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Biomedical subjects

P C Kuo

Publications and source records attributed to P C Kuo.

At least 19 recordsLinked to original sources
PubMed2007

One-year results with extended-release tacrolimus/MMF, tacrolimus/MMF and cyclosporine/MMF in de novo kidney transplant recipients.

Once-daily tacrolimus extended-release formulation (Prograf XL, formerly referred to as MR or MR4) was compared with the twice-a-day tacrolimus formulation (TAC) and cyclosporine microemulsion (CsA), all administered in combination with mycophenolate mofetil (MMF), corticosteroids and basiliximab induction, in a phase 3, randomized (1:1:1), open-label trial in 638 de novo kidney transplant recipients. In combination with MMF and corticosteroids, XL had an efficacy profile comparable to TAC and CsA. XL/MMF and TAC/MMF were statistically noninferior at 1-year posttransplantation to CsA/MMF for the primary efficacy endpoint, efficacy failure (death, graft loss, biopsy-confirmed acute rejection (BCAR) or lost to follow-up). One-year patient and graft survival were 98.6% and 96.7% in the XL/MMF group, 95.7% and 92.9% in TAC/MMF group and 97.6% and 95.7% in CsA/MMF group. The safety profile of XL in comparison with CsA was similar to that observed with TAC in this study and consistent with previously published reports of TAC in comparison with CsA. The results support the safety and efficacy of tacrolimus in combination with MMF, corticosteroids and basiliximab induction, as well as XL as a safe and effective once-daily dosing alternative.

Adolescent↗
PubMed2005

Obesity predicts increased overall complications following pancreas transplantation.

PURPOSE: We sought to evaluate the role of recipient body mass index (BMI) on postoperative complications in patients receiving pancreas transplants. METHODS: A single-institution retrospective study of 145 consecutive patients undergoing either simultaneous kidney pancreas (SPK) or pancreas after kidney (PAK) transplantation from January 1997 through December 2003. Variables analyzed included: age, sex, BMI, number of prior transplants, cytomegalovirus status of donor and recipient, postoperative insulin resistance, complications, and overall patient and graft survival. Differences in continuous variables and dichotomous variables were evaluated using two-tailed t test and Fisher exact test, respectively. Univariate and multivariate logistic regression analyses were employed to identify predictors of overall complications following surgery. RESULTS: Obesity was defined by a BMI > or = 30. Of the 145 patients, 33 (23%) had a BMI > or = 30 and 112 (77%) had a BMI < 30. There was no significant difference in age or sex between obese and nonobese patients (P = .98 and P = .56, respectively). The type of transplantation, SPK or PAK, did not affect the complication rate (P = .36). Overall complications (infection, dehiscence, evisceration, ventral hernia, allograft failure, gangrene, necrotizing fasciitis, postoperative bleeding, or death) were significantly higher in the obese group (81% vs 40%, P < .001). Obesity was specifically associated with increased frequency of dehiscence, ventral hernia, intra-abdominal infection, gangrene, necrotizing fasciitis, and repeat laparotomy. Obese patients also had a threefold higher rate of graft pancreatitis/enteric leak. Multivariate logistic regression analysis identified age > or = 50 and BMI > or = 30 as independent predictors of overall complications following surgery (odds ratio 4.0, P = .014 and OR 6.8, P < .001, respectively). There was no difference identified between groups with regards to allograft failure, posttransplant insulin resistance, and death. CONCLUSION: Obese patients are at increased risk of overall complications following pancreas transplantation. Specifically, obese patients experience higher frequency of dehiscence, ventral hernia, intra-abdominal infection, gangrene, and necrotizing fasciitis. This study demonstrates the need for careful postoperative monitoring in the obese patient.

Adult↗
PubMed2002

Pharmacokinetics and biochemical effects of hepapoietin in patients with chronic liver disease.

BACKGROUND: Hepapoietin is a naturally occurring cytokine that promotes hepatocyte growth. Animal studies have suggested that hepapoietin and hepatocyte growth factor have a potential role in the prevention and management of liver diseases. However, human studies have been lacking. AIM: To evaluate the safety and pharmacokinetics of single escalating doses of hepapoietin in patients with chronic liver disease. METHODS: An open-label, single escalating dose trial with five different doses of hepapoietin (1, 3, 10, 30 and 100 mg) was performed. Adults with chronic, compensated, non-viral liver disease were included. Liver function tests were obtained before dosing, 24 h after hepapoietin administration and on days 4, 7, 30 and 45. All patients were followed for 45 days. RESULTS: Twenty-five subjects received hepapoietin, with five subjects each at 1, 3, 10, 30 and 100 mg of hepapoietin. Significant decreases occurred in total bilirubin, ammonia, partial thromboplastin time and cholesterol levels overall, and both high-density and low-density lipoprotein cholesterol showed a downward trend. An increase in albumin was observed at the 30 mg dose level. Slight decreases in haemoglobin and red blood cell levels were observed at day 4, but returned to normal levels immediately thereafter. Child-Pugh scores from day 0 to day 7 were improved in 24%, stable in 64% and worse in 12% of patients. Hepatic encephalopathy displayed changes from day 0 to day 45 with improvement in 16%, no change in 80% and worsening in 4%. CONCLUSIONS: Hepapoietin in doses up to 100 mg is safe for use in humans. Potential benefits are suggested by significant decreases in bilirubin, ammonia, partial thromboplastin time and cholesterol levels and an increase in albumin. Further studies with multiple dosing regimens are needed to identify the clinical utility of hepapoietin in the management of chronic liver disease.

Area Under Curve↗
PubMed2001

Nitric oxide inhibits expression of cytochrome B in endotoxin-stimulated murine macrophages.

In LPS-mediated states of sepsis, inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production inhibit cellular respiration and mitochondrial electron transport. NO has been demonstrated to inhibit mitochondrial respiration by nitrosylation of the iron-sulfur centers of aconitase, complex I (NADH-ubiquinone oxidoreductase), complex II (succinate-ubiquinone oxidoreductase), and complex IV (cytochrome c oxidase). However, little is known of the effect of NO on expression of critical proteins in the electron transport chain. In ANA-1 murine macrophages, LPS-mediated NO synthesis decreases Cyt b protein expression and steady-state mRNA levels. Mitochondrial run-on analysis demonstrates unaltered Cyt b mitochondrial gene transcription. In this study utilizing LPS-stimulated ANA-1 murine macrophages, we demonstrate that expression of the mitochondrial protein, Cyt b, is significantly decreased as the result of a unique and previously unknown, NO-dependent posttranscriptional regulatory mechanism. (c)2001 Elsevier Science.

Animals↗
PubMed2001

Candida fasciitis following renal transplantation.

BACKGROUND: We describe a rare case of necrotizing fasciitis involving Candida albicans, an organism that has been reported to have a minimal potential for invasive soft tissue infection. In this case, immunosuppression, chronic renal failure, and a history of diabetes mellitus were predisposing factors. METHODS: The medical record and histopathologic material were examined. The clinical literature was reviewed for previous cases of C albicans necrotizing fasciitis. RESULTS: A review of the literature showed that in solid organ transplant recipients, localized fungal soft tissue infection is infrequent, with only 35 cases reported between 1974 and 1992. Necrotizing fasciitis caused by C albicans is extremely rare in the modern era of solid organ transplantation. CONCLUSIONS: The management of transplant patients at risk for invasive fungal infection warrants a high index of suspicion for fungal necrotizing fasciitis in the setting of wound infection and merits a thorough investigation for atypical pathogens.

Candidiasis↗
PubMed2001

Osteopontin is a negative feedback regulator of nitric oxide synthesis in murine macrophages.

In a system of endotoxin (LPS)-mediated NO production in ANA-1 murine macrophages, suppression subtractive hybridization was used to identify genes up-regulated by NO. Osteopontin (OPN), a secreted acidic phosphoprotein that binds to a cell surface RGD integrin-binding motif, was found to be differentially expressed in the presence of NO. OPN has been demonstrated to inhibit NO production in a variety of cell types. Northern blot and nuclear run-on analyses demonstrated that OPN mRNA levels and gene transcription were significantly increased in the presence of LPS-induced NO synthesis. Transient transfection of an OPN promoter-luciferase reporter plasmid construct showed that promoter activity is increased in the presence of LPS and NO. Immunoblot analysis showed that OPN protein is secreted into the extracellular fluid. Similar results were noted with an alternative cell system, RAW 264.7 macrophages, and alternative inducers of NO synthesis, IFN-gamma and IL-1beta. In the presence of GRGDSP, a hexapeptide that blocks binding of RGD-containing proteins to cell surface integrins, NO production is significantly increased in the presence of LPS stimulation. These data suggest a unique trans-regulatory mechanism in which LPS-induced NO synthesis feedback regulates itself through up-regulation of OPN promoter activity and gene transcription.

Animals↗
PubMed2001

Outcome of extra-anatomic vascular reconstruction in orthotopic liver transplantation.

BACKGROUND: Portal venous and hepatic arterial reconstruction are critical to successful outcomes in orthotopic liver transplantation (OLT). With portal vein thrombosis or inadequate hepatic arterial inflow, extra-anatomic vascular reconstruction is required. However, the clinical outcomes following extra-anatomic vascular reconstruction are largely unknown. METHODS: To determine the outcomes associated with extra-anatomic vascular reconstruction, we performed a retrospective review of 205 OLT recipients transplanted between 1995 and 2000. RESULTS: Extra-anatomic portal venous inflow was based upon the recipient superior mesenteric vein using donor iliac vein graft in a retrogastric position (n = 12). Extra-anatomic arterial inflow was based on recipient infrarenal aorta using donor iliac artery graft through the transverse mesocolon (n = 25). OLT with routine anatomic vascular construction served as control (n = 168). Extra-anatomic vascular reconstruction was not associated with increased morbidity, mortality, operating room time, length of stay, or thrombosis. CONCLUSION: We conclude that extra-anatomic vascular conduits are associated with excellent long-term outcomes and provide acceptable alternatives for vascular reconstruction in OLT.

Female↗
PubMed2001

Transplantation in the HIV+ patient.

The historical exclusion from transplantation of HIV-infected people was based on the logical premise that immunosuppression required for organ transplantation would exacerbate an immunocompromised state. However, the prognosis for people with HIV infection has dramatically improved with the clinical use of highly active antiretroviral (ARV) therapy (HAART). Clinical trials of ARV agents have demonstrated significant virologic, immunologic and survival benefits associated with the use of protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) containing regimens, when combined with two nucleoside analogues. The incidence of opportunistic infections and hospitalizations has decreased with the use of HAART. In combination with historical data suggesting that a subpopulation of HIV+ transplant recipients tolerate immunosuppression and have allograft survival comparable to that of HIV- transplant recipients, these results indicate that the medical community should readdress HIV infection as a contraindication to transplantation.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Transplantation of hepatitis C-positive livers in hepatitis C-positive patients is equivalent to transplanting hepatitis C-negative livers.

A significant number of patients with end-stage liver disease secondary to hepatitis C die of disease-related complications. Liver transplantation offers the only effective alternative. Unfortunately, organ demand exceeds supply. Consequently, some transplant centers have used hepatitis C virus-positive (HCV(+)) donor livers for HCV(+) recipients. This study reviews the clinical outcome of a large series of HCV(+) recipients of HCV(+) liver allografts and compares their course with that of HCV(+) recipients of HCV-negative (HCV(-)) allografts. The United Network for Organ Sharing Scientific Registry was reviewed for the period from April 1, 1994, to June 30, 1997. All HCV(+) transplant recipients were analyzed. Two groups were identified: a group of HCV(+) recipients of HCV(+) donor livers (n = 96), and a group of HCV(+) recipients of HCV(-) donor livers (n = 2,827). A multivariate logistic regression model was used to determine the odds of graft failure and patient mortality, and unadjusted graft and patient survival were determined using the Kaplan-Meier method. There were no differences in demographic criteria between the groups. A greater percentage of patients with hepatocellular carcinoma received an HCV(+) allograft (8.3% v 3.1%; P =.01). Patient survival showed a significant difference for the HCV(+) group compared with the HCV(-) group (90% v 77%; P =.01). Blood type group A, group B, group O incompatibility was significant, with 4.2% incompatibility in the HCV(+) group and only 1.3% in the HCV(-) group (P =.04). Donor hepatitis C status does not impact on graft or patient survival after liver transplantation for HCV(+) recipients. Their survival was equivalent, if not better, compared with the control group. Using HCV(+) donor livers for transplantation in HCV(+) recipients safely and effectively expands the organ donor pool.

Female↗
PubMed2000

Endotoxin and NO induce MIP-1gamma gene transcription in ANA-1 murine macrophages.

The host response to gram-negative endotoxin is characterized by an influx of inflammatory cells into host tissues, mediated in part by localized production of chemokines. In this study, using subtractive suppression hybridization analysis, we demonstrate that ANA-1 murine macrophages produce the CC chemokine, MIP-1gamma, in response to LPS-mediated NO production. Gene transcription and protein translation are upregulated in the setting of LPS-induced NO synthesis. However, NO alone is a necessary but insufficient cofactor for induction of MIP-1gamma protein expression; an NO-independent LPS signalling pathway is also required. This study suggests a novel mechanism by which NO modulates the host inflammatory response to endotoxin.

Animals↗
PubMed2000

Nitric oxide-dependent ribosomal RNA cleavage is associated with inhibition of ribosomal peptidyl transferase activity in ANA-1 murine macrophages.

NO can regulate specific cellular functions by altering transcriptional programs and protein reactivity. With respect to global cellular processes, NO has also been demonstrated to inhibit total protein synthesis and cell proliferation. The underlying mechanisms are unknown. In a system of ANA-1 murine macrophages, iNOS expression and NO production were induced by exposure to endotoxin (LPS). In selected instances, cells were exposed to an exogenous NO donor, S-nitroso-N-acetylpenicillamine or a substrate inhibitor of NO synthesis. Cellular exposure to NO, from both endogenous and exogenous sources, was associated with a significant time-dependent decrease in total protein synthesis and cell proliferation. Gene transcription was unaltered. In parallel with decreased protein synthesis, cells exhibited a distinctive cleavage pattern of 28S and 18S rRNA that were the result of two distinct cuts in both 28S and 18S rRNA. Total levels of intact 28S rRNA, 18S rRNA, and the composite 60S ribosome were significantly decreased in the setting of cell exposure to NO. Finally, 60S ribosome-associated peptidyl transferase activity, a key enzyme for peptide chain elongation, was also significantly decreased. Our data suggest that NO-mediated cleavage of 28S and 18S rRNA results in decreased 60S ribosome associated peptidyl transferase activity and inhibition of total protein synthesis.

Animals↗
PubMed2000

Use of aerosolized inhaled epoprostenol in the treatment of portopulmonary hypertension.

BACKGROUND: Portopulmonary hypertension is a known complication in the liver transplant candidate. Intravenous epoprostenol has been demonstrated to decrease pulmonary artery pressures and possibly remodel right ventricle geometry. METHODS: In this report, we document the efficacy of inhaled aerosolized epoprostenol in a patient with portopulmonary hypertension. The effect was of rapid onset and offset. RESULTS: After 10 min of delivery, mean pulmonary artery pressure decreased 26%; cardiac output increased by 22%; pulmonary vascular resistance decreased by 42%; and the transpulmonary gradient decreased by 29%. There were no untoward side effects. CONCLUSION: The inhaled route of delivery of epoprostenol is potential alternative for the acute therapy of portpulmonary hypertension.

Acute Disease↗
PubMed2000

Laparoscopic donor nephrectomy increases the supply of living donor kidneys: a center-specific microeconomic analysis.

BACKGROUND: A tenet of microeconomics is that new technology will shift the supply curve to the right. Laparoscopic donor nephrectomy (LDN) is a new technique for removal of living donor kidneys. Centers performing this procedure have noted an increased number of patients presenting for donor evaluation. This has not been previously studied. METHODS: The records of all LDN performed from May 1998 to February 1999 were reviewed. The following variables were examined: sex, age, related vs. unrelated donation, estimated blood loss, i.v. analgesia, length of stay, and time out of work. Donors undergoing traditional open donor nephrectomy during January 1997 to May 1998 served as the control group. A composite cost index was constructed. RESULTS: LDN significantly decreased length of stay, pain, and time out of work; the supply function shifted to the right. Telephone interviews revealed that 47% donated solely because of the LDN procedure. CONCLUSIONS: LDN increases the supply of living donor kidneys.

Adult↗
PubMed2000

Outcome in recipients of dual kidney transplants: an analysis of the dual registry patients.

BACKGROUND: A novel but controversial method to increase the utilization of aged donor kidneys is the transplantation of both kidneys as a dual transplant. Initial single-center reports demonstrated outcomes similar to single kidneys from younger donors. In this report, we compare outcome in recipients of kidneys from donors > or =54 years of age who received a single kidney transplant reported to the United Network for Organ Sharing Scientific Registry versus a dual kidney transplant reported to the Dual Kidney Registry. METHODS: A retrospective analysis was performed, comparing four donor and nine recipient and outcome variables between recipients of a single versus a dual transplant between March 1993 and March 1999. RESULTS: Dual versus single transplants from donors > or =54 years of age have a significantly decreased incidence of delayed graft function, and lower serum creatinines up to 2 years after transplant despite having kidneys from significantly older donors with poorer HLA matching. CONCLUSIONS: Dual kidney transplants improve graft performance and outcome in recipients of kidneys from donors > or =54 years of age.

Aged↗