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Biomedical subjects

D Quan

Publications and source records attributed to D Quan.

At least 19 recordsLinked to original sources
PubMed2006

Recombinant factor VIIa reduces transfusion requirements in liver transplant patients with high MELD scores.

Patients undergoing orthotopic liver transplantation (OLT) often experience significant coagulopathy and remain at risk for excessive blood loss and massive transfusion. The ability of recombinant factor VIIa (rFVIIa) to reduce transfusion requirements during OLT has not been well established. This retrospective study investigates whether rFVIIa reduces transfusion requirements in liver transplant patients with a significantly prolonged prothrombin time (PT) and a model of end-stage liver disease (MELD) score of > 20. Eleven patients received a single dose of rFVIIa (58 +/- 18 microg kg(-1)) at the time of incision. This group was matched with a selected control group that fulfilled all of the inclusion/exclusion criteria. Patient characteristics, pre-operative PT, HCT, PLT and MELD were identical between groups. Prophylactic application of rFVIIA reduced packed red blood cells (3.9 +/- 2.6 versus 6.9 +/- 2.3 U, P = 0.01) and fresh-frozen plasma (FFP) (12.6 +/- 6 versus 19.8 +/- 7 U, P = 0.018) transfusion requirements when compared with the control group. FFP administration in the first 24 h after surgery was also significantly less in the rVIIa group when compared with the control group (388 +/- 385 versus 1225 +/- 701 mL, P = 0.003). Hospital stay following transplantation tended to be shorter in the rFVIIa group, albeit statistical significance was not achieved (11 +/- 7.3 versus 7.9 +/- 2.7, P = 0.2). All but one patient in the control group survived for 30 days after transplantation. In a selected group of patients with prolonged PT and high MELD score, the prophylactic application of rFVIIa at the start of the OLT may reduce perioperative transfusion requirements.

Adult↗
PubMed2005

Use of recombinant factor VIIa in pediatric patients with liver failure and severe coagulopathy.

BACKGROUND: Several reports have suggested a benefit for recombinant Factor VIIa (rFVIIa) in nonhematological conditions, including liver disease and transplantation. However, there are few reports of its use in children with liver failure. Recently, we used rFVIIa in four patients with liver failure and severe coagulopathy with bleeding who demonstrated significant laboratory and clinical improvement following its use with no side effects. PATIENTS AND METHODS: All four patients were hospitalized with liver failure, coagulopathy, and bleeding that was controlled with fresh frozen plasma, platelets, and other therapies, as indicated. Their international normalization ratios (INR) ranged from 1.7 to 5.8 (normal 0.9-1.1). All four patients received rFVIIa for bleeding episodes that were not responding to their usual therapy, for procedures with a high risk of bleeding, or both. The dose of rFVIIa ranged from 0.067 to 0.3 mg/kg. The INR improved to normal or near normal in all four patients. In all cases, bleeding stopped within 10 minutes of receiving the rFVIIa, and there were no complications observed. CONCLUSIONS: rFVIIa provided significant benefit in these children with liver failure and severe coagulopathy, in terms of clinical and laboratory improvement in their bleeding and coagulation profiles. There were no obvious side effects from the rFVIIa. This drug may be an important tool in the treatment of children with liver failure and more study is needed to define the optimal dosing for children.

Blood Coagulation Disorders↗
PubMed2003

Survival after liver transplantation for hepatocellular carcinoma.

BACKGROUND: Selection criteria for patients with hepatocellular carcinoma (HCC) suitable for liver transplantation (LT) include tumor size and number and vascular invasion. There has been a recent trend to expand the transplant criteria for HCC. We reviewed our experience to determine survival following LT based on tumor characteristics. METHODS: A retrospective analysis was performed on 72 patients with HCC who underwent LT between 1985 and July 2002. The Milan criteria were applied for LT candidacy for HCCs that were deemed unresectable from anatomical considerations and/or the severity of underlying cirrhosis. Patients were divided into four groups: group 1: patients with known HCC who satisfied the selection criteria (n = 22); group 2: patients with known HCC that exceeded the criteria (n = 17); group 3: patients with incidental HCC found at pathological examination of the explant (n = 33); group 4: contemporary LT recipients without HCC (n = 935). RESULTS: In the known HCC group, the interval between listing as status 2 and transplantation was 72.2 +/- 133.6 days (median 23 days). Three-year patient survival was 80.2% in group 1, 35.8% in group 2, 63.2% in group 3, and 81.5% in group 4. In group 2 patients, the tumors were significantly larger, had more nodules, and were more often bilobar. In group 3, five (15%) exceeded the criteria mainly because of tumor size and four patients died within 3 years post-LT (three from tumor recurrence). CONCLUSION: Liver transplantation for HCC yields acceptable survival in early-stage tumors, particularly if transplanted soon after listing. Long-term survival was inferior in patients with multiple tumors and tumors that were greater than 5 cm in diameter.

Carcinoma, Hepatocellular↗
PubMed2003

Liver transplantation for primary sclerosing cholangitis.

UNLABELLED: Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease that progresses to end-stage liver disease. This report is a retrospective analysis of a Canadian centre experience with liver transplantation (LT) for PSC. Of 1107 LTs performed between 1984 and 2002, 132 were performed on 111 patients with PSC. Patient survival at 1, 3, 5, and 10 years was 84.5%, 84.5%, 83.4%, and 68.9%, respectively. Graft survival at 1, 3, 5, and 10 years was 80.8%, 79.8%, 72.7%, and 55.3%. These were not significantly different from overall patient survival (P =.91) or graft survival (P =.28) in non-PSC patients transplanted over the same time period. Early mortality was predominantly related to primary nonfunction and multi-organ failure; late mortality was predominantly related to malignancy. No patient with known cholangiocarcinoma (CCA) underwent LT, but three patients had an incidental CCA noted on explant pathology. All three died of widespread metastatic disease (10.8, 38.0, and 39.8 months after LT). Nineteen patients lost their primary grafts requiring retransplantation, and two of these patients required a third transplant. Recurrent PSC was detected in six patients and suspected in another six. Four patients have been retransplanted for recurrent PSC. Chronic rejection was detected in nine patients. Eight have required retransplantation. The incidence of biliary complications was 16.2%. CONCLUSIONS: LT is effective therapy for PSC. Patient and graft survival is comparable to that seen in patients transplanted for indications other than PSC, but long-term graft survival may be lower. Recurrent PSC and chronic rejection are the major determinants of graft loss.

Actuarial Analysis↗
PubMed2001

Pharmacokinetics of the R- and S-enantiomers of oxybutynin and N-desethyloxybutynin following oral and transdermal administration of the racemate in healthy volunteers.

PURPOSE: To characterize the enantiomers of oxybutynin (OXY) and N-desethyloxybutynin (DEO) following transdermal and oral administration. METHODS: OXY was administered either as a single transdermal system over a 96 h wear period or as a single 5 mg immediate-release tablet to 18 healthy male and female subjects in a randomized, open-label, two-way crossover design. Blood samples were collected for 108 h after application of the transdermal system and for 6 h after oral administration. Plasma concentrations of the R- and S-enantiomers of OXY and DEO were assayed by LC-MS/MS. Enantiomer in vitro skin flux was evaluated using human cadaver skin. RESULTS: In vitro skin flux studies demonstrated equal absorption of R and S- OXY. Plasma concentrations and pharmacokinetic parameters of the R-enantiomers of OXY and DEO were slightly lower than the S-enantiomers following transdermal OXY. The relative AUC values were S-OXY>S-DEO>R-OXY>R-DEO. The AUC ratios of DEO/ OXY were less than 1 for both the R- and S- enantiomers. Following oral dosing, plasma DEO concentrations greatly exceeded OXY resulting in relative AUC values of R-DEO>S-DEO>S-OXY>R-OXY. The mean AUC ratios of S- and R-DEO/OXY were 3.25 and 8.93, respectively. CONCLUSIONS: Stereoselective metabolism of OXY was evident following both transdermal and oral administration of OXY. The reduced pre-systemic metabolism of transdermally administered OXY compared to oral administration resulted in not only significantly lower DEO plasma concentrations, but also a different metabolite pattern. The differences between R-OXY and R-DEO following the two routes of administration support the potential for comparable clinical efficacy and reduced anticholinergic side-effects with transdermal treatment.

Administration, Cutaneous↗
PubMed2000

Severe liver injury after treatment with the leukotriene receptor antagonist zafirlukast.

BACKGROUND: In registration trials, zafirlukast, an asthma medication, caused asymptomatic elevated aminotransferase levels in up to 5% of participants. Until now, however, no cases of severe hepatitis attributed to zafirlukast have been reported. OBJECTIVE: To report the clinical characteristics of three patients with severe hepatitis due to zafirlukast. DESIGN: Case report. SETTING: One community hospital and two university hospitals. PATIENTS: Three middle-aged women taking zafirlukast, 20 mg twice per day. INTERVENTION: Discontinuation of zafirlukast therapy in three patients, steroid therapy in two patients, and orthotopic liver transplantation in one patient. MEASUREMENTS: Serum aminotransferase and bilirubin levels, standard blood tests for causes of hepatitis other than drug toxicity, and liver biopsy in two patients. RESULTS: Patient 1 recovered spontaneously, had a severe relapse after inadvertent rechallenge with the medication, and ultimately made a complete recovery. Patient 2 developed subfulminant hepatic failure and required liver transplantation. Patient 3 developed severe hepatitis that improved after treatment with corticosteroids. Liver tissue was available from two patients and showed histologic changes commonly associated with drug reactions. CONCLUSION: Patients receiving zafirlukast may develop severe liver injury and should be observed for signs and symptoms of hepatitis.

Adrenal Cortex Hormones↗
PubMed2000

Experience with daclizumab in liver transplantation: renal transplant dosing without calcineurin inhibitors is insufficient to prevent acute rejection in liver transplantation.

BACKGROUND: Daclizumab is a monoclonal antibody directed against the alpha chain of the interleukin 2 receptor. We review our experience with the use of daclizumab in liver transplant recipients. METHODS: Thirty-two patients were given daclizumab as induction therapy in the setting of hepatic transplantation. Seven of these patients were enrolled in a pilot study to determine the efficacy of daclizumab in conjunction with corticosteroids and mycophenolate mofetil without the initial use of calcineurin inhibitors (CI). The remaining 25 patients received daclizumab, mycophenolate mofetil, and steroids, with the institution of CI generally within the first postoperative week. The majority of these patients (n = 17) had some degree of renal insufficiency. RESULTS: The pilot study was halted after the first seven patients were enrolled because of an unacceptably high rate of rejection (7/7 = 100%). The patients outside of this pilot study, however, had a much lower rate of rejection (36%). The incidence and severity of rejection correlated with the delay in institution of CI. The described dosing schedule resulted in subtherapeutic daclizumab levels in liver transplant recipients. CONCLUSIONS: Daclizumab used in liver transplant recipients without any CI was ineffective and can potentially lead to steroid-resistant rejection. The dosing regimen used in renal transplant recipients is most likely insufficient for liver transplant patients. However, daclizumab can be used safely in patients with preexisting or postoperative renal dysfunction in conjunction with low doses of CI given within the first week postoperatively.

Adolescent↗
PubMed2000

Experience with the use of sirolimus in liver transplantation--use in patients for whom calcineurin inhibitors are contraindicated.

Sirolimus (SRL) provides effective immunosuppression for kidney transplantation and may be useful in patients with delayed allograft function after kidney transplantation. We review our experience with SRL in liver transplant recipients for whom calcineurin inhibitors are undesirable. Fourteen patients with renal insufficiency or acute mental status impairment were administered SRL after liver transplantation (5- to 10-mg load, 1 to 4 mg/d). Immunosuppression also consisted of mycophenolate mofetil and corticosteroids. On resolution of neurological or renal dysfunction (return to baseline mental status or serum creatinine level), tacrolimus (TAC) therapy was initiated. Twelve patients received primary transplants, 1 patient received a combined liver-kidney transplant, and 1 patient received a third transplant. Follow-up was 2 to 7 months. Calcineurin inhibitors were initially withheld in 9 patients, and therapy was aborted because of toxicity in the remaining 5 patients. Mean times to the initiation of SRL and TAC therapy were 5.4 +/- 4.6 and 26.8 +/- 24.4 days, respectively. Serum trough levels of SRL did not correlate with dose or other patient variables. Two patients died after prolonged pretransplantation hospital courses in the intensive care unit. Six patients experienced acute rejection, but only 1 patient required antilymphocyte therapy. Serum creatinine levels at the start of SRL therapy were 2.2 +/- 1.1 and 1.2 +/- 0.6 mg/dL at 3 months. All 3 patients with neurological indications for SRL had a return to their baseline mental status. All patients had improved liver function chemistry test results and prothrombin times. No patients developed leukopenia or thrombocytopenia. SRL is safe after liver transplantation in patients with acute neurological or renal impairment. SRL is an attractive alternative when calcineurin inhibitors are undesirable, but serum trough levels of SRL should be monitored. A prospective randomized study of an SRL-based calcineurin inhibitor-avoiding regimen compared with standard therapy in patients with renal insufficiency will further evaluate the role for SRL in liver transplantation.

Adult↗
PubMed1999

Transient MRI enhancement in a patient with seizures and previously resected glioma: use of MRS.

A 35-year-old man presented with partial seizures 10 years after resection of a left-sided glioblastoma multiforme. At the old operative site MRI demonstrated extensive cortical and white matter gadolinium enhancement, and PET showed hypermetabolism. Biopsy of the area was postponed when MRS showed a normal biochemical spectrum. MRI and PET abnormalities resolved after control of the seizures. MRS is noninvasive and can provide essential information in the management of patients with seizures and previously treated cerebral neoplasms.

Adult↗
PubMed1999

[Clinical observation on radio- or chemotherapy plus Traditional Chinese medicine in treating brain metastatic tumor].

OBJECTIVE: To observe the clinical efficacy of radio- or chemotherapy plus traditional Chinese medicine (TCM) by Syndrome Differentiation in treating brain metastatic tumor. METHODS: Forty-one patients were randomized into four groups: Group A treated with chemotherapy plus TCM, Group B with radiotherapy plus TCM, Group C with chemotherapy alone and Group D with radiotherapy alone. The efficacies of the four groups were compared. RESULTS: The short-term response rate, living quality, 1-, 2-, 3- and 4-year survival rate, median survival period and immunity of the Group A and B were significantly higher than those of the Group C and D (P < 0.05). CONCLUSION: Radio- or chemotherapy plus TCM by Syndrome Differentiation has the effect of tumor growth inhibition, survival period extension and living quality enhancement in treating brain metastases.

Adult↗
PubMed1999

[Biocompatibility of self-designed absorbable hydroxyapatite/poly (DL-lactide) composites].

The biocompatibility of self-designed hydroxyapatite/poly (DL-lactide) rods was evaluated both in vitro and in vivo including Ames test, micronucleus test, acute and subacute systemic toxicity test, hemolysis test, hemopexis test and long-term muscle and bone implant test. The results indicate that the material has no toxicity, no stimulation and mutation, and it does not cause hemolysis and hemopexis. Consequently, the biocompatibility of the composite was good.

Absorbable Implants↗
PubMed1998

Seroprevalence of Taenia solium cysticercosis in pigs in a rural community of Honduras.

Several retrospective studies have shown that human Taenia solium cysticercosis is endemic in Honduras, but very few reports of porcine cysticercosis in rural communities have been published. To determine the local prevalence of this disease in pigs, a serological survey has been undertaken in a rural community, Salamá, in the Department of Olancho in central Honduras. Eighty-five families raising pigs in the community were randomly selected and sera were obtained from pigs older than one month of age. The sera were examined by the enzyme-linked immunoelectrotransfer blot assay (EITB). Of 192 porcine sera, 27.1% (52) were positive by the EITB. Seropositivity did not correlate with age and sex by statistical analysis. With respect to the number and the frequency of recognition of the seven diagnostic glycoprotein bands in the EITB, 67.3% of the positive serum specimens recognized only one band and 80.8% of them recognized GP42-39. Since recognition of GP42-39 has been reported as a characteristic of late infection, these results suggest that most of the seropositive pigs were in the late stage of infection (more than 5-8 weeks postinfection). It seems that pigs in this community may be infected with this parasite soon after the birth and be in a hyperendemic steady state. In view of a high prevalence of antibodies to T. solium in pigs or characteristics of the antigen detected by the EITB, the infection pressure of T. solium appears to be very high in this community. This is probably the case in most of the communities in Honduras.

Animals↗
PubMed1998

Human in vivo and in vitro hydroquinone topical bioavailability, metabolism, and disposition.

Hydroquinone is a ubiquitous chemical readily available as monographed in cosmetic and nonprescription forms for skin lightening, and is an important industrial chemical. The in vivo bioavailability for 24-h application in humans was 45.3+/-11.2% of dose from a 2% cream formulation containing [14C]hydroquinone, with the majority of radioactivity excreted in the first 24 h. Timed skin wash and skin tape-stripping sequences showed a rapid and continuous movement of hydroquinone into the stratum corneum of human volunteers. Plasma levels taken both ipsilateral and contralateral to the topical dosing site contained radioactivity at the first 0.5-h sampling time. Peak plasma radioactivity was at 4 h in the 8-h blood sampling period. In vitro percutaneous absorption with fresh viable human skin gave a bioavailability of 43.3% of dose, and flux was calculated at 2.85 microg/cm2/h. In vitro, some of the skin samples were pretreated with the metabolic inhibitor sodium azide, which had no effect on percutaneous absorption. Receptor fluid accumulations and 24-h skin samples were extracted and the extracts subjected to thin-layer chromatography (TLC). Control [14C]hydroquinone extraction and TLC had one radioactivity peak, hydroquinone. Receptor fluid and skin extraction had a second peak with the same Rf as benzoquinone, which was decreased with azide treatment. No other peaks were found. Ethyl acetate extraction of urine from the in vivo study showed all radioactivity to be only water-soluble, free hydroquinone released following glucuronidase treatment. Risk assessment should not only involve the bioavailability of intact topical hydroquinone, but also consider phase I and phase II metabolism in both humans and any animal for which toxicity potential was assessed.

Administration, Topical↗
PubMed1998

Case of the month: March 1998--48 year old man with back pain and weakness.

A 48 year old man with long history of end stage renal disease (ESRD) and secondary hyperparathyroidism presented with back pain and incontinence. MRI and CT showed T2 expansion with bony destruction and spinal cord compression. Other vertebral bodies showed destructive lesions as well. Microscopic examination showed a brown tumor composed of multinucleated giant cells and bone uninvolved by tumor showed "tunneling" resorption. Brown tumors are an exaggerated form of "local" osteitis fibrosa cystica in patients with ESRD and secondary hyperparathyroidism, but spinal cord compression is rare.

Back Pain↗
PubMed1997

Electron resonance studies on the influence of anionic surfactants on human skin.

BACKGROUND: When skin is exposed to chemicals, raw materials interact with the lipid structure of the stratum corneum. At least two types of disorders can be distinguished--that of alkyl chains inside one lipid bilayer and that of lipid layer arrangement. Electron spin resonance (ESR) spectroscopy of a nitroxide spin label is a valuable method in the study of biological membranes. OBJECTIVE: These experiments define the effect of anionic surfactants on the lipid bilayer of human stratum corneum. METHODS: 5-Doxyl stearic acid (5-DSA) was used as the spin label. Sodium lauryl sulfate (SLS) and sodium lauroyl-L-glutamate (SLG) were the anionic surfactants studied. ESR spectrum measurements of surfactant-treated stratum corneum were performed and order parameters calculated. RESULTS: 1% of SLS leads to an obvious change in ESR spectra--from strongly to weakly immobilized spectra. The molecular motion of spin labels (5-DSA) in SLS-treated stratum corneum is different from that of spin labels in the untreated stratum corneum. The ESR spectra suggest that SLS affects the spin label binding to the lipid membrane and causes an increase in the mobility of bilayers. On the other hand, there were minimal changes in ESR spectra of 1% of SLG-treated stratum corneum. An increase in fluidity of skin lipid bilayers suggests a decrease in the skin barrier function. CONCLUSION: ESR may provide a facile and robust method to define the subclinical irritancy potential of anionic surfactants and other materials.

Anions↗
PubMed1996

Pattern of liver, kidney, heart, and intestine allograft rejection in different mouse strain combinations.

With advances in microsurgery and molecular biology, the mouse model for organ transplantation has become increasingly popular. However, knowledge about these models is limited, as only a small number of centers have experience with murine models. In this study, we compared the rejection pattern after liver, kidney, heart, and small bowel transplantation in the three different mouse strain combinations: (1) C57BL/6 (H2b)-->BALB/c (H2d), (2) BALB/c (H2d)-->CBA (H2k), and (3) C57BL/6-->C3H/HeN (H2k). Our study demonstrated that mouse allograft survival varies depending on the organ graft and on the donor-recipient strain combinations. The majority of liver allografts were spontaneously accepted despite complete MHC disparity. A mixed pattern of acute rejection and acceptance occurred in kidney recipients depending on the donor-recipient strain combination. All the heart grafts developed rejection and all the intestinal grafts were rapidly rejected with no spontaneous acceptance. The criteria for rejection, the potential applications, and the limitations of each model are discussed. The models described in this article provide a number of useful choices for organ transplantation research.

Animals↗