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Biomedical subjects

S H Chu

Publications and source records attributed to S H Chu.

At least 19 recordsLinked to original sources

Postpartum myocardial infarction rescued with an intraaortic balloon pump and extracorporeal membrane oxygenator.

A 37-year-old woman had postpartum myocardial infarction complicated with cardiogenic shock. The infarction was attributed to diffuse coronary artery spasm caused by methylergonovine, which had been used to treat the postpartum haemorrhage due to placenta increta. The haemodynamics could not be maintained with catecholamine infusion and intraaortic balloon counterpulsation. At last, an extracorporeal membrane oxygenator was used to save her life, and the patient was successfully weaned from the machine 100 h later; she made an uneventful recovery thereafter.

Adult

Benzylacyclouridine enhances 5-fluorouracil cytotoxicity against human prostate cancer cell lines.

At a nontoxic growth inhibitory concentration benzyloxyacyclouridine (BAU), a potent and specific inhibitor of uridine phosphorylase (UrdPase), enhanced 5-fluorouracil (5-FU) cytotoxic activity against human prostate cancer PC-3 and DU-145 cell lines. The BAU/5-FU combination exhibited greater antitumor activity in vivo using PC-3 human xenografts compared to 5-FU alone, with no associated increase in animal host toxicity. The mechanism(s) responsible for the enhanced in vitro and in vivo activity of this combination may involve enhanced formation of the 5-FU nucleotide metabolites FdUMP, FdUTP, and FUTP resulting in enhanced inhibition of thymidylate synthase (TS) and increased incorporation of fluoropyrimidine metabolites into tumoral RNA and DNA.

Animals

Extracorporeal membrane oxygenation support for single lung transplantation in a patient with primary pulmonary hypertension.

Left single lung transplantation was performed under perioperative extracorporeal membrane oxygenation (ECMO) support for a patient of primary pulmonary hypertension. Continuous ECMO in this patient for one day after the transplantation decreased the pulmonary blood flow and probably served to minimize the potential complication of reperfusion edema of the graft. During this period, the ECMO was gradually weaned so that the grafted lung could adapt itself to the gradually increased blood flow through it. The patient was extubated without difficulty 2 days alter the removal of ECMO and made a smooth recovery.

Adult

Congenital renal arteriovenous malformations: two cases report.

Congenital arteriovenous malformation (AVM) of the kidney is a rare condition. Rupture of an AVM in the kidney may cause hematuria, flank pain, and urinary retention due to clots. We report 2 cases of congenital renal AVM. Both were treated with transcatheter renal arterial embolization. The signs and symptoms disappeared after embolization. On follow-up, renal function testing with a DMSA scan revealed only focal loss of renal cortical function. The clinical courses of 2 cases are reported and the literature is reviewed.

Adult

Phase I clinical and pharmacological studies of benzylacyclouridine, a uridine phosphorylase inhibitor.

Benzylacyclouridine (BAU, IND 039655) is a potent and specific inhibitor of uridine phosphorylase (UrdPase; EC 2.4.2.3). This enzyme plays a major role in regulating uridine homeostasis and also catalyzes the conversion of fluoropyrimidine nucleosides to their respective bases. Inhibition of UrdPase enzyme activity 18-24 h after 5-fluorouracil (5-FU) administration increased plasma levels of uridine and enhanced the therapeutic index of 5-FU by rescuing normal tissues. Moreover, in vitro preclinical studies have also shown that inhibiting UrdPase enzyme activity by BAU prior to administration of 5-FU increased cytotoxicity in a number of human cancer cell lines. A series of preclinical studies was performed in dogs and pigs to evaluate the pharmacological and pharmacodynamic properties of BAU. These data showed a sustained elevation in plasma uridine concentration in both animal models. The rapid degradation of a tracer dose of uridine into uracil was virtually arrested by BAU administered both p.o. or i.v. The t1/2 of BAU was 1.8-3.6 h in dogs, with bioavailability levels of 85% (30 mg/kg) and 42.5% (120 mg/kg). In pigs, the half-life varied from 1.6 to 2.3 h, with a bioavailability of 40% at 120 mg/kg. The drug was distributed into most tissues with a tissue: plasma ratio of approximately 0.7. On the basis of these preclinical studies, we performed a Phase I clinical trial of BAU in patients with advanced cancer. Patients received 200, 400, 800, and 1600 mg/m2 BAU as a single oral dose. Toxicities included grade 2 anemia, grade 1 fever, grade 1 fatigue, grade 1 constipation, and grade 1 elevation in alkaline phosphatase; none of these toxicities were observed to be dose dependent. The maximum tolerated dose and dose-limiting toxicity were not reached at the doses given. BAU plasma concentrations and area under the curve correlated linearly with the oral dose level. The pharmacokinetics of BAU were consistent with a first-order clearance, with average peak concentrations ranging from 19 microM (200 mg/m2) to 99 microM (1600 mg/m2) and tbeta1/2 ranging from 3.0 to 3.9 h at the four dose levels. Compared with baseline plasma uridine, treatment of patients with 200, 400, 800, and 1600 mg/m2 BAU increased peak uridine concentrations by 120, 150, 250, and 175%, respectively. On the basis of this clinical study, the suggested Phase II starting dose of BAU in combination with 5-FU is 800 mg/m2. Studies combining BAU with 5-FU and incorporating appropriate molecular and biochemical end points to assess the effects of this drug combination on tumor and/or surrogate tumor tissue are under way.

Aged

The impact of a clinical pathway for transurethral resection of the prostate on costs and clinical outcomes.

The purpose of this study was to evaluate the effects of implementing a clinical pathway for transurethral resection of the prostate on hospital costs and procedures, outcomes, and complications. Consecutive patients who underwent transurethral resection of the prostate for benign prostate hyperplasia in our hospital before (February-August 1996) and after (October 1996-March 1997) implementation of the clinical pathway were included. Statistical analyses included Student's t-test to test the impact of the clinical pathway on resource consumption and medical care processes, and multiple linear regression to control for patient characteristics such as age, severity of disease, and comorbidity. The major findings of this study were that implementation of the clinical pathway 1) decreased resource consumption and controlled medical care expenditure; 2) influenced physicians' patterns of practice and decreased the number of procedures performed; and 3) did not affect clinical outcomes or complication rates. In conclusion, our results support the hypothesis that the clinical pathway is an effective medical management tool to contain costs, which does not adversely affect quality of care. We suggest health policy makers promote clinical pathways in more hospitals to encourage appropriate resource consumption.

Aged

Adrenal extramedullary hematopoietic tumor in a patient with beta-thalassemia.

We report a case of adrenal extramedullary hematopoiesis in a 27-year-old woman with beta-thalassemia. She underwent cholecystectomy for gallstones and splenectomy for splenomegaly at the age of 20 years. In January 1996, she was admitted to our hospital because of a palpable nontender mass in the right subcostal area. Ultrasound, computed tomography, and magnetic resonance imaging disclosed a right suprarenal mass 7.5 x 5.8 cm in size. Surgical exploration and biopsy confirmed the diagnosis of extramedullary hematopoietic (EMH) tumor. The tumor was left in situ. Subsequent follow-up showed no increase in the size of the tumor and no progression of anemia. The patient remained asymptomatic, and no additional EMH tumor developed. Surgery or radiotherapy should be performed only when EMH tumors cause symptoms, such as during spinal cord compression. Adrenal EMH tumors should be considered in thalassemia patients with an adrenal mass, to avoid unnecessary surgical procedures.

Adrenal Gland Neoplasms

Effects of dobutamine on aortic valve indexes in asymptomatic patients with bileaflet mechanical prostheses in the aortic valve position.

We investigated the effects of alternating transvalvular flow rate on Doppler-derived aortic valve resistance and valve area in asymptomatic patients with mechanical aortic valve replacement under dobutamine infusion. The Gorlin-derived aortic valve area and continuity equation-derived aortic valve area seem to be less flow dependent; valve resistance tends to be flow dependent.

Adrenergic beta-Agonists

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