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Biomedical subjects

M H Wu

Publications and source records attributed to M H Wu.

At least 55 records · Page 3Linked to original sources

Echocardiographic assessment of total anomalous pulmonary venous connections in pediatric patients.

BACKGROUND AND PURPOSE: Cardiac catheterization can be superfluous and risky for sick babies, infants, and young children with total anomalous pulmonary venous connection (TAPVC). This study assessed the accuracy of echocardiography in the clinical assessment of pediatric patients with TAPVC before cardiac surgery. PATIENTS AND METHODS: A total of 15 consecutive patients with TAPVC treated between July 1, 1993, and December 31, 1999, were included in this retrospective study. Patients with TAPVC with heterotaxy syndrome were excluded. We assessed this cardiac anomaly preoperatively using plain chest roentgenograms, echocardiography, and magnetic resonance imaging. A combination of suprasternal, parasternal, subcostal, and apical four-chamber views and their tilting scans were employed for diagnosis and to trace the course of the anomalous pulmonary venous connection. RESULTS: Interatrial right-to-left shunt via atrial septal defects were documented by two-dimensional echocardiography with color Doppler mapping in all 15 patients. Patent ductus arteriosus was found in six patients. Cardiomegaly with enlargement of the right atrium and the right ventricle could be seen on plain chest roentgenograms and by echocardiography in all but two patients with infracardiac TAPVC. In all patients, the left innominate vein, coronary sinus or right atrium, and portal vein were the draining sites of supracardiac, cardiac, and infracardiac TAPVC, respectively. A pattern of continuous flow without phasic variation, which is suggestive of stenosis of the pulmonary vein, was found in two patients with infracardiac TAPVC with obstruction. The surgical findings were reviewed and correlated well with those of the echocardiography. CONCLUSIONS: In infants and children with TAPVC, the drainage sites and flow profiles of the pulmonary veins can be exactly determined by Doppler echocardiography preoperatively, which makes cardiac catheterization and angiocardiography unnecessary.

Child↗

Effect of O6-benzylguanine on alkylating agent-induced toxicity and mutagenicity. In Chinese hamster ovary cells expressing wild-type and mutant O6-alkylguanine-DNA alkyltransferases.

The DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) has been shown to protect cells from the toxic and mutagenic effect of alkylating agents by removing lesions from the O6 position of guanine. O6-Benzylguanine (BG) is a potent inactivator of AGT, resulting in an increase in the sensitivity of cells to the toxic effects of chemotherapeutic alkylating agents. Chinese hamster ovary (CHO) cells and CHO cells transfected with wild-type AGT (CHOWTAGT) and a mutant AGT [P138 M/V139I/P140K (CHOMIK)] known to be resistant to BG were treated with BG and various alkylating agents. BG treatment alone dramatically decreased AGT activity in CHOWTAGT cells but resulted in no depletion in AGT activity in CHOMIK cells. In the absence of AGT, these cells are highly sensitive to the toxic and mutagenic effects of temozolomide and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), and no further sensitization occurs in the presence of BG. In contrast, CHOWTAGT cells are resistant to temozolomide and BCNU, and treatment with BG resulted in a significantly higher cell killing and mutation frequency. CHOMIK cells were completely resistant to temozolomide or BCNU in the presence and absence of BG. Both cell killing and mutation frequency of 4-hydroperoxycyclophosphamide (4-HC) in CHO, CHOWTAGT, and CHOMIK cells were increased in the presence of BG. 4-HC generates two active metabolites, phosphoramide mustard (PM) and acrolein. BG had no effect on 4hydroperoxydidechlorocyclophosphamide (which generates acrolein and a nonalkylating form of PM) in CHO cells and CHOMIK cells, but enhancement of toxicity was observed with PM in both these cell lines. Therefore, we attribute the enhancement to the PM metabolite of 4-HC. Our results demonstrate that wild-type AGT plays an important role in protecting against the toxic and mutagenic effect of O6 alkylating agents and that a mutant AGT resistant to inactivation by BG effectively prevents BG-enhanced toxicity and mutagenicity induced by these agents. Expression of the AGT protein contributes to resistance of 4-HC. BG also enhances the toxicity of 4-HC and PM by a mechanism that may not involve the AGT repair protein.

Animals↗

Protein kinase C activation contributes to microvascular barrier dysfunction in the heart at early stages of diabetes.

The functional disturbance of microvasculature is recognized as an initiating mechanism that underlies the development of various diabetic complications. Although a causal relationship between microvascular leakage and tissue damage has been well documented in diabetic kidneys and eyes, there is a lack of information regarding the barrier function of coronary exchange vessels in the disease state. The aim of the present study was to evaluate the permeability property of coronary microvessels during the early development of experimental diabetes with a focus on the protein kinase C (PKC)-dependent signaling mechanism. The apparent permeability coefficient of albumin (Pa) was measured in isolated and perfused porcine coronary venules. The administration of high concentrations of D-glucose induced a dose-dependent increase in the Pa value, which was prevented by blockage of PKC with its selective inhibitors bisindolylmaleimide and Goe 6976. More importantly, an elevated basal permeability to albumin was observed in coronary venules at the early onset of streptozotocin-induced diabetes. The hyperpermeability was corrected with bisindolylmaleimide and the selective PKCbeta inhibitor hispidin. Concomitantly, protein kinase assay showed a high PKC activity in isolated diabetic venules. Immunoblot analysis of the diabetic heart revealed a significant subcellular translocation of PKCbetaII and PKCepsilon from the cytosol to the membrane, indicating that the specific activity of these isoforms was preferentially elevated. The results suggest that endothelial barrier dysfunction attributed to the activation of PKC occurs at the coronary exchange vessels in early diabetes.

Albumins↗

Influence of aortopulmonary rotation on the anomalous coronary artery pattern in tetralogy of fallot.

Three main patterns of aortic sinus rotation were defined on 517 lateral angiograms of tetralogy of Fallot with 14 cases of anomalous coronary artery pattern occurring only in patients with a right anterior or right lateral aorta. The significant dependence of coronary artery types on the aortic sinus pattern made it possible to predict the predisposing coronary artery pattern in tetralogy of Fallot based on the aortic sinus pattern.

Coronary Angiography↗

Radiofrequency catheter ablation of tachycardia in children with and without congenital heart disease: indications and limitations.

From 1993 to 1998, a total of 100 consecutive pediatric patients with tachycardia (45 male and 55 female, aged 1 year 10 months to 17 years, 11+/-4 year) who underwent electrophysiological study were reviewed. Eleven of them were younger than 5 years. Two had tachycardia-related cerebrovascular accident. Congenital heart disease was found in 12 patients. After propofol anesthesia, the clinical tachycardia could not be induced in three (two atrial tachycardia and one AV nodal re-entrant tachycardia) and became nonsustained in five (atrial tachycardia). Mechanical ablation occurred in three and two had subsequent recurrences. Among the 85 cases who received radiofrequency ablation, the overall final success rate of RF ablation for all diagnoses was 94% with a diagnosis-specific success rate ranging from 100 to 57%. Tachycardia cardiomyopathy was noted in four (three atrial tachycardia and one junctional ectopic tachycardia) and all regressed after successful ablation. Success in two patients with left posterioseptal accessory pathway could only be achieved by delivering the energy at the middle cardiac vein. Two patients with right atrial isomerism had an 'AV nodal-to-AV nodal tachycardia' which was eliminated by ablation. Total recurrence rate was 13% but final success was achieved in all during re-study except the three patients who refused re-intervention. The atrial tachycardia developed in postoperative congenital heart disease was associated with the lowest success rate (57%) and highest recurrence rate (25%). Procedure-related complications occurred in four; two with transient brachial palsy, one with first-degree AV block and one with blood loss requiring blood transfusion. In conclusion, the experience of this single center confirmed the efficacy and safety of radiofrequency catheter ablation in treating pediatric arrhythmias, but the limitations in postoperative arrhythmias and the effects of propofol on tachycardia induction (especially the atrial tachycardia) need to be improved.

Anesthetics, Intravenous↗

Enhanced endothelialization and microvessel formation in polyester grafts seeded with CD34(+) bone marrow cells.

The authors have shown accelerated endothelialization on polyethylene terephthalate (PET) grafts preclotted with autologous bone marrow. Bone marrow cells have a subset of early progenitor cells that express the CD34 antigen on their surfaces. A recent in vitro study has shown that CD34(+) cells can differentiate into endothelial cells. The current study was designed to determine whether CD34(+) progenitor cells would enhance vascular graft healing in a canine model. The authors used composite grafts implanted in the dog's descending thoracic aorta (DTA) for 4 weeks. The 8-mm x 12-cm composite grafts had a 4-cm PET graft in the center and 4-cm standard ePTFE grafts at each end. The entire composite was coated with silicone rubber to make it impervious; thus, the PET segment was shielded from perigraft and pannus ingrowth. There were 5 study grafts and 5 control grafts. On the day before surgery, 120 mL bone marrow was aspirated, and CD34(+) cells were enriched using an immunomagnetic bead technique, yielding an average of 11.4 +/- 5. 3 x 10(6). During surgery, these cells were mixed with venous blood and seeded onto the PET segment of composite study grafts; the control grafts were treated with venous blood only. Hematoxylin and eosin, immunocytochemical, and AgNO(3 )staining demonstrated significant increases of surface endothelialization on the seeded grafts (92% +/- 3.4% vs 26.6% +/- 7.6%; P =.0001) with markedly increased microvessels in the neointima, graft wall, and external area compared with controls. In dogs, CD34(+) cell seeding enhances vascular graft endothelialization; this suggests practical therapeutic applications. (Blood. 2000;95:581-585)

Animals↗

Right lung agenesis with left pulmonary artery sling.

We report on a 2-month-old infant girl who had right pulmonary agenesis and an unusual course of the left pulmonary artery. Computed tomography and cardiac catheterization showed that the left pulmonary artery arose from the main pulmonary artery, crossing the midline, and reaching the left lung via an aberrant course between the esophagus and trachea. The coexistence of right pulmonary agenesis and left pulmonary sling is extremely rare. Unlike in other reports, our patient remained symptom-free and in good health, with normal growth and development until age 2 years, when she died from complications during an attack of bronchiolitis caused by respiratory syncytial virus.

Bronchiolitis↗

Modified arterial switch operation by spiral reconstruction of the great arteries in transposition.

BACKGROUND: Spiral relationship of the normally related great arteries (SRGA) has never been reconstructed in an arterial switch operation. METHODS: From March 1998 to April 1999, 9 consecutive cases of transposition of the great arteries (TGA) family (from 2 days to 1.6 years old) underwent arterial switch operations with SRGA at our hospital. Two had a congenitally corrected TGA (plus atrial redirection). Lecompte maneuver was not used in all. The posterior wall of pulmonary trunk was not divided but three were reattached, two of whom had had previous pulmonary trunk banding. Thus the wall was shared between the great arteries facing each other. RESULTS: All survived the operation. Supraaortic stenosis was balloon-dilated in 2 cases of early series, but technical modifications later were able to avoid it. Angiogram showed smooth flow into SRGA without upward and anterior tilting of the pulmonary bifurcation. All great and coronary arteries were patent. All were doing well on follow-up (16.5 +/- 4.2 months). CONCLUSIONS: We concluded that the techniques to relocate the coronary arteries using common wall and in situ switch could also be applied to pulmonary arterial reconstruction, so that SRGA can be resumed in TGA.

Anastomosis, Surgical↗

DNA adduct level in lung tissue may act as a risk biomarker of lung cancer.

Lung cancer is a leading cause of mortality in Taiwan. We hypothesised that high susceptibility to DNA damage in the target organ acts as a risk biomarker for the development of lung cancer. To verify this hypothesis, the aromatic/hydrophobic DNA adduct levels of non-tumorous adjacent lung tissues from 73 primary lung cancer patients and 33 non-cancer controls were evaluated by 32P-postlabelling assay. Wilcoxon rank sum test showed that DNA adduct levels in lung cancer patients (49.58+/-33.39 adducts/10(8) nucleotides) were significantly higher than those in non-cancer controls (18.00+/-15.33 adducts/10(8) nucleotides, P<0.001). The DNA adduct levels among lung cancer and non-cancer samples were not influenced by smoking behaviour and cigarette consumption. Our data also showed that the polymorphisms of cytochrome P4501A1 (CYP1A1) Msp1, glutathione S-transferase M1 (GSTM1) and the combination of both genetic polymorphisms were not related to the DNA adduct levels. Interestingly, positive association between CYP1A1 protein expression and DNA adduct levels was found when CYP1A1 protein expression in lung specimens from lung cancer patients was examined by immunohistochemistry. Multivariate linear regression analysis indicated that the DNA adduct level was not associated with gender, smoking behaviour, or genetic polymorphisms of CYP1A1 and GSTM1. Moreover, multivariate logistic regression analysis showed that persons with high DNA adduct levels (>48.66 adducts/10(8) nucleotides) had an approximately 25-fold risk of lung cancer compared with persons with low DNA adduct levels (</=48.66 adducts/10(8) nucleotides). In conclusion, DNA adduct levels in lung tissue may be a more reliable lung cancer susceptibility biomarker than DNA adduct levels in leucocytes. In addition, higher susceptibility to DNA damage in lung cancer patients may partly play a role in the development of lung cancer.

Adenocarcinoma↗

Intrathoracic muscle flap transposition in the treatment of fibrocavernous tuberculosis.

BACKGROUND AND OBJECTIVE: Conventionally, pulmonary resection with thoracoplasty is used to treat fibrocavernous complication of pulmonary tuberculosis. This operation is usually bloody, time-consuming with complicated postoperative course. To prevent massive blood loss and preserved pulmonary function, a more simplified operative procedure, cavernostomy combined intrathoracic muscle flap transposition was used and the outcome was evaluated in this study. DESIGN: Retrospective review. METHODOLOGY: Between December 1989 and June 1996, a total of ten patients with fibrocavernous pulmonary tuberculosis were managed using cavernostomy combined with intrathoracic muscle flap transposition. Five of them had concomitant aspergilloma within the cavity while three had multiple drug resistant pulmonary tuberculosis. The muscle flap was used to plombage the cavity and reinforce the closure of bronchopleural fistula after cavernostomy. RESULTS: Six postoperative complications occurred in five patients, including reformation of cavity (2), bronchopleurocutaneous fistulae (3), and postoperative bleeding (1). The success or failure of intrathoracic muscle flap transposition on patients with fibrocavernous tuberculosis was significantly correlated with the size of the cavity (194.0+/-11.2 vs. 283.0+/-44.6 cm(3), P=0.016) and the number of bronchopleural fistulae (1.6+/-0.4 vs. 4.0+/-0.4, P=0.008). There was no operative death and in long term follow-up, there was no recurrence of hemoptysis or deterioration of pulmonary function in the successful group of patients. CONCLUSIONS: Cavernostomy combined with intrathoracic muscle flap transposition can be used to treat well-selected fibrocavernous pulmonary tuberculosis patients, except on patients with large size cavity, multiple bronchopleural fistulae or multiple drug resistance tuberculosis.

Adult↗

Esophageal varices in congenital heart disease with total anomalous pulmonary venous connection.

Total anomalous pulmonary venous connection (TAPVC) is an uncommon congenital anomaly in which the anatomical presentations vary widely among patients. We hereby present two newborns with TAPVC associated with asplenia syndrome; both had severe esophageal varices due to infradiaphragmatic pulmonary venous drainage. Ultrafast computed tomography (CT) scanning was superior to color Doppler echocardiography and cardiac catheterization as it provided a detailed portrait of the pulmonary drainage. The remarkable radiographic manifestations are presented.

Cardiac Catheterization↗

A mouse model for spinal muscular atrophy.

The survival motor neuron gene is present in humans in a telomeric copy, SMN1, and several centromeric copies, SMN2. Homozygous mutation of SMN1 is associated with proximal spinal muscular atrophy (SMA), a severe motor neuron disease characterized by early childhood onset of progressive muscle weakness. To understand the functional role of SMN1 in SMA, we produced mouse lines deficient for mouse Smn and transgenic mouse lines that expressed human SMN2. Smn-/- mice died during the peri-implantation stage. In contrast, transgenic mice harbouring SMN2 in the Smn-/- background showed pathological changes in the spinal cord and skeletal muscles similar to those of SMA patients. The severity of the pathological changes in these mice correlated with the amount of SMN protein that contained the region encoded by exon 7. Our results demonstrate that SMN2 can partially compensate for lack of SMN1. The variable phenotypes of Smn-/-SMN2 mice reflect those seen in SMA patients, providing a mouse model for this disease.

Animals↗

Paroxysmal supraventricular tachycardia in identical twins with the same left lateral accessory pathways and innocent dual atrioventricular pathways.

We report on 16-year-old, female identical twins who both have atrioventricular reentrant tachycardia caused by the same left lateral atrioventricular accessory pathway. The Kent pathway in twin A was a unidirectional retrograde accessory pathway. A manifest Kent pathway was demonstrated in twin B. Both pathways were successfully ablated by radiofrequency (RF) energy and without recurrence. In addition, innocent dual AV nodal pathways were shown in both patients. These findings suggest that genetic factors may play a role in the pathogenesis of the formation of accessory atrioventricular pathways and dual AV nodal pathways.

Adolescent↗

Role of electrophysiological studies and arrhythmia intervention in repairing Ebstein's anomaly.

BACKGROUND: Repairing Ebstein's anomaly without correction of associated arrhythmia may result in sudden death. Catheter or surgical ablation is indicated for various symptomatic tachyarrhythmias in Ebstein's anomaly. METHODS: Between October 1973 and October 1997, 30 patients with Ebstein's anomaly underwent surgical repair in our hospital. Tricuspid valve replacement was performed in 13 patients, tricuspid annuloplasty and valvuloplasty in the remaining 17 patients. Preoperative electrophysiological studies were performed in 11 patients after 1980. Concomitant arrhythmia ablation was done in 10 patients: 4 for Wolff-Parkinson-White syndrome, 2 for atrioventricular (AV) nodal reentrant tachycardia, one for ventricular tachycardia and 3 for paroxysmal atrial flutter and fibrillation. RESULTS: No mortality or major morbidity occurred in those patients undergoing arrhythmia intervention. There were 7 deaths in total; 6 died suddenly, and the other died of purulent mediastinitis. None of the 6 sudden deaths underwent preoperative electrophysiological evaluation. The functional recovery was good in all survivals. CONCLUSIONS: We conclude that detailed preoperative electrophysiological evaluation in patients with Ebstein's anomaly is mandatory. Aggressive surgical intervention of the associated arrhythmias in addition to anatomic correction can reduce the sudden death in Ebstein's anomaly.

Adolescent↗

Administration of granulocyte colony-stimulating factor enhances endothelialization and microvessel formation in small-caliber synthetic vascular grafts.

OBJECTIVE: The purpose of this study was to determine whether systemic administration of granulocyte colony-stimulating factor (G-CSF) would promote endothelialization for small-caliber Dacron vascular grafts. METHODS: We implanted 4-mm preclotted Dacron grafts in both carotids of 12 dogs. For a fair comparison, all dogs had a comparable platelet aggregation profile with platelet aggregation scores less than 30. Five dogs served as controls, and the others were given 7-day subcutaneous injections of G-CSF (10 microg/kg per day), starting on the seventh postoperative day. The effect of G-CSF was evaluated by white blood cell count, which showed a 3.7-fold (+/- 2.7-fold) increase at the end of treatment. Grafts were harvested at 4 weeks. All G-CSF grafts were patent, and one control occluded. Endothelial-like cell coverage averaged 80.8% on G-CSF grafts, but only 35.6% for control grafts (P <.0004). With the exclusion of the anastomotic pannus healing factor, the difference in endothelial-like cell coverage was even greater (68.5% vs 9.8%; P <.0001). Immunocytochemical staining and electron microscopy studies demonstrated endothelial cells. Light microscopy also showed that there were more microvessels on and in the G-CSF grafts than in the control grafts. This study suggests that G-CSF can enhance early endothelialization of small-caliber vascular grafts. Further studies to determine the proper dosage and timing are needed before clinical application can be recommended.

Animals↗

Simplified rat intubation using a new oropharyngeal intubation wedge.

Our new oropharyngeal intubation wedge made from a plastic 3-ml syringe has been used successfully for the expansion of the oropharyngeal cavity and visualization of vocal cords for endotracheal intubation in the rat. All the animals we used tolerated the intubation and ventilation procedures in a series of experiments. After the proper setting of the respirator, vital signs were maintained within normal range. The postmortem examination and measurements in the upper airway confirmed that the endotracheal tube was properly sited and also demonstrated the precise size of the device that should be used. The main advantages of this method include low cost, simplicity, and reliability. Furthermore, because no expensive, elaborate, difficult-to-operate, or hard-to-get special equipment is needed, this technique can be used in every laboratory.

Animals↗

Fibrinofibrous pericarditis mimicking a pericardial tumor.

Primary pericardial disease is rare in children. The clinical features usually reflect limited venous return and cardiac output. Tuberculous pericarditis is the leading cause of pericardial disease in developing nations. A definitive diagnosis in children is frequently difficult and the manifestations are protean. We report a 10-month-old girl with fibrinofibrous pericarditis that manifested as constrictive pericarditis with prolonged fever, hepatomegaly, edema, and poor appetite. Echocardiography showed a solid mass that originated from the thickened pericardium and compressed the whole heart. In contrast, computed tomography revealed pericardial thickening with fluid collection. The symptoms and signs dramatically improved after surgical pericardiectomy. Pathologic analysis confirmed the diagnosis of tuberculous fibrinofibrous pericarditis. The patient received a 1-year course of antituberculosis therapy and has remained symptom free for 2 years. We suggest that a discrepancy between echocardiography and computed tomography (CT) findings might indicate a diagnosis of fibrinofibrous pericarditis.

Diagnosis, Differential↗

First successful ventricular septation of double inlet left ventricle in Taiwan.

Patients with a double inlet ventricle may undergo surgery using a modified Fontan procedure, in which the pulmonary ventricle is not utilized, or a procedure in which a pulmonary ventricle is created through ventricular septation. Ventricular septation is preferred to the Fontan procedure because there is better cardiorespiratory response to exercise after surgery. A 4-year-old girl with Holmes heart underwent ventricular septation on 12 May 1998. Pulmonary artery banding had been performed at 3 months of age and rebanding 16 days later. She was well and continued to grow. Ultrafast computed tomography and cardiac catheterization prior to surgery showed a double inlet left ventricle (LV) connected to a right posterior aorta with a right-sided rudimentary right ventricle that drained to the left anterior pulmonary trunk. Left ventricular end diastolic volume was 218% of normal and the ejection fraction was 79%. After debanding and enlargement of the bulboventricular foramen, a 3 x 4-cm composite patch of equine pericardium and Dacron velour was used to septate the ventricle, with transmural stitching at the apical portion. The patient survived the operation with complete atrioventricular block, and was extubated 6 days later. A permanent pacemaker was implanted 1 month later. One year after surgery, she was doing well. Echocardiography revealed paradoxical septal motion with good ventricular function. This is the first report of successful ventricular septation of a double inlet left ventricle performed in Taiwan.

Cardiac Surgical Procedures↗