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Biomedical subjects

P C Kuo

Publications and source records attributed to P C Kuo.

At least 37 records · Page 2Linked to original sources
PubMed2000

Outcomes of laparoscopic donor nephrectomy in obese patients.

The applicability of laparoscopic donor nephrectomy (LDN) has not been assessed in the obese donor. We hypothesized that obesity is not a technical contraindication to LDN. From May 1998 to February 1999, 40 patients underwent LDN at the Georgetown Transplant Institute with the transperitoneal technique. Prophylaxis against deep venous thrombosis consisted of venous compression stockings, low-molecular weight heparin in obese patients, and early ambulation. The following variables were examined: donor sex, age, weight, height, related versus nonrelated donation, body mass index (BMI; wt/ht2), operating room time, estimated blood loss, length of stay, time out of work, and complications. BMI>31 indicates morbid obesity, BMI>27 indicates >20% over ideal body weight, and normal BMI is 25. The patients were divided into nonobese (BMI< or =31) and obese groups (BMI>31). The two groups do not differ in outcome after LDN. Our data indicate that obesity is not associated with increased morbidity or mortality after LDN.

Adult↗
PubMed2000

Superoxide enhances interleukin 1beta-mediated transcription of the hepatocyte-inducible nitric oxide synthase gene.

BACKGROUND & AIMS: Exposure to oxidative stress, as in states of shock, ischemia-reperfusion injury, or sepsis, commonly initiates a complex cellular cascade of interlocking redox modulatory systems that detoxify electrophiles. In interleukin 1beta (IL-1beta)-treated rat hepatocytes, we have previously demonstrated that inducible nitric oxide synthase (iNOS) protein expression, steady-state iNOS messenger RNA (mRNA) levels, and NO synthesis are increased by oxidative stress induced by superoxide. The effect of hepatocellular redox state upon iNOS gene transcription has not been previously studied. METHODS: Using rat hepatocytes in primary culture, iNOS gene transcription was induced by IL-1beta. Oxidative stress was mediated by 1,2,3-benzenetriol (BZT), an autocatalytic source of superoxide. Nuclear run-on assays and transient transfection assays using the rat hepatocyte iNOS full-length promoter and deletion constructs were designed to isolate a cis-acting regulatory element. Specificity was confirmed by site-directed mutagenesis. Gel shift analysis determined the presence of a corresponding trans-acting regulatory factor. RESULTS: In IL-1beta-treated cells, BZT increased iNOS gene transcription without altering mRNA half-life. An antioxidant-responsive element (ARE) was found in the iNOS promoter at base pair -1347, which conferred redox sensitivity. Gel shift analysis identified a corresponding nuclear protein capable of binding to ARE in IL-1beta- and BZT-treated rat hepatocytes. CONCLUSIONS: An ARE in the rat hepatocyte iNOS promoter confers redox sensitivity and augments IL-1beta-mediated iNOS gene and protein expression in the setting of superoxide treatment.

Animals↗
PubMed2000

Pulmonary expression of iNOS and HO-1 protein is upregulated in a rat model of prehepatic portal hypertension.

Portal hypertension is associated with a wide range of pulmonary pathophysiologies, ranging from portopulmonary hypertension to hepatopulmonary syndrome. Although the clinical and pathological features of pulmonary dysfunction in this setting have been extensively characterized, the underlying biology is not well understood. Specifically, the role of mediators that regulate mesenteric vascular hemodynamics in portal hypertension, such as nitric oxide and endothelin, have not been studied in the lung. Using a rat model of prehepatic portal hypertension with preserved hepatic function, we examined pulmonary elaboration of endothelial nitric oxide synthase (NOS), inducible NOS, heme oxygenase- 1 (HO-1), heme oxygenase-2 (HO-2), endothelin-1 mRNA, and protein. In comparison to sham controls, portal hypertensive animals exhibited significantly increased pulmonary iNOS and HO-1 mRNA and protein. Cyclic GMP was significantly increased in portal hypertensive lung tissue, suggesting activation of guanylyl cyclase by the endproducts of iNOS and/or HO-1 activity. Using immunohistochemical analysis, iNOS expression was localized to the vascular endothelium, while HO-1 localized to bronchiolar epithelium and macrophages. These results suggest that production of nitric oxide and carbon monoxide may contribute to the pulmonary pathology associated with portal hypertension.

Animals↗
PubMed2000

Laparoscopic donor nephrectomy with a 23-hour stay: a new standard for transplantation surgery.

OBJECTIVE: To determine the outcomes associated with laparoscopic donor nephrectomy (LDN) performed as a 23-hour day surgery protocol. SUMMARY BACKGROUND DATA: Living donor renal transplantation is associated with immediate graft function and prolonged graft survival. The recent application of laparoscopic technology to living renal donation has refocused attention on the advantages of this donor source. LDN is associated with decreased donor pain, length of stay, time out of work, and opportunity costs. The authors hypothesized that LDN would be a viable 23-hour stay procedure. METHODS: All living donation procedures since May 1998 have been performed with LDN. The 23-hour protocol was initiated in January 1999. LDNs performed from May 1998 to December 1998 and traditional open donor nephrectomy procedures from May 1996 to May 1998 served as historical controls. The following variables were examined: donor sex, related versus nonrelated donation, operative time, blood loss, length of stay, time out of work, recipient and donor serum creatinine levels, hospital charges, and complications. RESULTS: The 23-hour LDN protocol was associated with high degrees of donor satisfaction. Thirty-six of the 41 donors were discharged within 23 hours; 1 was readmitted. Time out of work was equivalent to that of the control group; graft function was identical among all three comparison groups. Hospital charges were equivalent between the control group and the open nephrectomy group and were significantly decreased in the 23-hour group. CONCLUSIONS: Laparoscopic donor nephrectomy can be performed as a 23-hour stay procedure without incurring additional complications or donor dissatisfaction. By further decreasing opportunity costs and disincentives for donation, LDN may increase the number of potential donors appearing for evaluation.

Adult↗
PubMed1999

Laparoscopic versus open donor nephrectomy: comparing ureteral complications in the recipients and improving the laparoscopic technique.

BACKGROUND: Laparoscopic live donor nephrectomy (LDN) is a recently developed procedure, the performance of which needs to be studied. Given the reported advantages in the donors, this study looks at graft outcome and ureteral complications in recipients of kidneys procured by open donor nephrectomy (ODN) versus LDN. METHODS: The LDN recipients consisted of 193 patients since 3/27/96. A total of 168 ODN recipients from 1991 to 1998 served as controls. Immunosuppression protocols were similar for both groups. RESULTS: Two-year graft survival for LDN and ODN was 98% and 96%, respectively. Two-year patient survival for LDN and ODN was 98% and 97%, respectively. The incidence of delayed graft function and mean serum creatinine at 3 and 12 months was similar in both groups. However, the number of ureteral complications that required operative repair was significantly higher for LDN recipients compared to ODN recipients, 7.7% (n=15) vs. 0.6% (n=1) respectively (P=0.03). Ureteral stenting was required in an additional 3.1% (n=6) of LDN and 2.4% (n=4) of ODN (P=NS). There was, however, a learning curve with time. For the first 130 LDN patients, a total of 20 ureteral complications were recorded, whereas only one occurred in the more recent 63 patients (P=0.03). CONCLUSIONS: The higher ureteral complication rate in LDN recipients has improved over time as technical causes have been identified. We have noted significant improvement in ureteral viability by using the endogastrointestinal anastomosis instrument on the ureter and peri-ureteral tissue. LDN is therefore an excellent alternative to ODN. Identification of hazards unique to this technique is critical before its broader application.

Adult↗
PubMed1999

Portopulmonary hypertension and the liver transplant candidate.

The management of the liver transplant (OLT) candidate with portopulmonary hypertension (PPHTN) has dramatically changed in the past 3 years. Careful preoperative evaluation with functional characterization of right ventricular function plays a critical role. The pulmonary vascular response to epoprostenol infusion serves as a deciding factor for OLT candidacy. Careful perioperative attention to avoid right ventricular failure from acutely elevated pulmonary artery pressures or sudden increases in right ventricular preload is a key physiologic tenet of management. With increased surgical expertise, anesthetic sophistication, and availability of epoprostenol, PPHTN is no longer considered an absolute contraindication for OLT.

Humans↗
PubMed1999

Endotoxin-mediated S-nitrosylation of p50 alters NF-kappa B-dependent gene transcription in ANA-1 murine macrophages.

Nitric oxide (NO) regulates cellular function, in part, by S-nitrosylating active site thiol groups of proteins. Ex vivo S-nitrosylation of NF-kappa B p50 significantly decreases its capacity for DNA binding. To determine the cellular relevance of this observation, we utilized the ANA-l murine macrophage model of endotoxin (LPS)-mediated NO synthesis. In selected instances, the NO synthase inhibitor, L-arginine methyl ester (L-NAME; 100 microM), or the NO donor, S-nitroso-N-acetylcysteine (SNAC; 100 microM), was added. In contrast to that of LPS cells, nuclear extracts from LPS + L-NAME cells demonstrated increased NF-kappa B DNA binding on gel shift analysis. Addition of SNAC to LPS + L-NAME cells restored binding to a level equivalent to that of LPS cells. Spectrophotometric analysis of NF-kappa B p50 immunoprecipitates demonstrated S-NO bonds exclusively in LPS cells; these p50 protein isolates retained the same DNA binding characteristics as that of the nuclear extracts. Transfection assays utilizing NF-kappa B-dependent promoter-reporter constructs demonstrated increased activity in LPS + L-NAME cells compared with LPS cells; nuclear run-on assays confirmed increased transcription of the corresponding genes. These results suggest that LPS-mediated NO synthesis is associated with S-nitrosylation of NF-kappa B p50 and inhibition of NF-kappa B-dependent DNA binding, promoter activity, and gene transcription. We conclude that NO can regulate gene transcription by S-nitrosylation of NF-kappa B.

Animals↗
PubMed1999

Transverse hepatectomy for symptomatic polycystic liver disease.

Polycystic liver disease can result in massive enlargement of the liver with resultant debilitating symptoms of abdominal pain, chronic fatigue, and severely compromised functional status. Fenestration of hepatic cysts has been advocated as a treatment for polycystic disease. However, in patients with predominant small cyst replacement, fenestration alone often results in limited hepatic volume reduction without improvement in patient functional status. Liver transplantation has also been previously advocated for polycystic liver disease with predominant small cyst replacement, but, with the severe shortage of donor organs, alternative treatment should be considered. In this report we present a case of massive enlargement of the liver with severe clinical debilitation due to polycystic liver disease. Transverse hepatectomy provided a safe and effective alternative to fenestration or liver transplantation.

Cysts↗
PubMed1999

Endotoxin-mediated nitric oxide synthesis inhibits IL-1beta gene transcription in ANA-1 murine macrophages.

On the basis of previous work demonstrating nitric oxide (NO)-mediated inhibition of nuclear factor-kappaB (NF-kappaB) DNA binding, we hypothesized that NO downregulates NF-kappaB-dependent interleukin-1beta (IL-1beta) production in an ANA-1 macrophage model of lipopolysaccharide (LPS) stimulation. In the presence of LPS (100 ng/ml), levels of IL-1beta protein and mRNA were significantly upregulated with NO synthase inhibition. Using nuclear run-on analysis and transient transfection studies, IL-1beta gene transcription and IL-1beta promoter activity were also found to be increased with inhibition of NO production. Parallel transfection studies using an NF-kappaB long terminal repeat-reporter plasmid exhibited similar findings, suggesting an NO-mediated effect on NF-kappaB activity. Gel shift studies showed that LPS-associated NF-kappaB DNA binding was increased, both in the setting of NO synthase inhibition and in a reducing environment. Repletion of NO by addition of an S-nitrosothiol restored IL-1beta protein synthesis, mRNA levels, gene transcription, promoter activity, and NF-kappaB DNA binding to levels noted in the presence of LPS alone. Our studies indicate that NO may regulate LPS-associated inflammation by downregulating IL-1beta gene transcription through S-nitrosation of NF-kappaB.

Animals↗
PubMed1999

Redox regulation of the rat hepatocyte iNOS promoter.

BACKGROUND: The purpose of this study was to define the redox sensitive cis-acting transcriptional mechanisms that regulate inducible nitric oxide synthase (iNOS) promoter function in the hepatocyte. METHODS: Clonal deletion constructs of the rat hepatocyte iNOS promoter (Genbank X95629; 1845 base pair)-reporter plasmid were transiently transfected into HepG2 cells treated with IL-1 beta and IL-1 beta + hydrogen peroxide. RESULTS: A segment of the promoter upstream from nucleotide -1126 was associated with redox-sensitive augmentation of promoter activity. Site-directed mutagenesis of 2 antioxidant response elements (AREs) was combined with transfection analysis to demonstrate that mutation of the ARE at nt-1347 ablated oxidant stress-mediated activation of the iNOS promoter. CONCLUSIONS: This ARE conveys the redox-sensitive response of the rat iNOS promoter. Hepatocyte iNOS expression is a novel and, as yet, poorly described antioxidant mechanism that is cytokine and redox sensitive and that plays a pleuripotent regulatory role in hepatocellular function in the face of sepsis and shock.

Animals↗