Fontan conversion with arrhythmia surgery.

OBJECTIVE: Hemodynamic abnormalities and refractory atrial arrhythmias in patients late after the Fontan operation result in significant morbidity and mortality. We reviewed our experience with Fontan conversion and concomitant arrhythmia surgery. METHODS: Between January 1996 and February 2004, 16 patients underwent Fontan conversion and arrhythmia surgery. Mean age at the initial Fontan operation was 5.1+/-3.5 (range: 2-15) years and mean age at Fontan conversion was 17.0+/-5.8 (range: 6-30). The initial Fontan operations were atriopulmonary connections in 14 patients, extracardiac lateral tunnel in 1, and intracardiac lateral tunnel in 1. The types of arrhythmia included atrial flutter in 10 patients and atrial fibrillation in 3. Fontan conversion operation was performed with intracardiac lateral tunnel in 5 patients and extracardiac conduit in 11. Arrhythmia surgery included isthmus cryoablation in 10 patients and right-sided maze in 3. RESULTS: There has been no mortality. At Fontan conversion operation, 7 patients required permanent pacemaker. All patients have improved to New York Heart Association class I or II. With a mean follow-up of 26.9+/-30.6 (range:1-87) months, 16 patients had sinus rhythm, 2 patients had transient atrial flutter which was well controlled, and 2 patients required permanent pacemaker during follow-up. CONCLUSIONS: Fontan conversion with concomitant arrhythmia surgery and permanent pacemaker placement is safe, improves New York Heart Association functional class, and has a low incidence of recurrent arrhythmias. In most patients, concomitant permanent pacemakers are needed.     

Fibroblast growth factor 2 induces differentiation and apoptosis of Askin tumour cells

Peripheral primitive neuroectodermal tumour (PNET)/Ewing's sarcoma (ES) and neuroblastoma (NB) are related tumours of neural crest origin with primitive neural characteristics. Fibroblast growth factor 2 (FGF2) is a critical signalling molecule for primitive neural crest cells. The treatment of NB cells with FGF2 variably affects biological characteristics such as growth and differentiation, while in PNET/ES, FGF2 predominantly induces apoptosis. The JK-GMS Askin tumour cell line can be induced to differentiate upon treatment with nerve growth factor (NGF), indicating the integrity of the cellular machinery necessary for differentiation. The present study assesses whether FGF2 can induce differentiation in JK-GMS cells. JK-GMS cells expressed high-affinity FGF receptors (FGFRs), and treatment with FGF2 induced phosphorylation of FGFR1 together with activation of extracellular signal-regulated kinases (ERK1/ERK2) and c-Jun N-terminal kinase (JNK). Subsequent biological effects were growth inhibition, neuronal differentiation, and apoptosis, and these changes were associated with increased expression of neurofilaments, reduction of c-myc and bcl-2 expression, and activation of caspase 3. Treatment of the cells with a specific inhibitor of the MAPK/extracellular signal-regulated kinase (MEK)-1, PD98059, predominantly inhibited the effects of FGF2 on growth, differentiation, and apoptosis, while an inhibitor of JNK reduced apoptosis, indicating that the ERK1/2 and JNK pathways are critical components of FGF2-mediated effects in JK-GMS cells. Additional comparative analyses of FGF2-mediated effects in two ES cell lines (CADO-ES, RD-ES) and a PNET cell line (SK-N-MC) showed pronounced differentiation in SK-N-MC, but not in CADO-ES or RD-ES cells. This study demonstrates that FGF2 can induce neuronal differentiation of PNET including Askin tumour. These findings clearly indicate that the FGF2-mediated signalling pathway plays a critical role in controlling the major properties of PNET cells and may provide a potential therapeutic target for PNET.     

Pulmonary damage by Vibrio vulnificus cytolysin.

Vibrio vulnificus is an estuarine bacterium that causes septicemia and serious wound infection. Cytolysin produced by V. vulnificus has been incriminated as one of the important virulence determinants of bacterial infection. Cytolysin (8 hemolytic units) given intravenously to mice via their tail veins caused severe hemoconcentration and lethality. Cytolysin treatment greatly increased pulmonary wet weight and vascular permeability as measured by (125)I-labeled albumin leakage without affecting those factors of other organs significantly. Blood neutrophils were markedly decreased in number after cytolysin injection, with a concomitant increase in the level of pulmonary myeloperoxidase activity, indicating that cytolysin-induced neutropenia might be due to pulmonary sequestration of neutrophils. By microscopic examination, severe perivascular edema and neutrophil infiltration were evident in lung tissues. These results suggest that increased vascular permeability and neutrophil sequestration in the lungs are important factors in lethal activity by cytolysin.     

Differentiation of human bone marrow cells into T lymphocytes by in vitro incubation with thymic extracts

Extracts of human or calf thymus influence differentiation of human bone marrow cells in vitro. Incubation of a putative stem cell fraction of human marrow with extracts of thymus for a period of 2 hr led to the appearance of lymphocytes with surface antigens recognized by a highly specific anti-T-cell antiserum. To a lesser degree, development of lymphocytes having the capacity to form rosettes with sheep erythrocytes was observed. Treatment of the so-called stem cell fraction with thymic extracts did not yield cells responsive to mitogenic influences of phyto-haemagglutinin or allogeneic cells. This model should permit further analyses of immunodeficiency diseases and provide a useful technique for purification and analysis of thymus extracts active with human haematopoietic cells.     

Ankylosing spondylitis susceptibility loci defined by genome-search meta-analysis

In genome scans of ankylosing spondylitis (AS), with the exception of the HLA loci, linkage has not been easy to replicate across studies. We applied the genome-search meta-analysis (GSMA) method to genome scans of AS and spondyloarthropathy (SpA) to assess evidence for linkage across studies. Three AS genome scans and one SpA scan including 430 families with 1,048 affected individuals were used. All four original genome scans mainly analyzed Caucasian families. Seven bins had both Psumrnk and Pord<0.05, suggesting these bins most likely contain AS-linked loci; bin 6.2, 6.1, 6.3, 16.3, 19.2, 17.1, and 16.4. The GSMA produced significant genome-wide evidence for linkage on chromosome 6p22.3–6p21.1 (Psumrnk=0.000003), including the HLA locus. In addition to the HLA-B27 locus, strong linkage evidence was found on chromosome 6p25.3–6p22.3 (Psumrnk=0.0013) and 6p21.1–6p15 (Psumrnk=0.043). In the GSMA of four genome scans including one SpA study, the bin 9.4 (9q21.32–9q33.1) was newly found for linkage (Psumrnk=0.043, Pord=0.013). This GSMA added the evidence of the HLA loci as the greatest susceptibility factor to AS and showed evidences of chromosome 6, 16q, 19, 17p, and 9q as non-HLA susceptibility loci.     

Heart-lung transplantation in Korea

Heart-lung transplantation is an effective treatment for patients with various forms of congenital heart disease or pulmonary hypertension. Since the first heart-lung transplantation in 1997, five transplants have been performed in Korea. Three cases were performed in 1997, one in 1998, and the latest one in 2002. The preoperative diagnoses were complex congenital heart disease (CHD) in 2, and CHD with Eisenmenger's syndrome in 3. In this paper, we report five cases of heart-lung transplantation performed in Korea, and include a review of the relevant literature.     

Applications of the pulsatile flow versatile ECLS: in vivo studies

INTRODUCTION: T-PLS (Twin-Pulse Life Support) is the first commercial pulsatile ECLS (Extra Corporeal Life Support) device (1). The dual sac structure of T-PLS can effectively reduce high membrane oxygenator inlet pressure and hemolysis. To verify both the use of T-PLS for ECLS and the advantages of T-PLS, we tested various models. METHOD AND RESULTS: In the partial CPB (cardio pulmonary bypass) model (swine), T-PLS (N = 6), and Biopump (N = 2), a single pulsatile pump (N = 2), were compared. In the case of single pulsatile flow, during pump systole, pressure increased to 700 - 800 mmHg at the inlet port of the membrane oxygenator. fHb, a hemolysis measurement value, was about 80 mg/dL at 3 hours. On the contrary, because of T-PLS's dual sac system, the pressure of T-PLS had a maximum value of about 250 mmHg and fHb was similar to that of the commercial centrifugal pumps. In the total CPB model (bovine, N = 6), the heart was stopped via cardioplegia (Kcl). T-PLS flow was maintained at 3.0-4.5 L/min. T-PLS functioned like a natural heart, having a pulse pressure of 26-43 mmHg and a pulse rate of 40-60 bpm (beats per minute). In the emergency case model (canine, N = 6), T-PLS was started 10 minutes after cardiac arrest from electronic shock. In spite of cardiac arrest for a period of 40 minutes, the heart was recovered after defibrillation. In the ARDS (Acute Respiratory Distress Syndrome) model (canine, N = 6), minimal ventilator parameters were set: tidal volume 130 ml, respiration rate = bpm, FiO2 = 10%. Three hours after starting T-PLS, PO2 of the carotid artery blood (after 2 hours: 195 +/- 89.4; after 3 hours: 258 +/- 99.3 mmHg) was above half the value of the femoral artery but was within normal range. CONCLUSION: It is suggested that a portable pulsatile ECLS like T-PLS may be used as a CPB device and as an alternative CPR (cardiopulmonary resuscitation) device in the case of cardiac arrest. Due to the pulsatile flow, oxygenated blood is delivered to the patient without overloading the ARDS patients heart.     

The changing epidemiology of hepatitis A in children and the consideration of active immunization in Korea

Currently, Korea is a low endemicity country for HAV, especially in children. However, recent reports of hepatitis A outbreaks show that there has been a shift of disease incidence to adolescents and young adults, with 2 cases of acute liver failure in one reported outbreak. We need to study the immune status for HAV in order to provide information for the establishment of preventive measures and possible consequences of HAV in Korea. A total of 334 infants, children and adolescents less than 20 years of age living in rural areas of Kyonggi Province, Korea were evaluated for anti-HAV immune status in 1996. Five hundred and eighty-four primary school children living in the same area were separately evaluated for the natural seroconversion rate between 1993 and follow-up samples taken in 1996. Anti-HAV IgG antibody was measured by enzyme immunoassay (HAVAB EIA kit, Abbott Laboratories, Chicago, Illinois, USA). In comparison with previous reports of seroprevalence rates, our data confirmed a dramatic drop in seroprevalence rates among children and adolescents under 20 years of age living in rural areas, from over 63.8% two decades ago to 4.6% in 1996. Natural acquisition of HAV antibody in primary school children rarely occurs, registering only 0.5% during three years. Several outbreaks in young adults during 1996-1998 suggested that immunity against HAV in this population is so low that massive outbreaks are unavoidable. Teenagers and young adults, especially soldiers, who are likely to be exposed to contaminated food or water, would also have a greater risk of hepatitis A. Immunizing children with HAV vaccine as a routine schedule should also be considered in Korea in the future, particularly if the disease burden could be estimated and the cost-effectiveness of the vaccine could be proved.     

Effect of marrow on the high frequency ultrasonic properties of cancellous bone

A number of investigators have performed in vitro measurements of cancellous bone to determine how various ultrasonic parameters depend on bone density and trabecular orientation. To facilitate handling and storage of bone specimens, the marrow is often removed prior to ultrasonic measurements. However, the assumption that marrow does not affect ultrasonic measurements at high frequencies (>1 MHz) has not been tested. The goal of this study is to determine the effect of marrow on the ultrasonic properties of bovine cancellous bone at frequencies greater than 1 MHz. Twelve specimens of cancellous bone were obtained from the proximal end of four bovine tibia. Ultrasonic measurements consisting of normalized broadband ultrasonic attenuation (nBUA), speed of sound (SOS) and apparent integrated backscatter (AIB) were measured in each specimen using 2.25 MHz (centre frequency) broadband ultrasonic pulses. These measurements were performed before and after marrow removal either along the superoinferior (SI) or mediolateral (ML) direction. SOS and nBUA showed no significant difference (p > 0.05) for either direction of propagation after marrow removal. AIB showed no significant difference in the SI direction. For the ML direction, a small but statistically significant difference (p = 0.044) was observed after marrow removal.     

Low Bone Mineral Density at Initial Diagnosis in Children and Adolescents with Graves’ Disease

Previous studies have reported reduced bone mineral density (BMD) in patients with hyperthyroidism. We assessed the association of BMD in children and adolescents with Graves’ disease (GD) after correcting for potential confounders affecting BMD such as age, sex, and pubertal status. Forty-four children and adolescents with GD and 172 age- and sex-matched healthy controls were enrolled in this study. We analyzed auxological features, BMD, and levels of thyroid hormone, thyroid-stimulating hormone, and thyroid autoantibodies. We measured BMD by dual-energy X-ray absorptiometry at the time of diagnosis in all patients. The mean age of all patients with GD (9 boys and 32 girls) was 12.1 ± 2.2 years (range, 7.0–16.0). Their initial mean free T4 and thyroid-stimulating hormone levels were 3.51 ± 1.56 ng/dL and 0.04 ± 0.03 IU/L, respectively. The mean BMD Z-scores of the lumbar spine (LS), femoral neck, and total body less head of patients with GD were significantly lower than those of control subjects. Eleven patients (26.8%) had low bone density (LS BMD Z-scores < ?2.0). To identify correlations of patient characteristics with BMD Z-scores at each site, alkaline phosphatase had a significant negative correlation with BMD Z-scores at LS and femoral neck, but not total body less head (r = ?0.441; p = 0.004 and r = ?0.351; p = 0.025, respectively). Children and adolescents with newly diagnosed GD had lower bone mass than their healthy peers. These results suggest that BMD measurement at initial evaluation may be necessary in this population.