Characterization of T cell repertoire changes in acute Kawasaki disease.

Kawasaki disease (KD) is an acute multisystem vasculitis of unknown etiology that is associated with marked activation of T cells and monocyte/macrophages. Using a quantitative polymerase chain reaction (PCR) technique, we recently found that the acute phase of KD is associated with the expansion of T cells expressing the V beta 2 and V beta 8.1 gene segments. In the present work, we used a newly developed anti-V beta 2 monoclonal antibody (mAb) and studied a new group of KD patients to extend our previous PCR results. Immunofluorescence analysis confirmed that V beta 2-bearing T cells are selectively increased in patients with acute KD. The increase occurred primarily in the CD4 T cell subset. The percentages of V beta 2+ T cells as determined by mAb reactivity and flow cytometry correlated linearly with V beta expression as quantitated by PCR. However, T cells from acute KD patients appeared to express proportionately higher levels of V beta 2 transcripts per cell as compared with healthy controls or convalescent KD patients. Sequence analysis of T cell receptor beta chain genes of V beta 2 and V beta 8.1 expressing T cells from acute KD patients showed extensive junctional region diversity. These data showing polyclonal expansion of V beta 2+ and V beta 8+ T cells in acute KD provide additional insight into the immunopathogenesis of this disease.

Kawasaki syndrome: a 1986 perspective.

The history of Kawasaki Syndrome is reviewed from its first description as a rare but benign disease in Japan to its current recognition as a multisystem vasculitis with predilection for arthritis and coronary disease occurring with increasing frequency in diverse areas of the world. Recent studies on efficacy of intravenous gamma globulin therapy are described.

Gowning does not affect colonization or infection rates in a neonatal intensive care unit.

OBJECTIVE: To study the effect of gowning in a neonatal intensive care unit on colonization patterns, necrotizing enterocolitis, respiratory syncytial virus and other infections, mortality, and traffic and handwashing patterns. METHODS: Alternate 2-month gowning and no-gowning cycles were established in a 24-bed level III neonatal intensive care unit for 8 months, with respiratory site, umbilical, and stool surveillance cultures done weekly on all patients. Traffic flow and handwashing compliance were evaluated by direct observation. RESULTS: Demographic data did not differ between periods. There were no significant differences between the gowning and no-gowning periods in the rates of bacterial colonization, any type of infection, or mortality. There was no effect on traffic flow or handwashing compliance. CONCLUSION: Gowning in the neonatal intensive care unit is an unnecessary custom without benefit in neonatal colonization, infection rates, mortality, traffic patterns, and handwashing behavior.

Kawasaki syndrome.

Kawasaki's syndrome is an acute, largely self-limited multisystem vasculitis of childhood with prominent rheumatic complaints, involving both the heart and the joints. Although the etiologic agent has not been discovered, the evidence appears overwhelming that a microbial agent is the responsible trigger for this multisystem disease. Immunologically mediated phenomena appear to be important in the development of the significant complications of KS carditis, coronary vasculitis, and arthritis. Although truly effective therapy is not yet available, there is an exciting possibility that immunologic treatment may have beneficial effect. More effective preventive and therapeutic methods will become available when the elusive agent is discovered.

The impact of pediatric HIV infection on emergency services.

A thorough understanding of the spectrum and ramifications of pediatric HIV infection is important to the emergency physician. Rising reports of cases in rural populations and the vertical transmission from mother to infant are important changes in HIV epidemiology. Nearly all organ systems are either directly or indirectly involved and problems encountered, including diagnostic and therapeutic considerations by organ system, are reviewed. The role of the emergency physician in caring for HIV-infected infants and children includes recognition, timely treatment of complications, protection of self and other health care workers, and protection of the immunocompromised child.

Kawasaki syndrome (the mucocutaneous lymph node syndrome).

Kawasaki syndrome is a newly-recognized clinical entity characterized by multisystem involvement. It has an acute onset and triphasic clinical course. Although essentially a self-limiting disease, permanent vascular damage, especially involving the coronary arteries, may result. Pathologically, the disease is characterized by widespread vasculitis. There is a monomodal age distribution, with peak occurrence during the first two years of life and few affected over the age of 8 years. Males outnumber females 1.5:1; persons of Japanese extraction are overrepresented compared with other races, caucasians underrepresented. Community-wide epidemics have been reported from diverse locations but there is no evidence for direct person-to-person transmission. Etiology remains unknown. Therapy is supportive and should be directed at careful clinical evaluation for cardiovascular abnormalities and antiplatelet aggregation therapy.

Kawasaki syndrome (the mucocutaneous lymph node syndrome).

Kawasaki Syndrome is a newly recognized clinical entity characterized by multisystem involvement. It has an acute onset and a triphasic clinical course. Although essentially a self-limited disease, permanent vascular damage, especially involving the coronary arteries, may result. Pathologically the disease is characterized by widespread vasculitis. There is a monomodal age distribution with peak occurrence during the first 2 years of life; few affected over the age of 8 years. Males outnumber females 1.5:1, persons of Japanese extraction are overrepresented compared with other races, and Caucasians are underrepresented. Community-wide epidemics occur in diverse locations but there is no evidence for direct person-to-person transmission. Etiology remains unknown. Therapy remains supportive and should be directed at careful clinical evaluation for cardiovascular abnormalities and antiplatelet aggregation therapy.

Kawasaki syndrome: a new infectious disease?

Kawasaki syndrome is a newly described, acute symptom complex of children that has a predictable clinical course. The acute febrile phase of the syndrome is characterized by multisystem acute inflammatory changes. The subacute phase follows with the rheumatic manifestations of arthritis, myocarditis, and thrombocytosis. The syndrome is self-limited in most children but is associated with coronary artery aneurysms in 15%--20% and sudden death due to coronary thrombosis in 2%. Vasculitis of coronary and other medium-sized muscular arteries characterizes fatal cases. The peak age affected is 12 months (range, six weeks to eight years). Japanese children are overrepresented among cases, whereas Caucasian children are underrepresented. Cases have been reported worldwide with the highest prevalence in Japan and among Japanese in Hawaii. Epidemic outbreaks have occurred in scattered areas of the United States and Japan. The etiology is unknown, although clinical, epidemiologic, and immunologic features suggest an acute infectious trigger to an immunologically mediated, generalized vasculitis.

Growth of toxic shock syndrome toxin 1-producing, tryptophan-requiring strains of Staphylococcus aureus associated with the presence of Escherichia coli.

More than 80 percent of TSST-1-positive strains of Staphylococcus aureus are tryptophan auxotrophs (Trp-). Chromosomal mapping has located the genetic determinant for TSST-1 (tst) in the trp operon for strain S411 (Trp-) and near the tyrB site for strain FRI1169 (Trp*). Auxonographic screening on tryptophan-free medium of 28 strains of S. aureus (TSST-1-positive and -negative, Trp+ and Trp-) against Escherichia coli (strains 6094, 7603, and 7877) and other strains of Enterobacteriaceae showed that Trp- S. aureus strains responded only to E. coli and tryptophan. Neither E. coli nor tryptophan inhibited TSST-1 production. Cocultivation of strain FRI1169 or S411 with E. coli strain 7877 showed that TSST-1 production by FRI1169 was not enhanced. In contrast, TSST-1 production by S411 was equal to that of S. aureus alone (less than 640 ng/mL) or enhanced (greater than 12,000 ng/mL) if the input log10 cfu of S. aureus was of equal or greater ratio to input E. coli and if the recovered S. aureus was greater than log10 5 cfu. These results suggest that nutritionally deficient toxicogenic strains of S. aureus may overcome growth limitation by coexisting in dynamic balance with strains of E. coli.

Direct effects of purified staphylococcal toxic shock syndrome toxin 1 on myocardial function of isolated rabbit atria.

Toxic shock syndrome is associated with reversible cardiomyopathy. The cardiac dysfunction may be mediated by toxic shock syndrome toxin 1 (TSST-1), an exotoxin generated by Staphylococcus aureus. However, the effects of purified TSST-1 on cardiac function are unknown. In a study of the toxin's effect on myocardial function, TSST-1 (200 ng/mL) was added to muscle baths containing isolated rabbit atria. TSST-1 caused time-dependent inhibition of developed force (systolic function) but did not alter resting force (an index of muscle stiffness or cardiac compliance). These data show that TSST-1 can directly inhibit myocardial function, but the significance of this effect in patients with toxic shock syndrome remains to be determined.

Mucocutaneous lymph node syndrome in the United States.

Sixteen patients with an unusual and distinct symptom complex were encountered during a four-year period. Principal features of this syndrome are (1) fever lasting more than seven days; (2) conjunctival injection; (3) changes in the mouth consisting of erythema of the oropharynx, "strawberry tongue", and erythema of the lips; (4) indurative edema of hands and feet with palm and sole erythema followed by desquamation of the fingertips; and (5) an erythematous rash. Associated features were lymphadenopathy, pyuria, aseptic meningitis, diarrhea, arthritis, and arthralgia. Although usually a self-limited illness, one patient died with massive coronary artery thrombosis on the 19th day of illness. This syndrome appears to be clinically and pathologically similar to mucocutaneous lymph node syndrome, an illness prevalent in Japan but previously unrecognized by American clinicians. Pathologic features suggest a relationship to infantile periarteritis nodosa.

Epstein-Barr virus and other herpesvirus infections in Kawasaki syndrome.

Epstein-Barr virus (EBV), a possible cause of Kawasaki syndrome (KS), is not pathenogenically associated with KS in Hawaii. The prevalence of EBV capsid antibody in KS patients was found not to differ significantly from that in controls, and the antibody response in those infected with EBV was the same as that in other children similarly infected. No EBV was isolated from acute-phase patients. All patients with capsid antibody at the onset of KS also had Epstein-Barr nuclear antigen antibody: 36 patients developed antibody within 3 months after onset of KS; in 10, EBV infection could have been coincidental with the disease. Cytomegalovirus (CMV) was isolated from 9 patients with KS and 10 controls. A similar number of controls and patients had antibody to human herpesvirus 6 (HHV6); one patient seroconverted. None of the herpes viruses (EBV, CMV, HHV6, varicella-zoster virus, or herpes simplex virus) plays a unique or dominant role in the etiology or pathogenesis of KS in Hawaii.

Endotoxin is not an essential mediator in toxic shock syndrome.

The hypothesis that toxic shock syndrome toxin 1 (TSST-1) exerts its deleterious effects in toxic shock syndrome (TSS) primarily by enhancing the lethality of small amounts of endogenous endotoxin derived from mucosal colonization with gram-negative bacteria was assessed by evaluating two means of inactivating endotoxin in rabbit models of TSS. In both of these models, toxins and TSST-1 are allowed to diffuse constantly from a subcutaneous depot. Immunologic inactivation of endotoxin with antiserum to the core lipopolysaccharide did not change the clinical course or mortality among animals infected with live TSS-associated staphylococci or among animals with a subcutaneous depot of TSST-1. Anti-TSST-1 was successful in preventing disease and death in these models. Pharmacologic inactivation of endotoxin by pretreatment or continuous treatment with polymyxin B did not prevent illness or mortality in the toxin depot model. Endotoxin thus appears not to be an essential mediator in TSS, since TSS-like illness develops and progresses despite inactivation of endotoxin in animal model systems that are faithful both physiologically and clinically to TSS in humans.

Vaginal tampon model for toxic shock syndrome.

The effects of tampon composition, inoculum size, and simulated menses on production of toxic shock syndrome toxin 1 (TSST-1) and toxic shock syndrome (TSS) were evaluated in a rabbit model that simulates tampon use in humans. Three small generic compressed-fiber tampons were successively inserted vaginally (remained in place 4.5 hours x 2; overnight x 1). Tampon no. 1 was inoculated with live TSST-1-positive staphylococci plus 5 mL of saline or simulated menses (defibrinated rabbit blood plus 2.5 g of bovine serum albumin/dL) immediately after insertion; saline or simulated menses alone were used with tampons no. 2 and 3. The vagina was washed after removal of tampon no. 3. TSS-like illness was produced consistently in animals with carboxymethyl cellulose/polyester foam tampons, which supported higher organism counts and greater TSST-1 production in association with subsequent tampons. Cotton and rayon tampons were not associated with as much clinical illness, organism growth, or TSST-1 production. Simulated menses supported toxin production and clinical illness when the inoculum was one-tenth that required for controls. Sham tampon insertion was associated with TSS-like illness in two of 10 rabbits; thus, other factors may promote TSS in the absence of vaginal tampons. This model reliability reproduces menstrual TSS, since one-time vaginal inoculation with TSST-1-positive staphylococci in the presence of blood and certain tampons leads to TSS, and may be useful in evaluating catamenial products and in understanding other factors important in TSST-1 production in vivo and the development of TSS.

Modulation of adhesion molecules and monocyte chemoattractant protein by tumor necrosis factor-alpha and salicylic acid in primary human coronary artery endothelial cells.

Kawasaki disease (KD) is an illness characterized by vascular inflammation of coronary arteries leading to coronary aneurysms and thromboses. Infiltration of immune cells into the intima and adventitia are observed in autopsy tissues of patients with KD. Using semi-quantitative RT-PCR and cell-based ELISA, we demonstrated that tumor necrosis factor-a induced the expression of intercellular adhesion molecules-1 and E-selectin, as well as monocyte chemoattractant protein-1, in a time- and dose-dependent manner in primary human coronary artery endothelial cell cultures. This increase was inhibited by salicylic acid (NaSal), and involved the transcription factor NF-kappaB. Based on these data, we suggest a pathogenetic mechanism for KD, whereby immune cells are attracted to sites of inflammation, undergo extravasation, release enzymes that assist in vascular remodeling, thereby weakening the endothelium and hastening the process of aneurysm formation. NaSal, in addition to preventing thrombosis and lowering fever in KD, may also function in down-regulating adhesion molecules during the inflammatory stage of KD.

An epidemic of Kawasaki syndrome in Hawaii.

A community-wide outbreaks of Kawasaki syndrome, apparently the first in the United States, occurred in Hawaii in the first half of 1978. Twenty-seven of the 33 cases were subjected to intensive epidemiologic and microbiologic study. Patients with Kawasaki syndrome, compared to the general population, more often had Japanese ancestry, high-income status, and possibly a history of respiratory infection in the preceding month (44%). Staphylococcus aureus was not found in high frequency in the patients (15%), and viral cultures and serologic studies, immune electron microscopy, and guinea pig and primate inoculation did not reveal a causative microorganism. Febrile illnesses in guinea pigs inoculated with a skin biopsy specimen should not be further passaged.