia is increasing as a complication or a terminal event in patients with malignancy or immunocompromised state. In some tertiary medical centers, Pseudomonas is reported involved in as many as 20% (range, 6%-25%) of bacteremic episodes.

Calymmatobacterium granulomatis (Donovania granulomatis)

Granuloma inguinale is a venereal disease caused by a gramegative rod bacterium that has some antigenic similarity to the Klebsiella group. Infection is transmitted by sexual contact. After incubation, an elevated irregular flattened granulomatous lesion develops, usually in or around the medial aspect of the inguinal area or on the labia. The organism is difficult to culture and requires special media, so culture is not usually done. Diagnosis is accomplished by demonstration of the organisms in the form of characteristic Donovan bodies, found in the cytoplasm of histiocytes. The best technique is to take a punch biopsy of the lesion, crush the fresh tissue between two glass slides, and make several smears with the crushed tissue. These smears are air-dried and stained with Wright’s stain. (It is possible to process a biopsy specimen in the routine manner and do special stains on tissue histologic sections, but this is not nearly as effective.) Granuloma inguinale is sometimes confused with lymphogranuloma venereum, a totally different disease, because of the similarity in names and because both are venereal diseases.

Haemophilus (hemophilus)

This genus is one of three in the family Pasteurellaceae (the other two are Pasteurella and Actinobacillus). The genus Haemophilus contains several species, most of which are normal nasopharyngeal inhabitants, that on Gram stain are very small gramegative rods (“coccobacilli”). The most important species is Haemophilus influenzae, which is the most common etiology of meningitis between the ages of 2 months and 5 years (about 70% of cases). H. influenzae occasionally produces a serious type of laryngitis (croup) in children known as acute epiglottitis and occasionally is associated with childhood otitis media, sinusitis, meningitis, bacteremia, and pneumonia. H. influenzae infection in adults is far less common than in early childhood, but the same types of diseases may occur. H. influenzae exists in both capsulated and noncapsulated forms. In early childhood, 90%-95% of cases of meningitis or bacteremia are caused by capsulated type B. Non-B encapsulated serotypes and nonencapsulated forms increase in frequency in localized pediatric infection and in adult infection. Currently, most typing of Haemophilus organisms is done with antibodies to the capsular antigens of H. influenzae. “Nontypable” H. influenzae means a noncapsulated strain and cannot be ignored, on this basis alone, as a cause for serious disease. Organisms in the genus Haemophilus require one or both substances called X and V factors. Therefore, the traditional H. influenzae culture plate contains blood agar (supplying the X factor) on which is a small area previously inoculated with S. aureus (“staph streak”), which supplies V factor (“satellite test”). However, other satisfactory culture and identification systems are now available. In addition to culture, latex agglutination tests are available to detect H. influenzae antigen in spinal fluid. These will be discussed in more detail in the chapter on CSF tests. In very limited studies involving patients with infections other than CSF, latex agglutination test results on urine were positive in 92%-100% of cases. Haemophilus influenzae is considered normal flora of the nasopharynx (3%-5% of children over age 6 months) and also sputum (which acquires these organisms as it passes through the oropharynx). Heavy growth or predominance of a single “normal flora” organism increases the suspicion that it may be pathogenic.

Other members of the Haemophilus genus that deserve special mention are H. aegyptius (Koch-Weeks bacillus), which produces purulent conjunctivitis; and H. ducreyi, which is the etiologic agent of the venereal disease chancroid. Haemophilus aphrophilus is being reported more often in recent years as a pathogen.

Pasteurella

The most important organism in this genus is Pasteurella multocida. This is a small gramegative bacillus found normally in the mouth of many (but not all) cats and dogs. Dog bites and either cat bites or cat scratches inoculate the organism, leading to cellulitis and occasionally to osteomyelitis or infection of prosthetic devices. The organism grows on ordinary laboratory media. Isolation and identification is made much easier if the laboratory knows that the specimen is from a dog- or cat-inflicted wound.

Bordatella

For a long time these organisms were included in the genus Haemophilus. The most important of this group is Bordatella pertussis, the etiologic agent of pertussis (“whooping cough”). The disease is spread by aerosol droplets and is highly contagious, with attack rates in family members of patients ranging from 50% to over 90%. In one study about two thirds of those infected were asymptomatic. The incubation period averages 7 days (range, 6-20 days). In children there are three clinical stages. The catarrhal stage lasts 1-2 weeks (range, 1-3 weeks), associated with symptoms similar to a mild or moderate viral upper respiratory infection. The paroxysmal stage lasts 2-4 weeks (sometimes more), with paroxysms of coughing alternating with relatively asymptomatic periods being the main symptoms. The convalescent stage usually lasts 1-2 weeks but may persist up to 6 months. The most frequent complication is pneumonia (15% of cases in one study); this is responsible for over 90% of deaths. In adults, clinical symptoms most often consist of chronic cough. In one study, 20%-25% of adults with chronic cough had serological evidence of pertussis.

Laboratory findings consist mostly of leukocytosis (64% of cases in one study) that averages 21,000/mm3 (21 Ч 109/L) but can reach 70,000/mm3(70 x 109/L). There typically is an absolute lymphocytosis; since young children normally have more lymphocytes than neutrophils on peripheral smear, the percentage of lymphocytes is most often within the age-adjusted reference range for young children. There typically is a significant percentage of small lymphocytes with a clefted or distorted nucleus (12%-56% of the lymphocytes). Most of these are T-lymphocytes. In one study lymphocytosis persisted for more than 1 week in 70% of cases and for more than 2 weeks in 14% of cases. In young children, one study found an abnormal chest x-ray in 42% of patients.

Options for diagnosis include posterior nasopharyngeal culture, direct tests for antigen on nasopharyngeal swabs, and serologic tests. Material for culture or antigen tests should be obtained from the pharynx at the posterior end of the nose, using a calcium alginate or Dacron-tipped flexible wire swab. Cotton-tipped swabs decrease chances of a positive culture. A positive culture is most likely (80%-90% of cases) during the first and second weeks of the catarrhal stage; during the later part of the third week, and the beginning of the paroxysmal (fourth week) stage, culture positivity falls off rapidly. After the fifth week only 15%-20% of cases are culture-positive. The original (and still useful) culture medium was Bordet-Gengou; however, the newer Regan-Lowe media can increase culture yield by 20% or more. Reported rates of culture diagnosis vary considerably (30%-60%; range, 20%-90%), depending on the stage of disease culture was obtained and the details of culture technique. Culture takes 4-7 days. As noted previously, recovery results over 50% are most likely to be obtained in the first 3 weeks except during epidemics. Direct fluorescent antibody (DFA) tests on posterior nasopharyngeal specimens are less sensitive than culture in the early nontreated stage but may be more sensitive later in clinical illness or after antibiotic therapy. In general, DFA is 50%-90% as sensitive as culture (range, 11%-100% depending on circumstances). False positive rates of 7%-40% have been reported (although some of these may have been true but nonconfirmed positives). Serologic tests are available but difficult to obtain. The most useful clinically are IgG antibodies against pertussis toxin or filamentous hemagglutinins (FHA). Acute and convalescent specimens give best results. Sensitivity of FHA-IgG tests is reported to be 75%-80% (range, 54%-100%).

Campylobacter

There are several species within this genus, of which the most important is Campylobacter fetus. This is a gramegative curved or spiral organism that originally was classified as a Vibrio. There are three subspecies (ssp.) of which two may infect humans. One of these is Campylobacter fetus ssp. fetus (formerly, ssp. intestinalis), which causes abortion in sheep and cattle and which can rarely infect humans. It produces disseminated disease without diarrhea, presenting as newborn or infant meningitis and childhood or adult septicemia. It also can produce thrombophlebitis. Patients usually are immunocompromised or have some debilitating disease such as alcoholism, cancer, or renal failure. Diagnosis is made by blood culture in septicemia and by spinal fluid culture in meningitis. Ordinary culture media can be used. The other Campylobacter organism, C. fetus ssp. jejuni, is much more common and infects cattle, dogs, and birds, in addition to humans. Poultry, especially turkeys, have been responsible for some epidemics. C. fetus ssp. jejuni produces enteric infection with diarrhea, which in some areas is responsible for as many cases as Salmonella and Shigella combined. Overall, both children and adults are affected in about equal proportion, although there is variance in different reports. Published studies indicate that C. fetus ssp. jejuni can be isolated from approximately 4%-8% of patients with diarrhea (literature range, 3%-32%).

Typical symptoms include a prodromal period of 12-24 hours with fever, headache, abdominal pain, and malaise, followed by diarrhea with crampy abdominal pain. Fever often disappears after onset of diarrhea. The diarrhea is sometimes grossly bloody, typically lasts 2-3 days, and usually is self-limited. In some patients it is more prolonged. The severity of illness varies considerably.

Laboratory tests. Helpful laboratory studies include tests for fecal blood and Gram stain of the feces for WBCs. About two thirds of patients demonstrate gross or occult stool blood (literature range, 60%-90%), and about the same number have segmented neutrophils in the stool. About two thirds of patients have peripheral blood leukocytosis. Fecal culture is the mainstay of diagnosis (blood cultures are usually negative in ssp. jejuni infection). However, routine stool culture will be negative, because the organism is microaerophilic and must be incubated 48-72 hours on special media in special gas mixtures. It grows best at 42°C but will grow at 37°C. Routine laboratories can perform the cultures, but it takes special effort and special techniques. The organism is extremely sensitive to drying. If specimens are sent to an outside laboratory, they should be inoculated into special transport media (not ordinary media) and sent with ice if more than 1 day’s travel is necessary. Gram stain of the feces can demonstrate Campylobacter in about 50% of cases (range, 43%-65%). The organism is gram negative and has different shapes; most typically curved, S-shaped, and “gull winged.” A few reports indicate that 1% aqueous basic fuchsin stain is more sensitive than Gram stain.

Aeromonas

The Aeromonas organism, a gramegative rod, is frequently found in water (usually nonchlorinated although chlorinated water is not always safe) and in soil. It infects fish and amphibians as well as humans. Sources of human infection are water; uncooked or poorly cooked meat, poultry, shellfish, and fish; and raw milk. Clinical infection in humans is not common but has been reported in those with traveler’s diarrhea, immunosuppressed patients, and sporadic cases. Asymptomatic infection has been reported in 0.1%-27% of persons examined. Diarrhea and abdominal cramps are the most common symptoms. Persons of all ages can become infected; acute self-limited diarrhea is more common in infants and young children and chronic infection in adults. Occasional extraintestinal disease (osteomyelitis, urinary tract infection, septicemia, and others) has been reported. Diagnosis is most often made by stool culture; enrichment media followed by special selective media is said to give best overall results, although the organisms can grow on standard culture media.

Helicobacter

Helicobacter pylori (formerly Campylobacter pylori or pyloridis) is an S-shaped (curved, or “gull-winged” like Campylobacter), small gramegative bacillus found in the mucus covering the gastric mucosa, with the organisms located next to the gastric lining cells of the surface and gastric pits. H. pylori is associated with acute and chronic gastritis in the gastric antrum and is present in about 90% (range, 70%-100%) of patients with duodenal ulcer, in 70%-75% (range, 40%-90%) of patients with gastric ulcer, about 50% (range, 30%-75%) of patients with nonulcer dyspepsia, and about 20%-25% of patients with gastric cancer. Significant H. pylori antibody levels can be detected in about 20%-25% of clinically normal U.S. and European adults (range, 5%-75% depending on age). This suggests that H. pylori infection is often subclinical. Indeed, in patients with clinical infection, biopsy of normal-appearing gastric mucosal areas often contains demonstrable H. pylori organisms. Chronic or recurrent duodenal ulcer is very highly associated with both excess acid production and H. pylori infection. However, one exception is duodenal ulcer due to the Zollinger-Ellison syndrome, in which incidence of H. pylori infection is zero.

Incidence of H. pylori is age-related; in one study 5% or less of adults age 25-45 had antibodies to H. pylori; 20% of adults age 45-55, 50% of adults 55-65, and 75% of adults over age 65 had the antibodies. African Americans are reported to have about twice the incidence seen in Europeans. Besides antral gastritis, H. pylori is associated to a lesser degree with patchy gastritis in the body of the stomach.

The traditional gold standard for diagnosis has been culture of gastric mucosal biopsy specimens. This should be placed in 2-3 ml of sterile isotonic saline, plated on enriched media such as chocolate agar or selective media such as Skirrow’s, and incubated 5-7 days at 37°C. However, based on comparison with results of other tests, culture only detects about 75% (range, 50%-95%) of cases. Giemsa stain of gastric mucosa biopsy tissue is reported to detect about 90% of cases (range, 88%-93%), although in my experience it has been less. Warthin-Starry silver stain has a little better sensitivity than Giemsa stain and Gram stain has somewhat less (about 75%; range, 69%-86%). H. pylori has considerable ability to metabolize urea by means of the enzyme urease that forms the basis for several other tests. The urea breath test using radioactive carbon-13 or carbon-14 incorporated into a urea test dose is administered orally and expired air is then tested for radioactivity 20-120 minutes later. This is probably the best test of all those available, with sensitivity in most reports over 95% (range, 90%-100%) and specificity over 95%. In fact, at present it is probably a better gold standard than culture. However, the test is available only in a relatively few large medical centers, is expensive, requires special equipment, and uses long-lived isotopes that are becoming serious disposal problems. Other tests are based on fresh gastric mucosal biopsy tissue placed in a urea-containing medium with some indicator system to signal metabolism of the urea. The best-studied of these is the CLO test; it is reported to have a sensitivity of about 90% (range, 86%-96%).

Some immunoassays for antibody to H. pylori have become commercially available, mostly in EIA format, which detects IgG, IgA, or IgM anti- body alone or total antibody. In experimental H. pylori infection, an IgM elevation first begins at about 3 weeks, becoming nondetectable about 8 weeks later. IgA and IgG levels rise at about 8-9 weeks after infection, with the IgG level remaining elevated a year or more. The height of elevation does not correlate well with severity of infection. IgM and IgA levels often fall in about 4 weeks after successful treatment, whereas IgG levels are not affected. Most of the antibody assays evaluated in the literature to date have been homemade (which often give better results than commercially available kits); these have reported sensitivity of 80%-100%. Several new commercial kits claim sensitivity of 95% or more. However, some of these sensitivity claims are less because the tests against which the commercial EIA was compared had sensitivity themselves less than 100%. Also, more evaluations must be done to get adequate information about each EIA kit. In general, most current interest seems to be toward IgG antibody. However, this antibody has the disadvantage that it often remains elevated for a year or more after adequate therapy.

Brucella

Three members of the Brucella genus produce an uncommon febrile disease known as “brucellosis,” which sometimes must be considered in the differential diagnosis of fever of unknown origin. The Brucella organism is a gramegative coccobacillus with three main species. One species infects cattle, the second one infects goats, and the third is found in swine. Classic brucellosis was most often transmitted to humans by infected milk or milk products. However, persons most likely to contact the infection today in the United States are workers in the meat-processing industry, especially those working with swine. Veterinarians and dairy farmers are also at risk. Clinical symptoms include fever, chills, and myalgia. About 25% of patients develop single-joint arthralgia. Lymph nodes are usually not enlarged. Splenomegaly occurs in about 20% of cases. Some patients develop pneumonia. WBC counts are usually normal or decreased. Blood culture is positive in 30%-50% of cases, but the organisms need added carbon dioxide and grow very slowly on ordinary culture media, so that under ordinary circumstances the brucellae may either not grow at all or the culture bottle is discarded as negative before growth is evident. Special media are available that will assist growth. A slide agglutination test is the most frequent method for diagnosis. Test results greater than 1:80 are suspicious for brucellosis. After recovery, antibody titer elevation lasts 1-2 years.

Francisella

Formerly included in the genus Pasteurella, the genus Francisella contains one medically important species, Francisella tularensis, which is the causative agent of tularemia. F. tularensis is a very small gramegative aerobic coccobacillus that requires special media for adequate growth. The major reservoir for human infection in the United States is wild animals, predominantly wild rabbits, and in some cases deerflies or ticks. Most persons who contract the disease are those who handle raw wild rabbit meat. Tularemia may exist in several clinical forms, but the most common symptoms are painful single-area lymphadenopathy (ulceroglandular form, comprising 75%-80% of cases) and prolonged low-grade fever. Much less common is a septicemic form (5%-15% of cases). Pneumonia may occur in 15% or more of either the ulceroglandular or the septicemic forms, especially the septicemic type. Rabbit-associated infection is usually associated with a small ulcerated skin lesion at the place of entry on the hand and also with axillary adenopathy, whereas in tick-associated infection the ulcer is located on the trunk or lower extremities and the lymph nodes affected are most commonly in the inguinal area. About 15% of affected persons lack either the ulcer or both the ulcer and the adenopathy. WBC counts are normal in at least 50% of patients and slightly or mildly elevated in the remainder. The differential cell count is usually normal. Inconsistent elevation of one or more liver function test results is present in about one half of the patients.

Tularemia must occasionally be considered in the differential diagnosis of fever of unknown origin. The organisms will not grow on standard laboratory culture media. Special media can be obtained and culture performed from lymph node aspiration, but this is rarely done because of an unusually high rate of laboratory technologist infection from the specimens. The standard diagnostic test is a slide agglutination procedure. Titers are said to be negative during the first week of illness and begin to rise at some time during the second week, become maximal in 4-8 weeks, and remain elevated for several years. A fourfold rising titer is necessary to prove acute infection. There is considerable disagreement regarding a single titer level that could be considered presumptive evidence of infection; 1:160 seems to be the least controversial value.

Vibrios

Vibrios are gramegative small curved rods. The most important species is Vibrio cholerae, which produces cholera by means of an enterotoxin. The V. cholerae species is subdivided into many serotypes, of which only one, the 01 strain, is associated with epidemic cholera in the United States. A different strain is found in Latin America than in the United States. About 75% of cholera organism infections are asymptomatic, about 20% produce mild to moderate diarrhea, and about 5% produce the severe watery diarrhea ordinarily associated with the name “cholera” that can lead to death from loss of fluid and electrolytes. Humans usually become infected by drinking contaminated water or eating shellfish from contaminated water. Diagnosis has traditionally been made by stool culture. The organism is very sensitive to drying, and if swabs are used, they must be placed in transport media as soon as the specimen is obtained. Also culture has been reported to miss 10%-20% of cases.

Recently, two stool tests have been developed by the same manufacturer using a monoclonal antibody called COLTA that is claimed to be specific for V. Cholerae 01 strain. CholeraScreen is a coagglutination slide test and CholeraSmart is a tube agglutination test. Both are said to be 95%-100% sensitive compared to culture. Only a few evaluations have been published to date.

July 24, 2009
Recognizing Symptoms of a Heart Attack

Clearly, knowing the signs of a heart attack and responding quickly are important. If people live long enough to reach the hospital, their chances of dying are dramatically reduced. Treatment to open clogged arteries is most effective within the ?rst 60 to 90 min- utes after symptoms (such as chest pain) occur. If the blood ?ow is completely shut off, permanent damage to heart muscle occurs in about 20 minutes. So every minute counts, both to save your life (or someone else’s) and to improve the quality of life after the attack.
Calling 911 or the emergency services (?re depart- ment or ambulance) in your area should be your ?rst step, before doing anything else. Paramedics can begin treatment immediately, even before you reach the hos- pital. If your heart actually stops beating, paramedics have the knowledge and equipment to begin advanced life support and to restore a heartbeat. Also, a heart attack victim who arrives by ambulance gets faster treatment at the hospital, because emergency medical technicians begin treatment as soon as the ambulance arrives.
Take an aspirin if you have one on hand. Chew it; don’t swallow it. If you’re unsure whether you person- ally should take aspirin, wait until the paramedics arrive. If you’re alone, unlock your door, then sit down or lie down while you wait for the ambulance.

What to Do If Symptoms Occur

Many people delay going to a hospital, sometimes for as long as 2 hours after they ?rst notice symptoms. Some people are just hoping the symptoms will disappear, some don’t want to feel embarrassed by a false alarm, some think that a “real” heart attack would be dramatic and unmistakable, and some don’t realize the enor- mous advantage of immediate treatment. Although these feelings are understandable, doctors urge you to seek help at the ?rst signs of a heart attack, so that effective treatment begins as soon as possible.
It’s easier to respond quickly to symptoms—either your own or some- one else’s—if you have thought through the steps you will take before an emergency arises. First, of course, you have to learn the warning signs. Talk to your doctor about your personal risk of a future heart attack and how you should respond—for example, whether you should take aspirin or use nitroglycerin. If you are at risk, talk with your family, friends, and coworkers about the warning signs and the best response. Find out who, if anyone, knows cardiopulmonary resusci- tation (CPR) and alert him or her to the possible need for it. If 911 serv- ices are not available, keep the numbers for your area’s emergency medical services (?re department and ambulance) next to the telephone. Find out which hospitals nearby have 24-hour emergency cardiac care.
When you arrive at the emergency room, a doctor or other staff may ask you questions about your symptoms. If you are able to respond, the information you give them will help guide your treatment. Questions may include:

• When did you ?rst notice symptoms?
• What were you doing at the time?
• Were the symptoms most intense right away, or did they build up gradually?
• Did you notice any symptoms other than the ?rst or most intense ones?
• On a scale of 1 to 10, how would you rate the discomfort you felt?
• What medicines have you taken today?
• What medicines do you usually take?

Chest Pain

Most people would probably name chest pain as the symptom they associate most closely with heart attack. But very often the symptom that a person experiences from a blockage in the coronary arteries is not a sharp or stabbing pain. People who have experienced a heart attack often go to great lengths to say that the sensation they had was not exactly pain, but rather an uncomfortable feeling of squeezing or pressure (angina pectoris; ).
The somewhat confusing fact is that chest pain may be caused by a heart condition other than heart attack, and it can also result from problems having nothing to do with the heart, such as gallbladder dis- ease, a muscular disorder, or a digestive problem. The most important distinguishing feature of pain caused by coronary artery disease is prob- ably a link to some sort of stress, either physical or emotional—an indication that the heart’s increased need for oxygen is not being met. Chest pain at rest deserves immediate medical attention, especially in a person with risk factors for heart attack. The ?rst episode of chest pain in a per- son’s life may be the sign of an impending heart attack, so don’t delay seeking medical help.
For reasons that are not at all clear, women with heart disease are more likely to experience symptoms other than chest pain—such as shortness of breath, indigestion, or fatigue—making diagnosis more complex. People with diabetes also may not experience typical chest pain. Some people may have jaw pain or arm pain that for them is the equivalent of chest pain—a sign of a heart attack. If you have experi- enced symptoms of heart attack before, the important point is to learn to recognize them when they occur so that you can respond without hesitation.
A form of chest pain related to heart disease may also be caused by in?ammation of the outer surface of the heart, the pericardium. Like in?ammation anywhere in the body, an in?amed pericardium swells and causes pressure on nerve endings that may result in pain when you breathe in, when you move in certain ways such as leaning forward, or when you lie down. Even though not all chest pain indicates a heart attack, you should still get medical help if you experience any kind of a chest pain that lasts for as long as 5 minutes. It is de?nitely better to be safe than sorry.

Angina Pectoris

Angina, or angina pectoris, is the term that describes the typical chest discomfort or pain that signals an inadequate ?ow of blood to the heart, most often the result of a blockage in the coronary arteries. Many people who have experienced angina struggle to characterize it, but they often describe it as a constricting pressure or fullness; a squeez- ing, crushing, or burning sensation; or a dull pain in the center of the chest. It may radiate out to the arms, shoulder, back, neck, or jaw. But it may also be con?ned to a small area of the chest, and it can last several minutes. Alternatively, it goes away and returns over a period of minutes. However, pain that lasts less than 30 seconds or more than 30 minutes is usually not anginal pain.
Angina usually occurs when the heart demands more blood for a variety of reasons: physical exertion, such as walking uphill or having sexual intercourse; mental or emo- tional stress, including fright or anxiety; cold temperatures; or even eating a meal that trig- gers digestive activity. When pain brought on by exercise is relieved by rest, angina is suspected by your doctor. Many people have “stable angina”—that is, they have episodes of angina that occur in a fairly predictable pattern. This is the reason behind stress testing as a way to reproduce a person’s chest pain symptoms during exercise: to help diagnose coronary artery disease. Usually, a person with stable angina can relieve the symptom with rest or nitroglycerin, or both.
Unstable angina is a form of chest discomfort that occurs for the ?rst time in that person or occurs when the person is at rest. It can be more severe and prolonged than stable angina. The blockage in the arteries that brings on unstable angina may be atherosclerosis, a blood clot, in?ammation, or infection. The experience of unstable angina is an emergency situation. If you have new, unpredictable, or increasingly severe chest discomfort, go to a hospital emergency department imme- diately for evaluation.
A variant form of angina, sometimes called Prinzmetal’s angina, dif- fers from other types because it is not related to physical or emotional stress. It usually occurs when the person is at rest or asleep, often between midnight and 8 o’clock in the morning. Variant angina is a symptom of coronary artery spasm, which may occur in an open artery or in an artery already blocked by atherosclerosis. The spasm occurs close to the blockage and obstructs blood ?ow to the heart muscle.
Angina can occur more rarely as a symptom of other heart condi- tions such as valve disease, cardiomyopathy (disease of the heart muscle; , or extreme high blood pressure. Angina may be treated with nitroglycerin or other medication .

Shortness of Breath

Shortness of breath is another common symptom of a heart attack that can be dif?cult to differentiate and describe. Dif?culty breathing can take the form of feeling unusually breathless with exertion; experienc- ing rapid or shallow breathing; or feeling short of breath at rest. Some people report that they feel conscious of the need to draw breath.
Of course, it is normal to feel short of breath for a while after stren- uous exercise. Anxiety can cause hyperventilation, a form of rapid or shallow breathing. An overweight person may breathe more heavily just from the exertion of carrying extra weight, or someone who is out of shape may feel short of breath with even limited exercise. You are the best judge of when your shortness of breath feels abnormal.
If you feel short of breath at what for you is a moderate level of exer- cise, or if you become short of breath while at rest, or if your breathless- ness occurs with chest pain, don’t hesitate to get medical help.

Light-headedness and Other Symptoms

Some people feel light-headed—like they might pass out—as a symp- tom of a heart attack. (This sensation is different from dizziness, which makes you feel as if you or your surroundings are whirling.) Light- headedness can also signal other heart conditions, such as heart rhythm problems or problems unrelated to your heart.
Women are more likely than men to have atypical or more vague symptoms of heart attack such as light-headedness, nausea or queezi- ness, or fatigue, rather than chest pain. Researchers have only relatively recently recognized this gender difference, and the reasons for it are not yet clear. Genes, hormones, or lifestyle differences may be at work. Both women and their doctors need to be aware of the nature of a

woman’s symptoms and respond quickly to the possibility of heart attack. It is vital to keep in mind that heart disease is the leading cause of death for women, just as it is for men.

Silent Ischemia

A person can have an episode of ischemia (lack of blood to the heart) without angina or other symptoms, a phenomenon called silent ischemia. If the ischemia is severe or lasts too long, it may cause a heart attack with all the attendant dangers of heart damage or cardiac arrest, even if there is no chest pain. For many people the ?rst sign of heart dis- ease may be a cardiac arrest. Cardiologists estimate that 3 to 4 million Americans have silent ischemia every year. The resulting damage to the heart muscle is a leading cause of heart failure (when the heart’s pump- ing action is inadequate). Most people who have episodes of angina or chest pain are likely to have episodes of silent ischemia, too. Although there is no way to know when silent ischemia occurs, an exercise stress test (see page 125) indicates how the blood ?ow in your coronary arter- ies is affected by exercise, and Holter monitoring (see page 124) records an episode of silent ischemia if it occurs while you wear the monitor.
Treatment for silent ischemia is aimed at improving the ?ow of blood to your heart and reducing your heart’s need for oxygen—just like the treatment for any other symptoms of coronary artery disease. Your doctor will recommend lifestyle changes, medications, or perhaps ulti- mately surgical procedures such as angioplasty to reach these goals.

Coronary Artery Spasm

Chest pain may result from a spasm of the artery. Some people’s coro- nary arteries have a tendency to go into spasm periodically (doctors are not sure why). The spasm, called a vasospasm, temporarily constricts the passageway and blocks blood ?ow to the heart. A spasm usually occurs in a coronary artery that is already blocked by atherosclerosis, but it can occur in an otherwise healthy vessel.
The spasm is temporary, but it can cause a heart attack, irregular heart rhythm (arrhythmia), or even sudden cardiac death. The major symptom of coronary artery spasm is a variant form of angina that is particularly painful and often occurs at the same time each day. To treat coronary artery spasm, your doctor may prescribe a medication called a calcium channel blocker , which relaxes the smooth muscle in the artery walls and eases the discomfort of angina. In some cases, a nitrate may be prescribed also.

Heartburn or Heart Attack?

It’s not always easy to distinguish between the chest discomfort of a heart attack and the burning sensation of heartburn (acid reflux). About one out of ten people who go to an emergency department complain- ing of chest pains has heartburn. Either symptom occurs in the general area of the chest, may have a burning quality, and may occur after a big meal. The location of the pain may be a clue: heart attack pain is likely to radiate from the chest into the shoulder, arm, or neck, especially on the left side, while heartburn usually stays more centered and travels into the neck or throat. But don’t take any chances. Remember that most of the damage done by a heart attack occurs in the first hour or so. Get to an emergency department quickly if you have any doubt about the nature of your discomfort.

What Is a STEMI?

You may hear or read about the danger of a STEMI—an ST elevation myocar- dial infarction. This technical term describes a severe heart attack in which an artery is completely blocked. An ST elevation is a characteristic rise in a partic- ular segment of the waves seen in an ECG reading for a person who is having symptoms of a heart attack. Cardiologists identify certain parts of the wave by the letters of the alphabet from Q through T. Injured heart muscle does not conduct electrical impulses normally. The characteristic wave patterns on an ECG show how the electrical impulses are being affected by the injury, and what part of the heart appears to be affected. Also, problems with the heart’s rhythm can be detected. An ST elevation when you have chest pain is a strong indication of a heart attack. Also, a non-Q-wave heart attack may be indicated by a drop in the pulse rate; this type of attack is called minor but may indicate that a major heart attack is imminent.
What does your doctor want you to know about STEMI? A STEMI is likely to be preceded by chest pain, shortness of breath, or feelings of weakness, nausea, or light-headedness. If you have these symptoms for 5 minutes or more, call 911 or your local emergency number immediately. The sooner you get help, the more likely you are to survive and to return to an active lifestyle. Every minute counts.

Calling for Emergency Help

If you or someone you know might be hav- ing a heart attack, call 911 or the emer- gency services number for your area. More than 90 percent of the United States now has 911 service, but in some communities the emergency number is that of the fire department, police department, or town hall. Keep the number handy at home for all family members. If you call for emer- gency services from a cell phone, be sure to mention the location you’re calling from because the location can’t be traced quickly, as it can from a landline. Also, if you use cable or broadband service for Internet-generated calls, find out whether your service will give you access to a 911 service or to some other administrative service office that does not handle emer- gency calls.

Warning Signs of Heart Attack

Heart attacks may start with relatively mild symptoms. Call 911 or the emergency medical services in your area if you experience any of these symptoms for as much as 5 minutes:
• Chest discomfort. An uncomfortable feeling—such as pressure, squeezing, or a sensation of fullness—in the center of the chest that lasts for a few minutes or that goes away and then comes back. The feel- ing may not be truly painful.
• Discomfort in other parts of the upper body. The uncomfortable feeling or pain may spread to one or both arms, the back, the neck, the jaw, or maybe the stomach.

• Shortness of breath. Difficulty breath- ing often occurs with or just before chest discomfort. It may be the only sign of a heart attack.
• Light-headedness, cold sweats, nau- sea, or indigestion. Some people, par- ticularly women, experience these symptoms, and some report having a sense of impending doom.
If you have heart attack symptoms and for some reason cannot call 911 (or the emergency number for your area), have someone else drive you to the nearest hospital immediately. Never drive yourself unless you have absolutely no other choice.

July 24, 2009
The Role of Inflammation

Scientists now know that in?ammation is a major component of the process of atherosclerosis. Just as in?ammation of bones and joints can, over time, lead to arthritis, an in?ammatory process inside blood vessels can lead to coronary artery disease or stroke.
Research has not yet pinpointed what causes the low-grade in?am- matory process that may contribute to or even cause atherosclerosis in some people. In the future, a speci?c bacterial or viral infection may be identified, and treatment for coronary artery disease may include antimicrobial or antiviral agents, just as treatment for stomach ulcers now involves antibiotics for the bacteria that is known to be the cause.
In many people who have heart attacks, in?ammation has caused the artery wall itself to absorb fat particles to form a type of plaque some- times called “soft” or “vulnerable” plaque. This plaque, buried in the wall of the artery, is not the same as the plaque that builds up in the channel of an artery. Soft plaque is composed of fat-?lled cells con- tained in a thin shell. If the shell containing the soft plaque breaks open, the plaque spills into the bloodstream, and a blood clot forms at the site of the rupture—the body’s usual response to injury. This blood clot— rather than the plaque—may be the blockage that shuts off the blood supply. The in?amed and swollen artery may be less elastic as well. This process, starting with a type of in?ammation and leading to a blood clot, may explain heart attacks in some people who do not have the tra- ditional risk factors for coronary artery disease, such as high cholesterol.
A marker of the in?ammatory (or immune) response is the presence of a substance called C-reactive protein (CRP) in the blood. Everyone’s body makes CRP, but in different amounts, depending in part on genetic factors and in part on lifestyle. The same factors that tend to contribute to increased risk of heart attack—smoking, overweight, high blood pressure, lack of exercise—contribute to high levels of CRP. A person’s CRP levels can be elevated early in the development of plaque in the arteries, and at the time of a rupture. When a heart attack occurs, CRP levels rise dramatically. As a result, measuring CRP levels in a person’s blood is a good predictor of the development of coronary artery dis- ease and the risk of future heart attacks, as well as a good indicator in an emergency department that a heart attack has occurred.
Nowadays, CRP is measured through a relatively simple test that can be done in a doctor’s of?ce. An elevated CRP level may be as reliable a predictor of heart attack risk in some people as a high level of LDL ( low-density lipoprotein, the harmful choles- terol; see page 132). Research suggests that in some people, high levels of CRP are a signi?cant risk fac- tor for heart disease, independent of high choles- terol. It may be a better predictor in women than in men. Other factors may raise the CRP level in the blood, however. At present, there is no speci?c treat- ment for high CRP levels, except for treating any underlying conditions.

Signs of Cardiac Arrest
A person in cardiac arrest:
• Loses consciousness
• Stops breathing
• Lacks a pulse
Respond immediately:
• Call 911 or the emergency number for your area.
• If you are trained in CPR, use it to help keep the person alive until emergency help arrives to perform defibrillation.
• Look for automated external defibrillator (AED) equipment to use on the person. See also the box on page 155 on using an AED.

July 24, 2009
Atherosclerosis

Most coronary artery disease leading to heart attack results from the process of atherosclerosis, the stiffening and narrowing of arteries. Early changes are seen in people as young as their twenties. A healthy artery is highly elastic, responding readily to changes in the amount or pressure of the blood ?owing through it. As you age, the walls of your arteries tend to become somewhat thicker and stiffer, causing some resistance to the pumping action of the heart. This loss of ?exibility in the arteries, which tends to accelerate as you get older, is the cause of higher blood pressure in older people and con- tributes to several forms of heart disease.
Apart from or in addition to these effects of aging, atherosclerosis is a disease process affecting the interior walls of the major arteries, including the coronary arteries that supply the heart. The inner walls of the arteries become in?amed and irregular and begin to accumulate fatty materials, cholesterol, and other debris that together form plaque. The plaque gradually builds up until it sig- nificantly narrows the channel through which blood is ?owing. This unhealthy process of athero- sclerosis is not fully understood, although a high- fat diet, high levels of cholesterol, smoking, and other known risk factors (see pages 19–22), along with genetic background, are major contributing causes. As plaque builds up, it can form accumulations (called athero- mas or plaques) that ultimately shut off the blood ?ow. A blood clot traveling through the bloodstream can lodge on an accumulation of plaque and block the already narrowed channel altogether.
When a coronary artery is temporarily blocked, it can deprive some portion of the heart of oxygen and nutrients, resulting in a condition called myocardial ischemia. Prolonged ischemia can damage or destroy tissue anywhere in the heart, leading to an infarction (or death of tis- sue), depending on what part of the heart the affected artery supplies. Extensive damage to the left ventricle, the main pumping chamber of the heart, will affect a person’s long-term health and activity level.

July 24, 2009