Clinical Director, University of Rochester School of Medicine and Dentistry
Association of Virulence Mechanisms with Specific Meningococcal Infections Specific disease manifestations of meningococcal infections have specific virulence and pathogenic mechanisms diabetes mellitus definition medical order glimepiride with american express, as described below for fulminant meningococcemia and meningitis diabetes diet kenya buy 4 mg glimepiride with amex. Fulminant Meningococcemia Purpura Fulminans 453 Fulminant meningococcemia is perhaps the most rapidly lethal form of septic shock experienced by humans diabetic diet alcohol glimepiride 2mg free shipping. The concentrations of endotoxin detected in the blood of patients with fulminant meningococcemia are 10- to 1000-fold higher than those found in the blood of patients with bacteremia due to other gram-negative bacteria diabetes insipidus support group buy generic glimepiride 2mg online. The bacteria and endotoxin-containing blebs stimulate monocytes, neutrophils, and endothelial cells, which then release cytokines and other mediators that can activate many distant targets, including other leukocytes, platelets, and endothelial cells. When activated, the endothelium produces molecules that can be procoagulant as well as adhesive for leukocytes. Patients with fulminant meningococcemia usually have extremely high blood levels of both proinflammatory mediators-i. Procoagulant, antifibrinolytic forces are also active in the blood of patients with fulminant meningococcemia. Fibrinopeptide A and thrombin-antithrombin levels are high, reflecting active clotting, whereas antithrombin and fibrinogen levels are low. Striking deficiencies of antithrombin and proteins C and S can occur; studies have found a strong negative correlation between protein C activity and both the size of purpuric skin lesions and the mortality rate. Both platelets and leukocytes doubtless contribute to the formation of microthrombi and to the vascular injury that ensues. Thrombosis of small- to midsized arteries can produce peripheral necrosis and gangrene, necessitating limb or digit amputation. Meningitis blood, may have antibodies or phagocytes that slow meningococcal growth, or may lack the (unknown) factors that allow N. If disease is recognized early, the prognosis of patients with meningococcal meningitis is substantially better than that of patients with fulminant meningococcemia. Meningococcal bacteremia can result in the seeding of the meninges, pericardium, and large joints. Up to onethird of patients with meningococcal disease present with meningitis or other closed-space infections without signs of sepsis. Meningococci have been shown to invade endothelial cells both experimentally and in vivo. The inflammatory response is largely confined to the subarachnoid space and contiguous structures. For example, meningitis and its sequelae are due to the induction of local inflammatory cytokines and other mediators. The major bactericidal antibodies are IgM and IgG, which (except for serogroup B) bind to the capsular polysaccharide. Antibodies to other surface (subcapsular) antigens may confer crossserogroup protection. Infants are protected from meningococcal disease during the first months of life by passively transferred maternal IgG antibodies. Disease incidence declines as protective antibodies are induced by colonization with nonpathogenic bacteria that have cross-reactive antigens. One theory relates the occurrence of some cases of meningococcal disease to the presence of high levels of IgA antibodies to meningococci, since these antibodies can block the bactericidal activity of IgM. Although only one-half of individuals with known late-complement-component deficiency ever experience meningococcal disease, some affected persons have several episodes. Deficiency of each of the terminal complement components is inherited in an autosomal recessive fashion. Properdin deficiency, in contrast, is X-linked; some affected males develop overwhelming meningococcal disease, an observation indicating that the alternative complement pathway is also needed for antimeningococcal host defense. Disease onset in properdin-deficient individuals typically occurs in the teens or twenties. Although many of these associations await confirmation in other populations of patients, in sum they point to important genetic influences on the acquisition and severity of meningococcal disease. Meningococcemia Patients with meningococcal disease may have both meningococcemia and meningitis. Although meningococcal bacteremia may occasionally be transient and asymptomatic, in most individuals it is associated with fever, chills, nausea, vomiting, and myalgias. Although the lesions are typically found on the trunk and lower extremities, they may also occur on the face, arms, and mucous membranes. The petechiae may coalesce into hemorrhagic bullae or may undergo necrosis and ulcerate. Patients with severe coagulopathy may develop ischemic extremities or digits, often with a sharp line of demarcation between normal and ischemic tissue.
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Depending on the inciting event diabet-x skin therapy best buy glimepiride, local symptoms may occur in secondary peritonitis-for example diabetes type 2 treatment options purchase glimepiride us, epigastric pain from a ruptured gastric ulcer diabetic desserts 1mg glimepiride free shipping. Unusual locations of the appendix (including a retrocecal position) can complicate this presentation further diabetes symptoms hypo buy discount glimepiride 2mg on-line. Once infection has spread to the peritoneal cavity, pain increases, particularly with infection involving the parietal peritoneum, which is innervated extensively. Patients usually lie motionless, often with knees drawn up to avoid stretching the nerve fibers of the peritoneal cavity. Coughing and sneezing, which increase pressure within the peritoneal cavity, are associated with sharp pain. There may or may not be pain localized to the infected or diseased organ from which secondary peritonitis has arisen. Patients with secondary peritonitis generally have abnormal findings on abdominal examination, with marked voluntary and involuntary guarding of the anterior abdominal musculature. Although recovery of organisms from peritoneal fluid is easier in secondary than in primary peritonitis, a tap of the abdomen is rarely the procedure of choice in secondary peritonitis. An exception is in cases involving trauma, where the possibility of a hemoperitoneum may need to be excluded early. Mild to moderate disease can be treated with many drugs covering these organisms, including broad-spectrum penicillin/-lactamase inhibitor combinations. Secondary peritonitis usually requires both surgical intervention to address the inciting process and antibiotics to treat early bacteremia, to decrease the incidence of abscess formation and wound infection, and to prevent distant spread of infection. These infections may be accompanied by localizing pain and/or nonlocalizing symptoms such as fever, malaise, anorexia, and toxicity. Historically, coagulase-negative staphylococcal species were identified most commonly in these infections, but more recently these isolates have been decreasing in frequency. Staphylococcus aureus is more often involved among patients who are nasal carriers of the organism than among those who are not, and this organism is the most common pathogen in overt exitsite infections. The finding of more than one organism in dialysate culture should prompt evaluation for secondary peritonitis. To facilitate diagnosis, several hundred milliliters of removed dialysis fluid should be concentrated by centrifugation before culture. In experimental models of abscess formation, mixed aerobic and anaerobic organisms have been implanted intraperitoneally. As in humans, these experimental abscesses may stud the peritoneal cavity, lie within the omentum or mesentery, or even develop on the surface of or within viscera such as the liver. Pathogenesis and Immunity There is often disagreement about whether an abscess represents a disease state or a host response. In any event, abscesses do cause significant symptoms, and patients with abscesses can be quite ill. Experimental work has helped to define both the host cells and the bacterial virulence factors responsible-most notably, in the case of B. Structural analysis of these polysaccharides has shown an unusual motif of oppositely charged sugars. The alternative pathway of complement and fibrinogen also participate in abscess formation. Guidelines issued in 2005 suggest that agents should be chosen on the basis of local experience with resistant organisms. In some centers, a first-generation cephalosporin such as cefazolin (for gram-positive bacteria) and a fluoroquinolone or a third-generation cephalosporin such as ceftazidime (for gram-negative bacteria) may be reasonable; in areas with high rates of infection with methicillin-resistant S. Broad coverage including vancomycin should be particularly considered for toxic patients and for those with exit-site infections. The clinical response to an empirical treatment regimen should be rapid; if the patient has not responded after 48 h of treatment, catheter removal should be considered. Clinical Presentation Of all intraabdominal abscesses, 74% are intraperitoneal or retroperitoneal and are not visceral. Most intraperitoneal abscesses result from fecal spillage from a colonic source, such as an inflamed appendix. They usually form within weeks of the development of peritonitis and may be found in a variety of locations-from omentum to mesentery, pelvis to psoas muscles, and subphrenic space to a visceral organ such as the liver, where they may develop either on the surface of the organ or within it. Infections of the female genital tract and pancreatitis are also among the more common causative events. When abscesses occur in the female genital tract-either as a primary infection. For example, it is encountered less commonly in pelvic inflammatory disease and endometritis without an associated abscess. In pancreatitis with leakage of damaging pancreatic enzymes, inflammation is prominent. Therefore, clinical findings such as fever, leukocytosis, and even abdominal pain do not distinguish pancreatitis itself from complications such as pancreatic pseudocyst, pancreatic abscess, or intraabdominal collections of pus. Many centers prescribe preemptive antibiotics for patients with necrotizing pancreatitis. Imipenem is frequently used for this purpose since it reaches high tissue levels in the pancreas (although it is not unique in this regard). If needle aspiration yields infected fluid, most experts agree that surgery is superior to percutaneous drainage. Diagnosis Scanning procedures have considerably facilitated the diagnosis of intraabdominal abscesses. Abscesses contiguous with or contained within diverticula are particularly difficult to diagnose with scanning procedures.
Cellulitis diabete tipo 01 buy cheap glimepiride 2 mg line, an acute spreading inflammation of the skin diabetes vitamins buy glimepiride once a day, is most often caused by infection with group A Streptococcus or Staphylococcus aureus diabetes type 1 versus diabetes type 2 buy glimepiride 2mg cheap, virulent organisms normally found on the skin (Chap diabetes high blood sugar symptoms order glimepiride 2mg free shipping. Although cellulitis tends to be circumscribed in normal hosts, it may spread rapidly in neutropenic patients. A tiny break in the skin may lead to spreading cellulitis, which is characterized by pain and erythema; in the affected patients, signs of infection. What might be a furuncle in a normal host may require amputation because of uncontrolled infection in a patient presenting nedasalamatebook@gmail. Pertussis vaccines have not been recommended for people >6 years of age in the past. It is anticipated that future vaccines will include more serotypes and will be recommended for adults. Papules related to Escherichia coli bacteremia in a neutropenic patient with acute lymphocytic leukemia. A dramatic response to an infection that might be trivial in a normal host can mark the first sign of leukemia. Fortunately, granulocytopenic patients are likely to be infected with certain types of organisms (Table 11-4); thus the selection of an antibiotic regimen is somewhat easier than it might otherwise be (see "Antibacterial Therapy" later in the chapter). Patients who are neutropenic or have previously received antibiotics for other reasons may develop cellulitis with unusual organisms. Early treatment, even of innocent-looking lesions, is essential to prevent necrosis and loss of tissue. The disease is characterized by the presence of leukocytes in the lower dermis, with edema of the papillary body. Ironically, this disease now is usually seen in neutropenic patients with cancer, most often in association with acute leukemia, but also in association with a variety of other malignancies. The edema may suggest vesicles, but on palpation the lesions are solid, and vesicles probably never arise in this disease. The development of lesions is often accompanied by high fevers and an elevated erythrocyte sedimentation rate. Both the lesions and the temperature elevation respond dramatically to glucocorticoid administration. Since cancer patients are both immunosuppressed (and therefore susceptible to herpes infections) and heavily treated with drugs (and therefore subject to StevensJohnson syndrome), both of these conditions are common in this population. Cytokines, which are used as adjuvants or primary treatments for cancer, can themselves cause characteristic rashes, further complicating the differential diagnosis. This phenomenon is a particular problem in bone marrow transplant recipients (Chap. Some catheter-associated infections can be treated with antibiotics, whereas in others, the catheter must be removed (Table 11-5). If the patient has a "tunneled" catheter (which consists of an entrance site, a subcutaneous tunnel, and an exit site), a red streak over the subcutaneous part of the line (the tunnel) is grounds for immediate removal of the catheter. Failure to remove catheters under these circumstances may result in extensive cellulitis and tissue necrosis. More common than tunnel infections are exit-site infections, often with erythema around the area where the line penetrates the skin. Treatment of coagulase-positive staphylococcal infection is associated with a poorer outcome, and it is advisable to remove the catheter if possible. Similarly, many clinicians remove catheters associated with infections due to P aeruginosa and Candida species, since such. The antimetabolic effects of chemotherapy cause a breakdown of host defenses, leading to ulceration of the mouth and the potential for invasion by resident bacteria. Mouth ulcerations afflict most patients receiving chemotherapy and have been associated with viridans streptococcal bacteremia. Fluconazole is clearly effective in the treatment of both local infections (thrush) and systemic infections (esophagitis) due to Candida albicans. If there are no contraindications to line removal, this course of action is optimal. Organisms like Stenotrophomonas, Pseudomonas, and Burkholderia are notoriously hard to treat. It has a counterpart in immunocompromised patients and is thought to be due to invasion of the tissues by Bacteroides, Fusobacterium, and other normal inhabitants of the mouth. Esophageal Infections the differential diagnosis of esophagitis (usually presenting as substernal chest pain upon swallowing) includes herpes simplex and candidiasis, both of which are readily treatable. It is most common in patients being treated for acute leukemia and usually presents symptomatically around the time the neutropenia resolves. The characteristic picture is that of persistent fever unresponsive to antibiotics; abdominal pain and tenderness or nausea; and elevated serum levels of alkaline phosphatase in a patient with hematologic malignancy who has recently recovered from neutropenia. The diagnosis of this disease (which may present in an indolent manner and persist for several months) is based on the finding of yeasts or pseudohyphae in granulomatous lesions. The pathology (a granulomatous response) and the timing (with resolution of neutropenia and an elevation in granulocyte count) suggest that the host response to Candida is an important component of the manifestations of disease.
Diseases
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Carnitine palmitoyltransferase II deficiency
ADAM complex
Xeroderma pigmentosum, variant type
Hypomagnesemia primary
Oculo digital syndrome
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