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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

Adrenal hemangioma: two cases report.

Adrenal hemangiomas are rare, nonfunctioning benign tumors. They are well circumscribed and comprise of closely adjacent vascular channels of varying sizes that are lined with a single layer of endothelium. When they occur, they are frequently located in the skin and liver. There are no characteristic symptoms of adrenal hemangioma unless the tumor reaches a size large enough to exert pressure. To our knowledge, there have been 14 clinical cases of adrenal hemangiomas reported, all with similar pathologic features. We present 2 additional cases, which were identified incidentally after non-urologic complaints (epigastric fullness and low back pain in patient 1 and patient 2, respectively). In these 2 patients, the tumors were surgically removed and diagnosed postoperatively as adrenal hemangiomas. Preoperative radiologic findings on plain film and abdominal computerized tomography showed the characteristic round calcifications with translucent centers, typical of phleboliths, to be pathognomonic of adrenal gland hemangiomas. Unfortunately, this characteristic feature of adrenal hemangioma existed in only one case report. In conclusion, the preoperative diagnosis of adrenal hemangioma is difficult but should be kept in mind as being part of the differential diagnosis of adrenal tumors.

Adrenal Gland Neoplasms↗

PubMed1998

Video-assisted endoscopic saphenous vein harvesting for coronary artery bypass grafting.

Saphenous vein grafts for coronary artery bypass can be harvested by means of the traditional long incision method, the skin bridge method, or a newly developed endoscopic technique. We applied the endoscopic technique to reduce the length of leg incision and to decrease the frequency of complications. Between September and December 1996, 47 patients underwent coronary artery bypass grafts, 17 of whom volunteered to undergo saphenous vein harvest with the Endopath video-assisted endoscopic saphenous vein harvest (ESVH) system; the other 30 patients underwent the traditional long incision harvest procedure. A total of 22 saphenous veins were harvested from the 17 patients who underwent ESVH. The mean length of the leg wound was 5.8 +/- 1.3 cm and the mean length of the vein harvested was 32.9 +/- 3.4 cm (wound/vein length ratio 17.6%). The wound/vein length ratio of the 30 patients who underwent the traditional open harvest method was 91.5% (30.8 +/- 2.2 cm/34.1 +/- 3.0 cm). ESVH failed and was converted to the conventional method in two cases. The mean time required to harvest the saphenous vein was 72.7 +/- 20.8 minutes in the ESVH group and 45.8 +/- 12.5 minutes in the open surgery group. No wound complications were noted in the ESVH group, except for ecchymosis in three cases. Five patients in the open surgery group had wound discharge (17%). The length of hospital stay was shorter (10.5 +/- 2.6 days vs 15.8 +/- 4.2 days) and fewer analgesics were used in the ESVH group. The rate of cardiac complications was not different between the two groups. Examination of the vein graft under light microscopy also did not reveal any differences. We conclude that the endoscopic technique can provide adequate vein grafts for use in coronary artery bypass grafting and reduce the leg wound complication rate, hospital stay, and use of analgesics.

Aged↗

PubMed1997

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↗

PubMed1997

Unbalanced cross circulation in conjoined twins.

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Blood Circulation↗