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Biomedical subjects

S H Chu

Publications and source records attributed to S H Chu.

At least 109 records · Page 6Linked to original sources

Cytotoxicity and mitogenicity of adenosine triphosphate in the cochlea.

Evidence is accumulating to indicate that extracellular adenosine 5'-triphosphate (ATP) may function as a neurotransmitter, neuromodulator, cytotoxin and mitogen. Many of the cells in the cochlea have ATP receptors, however, their function is unknown. The purpose of the present study was to test whether ATP may act as a cytotoxin in the cochlea. ATP was applied to acutely isolated outer hair cells (OHCs) and their shape changes monitored. In addition, ATP was applied into the cochlea by perfusion of the perilymph compartment for 2 h and the animals allowed to survive 3-4 weeks post drug application. At this time, sound-evoked cochlear potentials and distortion product otoacoustic emissions (DPOAEs) were monitored and the cochleas evaluated histologically. Results indicate that when applied to isolated OHCs, ATP (3-30 mM) induced a bleb formation in the infracuticular region of the cell that burst within a few minutes. Short OHCs were more sensitive to this effect of ATP than long OHCs. 3-4 weeks after the perilymph perfusion of ATP (60 mM; 2 h) cochlear potentials and DPOAEs were abolished, and histologically, cells in the organ of Corti and the stria vascularis were found to have been destroyed. In addition, there was loss of spiral ganglion cells and proliferating connective tissue filled varying proportions of the scala tympani and vestibuli. Application of sodium gluconate, a control, at the same concentrations had no effect either on the isolated OHCs or when applied in vivo. Results suggest that extracellular ATP or a metabolic product may act as a cytotoxin to some epithelial and neural elements in the cochlea and possibly as a mitogen to mesenchymal cells or fibrocytes.

Adenosine Triphosphate↗

Extracorporeal membrane oxygenation in the perioperative period of heart transplantation.

Mechanical circulatory support is occasionally needed in the perioperative period of heart transplantation. Between February and May 1995, three recipients of cardiac transplant at the National Taiwan University Hospital required the use of extracorporeal membrane oxygenation (ECMO) for temporary mechanical circulatory support in the perioperative period of heart transplantation. All three patients received ECMO through the percutaneous femoral veno-arterial route. The ECMO device has a heparin-bound Carmeda Bioactive surface and centrifugal pump. Patient 1 needed ECMO for treatment of a postoperative pulmonary hypertensive crisis. Patient 2 needed ECMO for early cardiac allograft failure, possibly due to ischemia. Patient 3 needed ECMO as a bridge to his first heart transplant after acute myocardial infarction complicated with cardiogenic shock, and again as a bridge to retransplantation because of acute failure of the first cardiac transplant and finally for a temporary circulatory support during rescue treatment for acute vascular rejection of the second cardiac transplant. All three patients were successfully treated with ECMO without major complications. In conclusion, ECMO provides excellent mechanical circulatory support for some situations in the perioperative period of heart transplantation.

Aged↗

Successful early separation of a premature xipho-omphalopagus conjoined twins: a case report.

Premature xipho-omphalopagus conjoined twins were successfully separated at 7 days of age. The total body weight of the twins before separation was 3502 g. One twin had persistent patent ductus arteriosus and signs of cardiac failure at 4 days of age. This was managed with indomethacin. Thirty-six hours later the second twin became anuric, necessitating early emergency separation. The twins were joined from the lower sternum to the infraumbilical area. The liver was fused, but there was no major vascular connection. There were no other major anomalies. The babies stood the procedure well and were healthy at follow-up 8 months after separation.

Abnormalities, Multiple↗

Application of cryoablation in the management of prostate cancer.

BACKGROUND: Radical prostatectomy is the most common and effective therapy for localized prostate cancer. But in addition to its surgical complications, even highly selected series carry a positive margin rate of 35 to 50%. Radiotherapy is another alternative for prostate cancer, but following radiotherapy there have been high positive biopsies reported. Cryosurgery, defined as in situ freezing and hence, devitalization of neoplastic tissues, has currently raised the interest of urologists in the management of localized prostate cancer or failed radiotherapy. MATERIAL: Five patients underwent transperineal cryosurgery of prostate in Chang Gung Memorial Hospital. Among them, three cases were stage D, one stage B and another failed radiotherapy of stage C prostate cancer. All patients received hormone therapy too. RESULTS: PSA declined in 3 patients and biopsies showed intraductal neoplasia. All 5 patients suffered from urine incontinence and one persisted. No mortality has been reported. CONCLUSION: Cryoablation of the prostate is an alternative for treatment of prostate cancer.

Aged↗

Effects of 8-oxoberberine on sodium current in rat ventricular and human atrial myocytes.

8-Oxoberberine (JKL1073A), a derivative of berberine, has been reported to exert positive inotropic action and antiarrhythmic activity, much like a class III antiarrhythmic agent. In addition to prolongation of cardiac action potential duration, JKL1073A also decreases the maximal rate of action potential upstroke. To characterize the mode of inhibition of action potential upstroke, the effects of JKL1073A on the sodium inward current (INa) of rat and human cardiac myocytes were examined by voltage clamp in a whole cell configuration. In rat ventricular myocytes, JKL1073A and quinidine inhibited INa with an average 50% inhibitory concentration (IC50) of 3.3 +/- 0.2 microM (n = 9) and 2.1 +/- 0.1 microM (n = 6), respectively. Voltage-dependent steady state inactivation curves of INa were shifted slightly by 10 microM JKL1073A but more significantly by 3 microM quinidine to negative potential. Though steady state inactivation of INa was not significantly changed by 3 microM JKL1073A, the time constant of INa recovery from inactivation state was partially prolonged from 51.7 +/- 18.5 ms to 74.1 +/- 23.8 ms. Quinidine (3 microM) prolonged the time course of INa recovery from inactivation with an associated increase of slow recovery component. Inhibition of INa by JKL1073A and quinidine was increased when cells were stimulated at higher frequency. The maximal INa obtained in cells held at -140 mV was significantly decreased by 10 microM quinidine to 45.3 +/- 2.5% of control but only partially suppressed by 10 microM JKL1073A to 85.9 +/- 8.6% of control. In human atrial myocytes, JKL1073A and quinidine suppressed INa with an average IC50 of 2.4 +/- 0.6 microM and 1.4 +/- 0.3 microM, respectively. Both JKL1073A and quinidine increased the time constant of INa recovery from inactivation. In conclusion, JKL1073A at concentrations of 3 microM and 10 microM may inhibit INa mainly by binding to open and inactivated channels. Quinidine 3 microM may inhibit INa by binding to resting, open and inactivated channels. Inhibition of INa by JKL1073A may explain the inhibition of the action potential upstroke and contribute partially to its antiarrhythmic activity.

Animals↗

Effects of modifications in the pentose moiety and conformational changes on the binding of nucleoside ligands to uridine phosphorylase from Toxoplasma gondii.

One hundred and fifty analogues of uridine, with various modifications to the uracil and pentose moieties, have been tested and compared with uridine with respect to their potency to bind to uridine phosphorylase (UrdPase, EC 2.4.2.3) from Toxoplasma gondii. The effects of the alpha- and beta-anomers, the L- and D-enantiomers, as well as restricted syn and anti rotamers, on binding were examined. Pseudo-, lyxo-, 2,3'-anhydro-2'-deoxy-, 6,5'-cyclo-, 6,3'-methano-, O5',6-methano- and carbocyclic uridines did not bind to the enzyme. Ribosides bound better than the corresponding xylosides, which were better than the deoxyribosides. The binding of deoxyribosides was in the following manner: 2',3'-dideoxynucleosides > 2',5'-dideoxynucleosides > 2'-deoxyribosides > 3'- and 5'-deoxyribosides. alpha-2'-Deoxyribosides bound to the enzyme, albeit less tightly than the corresponding beta-anomers. The acyclo- and 2,2'-anhydrouridines bound strongly, with the 2,2'-anhydro-derivatives being the better ligands. 2,5'-Anhydrouridine bound to UrdPase less effectively than 2,2'-anhydrouridine and acyclouridine. Arabinosyluracil was at best a very poor ligand, but bound better if a benzyl group was present at the 5-position of the pyrimidine ring. This binding was enhanced further by adding a 5-benzyloxybenzyl group. A similar enhancement of the binding by increased hydrophobicity at the 5-position of the pyrimidine ring was observed with ribosides, alpha- and beta-anomers of the 2'-deoxyribosides, acyclonucleosides, and 2,2'-anhydronucleosides. Among all the compounds tested, 5-(benzyloxybenzyl)-2,2'-anhydrouridine was identified as the best ligand of T. gondii UrdPase with an apparent Ki value of 60 +/- 3 nM. It is concluded that the presence of an N-glycosyl bond is a prerequisite for a nucleoside ligand to bind to T. gondii UrdPase. On the other hand, the presence of a 2'-, 3'-, or 5'-hydroxyl group, or an N-glycosyl bond in the beta-configuration, enhanced but was not essential for binding. Furthermore, the potency of the binding of 2,2'-anhydrouridines (fixed high syn isomers) in contrast to the weaker binding of the 6,1'-anhydro- or 2,5'-anhydrouridines (fixed syn isomers), and the complete lack of binding of the 6,5'-cyclo, O5',6-methano- and 6,3'-methanouridines (fixed anti isomers) to T. gondii UrdPase indicate that the binding of ligands to this enzyme is in the syn/high syn conformation around the N-glycosyl bond. The results also indicate that the parasite but not the mammalian host UrdPase can participate in hydrogen bonding with N3 of the pyrimidine ring of nucleoside ligands. T. gondii UrdPase also has a larger hydrophobic pocket adjacent to the C5 of the pyrimidine moiety than the host enzyme, and can accommodate modifications in the pentose moiety which cannot be tolerated by the host enzyme. Most prominent among these modifications is the absence and/or lack of the ribo orientation of the 3'-hydroxyl group, which is a requirement for a ligand to bind to mammalian UrdPase. These differences between the parasite and host, enzymes can be useful in designing specific inhibitors or "subversive" substrates for T. gondii UrdPase.

Animals↗

Increased ferritin gene expression in atherosclerotic lesions.

To identify genes potentially implicated in atherogenesis, a cDNA library was constructed from human atherosclerotic aorta and differentially screened with 32P-labeled-cDNAs prepared from human normal and atherosclerotic aortas. Two cDNA clones exhibiting higher hybridization to the 32P-labeled cDNAs from atherosclerotic vessels were isolated and identified to be genes encoding L-ferritin and H-ferritin, respectively. Northern blot analysis confirmed that the expression of both ferritin genes was notably higher in human and rabbit atherosclerotic aortas than in their normal counterparts. A time-course study illustrated that both L- and H-ferritin mRNAs were markedly increased in aortas of rabbits after feeding with a high cholesterol diet for 6 wk, which was also the time period after which the formation of lesions became evident. In situ hybridization revealed that both L- and H-ferritin mRNAs were induced in endothelial cells and macrophages of human early lesions. The signals were also detected in the smooth muscle cells of advanced lesions. Immunostaining further identified the presence of ferritin protein in atherosclerotic lesions. On the other hand, Prussian blue stain revealed the presence of iron deposits in advanced lesions but not in early human or rabbit lesions. Further experiments with cultured human monocytic THP-1 cells and aortic smooth muscle cells demonstrated that ferritin mRNAs were subjected to up-regulation by treatment with IL-1 or TNF, while TGF, PDGF, and oxidized LDL did not affect the expression of either ferritin gene in both cell lines. Collectively, these results clearly demonstrate that ferritin genes are susceptible to induction in the course of plaque formation.

Animals↗

Malalignment-type ventricular septal defect in double-chambered right ventricle.

Double-chambered right ventricle (DCRV) is commonly associated with ventricular septal defect (VSD). In this study, an assessment was made of the relevance of a malalignment-type VSD to hemodynamic and morphologic features in DCRV. During an 8.5-year period, 53 patients with DCRV were enrolled after study with echocardiography, catheterization, and angiography. Patients were divided into 2 groups: group I included 40 patients, aged 3.7 +/- 3.2 years, with a malalignment-type VSD; group II consisted of 13 patients, aged 8.6 +/- 2.7 years, without a malalignment-type VSD. History of congestive heart failure in infancy was present in 21 group I and 2 group II patients (53% vs 15%, respectively, p <0.05). The mean pulmonary-to-systemic flow ratio was significantly higher in group I than in group II (1.89 +/- 0.74 vs 1.14 +/- 0.21, respectively, p <0.05). The mean pressure gradient across the right ventricular outflow tract was lower in group I than in group II (41 +/- 16 vs, 73 +/- 33 mm Hg, respectively, p <0.05). Among 42 patients who had a series of echocardiograms recorded, progression of pressure gradient was evident in 35: 28 in group I and 7 in group II. A subaortic ridge was present exclusively in 29 group I patients (73%). Prolapse of the aortic valve was present in 26 (49%): 20 group I (50%) and 6 group II (46%) patients. Aneurysm formation of the septal defect was found in 17 (43%) and 7 (54%) group I and II patients, respectively. It can be concluded that a history of congestive heart failure was more common in DCRV patients with a malalignment-type VSD. Malalignment-type VSD is significantly associated with a larger pulmonary-to-systemic flow ratio and subaortic ridge.

Adolescent↗

Angiographic evidence of long-axis rotation in addition to short-axis aortopulmonary rotation: its implication in transposition of the great arteries.

To assess the pattern of aortic sinus in varied aortopulmonary rotations and its clinical implications, three aortic sinuses at the diastolic phase in true lateral view are identified in 53 angiograms of complete transposition of the great arteries recorded between 1988 and 1993. The patients with the high takeoff of the coronary arteries found at surgery and in the literature were selected for additional investigation. Six regions were defined on the horizontal plane. From left anterior 89 degrees to 61 degrees, the non-facing sinus moved toward the anterior aspect (one patient). From left anterior 60 degrees to left anterior 1 degree, the left-hand sinus moved gradually from an anterior toward a posterior location (two patients). From directly anterior 0 degree to right anterior 59 degrees, the right-hand sinus moved from posterior toward an anterior position (30 patients). From right anterior 60 degrees to right posterior 105 degrees, the non-facing sinus moved posteriorly (20 patients). On approaching directly anterior 0 degree and toward right anterior 60 degrees, the left-hand sinus was the lowest in anterior transposition of the great arteries instead of the non-facing sinus, as in left anterior 90 degrees and in posterior transposition of the great arteries. High takeoff occurred commonly above the lowest left-hand sinus in anterior transposition of the great arteries (2 cases here and 5 in the literature, 100%). In conclusion, aortopulmonary rotations about the short and long axes were both evident on identification of the aortic sinus in various rotations. The aortic sinus did not rotate along the long-axis in anterior transposition of the great arteries, thus making the left-hand sinus, the lowest of this group, vulnerable to the high takeoff of the coronary arteries in anterior transposition of the great arteries.

Aorta↗

Efficacy of ultrafiltration in removing inflammatory mediators during pediatric cardiac operations.

BACKGROUND: Conventional and modified ultrafiltration was used in pediatric cardiac operations to reduce volume overload and total body water. The purpose of this study was to compare the efficacy of these techniques in removing inflammatory mediators during cardiopulmonary bypass. METHODS: Fifty pediatric patients undergoing cardiac operations were randomized into a modified or conventional ultrafiltration group. Blood samples were obtained before and after ultrafiltration to assess the plasma concentrations of leukocyte elastase, tumor necrosis factor-alpha, interleukin-6, and interleukin-8. RESULTS: Except for plasma concentrations of tumor necrosis factor-alpha in the modified ultrafiltration group, the plasma concentrations of all the mediators measured increased after ultrafiltration in both groups of patients. The volume of ultrafiltrate and the total amounts of tumor necrosis factor-alpha and interleukin-6 removed by ultrafiltration were significantly greater in the modified group. The concentrations of mediators in the ultrafiltrate and the ratio of ultrafiltrate to plasma concentrations of the mediators did not differ between the groups. Ultrafiltration was more efficient in removing tumor necrosis factor-alpha than the other mediators. CONCLUSIONS: The efficacy in removing the inflammatory mediators generated during cardiopulmonary bypass did not differ between modified and conventional ultrafiltration.

Analysis of Variance↗

Comparative testing of pulsatile impeller total heart and sarns nonpulsatile roller as biventricular assist device in pigs.

A pulsatile impeller total heart was developed, which consists of two impeller pumps and a d.c. motor. As the motor changes its rotating speed periodically, both pumps eject the blood flow simultaneously. To evaluate its blood compatibility, the device and sarns roller pumps were compared in two series of acute biventricular assist experiments in four and three pigs, respectively. The experimental conditions were controlled to be as equal as possible. The experiments lasted 6 hours. Blood sampling was drawn preoperatively, at the beginning of the pumping and every 2 h postoperatively. Red blood cells (RBC), white blood cells (WBC), platelets (PLT), hematocrit (HCT), hemoglobin (HB), free hemoglobin (FHB) and lactate dehydrogenase (LDH) were measured. The results demonstrated that there was no significant blood damage caused by impeller total heart and the clinically used roller, and that the pulsatile impeller total heart is suitable for chronic animal experiments.

Animals↗

Haematological variations of experimental pigs during biventricular assistance with impeller total heart.

The impeller total heart was developed and published several years ago but its in-vivo evaluations could only be made recently. Originally, the device was designed for long-term implantation. As the first step, however, it was used this time in acute biventricular assistance, to demonstrate the blood compatibility of the pumps, and to demonstrate the feasibility of an impeller type centrifugal total heart. The haematological measurements made during the experiments indicated that no remarkable blood damage occurred and that all the biochemical datums remained relatively unchanged. Because the centrifugal pump has been considered, until now, to be able only to produce a nonpulsatile flow, its applications have been limited mainly to assist the heart. This first assessment of an impeller total heart reported here will open the application area of centrifugal pumps to include cardiovascular surgery.

Animals↗

Left atrial spontaneous echo contrast in asymptomatic patients with a mechanical valve prosthesis.

BACKGROUND: Valve thromboembolism may be a fatal complication of mechanical valve prosthesis if detected late. Spontaneous echo contrast (SEC) is a well-documented prothrombotic phenomenon; here we report it in asymptomatic patients with a mechanical valve prosthesis. METHODS: Ninety-two asymptomatic patients with a mechanical valve prosthesis for underlying rheumatic heart disease underwent transesophageal echocardiography. Appendage area, peak filling and emptying velocities of the left atrial appendage, and the presence or absence of SEC and thrombi were determined. The results of 56 patients without SEC or thrombi (group I) were compared with those of 24 patients with SEC and no thrombi (group II) and 12 patients with thrombi (group III). RESULTS: Spontaneous echo contrast was present in 39% of the asymptomatic patients with a mechanical valve prosthesis. Although 12 patients had cardiac thrombi, including valve thrombi in 4, no patients presented symptoms. Anticoagulant therapy had no significant association with SEC and atrial thrombi. There was a significantly greater prevalence of atrial fibrillation and mitral prosthesis in groups II and III than in group I. Two patterns of left atrial appendage flow were identified: one was organized biphasic flow with peak filling velocities of 41.2 +/- 17.2 cm/s and emptying velocities of 40.5 +/- 17.5 cm/s. The other showed irregular, very low peak filling velocities (104 +/- 11.5 cm/s) and emptying velocities (12.3 +/- 13.1 cm/s). The former flow pattern was associated with sinus rhythm and the latter form was associated with atrial fibrillation. CONCLUSIONS: There was a relatively high prevalence of SEC and thrombi in patients with a mechanical valve prosthesis. Patients with a valve prosthesis may not have clinical symptoms. Anticoagulation intensity was not associated with the occurrence of SEC and thrombi. Patients with the mitral valve prosthesis and atrial fibrillation were identified as a high-risk of subgroup for the development of SEC and thrombi.

Adult↗

Atrial compartment surgery for chronic atrial fibrillation associated with congenital heart defects.

In three adult patients, two with atrial septal defect and one with Ebstein's anomaly, chronic atrial fibrillation was documented for 13, 21, and 3 years, respectively. Atrial compartment surgery was performed for ablation of the atrial fibrillation concomitant with repair of the cardiac defects. The operation was performed with traditional cardiopulmonary bypass and crystalloid cardioplegia myocardial protection. A U-shaped incision was made in the right atrium: a longitudinal incision 1 cm lateral and parallel to the sulcus terminalis, extending along the borders of the atrial septum to 3 cm (upper margin) and 1 cm (lower margin) distant to the tricuspid anulus. Cryolesions of the atrial isthmus between the upper incision margin and the tricuspid valve anulus were created at -60 degrees C for 180 seconds at a time. After the operation, all three patients had restored and maintained normal sinus rhythm during follow-up periods of 32, 16, and 3 months. Doppler echocardiography detected the recovery of atrial contractility in all three patients. Atrial compartment surgery is a simple and effective method for elimination of chronic atrial fibrillation associated with congenital heart defects.

Adult↗