[Show abstract][Hide abstract] ABSTRACT: Background: Coronary aneurysms (CAA) appear around Day 10 of Kawasaki syndrome (KS). Enhanced perivascular echo brightness (PEB) is not widely accepted as a marker of vasculitis. To explore its utility in early diagnosis of KS, we examined interobserver agreement (IOA) and prevalence. Working definition: Appearance of bright broad echoes surrounding the coronary lumen extending for at least 1 cm along the artery, as compared to thin parallel echoes representing normal coronary artery walls distinct from the surrounding. Methods: IOA: 20 randomly mixed PEB positive and negative studies were reviewed blindly by 6 pediatric cardiologists after they were coached on the definition. Mean % IOA and 95% confidence intervals (CI) were calculated for presence/absence of PEB in right and left coronary arteries (RCA, LCA). Prevalence: 50 consecutive KS pts' echoes were reviewed for PEB and concomitant or subsequent coronary ectasia or aneurysm (CAE or CAA). Results: IOA: Overall IOA was 79.2% (95% CI: 74.4, 84.0). For RCA and LCA, IOAs were 76.7% (70.2, 83.1) and 81.7 (74.6, 88.7), respectively. Prevalence: 28/50 pts (56%) showed PEB in one or both CAs in the first echo. 13 and 4 of those (26% and 8%) showed CAE and CAA, respectively. PEB without CAE/CAA was noted on Day 7.2 + 4.24 (m + sd); PEB with CAE or CAA was noted on Day 9.29 + 5.77 (NS). PEB was noted in 11/18 (61%) typical KS pts (TKS), in 11/14 (79%) atypical KS pts (AKS) and in 4/14 (29%) possible KS pts (PKS) (p=0.025). All pts who later developed CAA or CAE initially showed PEB. All PEB-negative pts remained free of CAA or CAE. Conclusions: (1) PEB is a sufficiently objective finding. (2) PEB is detectable in majority of pts before Day 10. (3) PEB precedes CAE or CAA in some pts.
Pediatric Research 01/2003; 53(1):177-177. · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Previously Etheridge et al reported rapid resolution of large coronary artery aneurysms(CAA) after treatment with abciximab(Abc), an antibody to platelet GP IIb/IIIa receptors. We report our experience with this treatment on 8 pts from Southern California and Arizona. Patients and Methods: These pts either presented with CAA prior to IVIG or developed giant CAA despite IVIG. All pts received a standard recommended dose of Abc: 2.5 mg/kg IV bolus followed by continuous infusion of 0.125 mcg/kg/min for 12 to 24 hrs. Largest CAA diameters were echographically measured in each pt before Abc, and at various time points after Abc. Available coronary angiograms were also reviewed. All pts remained on low-dose aspirin. Platelet aggregation study immediately after Abc showed effective inhibition. Additionally, those pts with CAA greater than 7 mm received warfarin. Results: Average duration of follow-up was 215 days (14 to 351). Initially, 7 pts had aneurysms in right coronary artery (RCA) and 8 pts in LCA. At the end of follow-up greater than 50 % reduction in CAA diameter was noted in only in 1 pt, increase in CAA size in 2 pts and no change in the rest. Intracoronary thrombus was noted in 1 pt before Abc with subsequent resolution. Compared to echo, angiographic CAA measurements were slightly smaller. No CA stenosis or thrombotic occlusion was seen. Conclusions: (1) Abc at current dosage is well tolerated by KS pts. (2) Abc has failed to produce dramatic CAA regression. (3) Abc may prevent thrombotic complications in giant CAA. Speculation: The optimum dose of Abc in KS is unknown, and may be higher than the adult dose in order to counter systemic platelet activation.
Pediatric Research 01/2003; 53(1):164-164. · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous studies on the epidemiology of Kawasaki disease (KD) in the US have been limited to reports on epidemics or the epidemiologic characteristics of the illness in various populations over limited periods of time. Childrens Hospital Los Angeles is a 314 bed teaching hospital which serves a large urban, multi-ethnic population. We describe the epidemiology of KD in our hospital from 1979 through 2000 in a population of 980 KD patients seen over that period. We discuss trends in incidence, age, gender, ethnicity, geographic distributon, seasonality, and birth cohort information in this group of patients. We also describe clinical characteristics including rates of recurrence, incidence of cardiovascular abnormalities, myocardial infarction, and mortality. Results of theraputic interventions are detailed especially with regard to the use of intravenous gamma globulin and steroids. In addition, information on the occurence of KD in Los Angeles County obtained from government databases for the years 1989 through 1999 is evaluated for the incidence, age, ethnicity, geographic distribution, and other epidemiologic characteristics. Trends in the two populations are compared to determine if information derived from our population is representative of that of the population as a whole. This would allow for on going surveillance of KD in this large urban county by reporting from a single hospital site and inferring epidemiologic trends observed to the rest of the population. Since KD is greatly under reported in Los Angeles County at present, this would improve our understanding of its epidemiology here substantially.
Pediatric Research 01/2003; 53(1):159-159. · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We have developed a three-phase screening procedure aimed at identifying KD-associated viral cDNA. In the first phase suppression subtractive hybridization (SSH) was carried out using cDNA which was reverse-transcribed from pooled RNA from PBMNCs of 6 acute phase KD patients as the tester, and cDNA generated from pooled RNA from 6 non-KD febrile patients as the driver. In the second phase the subtracted cDNA sequences were inserted into a plasmid expression vector (pBAD), and an E. coli library was prepared. The expression library was screened using pooled convalescent KD sera as the primary antibody which was incubated with protein A or protein G alkaline phosphatase conjugates designed to identify the immunopositive clones. In the third phase the immunopositive clones were PCR amplified using primers based on flanking vector sequences and the recombinant inserts were sequenced. Molecular analysis of the immunopositive clones yielded 2 sequences: an 800 bp fragment identical to a portion of a known human gene and a 3400 bp PCR product which had no significant homology to known sequences using standard BLASTN or BLASTX database searches. However, using position specific iterated (PSI) BLAST search,the 3400 bp insert showed extensive but low-level homology (25-33% identities and 28-45% positives) throughout its entire length to gene pB602L of the African swine fever virus (ASFV), a lymphotropic virus which replicates in monocyte-macrophage lineage cells. Experiments are in progress to test the association of the novel virus with the course of KD by measuring the relative virus load in samples from acute, subacute and convalescent samples.
Pediatric Research 12/2002; 53(1):168-168. · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cardiac sequelae of Kawasaki syndrome may range from no detectable' abnormalities to giant aneurysms with thrombosis or stenosis. The issues often debated in long-term follow-up include interval and intensity of evaluations, type of diagnostic tests to be used, choice of drugs and indications for medical and surgical interventions directed toward coronary artery problems. Although echocardiography is a powerful tool in the early follow-up, its utility is diminished during the chronic phase. Although the value of coronary angiography is undisputed, its use should be limited to the patients with large or complex aneurysms. Repeat angiography should be guided for the most part by appearance or worsening of ischemic changes by non-invasive studies. Despite normal angiographic appearance of the coronary artery following regression, recent evidences from vasoactivity studies, intravascular ultrasound, and biochemical data suggest long-term abnormalities in vascular endothelium. Stress ECG lacks in sensitivity and specificity. Stress echocardiography with exercise or dobutamine may be an acceptable alternative, but its performance is subject to the ‘learning curve.’ Myocardial scintigraphy has been shown to be sensitive in detecting ischemia. However, its specificity in Kawasaki syndrome is still debatable. Recent ‘high-tech’ diagnostic tests have limitations in clinical applicability. Regarding therapy, our midterm experience with the combined use of low-dose warfarin and low-dose aspirin in patients with giant aneurysms suggests its efficacy in preventing coronary thrombosis. Thrombolytic therapy for acute infarction or coronary thrombosis appears safe and effective. The role of coronary balloon angioplasty in the management of Kawasaki syndrome is uncertain. Controversies surround the indications for coronary artery bypass graft surgery in Kawasaki syndrome. Decision for surgery seems justified in an asymptomatic child when evidence points to a large myocardial segment in jeopardy since a high mortality rate and lack of prior warning are characteristic of myocardial infarction due to Kawasaki disease.