Frank Leigh Lu

Diet-induced obesity causes innate airway hyperresponsiveness to methacholine and enhances ozone-induced pulmonary inflammation

We previously reported that genetically obese mice exhibit innate airway hyperresponsiveness (AHR) and enhanced ozone (O(3))-induced pulmonary inflammation. Such genetic deficiencies in mice are rare in humans, and they may not be representative of human obesity. Thus the purpose of this study was to determine the pulmonary phenotype of mice with diet-induced obesity (DIO), which more closely mimics the cause of human obesity. Therefore, wild-type C57BL/6 mice were reared from the time of weaning until at least 30 wk of age on diets in which either 10 or 60% of the calories are derived from fat in the form of lard. Body mass was approximately 40% greater in mice fed 60 vs. 10% fat diets. Baseline airway responsiveness to intravenous methacholine, measured by forced oscillation, was greater in mice fed 60 vs. 10% fat diets. We also examined lung permeability and inflammation after exposure to room air or O(3) (2 parts/million for 3 h), an asthma trigger. Four hours after the exposure ended, O(3)-induced increases in bronchoalveolar lavage fluid protein, interleukin-6, KC, macrophage inflammatory protein-2, interferon-gamma-inducible protein-10, and eotaxin were greater in mice fed 60 vs. 10% fat diets. Innate AHR and augmented responses to O(3) were not observed in mice raised from weaning until 20-22 wk of age on a 60% fat diet. These results indicate that mice with DIO exhibit innate AHR and enhanced O(3)-induced pulmonary inflammation, similar to genetically obese mice. However, mice with DIO must remain obese for an extended period of time before this pulmonary phenotype is observed.

Necrotising pneumonia is an increasingly detected complication of pneumonia in children

Necrotising pneumonia (NP) is a severe complication of community-acquired pneumonia characterised by liquefaction and cavitation of lung tissue. The present study describes the epidemiology, aetiology, management and outcomes of children hospitalised with NP over a 15-yr period. A retrospective observational study of NP cases was conducted from January 1990 to February 2005 analysing clinical presentation, laboratory data, hospital course and long-term follow-up. A total of 80 NP cases were identified, with the number of detected cases increasing from 12, in the period 1993–1996, to 40 in the period 2001–2004. In total, 69 (86%) cases had pleural effusion with a low pH (mean 7.08) and 38 (48%) patients had positive cultures, with Streptococcus pneumoniae as the predominant organism. Recently, other organisms, most notably methicillin-resistant Staphylococcus aureus, emerged. Patients had prolonged hospitalisations (median 12 days). A total of 69 patients required pleural interventions and those receiving chest drainage alone had similar outcomes to those managed surgically. All patients had full clinical resolution within 2 months of presentation. Necrotising pneumonia has increasingly been identified as a complication of paediatric pneumonia. Streptococcus pneumoniae remains the predominant organism, but since 2002, different bacteria have been isolated and the age range of cases has broadened. Despite the serious morbidity, massive parenchymal damage and prolonged hospitalisations, long-term outcome following necrotising pneumonia is excellent.

The human tail

The human tail is a congenital anomaly with a protruding lesion from the lumbosacrococcygeal region. A newborn with a tail-like structure over the coccygeal area observed since birth is presented. Lipoma accompanied by tethered spinal cord were found. In reviewing the literature from 1960 to 1997, 59 cases were described. Higher incidences of spinal dysraphism (49.15%) and tethered spinal cord (20.34%) compared with previous reports were evident. This fact plays an important role in understanding the disturbance of development and regression of human tails. A new classification according to whether the anomaly appears in combination with spinal dysraphism is proposed for clinical usage. Preoperative detailed image studies are needed to clarify the possibility of tethered spinal cord syndrome developing in the future and thus prevent it. Magnetic resonance imaging is the modality of choice if available. Long-term follow-up for possible sequelae after operation, especially in cases with spinal dysraphism, is necessary.

Survey of outcome of CPR in pediatric in-hospital cardiac arrest in a medical center in Taiwan

PURPOSE OF THE STUDY While the outcomes of cardiopulmonary resuscitation (CPR) for pediatric in-hospital cardiac arrest (IHCA) are reported for many regions, none is reported for Asian countries. We report the outcomes of CPR for pediatric IHCA in a tertiary medical center in Taiwan and also identify prognostic factors associated with poor outcome. METHODS Data were retrieved retrospectively from 2000 to 2003 and prospectively from 2004 to 2006 from our web-based registry system. We evaluated patients younger than 18 years of age who had IHCA and received CPR. The primary outcome was survival to hospital discharge, and the secondary outcomes were sustained return of spontaneous circulation (ROSC), and favorable neurological outcomes as assessed by pediatric cerebral performance categories (PCPC). RESULTS We identified 316 patients and the overall hospital survival was 20.9% and 16.1% had favorable neurological outcomes. Sixty-four patients ever supported with ECMO. We further analyzed 252 patients who underwent conventional CPR only and most had cardiac disease (133/252, 52.8%). The second most common preexisting condition was hematologic or oncologic disease (43/252, 17.1%). Of the 252 patients, 153 (60.7%) achieved sustained ROSC, 50 (19.8%) survived to discharge, and 39 patients (15.5%) had favorable neurological outcomes. CPR during off-work hours resulted in inferior chances of reaching sustained ROSC. Multivariate analysis showed that long CPR duration, hematology/oncology patients, and pre-arrest vasoactive drug infusion were significantly associated with decreased hospital survival (p<0.05). CONCLUSIONS Outcomes of CPR for pediatric patients with IHCA in Taiwan were comparable to corresponding reports in Western countries, but more hematology/oncology patients were included. Long CPR duration, hematologic or oncologic underlying diseases, and vasoactive agent infusion prior IHCA were associated with poor outcomes. The concept of palliative care should be proposed to families of terminally ill cancer patients in order to avoid unnecessary patient suffering. Also, establishing a balanced duty system in the future might increase chances of sustained ROSC.

Pulmonary responses to subacute ozone exposure in obese vs. lean mice.

The purpose of this study was to determine whether obesity affects pulmonary responses following a 3-day ozone exposure. Obese db/db and lean wild-type mice were exposed to ozone (0.3 ppm) for 72 h. In wild-type mice, ozone exposure caused pulmonary injury and inflammation, and these events were associated with reduced pulmonary compliance. In db/db mice, ozone-induced neutrophil recruitment to the lung was reduced and no reduction in compliance was observed. Similar results were obtained in obese Cpe(fat) mice, indicating that loss of leptin signaling in db/db mice does not account for these obesity-related changes. To examine the role of interleukin (IL)-6 in this obesity-related difference in ozone responsiveness, wild-type and IL-6-deficient mice were raised on 10% or 60% fat diets. Compared with 10% fat-fed mice, wild-type 60% fat-fed mice were obese and had reduced neutrophil recruitment following ozone. IL-6 deficiency reduced ozone-induced neutrophil recruitment in 10% fat-fed mice. In contrast, in obese mice, no effect of IL-6 deficiency on neutrophil recruitment was observed. Obesity-related differences in the effect of ozone on compliance were observed in both wild-type and IL-6-deficient mice. Obesity-related differences in serum IL-6 were observed and may account for obesity-related differences in the effect of IL-6 deficiency on neutrophil recruitment. In summary, the neutrophilic inflammation induced by prolonged low level ozone exposure was attenuated in obese mice and appeared to result from an absence of IL-6-dependent neutrophil recruitment in the obese mice.

Neonatal type of nonketotic hyperglycinemia

Two infants with the neonatal type of nonketotic hyperglycinemia that had manifested as early neonatal consciousness disturbance are presented. Transient hyperammonemia had been detected in both initially. High levels of glycine in plasma and cerebrospinal fluid disturb the nervous system, causing variable manifestations of this disease. Both cases were complicated by intracranial hemorrhage, which has never before been reported. After treatment with sodium benzoate and dextromethorphan, some neurologic improvement was observed, although the glycine levels did not lower. Recent clinical trials are reviewed, and because of the unfavorable outcomes, the special need for prenatal diagnosis is highlighted.

Body Mass Index May Modify Asthma Prevalence Among Low-Birth-Weight Children

Childhood asthma, a growing health concern, has been associated with low birth weight and elevated body mass index. This study tested the hypothesis that overweight and obese adolescents with a history of low birth weight are at even greater risk of developing asthma. A cohort of 75,871 junior high school students was screened for asthma during 1995-1996 in Taiwan. Birth weight and estimated gestational age were obtained from the birth registry. Logistic regression and simple regression analyses were adjusted for confounding variables. Asthma was more prevalent in those with birth weights below 3,000 g and higher adolescent body mass indexes. Furthermore, those with both characteristics were consistently most likely to have asthma. Whether the asthma diagnosis among low-birth-weight subjects was assigned by physicians or medical questionnaire, the risks were elevated for both overweight (physician diagnosis: odds ratio = 1.41; medical questionnaire: odds ratio = 1.25) and obese (physician diagnosis: odds ratio = 1.38; medical questionnaire: odds ratio = 1.47) boys as well as overweight (physician diagnosis: odds ratio = 1.63; medical questionnaire: odds ratio = 1.30) and obese (physician diagnosis: odds ratio = 1.44; medical questionnaire: odds ratio = 1.32) girls (P < 0.05). Low birth weight predisposes one to develop asthma, and excess body mass amplifies the risk. A sex difference was observed. This study suggests that prenatal care and nutritional counseling could reduce asthma prevalence.

Management of Congenital Cystic Adenomatoid Malformation and Bronchopulmonary Sequestration in Newborns

BACKGROUND Congenital cystic adenomatoid malformation (CCAM) and bronchopulmonary sequestration (BPS) are major embryonic pulmonary developmental anomalies. Early surgical excision is becoming an increasingly common option. We investigated the clinical features and management of patients with CCAM and BPS at the National Taiwan University Hospital. METHODS We conducted a retrospective review of neonates diagnosed with CCAM and/or BPS at the Hospital from July 1995 to January 2008. Prenatal examination, postnatal presentation, management and patient outcome were analyzed. We also propose a concise algorithm for the practical management of these conditions. RESULTS Sixteen patients were recruited including eight (50%) with CCAM, five (31%) with BPS and three (19%) with mixed-type lesions (CCAM with BPS). Thirteen (81%) patients were diagnosed antenatally at a median gestational age of 20 weeks. Eleven (69%) patients underwent surgical resection before 6 months of age because of respiratory distress or repeated pulmonary infection. There were no surgery-related complications among the seven patients who underwent early surgery within 1 month of age. Five (31%) patients remained asymptomatic and did not undergo surgery. All patients survived with no limitations to daily activity during follow-up periods of 1-8 years. CONCLUSION The high proportion of mixed-type lesions suggests that CCAM and BPS may share the same developmental ancestry. Early surgical resection within 1 month of age is safe in symptomatic patients.

Holt–Oram syndrome with right lung agenesis caused by a de novo mutation in the TBX5 gene†

Yu-Ru Tseng, Yi-Ning Su, Frank Leigh Lu, Suh-Fang Jeng, Wu-Shiun Hsieh,* Chien-Yi Chen, Hung-Chieh Chou, and Steven Shinn-Forng Peng Department of Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, ROC Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, and Department of Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan, ROC School and Graduate Institute of Physical Therapy, National Taiwan University College of Medicine, Taipei, Taiwan, ROC Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, ROC

Ventricular septal defect with secondary left ventricular-to-right atrial shunt is associated with a higher risk for infective endocarditis and a lower late chance of closure.

OBJECTIVE. Although ventricular septal aneurysm may diminish or even close the shunt through the ventricular septal defect (VSD), developing a left ventricular–to–right atrial (LV-RA) shunt may be unfavorable. This study sought to clarify this issue on the basis of an extended observation of such patients. METHODS. Sixty-eight patients (1201 patient-years) who had small perimembranous VSD and LV-RA shunt and were not operated on before 6 years of age were studied. RESULTS. The onset age of LV-RA shunt was 5.8 ± 3.3 years, with clinical improvement later observed in 23 (34%). The murmur disappeared and showed spontaneous closure in 5 (7%). Seven episodes of infective endocarditis occurred in 6 (8.7%, or 58 per 10000 patient-years), with 2 receiving surgery. Another 4 received surgery during follow-up. With echocardiography, aneurysmal transformation involving the anterior and septal leaflets of tricuspid valve (double sac) was found in 56 (85%), whereas only the septal leaflet (single sac) was involved in 10. Patients with double sac were less likely to show improvement, whereas patients who had superior QRS axis and were female showed clinical improvement more frequently. CONCLUSIONS. VSD with secondary LV-RA shunt is associated with a higher risk for infective endocarditis but still has a low chance for late improvement and even closure.