Th17- and Treg-related cytokine and mRNA expression are associated with acute and resolving Kawasaki disease.

BACKGROUND: Kawasaki disease is a vasculitis most commonly afflicting children <5 years of age. Many autoimmune diseases are associated with up-regulation of T helper (Th) 17 cells, and down-regulation Treg cells. Few studies have examined the Th17/Treg expression in Kawasaki disease. METHODS: Blood samples were obtained from 186 children with Kawasaki disease at 24 h before IVIG therapy, followed by 3 days and 21 days after IVIG therapy. Thirty children with an acute febrile infectious disease and 30 healthy children were obtained as control. Plasma levels of Th17- and Treg-related cytokines including IL-6, IL-17A, IL-10, TGF-ß, and mRNA expression levels of RORγt and Foxp3 were tested. RESULTS: Patients with Kawasaki disease had higher levels of plasma IL-17A (25.35 ± 3.21 vs 7.78 ± 1.78 pg/ml, P < 0.001) and IL-6 (152.29 ± 21.94 vs 38.63 ± 12.40 pg/ml, P < 0.001) when compared to the febrile control group. IVIG resulted in a reduction in IL-6 and IL-17A at both 3 and 21 days after IVIG therapy. FoxP3 levels increased significantly 3 days after IVIG therapy (2.28 ± 0.34 vs 0.88 ± 0.14, P < 0.001). IVIG resistance was associated with higher levels of IL-10 and IL-17A. CONCLUSION: Kawasaki disease was associated with higher IL-17A and IL-6, a cytokine profile similar to other autoimmune diseases. IVIG therapy resulted in increased expression of Treg-related FoxP3. IVIG resistance was associated with higher levels of IL-10 and IL-17A. Our findings provide further evidence that Kawasaki disease is an autoimmune-like disease.

Prolonged fever and pyuria: a urinary tract infection presentation of incomplete Kawasaki disease.

UNLABELLED: We report two patients with incomplete Kawasaki disease that presented as apparent urinary tract infection. Persistent fever and pyuria were the initial presentation without concomitant signs suggestive of Kawasaki disease; thus the patients were treated as urinary tract infection. Fever persisted despite antibiotic treatment. Diagnostic criteria of Kawasaki disease were not fulfilled for these two patients, yet aneurysmal dilatation of the coronary artery was noted 10 and 18 d, respectively, after the onset of fever. The diagnosis of incomplete Kawasaki disease was assigned when the coronary artery abnormality was detected. Fever subsided within 24 h of administration of intravenous immunoglobulin. CONCLUSION: This report highlights the potentially misleading presentation of fever and pyuria as the sole initial manifestation of incomplete Kawasaki disease. Echocardiography is indicated to detect coronary artery abnormality when fever persists in such patients after adequate antibiotic treatment and thorough urological evaluation.

Cardiac troponin I: a reliable marker and early myocardial involvement with meningoencephalitis after fatal enterovirus-71 infection.

OBJECTIVES: A major outbreak of enterovirus 71 (EV71) in Taiwan in 1998 caused many severe cases and 78 deaths. Our purpose was to find reliable markers and early indicators of fatal EV71 central nervous system (CNS) infection. METHODS: From June 2000 to November 2001, 21 patients with hand foot mouth disease or herpangina with CNS infection were admitted to Kaohsiung Veterans General Hospital. All 21 had culture-confirmed EV71 infection or were EV71 IgM positive. Patients were divided into two groups: group I included the five fatalities at our institution and group II, the 16 surviving patients. RESULTS: Of the 21 infants and children with EV71 infection with CNS involvement, MR imaging studies were completed on 17, and 15 showed hyperintensity in the posterior portions of brain stem. All patients received intravenous immunoglobulin (IVIG) 1 g/day for two days and supportive care. Five patients rapidly deteriorated owing to irreversible hypotension and died. The other 16 patients recovered completely without sequel. In group I patients, the decrease of cardiac ejection function is significant and laboratory findings showed lower platelet count (P=0.0192). The mean of initial cTnI level for groups I and II was 10.6+/-11.6 and 0.48+/-0.55 ng/dl, respectively, higher in group I than in II (P=0.0019). CONCLUSION: We hypothesized that like patients with severe burns, those with severe EV-71 CNS meningoencephalitis have varying degrees of non-ischemic cardiac injury, manifesting as leakage of cTnI from myocytes into the circulation. EV-71 CNS meningoencephalitis likely to die with an early myocardial involvement evidenced by reduced ejection fraction and release of cTnI. We conclude that fatal EV71 CNS infection quickly leads to death due to severe encephalopathy associated with cardiomyopathy.

Coronary artery fistulas in neonates, infants, and children: clinical findings and outcome.

Ten patients were diagnosed with coronary artery fistula (CAF) between 1991 and 1998 in our department. The ages of patients ranged from 3 days to 12 years. Five patients were male and five patients were female. Nine patients had single CAF and 1 patient had dual CAFs. CAFs of 7 patients originated from the left coronary artery, and CAFs of 3 patients originated from the right coronary artery. CAFs of 7 patients terminated at the right ventricle, CAFs of 2 patients terminated at the right atrium, and the CAF of 1 patient terminated at the pulmonary artery. Four patients were diagnosed with CAF in the neonate period. All presented with congestive heart failure. Medical therapy was successful in treating congestive heart failure in 2 of these patients, but the other 2 needed operations. One patient presented with subacute bacterial endocarditis at 12 years of age requiring surgical intervention. One patient had a large left-to-right shunt that was surgically repaired. One patient with dual CAFs underwent coil embolization and the larger CAF achieved complete embolization, but the smaller CAF failed. Follow-up data revealed that 1 patient who received an operation died of sepsis due to recurrent bronchiolitis 6 months later. Nine patients were asymptomatic. Because complications including endocarditis may be encountered in later life, we suggest early closure with coil embolization.

Quantitative analysis of end-tidal carbon dioxide during mechanical and spontaneous ventilation in infants and young children.

Capnography provides a substitute for monitoring of arterial carbon dioxide tension (PCO(2)). We performed a prospective study to evaluate a new application of capnography, using quantitative curve analysis in the pediatric ICU. Twenty-five infants and children admitted to the pediatric ICU after cardiovascular surgery for congenital heart diseases were included in the study. Capnographic curves were recorded during 3 phases of mechanical and spontaneous ventilation: phase 1, immediate postoperative period; phase 3, preextubation period; and phase 2, period between phases 1 and 3. Each recording included 17 sec of capnographic tracings from consecutive spontaneous and/or ventilator-driven breaths. Quantitative curve analysis was made to define parameters including peak value of exhaled PCO(2) (P), mean rate of rise of PCO(2) (R), and area under each capnographic curve (A). Qualitative inspection of the wave contour showed no obvious difference in phase 3 during spontaneous and mechanically assisted ventilator breaths. However, an obvious difference existed between spontaneous and mechanically assisted breaths in phase 2. For each parameter (P, R, and A), there was a significant difference in phases 2 and 3 from spontaneous breaths. However, there was no significant difference in phases 2 and 3 from ventilator-assisted breaths. We further calculated the ratio of parameters of spontaneous breaths (S) and ventilator-assisted breaths (V) in phase 2 and phase 3. The ratio of S/V for P, R, and A showed significant differences between phase 2 and phase 3. We conclude that quantitative analysis of exhaled end-tidal PCO(2) curves revealed significant changes of specific parameters during the transition from the ventilator-dependent state to the spontaneously breathing ventilator-independent state. This new approach provides a new way to estimate respiratory status in infants and children receiving ventilator therapy. Through quantitative capnographic curve analysis, if P, R, and A from spontaneous breaths approached those of ventilator-assisted breaths, patients have resumed reasonable pulmonary mechanics, and extubation may then be considered.

A comparison of clinical use of fluticasone propionate and beclomethasone dipropionate in pediatric asthma.

Inhaled steroids play a very important role in the prevention and treatment of asthma. Previous studies indicated that fluticasone propionate (FP) had low bioavailability and high local potency. However, the laboratory data in these studies were not obtained among Taiwan population. It is very important that native data should be established. Thus a 12-week research program was designed, involving 77 patients, 51 for FP group and 26 for beclomethasone dipropionate (BD) group. The objects were victims of moderate to severe asthma and their age ranged from 4 to 14 years old. An open, comparative and randomized method was adopted. Except for the 4-week-later daytime symptom score(P = 0.033, BD group was better), no other significant differences were found between the two groups in the symptom score improvement(P > 0.05). All the P-values for the daytime & night-time scores were lower than 0.001, which means obvious improvement after treatment in both groups. P-value for PEF improvement was 0.003 after 4 weeks (BD group was better) and 0.943 after 8 weeks; for FEV1 improvement, it was 0.005 after 4 weeks(BD group was better) and 0.252 after 8 weeks; and for FEV1/FVC improvements, it was 0.067 after 4 weeks and 0.097 after 8 weeks. There was no statistic significance in total eosinophil count (TEC), IgE, eosinophil cationic protein (ECP) serum level changes after 4 or 8 weeks. Adverse effects were all anticipated and no statistic significance showed up, either, between the two groups or in the cortisol levels (P > 0.05). In conclusion, native data indicated that the potency of 100 micrograms of FP was equal to that of 200 micrograms of BD and that few side effects were noted in FP group. It is recommended that this drug be introduced for clinical use.

Cryptococcus laurentii fungemia in a premature neonate.

Cryptococcus spp. other than Cryptococcus neoformans are generally considered nonpathogenic to humans. There are only 15 case reports of disease in humans caused by Cryptococcus laurentii infection. Underlying diseases and predisposing risk factors seem to play an important role in these cases. Our patient is the first case of an extremely low birth weight infant with C. laurentii fungemia reported in the English literature. In our case, the MIC of amphotericin B for C. laurentii was 0.25 to 1 microg/ml and the patient had a good outcome following the administration of amphotericin B at 10 mg/kg combined with central venous catheter removal. There will undoubtedly be an increasing occurrence of unusual fungal infections accompanying further advances in medicine. A high degree of suspicion and improvements in the techniques for culture and identification will contribute to the earlier diagnosis and treatment of unusual fungal infections.

The predisposing factors of coagulase negative staphylococcal bacteraemia in neonatal intensive care unit.

Coagulase negative staphylococci are the commonest blood culture isolate from infants on neonatal intensive care units. The differentiation of contaminants from isolates representing true infection remains a significant clinical problem. Data from two neonatal intensive care units were collected prospectively in order to find those parameters, which best correlated with actual sepsis. Each case was assessed using clinical parameters to categorise infants into infection and contaminant groups. Logistic regression was then performed to find significant correlates. Three correlates were found, namely the presence of a long line (P = 0.001), abnormal white cell count (P = 0.037) and abnormal white cell morphology (P = 0.027). Abnormal white cell morphology was assessed by two experienced hematologists. More than half the isolates were probable contaminants and true infection may occur in the absence of a long line in this patient group.

Important ECG diagnosis-aiding indices of ventricular septal defect children with or without congestive heart failure.

In this paper we perform a statistical study of the conventional RR intervals and two newly defined PR' and RT intervals of ECG data. A quadratic classification rule is applied to extract several important ECG diagnosis-aiding indices among normal children and children with ventricular septal defect (VSD) with or without congestive heart failure (CHF). The results show that certain statistics computed from PR', RR and RT intervals are important diagnosis-aiding indices. Best classification vectors are searched for pairwise classification. Two methods, minimum distance criterion and a two-stage classification procedure, are considered for three-way classification. Furthermore, logistic regression models based on transformations of these important diagnosis-aiding indices are proposed. The receiver operating characteristic curves of the proposed models show better performance than those of linear and quadratic logistic models. In order to proceed with this study, a computer algorithm to automatically detect the three intervals is developed and the related ECG data are collected and analysed. The algorithm is also enhanced with an outlier detection procedure for the automatic measurements of the PR' and RT intervals.

Severe pulmonary hemorrhage as the initial manifestation in systemic lupus erythematosus with active nephritis.

Pulmonary hemorrhage (PH) is an uncommon clinical manifestation of patients with systemic lupus erythematosus (SLE). In this report, we describe a 14-year-old male with PH as the sole clinical manifestation of his SLE. Kidney biopsy was performed and the report revealed lupus nephritis class IVb. He demonstrated a rapid clinical response to the therapy of intravenous pulse methylprednisolone. Awareness of the possibility of PH as a sole clinical presentation of SLE may aid in the diagnosis and early aggressive management of this condition.

Secondary erythrocytosis in distal renal tubular acidosis: report of one case.

The wide spectrum of distal renal tubular acidosis (RTA) has been reported. Children with distal RTA can present with failure to thrive, gastrointestinal symptoms, nephrocalcinosis, and renal failure, etc. So far, secondary erythrocytosis in pediatric patients with distal RTA has not been reported. Here we report a case of distal RTA with failure to thrive and nephrocalcinosis accompanied by secondary erythrocytosis in a 3-year-old boy. He has been followed up for 2 years and is under treatment with NaHCO3 and potassium citrate. The treatment contributes to the improvement of metabolic acidosis and his growth. There is normal renal function and constant erythrocytosis during the follow-up period. Further studies are needed to clarify the relationship between erythrocytosis and distal RTA.

Late coil migration due to thrombolysis after successful implantation of a coil for persistent ductus arteriosus.

Transcatheter coil occlusion of persistent ductus arteriosus (PDA) is now a widely accepted treatment for PDA. However, late complication might occur due to thrombolytic treatment during the interventional period. We discuss a case with late coil migration due to thrombolysis after successful implantation of a coil. It should be emphasized that early thrombus formation is important for successful closure of PDA shunt using coil.

Mastoiditis: a disease often overlooked by pediatricians.

Although mastoiditis can be a life threatening disease, clinicians often overlook it because it is uncommon. We reviewed the presentation and management of all children younger than 15 years of age with the discharge diagnosis of mastoiditis in our hospital from January 1994 through December 1999. Nineteen patients that fulfilled the case definition were included. The most common clinical presentation in this series was fever. More specific findings, such as otorrhea, postauricular pain, swelling, and redness of mastoid could be found in less than half of these patients. Only two patients had characteristic physical findings, and mastoiditis was diagnosed in only three patients upon admission. Plain radiographic evidence of mastoiditis was usually not apparent early in the course. In this series, the majority of patients were diagnosed by computed tomography (CT) scans. The present study demonstrates that mastoiditis most commonly presents without a clearly diagnostic set of physical examination and laboratory findings. Mastoiditis should be considered in patients with otitis media or with fever of unknown origin (FUO). The empirical antibiotic treatment should cover organisms commonly found in acute otitis media (AOM), including Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis.

Recognition of functional pulmonary atresia by color Doppler echocardiography.

Vigorous crying aids right ventricular ejection into the pulmonary artery. This phenomenon can differentiate functional pulmonary atresia from anatomic pulmonary atresia.

Kimura's disease in a teenage male: report of one case.

A 14-year-old boy gradually developed several subcutaneous masses over bilateral peri-auricular regions, neck, and both upper arms near the elbows over the past 2 years. The recent development of eyelid puffiness elicited his seeking medical attention. Hypereosinophilic syndrome was first considered due to the markedly elevated blood eosinophil count without other evidence of allergy or parasite infestation, but the absence of organ involvement made this diagnosis questionable. The histopathological investigation of the subcutaneous mass in the upper arm showed lymph node-like tissue with markedly reactive follicular hyperplasia and eosinophilic abscesses associated with granulomatous inflammation, thus leading to the final diagnosis of Kimura's disease. Oral prednisolone was prescribed successfully. This illness occurs mainly in young oriental males. We report this case to introduce it to pediatric clinicians as an important differential diagnostic entity in eosinophilia-associated diseases and reactive lymphadenopathy.

Pulse oximeter-associated toe injuries in a premature neonate: a case report.

Pulse oximetry is noninvasive and widely used in the intensive care unit and during surgery. Complications associated with the use of pulse oximetry have been reported, including burns, pressure erosion, skin necrosis and digital sensory loss. The causes of these complications may be due to the incompatibilities between the probes and the monitors used from different companies, pressure duration for too long on a single skin site or overheating induced by a short circuit of the probe cable. We report a 940-g premature infant who had severe pulse oximetry-associated injury to the oximetry site. This may have been due to the infant's susceptibility to injury resulting from his critical condition, including low cardiac output, poor peripheral circulation and poor heat dissemination. Our experience shows that, when pulse oximetry is used, especially in critically ill, premature infants, frequent checking of the sensor and the site where the sensor is applied is required to avoid burn injury or pressure erosion of the skin.

Left multicystic dysplastic kidney with contralateral ureteropelvic obstruction: report of one case.

Multicystic dysplastic kidney (MCDK) is a common cause of abdominal mass in neonates. It is frequently associated with malformation of the contralateral kidney, such as ureteropelvic obstruction, etc. Because MCDK is usually functionless, it is important to evaluate the condition of the contralateral kidney. The presence of severe obstruction in the contralateral ureteropelvic junction is life-threatening and prompt treatment should be made to preserve the remaining renal function. We report on a neonate with left MCDK and contralateral ureteropelvic obstruction, presenting as anuria after birth, and also we review the literature.

Neonatal intracardiac rhabdomyomatosis: a case report.

Intracardiac tumors are rare in neonates. Most of these lesions are rhabdomyomas and they occur almost exclusively during infancy. Rhabdomyomas are commonly associated with tuberous sclerosis and often involve the brain, kidneys and pancreas; they are frequently multiple and originate most commonly from the ventricular septum. Surgical intervention is indicated for rhabdomyoma with either mechanical cardiac obstruction or dysrhythmias resulting in symptoms or sudden death. A newborn with diffuse rhabdomyomatosis over the right atrium, right ventricle and left ventricle of the heart complicated with congestive heart failure and intractable supraventricular tachycardia is reported herein. No tuberous sclerosis or other organ involvement was noted. The tumor was resected.

Extremely high prevalence of nasopharyngeal carriage of penicillin-resistant Streptococcus pneumoniae among children in Kaohsiung, Taiwan.

Resistance (intermediate and high) to penicillin among Streptococcus pneumoniae strains is an emerging problem worldwide. From 1995 to 1997, isolates of S. pneumoniae not susceptible to penicillin were seen with increasing frequency from blood, cerebrospinal fluid, pleural fluid, and middle ear fluid from pediatric patients at the Veterans General Hospital-Kaohsiung. To determine the prevalence of carriage of these penicillin-nonsusceptible S. pneumoniae isolates, we obtained nasopharyngeal swab specimens from 2,905 children (ages, 2 months to 7 years) attending day-care centers or kindergartens or seen in our outpatient clinic. S. pneumoniae was isolated from 611 children, and 584 strains were available for analysis. The oxacillin disc test was used as a screening test to evaluate penicillin susceptibility. The MICs of 11 antibiotics (penicillin, cefaclor, cefuroxime, ceftriaxone, cefotaxime, imipenem, chloramphenicol, clarithromycin, rifampin, vancomycin, and teicoplanin) were determined by the E-test. Only 169 (29%) of the strains were susceptible to penicillin; 175 (30%) strains were intermediately resistant and 240 (41%) were highly resistant. The isolates also demonstrated high rates of resistance to other beta-lactams (46% were resistant to cefaclor, 45% were resistant to cefuroxime, 45% were resistant to ceftriaxone, 31% were resistant to cefotaxime, and 46% were resistant to imipenem). The rate of resistance to macrolide antimicrobial agents was strikingly high; 95% of the isolates were not susceptible to clarithromycin. However, 97% were susceptible to rifampin and 100% were susceptible to the two glycopeptides (vancomycin and teicoplanin). While reports of penicillin-resistant S. pneumoniae increased worldwide through the 1980s, the high prevalence (71%) of resistance reported here is astonishing. Surveillance of nasopharyngeal swab specimen cultures may provide useful information on the prevalence of nonsusceptible strains causing invasive disease. Such information could be used to guide therapy of pneumococcal infections.

Serum HDL level at acute stage of Kawasaki disease.

Kawasaki disease is a disease of acute vascular inflammation of unknown etiology and HDL is a known risk factor of vascular damage. So far, there is no specific serum marker for KD. The previous study has shown a remarkable change of serum HDL in the patients with KD. To find whether changes in serum HDL level is a specific serum marker for early diagnosis of KD, we measured the concentration of HDL, LDL, TC, TG and CRP immediately after admission and one week later in three groups of patients (56 patients with KD, 38 patients with clinical viral infection, and 42 patients with bacterial infection). There was a significant decrease of HDL and increase of TG immediately after admission in three groups of patients. HDL and TG did not return to normal one week later. HDL level is more adversely affected in severe diseases than in mild diseases. Our results indicated that low HDL level is noted in various acute infection and is not a specific serum marker in the early stage of Kawasaki disease. It is interesting that low HDL is a universal phenomenon in this series. Further research is needed to explain the mechanism of lipid alterations and its consequences.