Acute measles complicated by fatal adenovirus pneumonia with bone marrow failure: lack of evidence for direct viral invasion of the bone marrow.
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Biomedical subjects
Publications and source records attributed to S T Shulman.
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STUDY OBJECTIVES: (1) To determine those diseases that most often mimic Kawasaki disease (KD) in the United States. (2) To examine the physical findings and laboratory studies that influenced experienced clinicians to exclude the diagnosis of KD. (3) To compare epidemiologic features of patients with KD and patients referred for evaluation of possible KD in whom alternative diagnoses were established. DESIGN: Case comparison study. SETTING: Seven pediatric tertiary care centers. PATIENTS: Consecutive sample of 280 patients with KD and 42 comparison patients examined within the first 14 days after onset of fever. MEASUREMENTS AND MAIN RESULTS: (1) Infectious diseases, particularly measles and group A beta-hemolytic streptococcal infection, most closely mimicked KD and accounted for 35 (83%) of 42 patients in the comparison group. (2) The standard diagnostic clinical criteria for KD were fulfilled in 18 (46%) of 39 patients in whom other diagnoses were established. (3) Patients with KD were significantly less likely to have exudative conjunctivitis or pharyngitis, generalized adenopathy, and discrete intraoral lesions, and more likely to have a perineal distribution of their rash. The patients with KD were also more likely to have anemia and elevated erythrocyte sedimentation rate; leukocyte count less than 10 X 10(3)/mm3 and platelet count less than 200 X 10(3)/mm3 were significantly less prevalent in patients with KD. (4) Residence within 200 yards of a body of water was more common among KD patients. CONCLUSIONS: (1) Measles and streptococcal infection should be excluded in patients examined for possible KD. (2) Laboratory studies that may be useful in discriminating patients with KD from those with alternative diagnoses include hemoglobin concentration, erythrocyte sedimentation rate, and serum alanine aminotransferase activity. (3) Residence near a body of water may be a risk factor for the development of KD.
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We previously demonstrated that chronic pharyngeal carriage of group A beta-hemolytic streptococci (GABHS) can be terminated by intramuscular administration of benzathine penicillin plus 4 days of orally administered rifampin. Because an effective oral regimen would be desirable, we compared clindamycin with P + R for treating GABHS carriage. Healthy, symptom-free GABHS carriers were randomly assigned to receive orally administered clindamycin (20 mg/kg per day) three times a day for 10 days or intramuscularly administered benzathine penicillin with oral doses of rifampin (20 mg/kg per day) twice a day for 4 days. Compliance was documented by antibiotic activity in urine. Throat cultures for GABHS were obtained every 3 weeks for up to 9 weeks after treatment. Patients who had positive throat cultures for their original GABHS T type 3 weeks after randomization were crossed over to the other treatment. Treatment success was defined as eradication of the original GABHS T type, with all follow-up cultures negative. Clindamycin eradicated carriage in 24 (92%) of 26 patients; penicillin plus rifampin was effective in 12 (55%) of 22 patients (p less than 0.025). Including patients crossed over 3 weeks after enrollment, clindamycin was effective in 28 (85%) of 33 treatment courses compared with 12 of 22 courses of penicillin plus rifampin (p less than 0.05). We conclude that 10 days of oral clindamycin therapy was significantly more effective than benzathine penicillin plus 4 days of orally administered rifampin for treatment of symptom-free GABHS carriers.
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We review the epidemiology and clinical features of recent outbreaks of acute rheumatic fever. The history of this disorder as well as current management practices are also discussed.
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Because production of beta-lactamase by normal pharyngeal flora could account for penicillin treatment failure, we studied the effect of anaerobic and aerobic beta-lactamase-producing bacteria on bacteriologic outcome in acute group A beta-hemolytic streptococcal (GABHS) pharyngitis. We compared 10-day courses of orally administered phenoxymethyl penicillin and amoxicillin-clavulanic acid, using a randomized, single-blind treatment protocol. Eligible patients were 2 to 16 years of age and had culture-proven acute GABHS pharyngitis; 89 patients (43 penicillin, 46 amoxicillin-clavulanic acid) were compliant with therapy. beta-Lactamase-producing organisms were isolated before therapy from the throats of 67% of patients treated with penicillin and 63% treated with amoxicillin-clavulanic acid. Throat cultures after completion of therapy were positive for GABHS in 7 (7.9%) of 89 patients. The initial GABHS T type persisted (treatment failure) in only 4 (4.5%) of 89 patients, including 3 (6.5%) of 46 who received amoxicillin-clavulanic acid and in 1 (2.3%) of 43 who received penicillin (not statistically significant). Bacteriologic treatment failure was unrelated to recovery of beta-lactamase-producing bacteria at the time of enrollment or after treatment. We conclude that beta-lactamase production by normal pharyngeal flora does not fully explain the failure of penicillin therapy for acute streptococcal pharyngitis. Using an antibiotic effective against beta-lactamase-producing bacteria will not eliminate the problem of bacteriologic treatment failure.
Kawasaki disease (mucocutaneous lymph node syndrome) has emerged as a major pediatric disorder throughout the developed world, including the United States where it is now a leading cause of acquired heart disease in children. Coronary artery abnormalities, including ectasia, aneurysms, stenosis, and thrombosis, that may result in myocardial ischemia and/or infarction, develop in approximately 20-25% of patients as a consequence of coronary arteritis. Although epidemiologic and clinical findings strongly suggest an infectious etiology, the etiology of Kawasaki disease remains unknown. Marked immune activation is present in the acute state of Kawasaki disease. Investigators in Japan and a U.S. multicenter investigative group have demonstrated in controlled studies that administration of IVGG early in the course of Kawasaki disease is associated with (i) a striking anti-inflammatory effect, and (ii) a marked reduction in the development of coronary abnormalities, as assessed by echocardiography and/or angiography. The mechanism(s) by which IVGG produces these dramatic effects is unclear. Possible mechanisms include (i) Fc receptor blockade, (ii) a direct anti-etiologic agent (neutralization) effect, (iii) an anti-toxic effect, (iv) an immunomodulating effect possibly mediated either by anti-idiotypic antibodies or by induction of suppressor T cells, and (v) down-regulation of cytokine production by activated immune cells. Clarification of the mechanism of action of IVGG in Kawasaki disease should provide insights into the pathogenesis and/or the etiology of this fascinating disorder.
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