Increased Liver Function Tests Research Articles

Tinzaparin prophylaxis in brain tumor patients

12506 Background: Thromboembolic disease is the second leading cause of death in brain tumor patients. Various studies have documented a 20–40% risk of deep vein thrombosis and / or pulmonary embolus in brain tumor patients. When used as prophylaxis, Tinzaparin, a low molecular weight heparin with factor Xa activity, has a low complication rate and low incidence of bleeding complications. With the anticipated benefit exceeding any risk, prophylaxis with Tinzaparin may be safe and effective. Methods: A phase II trial of prophylactic tinzaparin for newly diagnosed brain tumor patients has completed accrual at 40 patients. A fixed daily dose of 4500 IU subcutaneous tinzaparin was given beginning a minimum of 48 hours post-operatively and a maximum of 4 weeks post-operatively. Patients consented to take tinzaparin daily for 12 months. Weekly blood counts were monitored during chemotherapy cycles. Tinzaparin was held if platelet count was <50,000 and resumed once the platelets were >100,000. Tinzaparin was discontinued in patients who began treatment with avastin. Results: Of 40 patients, 7 remain on treatment. Patients have taken tinzaparin for 4–52 weeks with a median of 21 weeks. One of the patients developed a grade 3 CNS hemorrhage and one had a grade 1 CNS hemorrhage, necessitating cessation of the tinzaparin, there have been no grade 4 or 5 CNS hemorrhages or treatment associated mortality. No patients developed = grade 2 systemic hemorrhages. One patient developed a deep venous thrombosis while taking tinzaparin, and three patients developed thromboembolic complications while off tinzaparin secondary to thrombocytopenia. One patient was taken off study for increased liver function tests, possibly secondary to tinzaparin. Conclusions: Thus far, daily prophylactic tinzaparin has proven safe and effective in decreasing the incidence of thromboembolic disease in brain tumor patients. We plan a phase III study upon the safe completion of the last 7 patients on this phase II study. No significant financial relationships to disclose.

Treatment with Pegylated Interferon-Alfa-2A (PEG-IFN-α-2A; PEGASYS™) for Patients with Essential Thrombocythemia (ET) and Polycythemia Vera (PV).

Patients (pts) with high-risk Philadelphia chromosome-negative myeloproliferative disorders (MPDs) are customarily treated with cytoreductive agents such as recombinant human interferon-alpha (IFN-α), hydroxyurea (HU), and anagrelide (AG). Despite the significant activity of IFN-α in MPDs, responses have been frequently limited by poor tolerance and inconvenient dosing schedules. PEG-IFN-α is formulated by covalently attaching polymers of ethylene glycol to the native IFN-α molecule, which results in increased serum half-life, decreased renal excretion, thus allowing for weekly administration while maintaining acceptable toxicity profile. Based on the superior pharmacokinetic and pharmacodynamic profile of PEG-IFN-α relative to IFN-α we designed a phase II study of subcutaneous (sc) PEG-IFN-α-2a (Pegasys™) for pts with ET and PV. A total of 23 pts have been enrolled so far (13 ET, 10 PV). First 3 pts received PEG-IFN-α-2a at 450mcg weekly but experienced toxicity and had to reduce the dose; next 3 pts started at 360mcg weekly and again had to reduce the dose due to toxicity; last 17 pts started at 270mcg weekly and tolerated therapy well. Dose modifications of 90 mcg are allowed according to response or toxicity. Median age is 54 years (range, 23 to 73), time from diagnosis to PEG-IFN-α-2a therapy 64 months (range, 1 to 282), Hb 13.5 g/dL (range, 8.9 to 18.5), WBC 5×109/L, (range, 4.3 to 49), platelets 592×109/L (range, 298 to 1000). All pts had prior therapies (median 2, range 1–6), including HU (n=17), AG (n=13), IFN-α (n=6: 4 oral and 2 sc), imatinib mesylate (n=2) and others (n=3). In addition, 8 PV pts had received phlebotomies. The JAK2 V617F mutation was detected in 6 (46%) of 13 ET pts and in 9 (90%) of 10 PV pts. All pts had diploid cytogenetics. After a median follow-up of 6 months (range, 1 to 15), 11 of 13 (85%) ET pts have achieved a complete response (platelets <440×109/L, off HU and AG, in the absence of thromboembolic events); 2 pts without response received less than 2 months of therapy so far. Six of 10 (60%) PV pts achieved complete remission (Hb <15 g/dL, off HU and AG, no phlebotomy, with disappearance of splenomegaly), 3 (30%) achieved partial response (no phlebotomy, off HU and AG, but still palpable spleen), and 1 have not responded so far (less than 3 months on the therapy), for overall response of 90%. The median time to response was 1.5 months (range, 0.5 to 5.6). While the first 6 pts on the study, that received high PEG-IFN-α-2a dose (450 or 360mcg weekly), experienced grade 3 toxicity, among last 17 pts that received 270mcg weekly, there were only 5 cases of grade 3 toxicity (anemia, increased liver function tests, and neutropenia x3) requiring dose reduction. However, to preserve pts quality of life, the dose of PEG-IFN-α-2a was also reduced for the persistent grade 2 toxicity (> 2 weeks). Overall, 17 pts (74%) reduced the dose so far, while 6 pts (all on 270mcg weekly) remain at the same initial dose. Only 2 pts (1 ET, 1 PV) discontinued therapy, due to retinal infiltrates and depression after 8 and 6 months on therapy, respectively. In summary, therapy with PEG-IFN-α-2a has an acceptable toxicity profile and significant activity in pts with ET and PV. Updated clinical and molecular results will be presented.

Divalproex utility in bipolar disorder with co-occurring cocaine dependence: A pilot study

Objective The aim of this open-label pilot study was to evaluate the utility of divalproex in decreasing cocaine use and stabilizing mood symptoms among patients with bipolar disorder with comorbid cocaine dependence. Method Fifteen patients enrolled in the study and seven met final inclusion criteria of DSM-IV/SCID diagnoses of bipolar I disorder and comorbid cocaine dependence with active cocaine use. Patients were started on open-label divalproex. After stabilization on divalproex sodium, weekly assessments were undertaken for 8 weeks. Subjects also attended dual recovery counseling. Results The results revealed significant improvement on % cocaine abstinent days, dollars spent on cocaine, ASI's drug use severity index, % alcohol abstinent days, drinks per drinking day, marijuana use and cigarettes smoking. They also had significant improvement on manic, depressive, and sleep symptoms and on functioning. There were no reported adverse events or increases in liver function tests. Conclusion The results of this open-label study point to the potential utility of divalproex in patients with bipolar disorder and primary cocaine dependence. Double-blind, placebo-controlled studies to fully evaluate the efficacy of divalproex in this high risk clinical population are warranted.

Tinzaparin prophylaxis against thromboembolic complications in brain tumor patients

1539 Background: Thromboembolic complications are common in brain tumor patients, contribute to the morbidity and mortality and complicate treatment. Twenty to 40% of brain tumor patients develop a deep venous thrombosis and/or pulmonary embolus during their course. Thromboembolic complications are the second leading cause of death in brain tumor patients. One of the low molecular weight heparins, tinzaparin, has increased factor Xa activity as opposed to thrombin inhibition, which may improve the therapeutic:toxicity ratio. Methods: We report a phase II trial of prophylactic tinzaparin for newly diagnosed brain tumor patients. Twenty-seven of the planned 40 patients have been accrued. Patients received daily tinzaparin at a fixed dose of 4500 IU subcutaneously beginning a minimum of 48 hours post-operatively and a maximum of 4 weeks post-operatively. Patients were scheduled to receive tinzaparin for 12 months. During chemotherapy cycles, the blood counts were monitored weekly. If the platelet count was &lt;50,000, the tinzaparin was held until the platelets were &gt;100,000. Results: One of the patients developed a grade 3 CNS hemorrhage, necessitating cessation of the tinzaparin, there have been no grade 4 or 5 CNS hemorrhages or treatment associated mortality. Also, there have been no ≥ grade 2 systemic hemorrhages. One patient developed a deep venous thrombosis while taking tinzaparin, and three patients developed thromboembolic complications while off tinzaparin secondary to thrombocytopenia. One patient was taken off study for increased liver function tests, possibly secondary to tinzaparin. The patients have taken the tinzaparin for 4–52 weeks, with a median of 18 weeks. Conclusions: Tinzaparin at a fixed prophylactic dose is safe and may decrease the incidence of thromboembolic complications in brain tumor patients. If the completed phase II study yields similar results, a phase III trial is warranted. No significant financial relationships to disclose.

OI-B-1Observed changes in liver-associated enzymes during long term inpatient Phase 1 clinical trials

BACKGROUND To characterize the alterations of liver function tests (LFTs), aspartate- (AST) and alanine transaminase (ALT) in healthy “normal” (HN) and cocaine experienced (actively using cocaine preadmission; CE) adults participating in long term inpatient clinical trials. METHODS LFT values from screening, admission, inpatient and inpatient discharge from 112 male and female volunteers, aged 18 to 45 years, with body mass index (BMI) from 20 to 30 kg/m2, participating in 3 inpatient Phase 1 trials were analyzed. 90 subjects received active drugs, and 22 subjects received matched placebo. 47 subjects were HN and 65 were CE. ANOVA method was applied to determine significant differences of various factors. RESULTS Both HN and CE subjects had an increase in LFTs during the studies. Gender, BMI, treatment (placebo or drug) did not predict LFTs changes (both for absolute LFTs values as well as differences (ΔALT, ΔAST) between screening day and during the inpatient period. CE study volunteers were found to have significantly higher AST and ALT values than HN volunteers (p< 0.05). All the subjects with abnormal LFTs were CE; 35.7% of them received placebo. CONCLUSIONS Despite normal LFT values at screening, most subjects demonstrated an increase in the ALT level even on placebo. For CE subjects, ΔALT and ΔAST were significantly higher than for HN subjects. The potential to obscure important signals for hepatotoxicity appears to be higher in the CE study population. Clinical Pharmacology & Therapeutics (2005) 79, P2–P2; doi: 10.1016/j.clpt.2005.12.006

Serum Laboratory Values Following Uncomplicated Laparoscopic Urological Surgery

Presentation of complications following laparoscopic surgery can be different from corresponding open surgical complications. While leukopenia has been identified as a common finding in patients with unrecognized bowel injury following laparoscopy, to our knowledge no study has determined if leukopenia or other serum abnormalities are unique to patients with laparoscopic complications. We present an analysis of postoperative laboratory values from patients after uncomplicated urological laparoscopic surgery. A retrospective review of 50 adult patients who had previously undergone uncomplicated laparoscopic urological procedures was performed. Exclusion criteria were preexisting hematological, immune, liver or pancreatic disorders. Common serum laboratory values were measured on postoperative day 1. All values for bilirubin were within normal limits. Of patients undergoing a right side renal procedure, 10 of 16 (63%) had a postoperative increase in liver function tests. Amylase or lipase was increased in a total of 12 (24%) patients. Patients undergoing laparoscopic prostatectomy accounted for the majority of this group with 9 of 21 (43%) patients having increased amylase or lipase. Finally, there were no patients with immediate postoperative leukopenia. Following uncomplicated laparoscopic procedures, bilirubin levels are rarely affected, amylase and lipase may be acutely increased following laparoscopic prostatectomy, and white blood count is commonly increased. While 16 (36%) patients had postoperative leukocytosis, leukopenia was not detected after uncomplicated laparoscopic urological surgery and should alert the surgeon to the possibility of an undiagnosed complication.

Comparative side effects of yttrium-90 based intra-arterial brachytherapy

3760 Background: Hepatic carcinoma as well as metastases are difficult to treat even though the chemotherapy regimens have significantly advanced over the last few years. More effort is now being made to treat these patients with loco-regional therapies to include the use of intra-arterially directed brachytherapy using yttrium-90 containing particles. There are two particle based therapies, a glass bead based and one that is plastic bead based. Methods: The first 50 patients using each of these therapies were compared to determine the side effects and complications. Each patient was followed during the procedure, the immediate post operative course until the side effects resolved. Results: The plastic bead therapy patients uniformly had the post embolization syndrome of nausea, vomiting, fever, leukocytosis, and increased liver function tests. These symptoms lasted 2–14 days (mean 4). Two patients had gastric ulcer formation due to the particles being embolized into accessory left gastric arteries. The glass bead therapy patients had fewer post embolization syndrome effects but more effects due to gravity since these beads are denser than blood, 14/50 patients had noticable overtreatment of posterior portions of the liver infused . There were more gastric ulcers present, 8/50. Conclusions: This is a promising therapy and the centers applying this treatment should be aware that the side effects and complications seen are specific to the agent utilized. No significant financial relationships to disclose.

Comparative side effects of yttrium-90 based intra-arterial brachytherapy

3760 Background: Hepatic carcinoma as well as metastases are difficult to treat even though the chemotherapy regimens have significantly advanced over the last few years. More effort is now being made to treat these patients with loco-regional therapies to include the use of intra-arterially directed brachytherapy using yttrium-90 containing particles. There are two particle based therapies, a glass bead based and one that is plastic bead based. Methods: The first 50 patients using each of these therapies were compared to determine the side effects and complications. Each patient was followed during the procedure, the immediate post operative course until the side effects resolved. Results: The plastic bead therapy patients uniformly had the post embolization syndrome of nausea, vomiting, fever, leukocytosis, and increased liver function tests. These symptoms lasted 2–14 days (mean 4). Two patients had gastric ulcer formation due to the particles being embolized into accessory left gastric arteries. The glass bead therapy patients had fewer post embolization syndrome effects but more effects due to gravity since these beads are denser than blood, 14/50 patients had noticable overtreatment of posterior portions of the liver infused . There were more gastric ulcers present, 8/50. Conclusions: This is a promising therapy and the centers applying this treatment should be aware that the side effects and complications seen are specific to the agent utilized. No significant financial relationships to disclose.

Rapid steroid withdrawal in hepatitis C virus-positive kidney transplant recipients.

The effects of rapid steroid withdrawal (SW) on kidney transplantation (KT) outcome were investigated in 12 HCV+ patients in a prospective cohort study. These results were compared with 17 HCV+ patients who received KT in the prior 2 yr and treated with a standard prednisone taper protocol. SW patients received only 6 d of steroid treatment after transplantation. Eleven received Thymoglobulin and one Basiliximab induction treatment along with a calcineurin inhibitor and mycophenolate mofetil. Patient and graft survival was 92% in SW group (median follow-up 12 months, range 6-17), and 92 and 82% in the historic control group respectively (median follow-up 21 months, range 11-27). In the SW and control group, acute rejection rates were 9 and 18%, and mean creatinine levels at last follow-up 1.30 +/- 0.36 and 1.68 +/- 0.58 mg/dL respectively. Only two SW patients had an increase in liver function tests during follow-up (18%), compared with six patients in the control group (43%). This study demonstrates that rapid SW is safe for HCV+ KT recipients, without an increase in acute rejection episodes or liver function abnormalities in the short term.

Indicated Cholangiography in Patients Operated on by Routine versus Selective Cholangiographers

Intraoperative cholangiography (IOC) remains a subject of much debate among laparoscopic surgeons. When IOC is indicated, the surgeon's preference for routine cholangiography (RC) or selective cholangiography (SC) may have an impact on the outcome of IOC and cholecystectomy. Hereafter, we present our experience with cholangiography in patients with clear indications for IOC when operated on by surgeons favoring SC versus RC. Between January 1, 1999, and December 1, 2000, 389 patients underwent laparoscopic cholecystectomy at Loyola University Medical Center. One hundred fifty-one patients had indication for IOC (jaundice, pancreatitis, increased liver function tests (LFTs), abnormal anatomy, ductal dilatation, or ductal stones identified on preoperative ultrasound), and they constitute the sample for this study. The results of IOC and subsequent outcome of cholecystectomy were reviewed using the electronic medical database. Thirty-nine patients were operated on by 2 surgeons favoring RC and 112 by 12 favoring SC. Patient demographics were similar in both groups. Only 30 (27%) of the SC group had attempted IOC with 28 successful IOCs (25% of all patients). In contrast, 38 (97%) of the RC group had successful IOC, which was significantly higher than the SC group (P < 0.0001 by chi2 test). Adverse events included conversions to open, postoperative endoscopic retrograde cholangiopancreatography, bile leak, repeat operative intervention, pancreatitis, elevated LFTs, intra-abdominal and wound infection, prolonged emesis, and persistent abdominal pain. Two (5%) adverse events occurred in the RC group, which was significantly less than the 33 (30%) adverse events in the SC group (P = 0.002 by chi2 test). Conversions to open were significantly less in the RC group, with no conversions in the RC group and 20 (18%) in the SC group (P = 0.005). There were no mortalities in this series. In a univariate analysis, age and gender did not correlate with increased risk of complications. In conclusion, surgeons who perform SC are less likely to attempt IOC even when IOC is indicated. More conversions to open and more adverse events occurred following cholecystectomy by those favoring SC. Our study further supports routine cholangiography during laparoscopic cholecystectomy.

Changes in liver enzymes after clinical islet transplantation.

Clinical islet transplantation (ITx) shows insulin independence with adequate metabolic control in patients with type 1 diabetes. The aim of this study was to characterize the pattern of elevation in liver enzymes observed after ITx and to investigate any correlation between these elevations and graft characteristics or graft functional outcome. Eighty-four consecutive ITx procedures were performed in 42 recipients. Liver function tests (LFT) were assessed during the first 40 days posttransplant. LFT elevated greater than or equal to 2.5 times above the upper limit of normal (ULN) were considered relevant. In 54% of the transplants, the aspartate aminotransferase (AST) increased by more than 2.5 times above ULN. A 5-fold increase in AST was observed in 27% of the procedures. The highest AST levels were observed after the first ITx. AST for all transplants peaked at 7+/-0.5 days at a value of 162+/-23 U/L (P<0.001, compared with the pretransplant values). Changes in alanine aminotransferase were similar to AST. Alkaline phosphatase increased more than 2-fold above ULN in 12% of the procedures. LFT normalized in 90% of the recipients within 4 weeks posttransplant. The remaining 10% normalized within 2 months after ITx. Graft characteristics and graft function were not significantly different when comparing LFT with greater than 5-fold versus less than 2.5-fold increase above ULN. The mean bilirubin remained within the normal range. After intraportal ITx, a significant increase in LFT levels was noticed in more than 50% of the procedures. These levels normalized spontaneously in 90% of the recipients within 4 weeks. No correlation between the increase in LFT and graft characteristics or graft function was found.

Concurrent infectious mononucleosis and measles: a potentially life-threatening association sharing underlying immunodeficiency

We report lethal interstitial pneumonia in an 18-year-old young man with measles infection following recent infectious mononucleosis. We speculate that the documented T cell immune impairment caused by the concurrent Epstein-Barr and measles viral infections (as expressed by a proportionately low CD4+ lymphocyte count) was responsible for the complicated clinical course and unfavorable outcome.

Response

The medical and nutritional management of chronic graft-versus-host disease (GVHD), a major and serious complication following allogeneic hematopoietic stem cell transplantation, is very challenging. The disease’s clinical presentation commonly involves multiple organs, is persistent by nature, requires numerous pharmacological treatments, and is associated with a high rate of infections. Chronic GVHD usually presents 3 to 6 months post-transplant and the reported incidence varies from 21% to 78% ( (1) Ustan C. Arslan O. Beksac M. Koc H. Gurman G. Ozcelik T. Yilmaz B. Ilhan O. Akan H. Ozcan M. Demirer T. Uysal A. Konuk N. Arat M. Dilek I. Celebi H. Coskun H.S. A retrospective comparison of allogeneic peripheral blood stem cell and bone marrow transplantation results from a single center a focus on the incidence of graft-vs-host disease and relapse. Biol Blood Marrow Transplant. 1999; 5: 28-35 Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar , (2) Solano C. Martinez C. Brunet S. Tomas J.F. Urbano-Ispizua A. Zuazu J. Ojeda E. Bargay J. Moraleda J.M. Bailen A. Sierra J. Garcia-Conde J. Rozman C. Chronic graft-versus-host disease after allogeneic peripheral blood progenitor cell or bone marrow transplantation from matched related donors. A case-control study. Spanish Group of Allo-PBT. Bone Marrow Transplant. 1998; 22: 1129-1135 Crossref PubMed Scopus (64) Google Scholar , (3) Brown R.A. Adkins D. Khoury H. Vij R. Goodnough L.T. Shenoy S. DiPersio J.F. Long-term follow-up of high-risk allogeneic peripheral-blood stem-cell transplant recipients graft-versus-host disease and transplant-related mortality. J Clin Oncol. 1999; 17: 806-812 PubMed Google Scholar ). An increased incidence of chronic GVHD is associated with the following: history of > grade II acute GVHD, female donor to male recipient (due to previous donor pregnancies), increasing age of donor and recipient, donor lymphocyte infusion, and use of blood stem cells versus bone marrow ( (4) Atkinson K. Horowitz M.M. Gale R.P. van Bekkum D.W. Gluckman E. Good R.A. Jacobsen N. Kolb H.J. Rim A.A. Ringdén O. Rozman C. Sobocinski K.A. Zwaan F.E. Bortin M.M. Risk factors for chronic graft-versus-host disease after HLA-identical sibling bone marrow transplantation. Blood. 1990; 75: 2459-2464 PubMed Google Scholar ). Chronic GVHD is described as an autoimmune-like disease and graded as limited (localized skin involvement or single organ involvement) or extensive (generalized skin involvement or multiple organ involvement). Its pathogenesis is related to donor T lymphocytes that identify minor histocompatibility complex differences and by T lymphocytes that are predominantly autoreactive, with specificity for histocompatibility antigens shared by donor and recipient cells. These activated T lymphocytes can cause cytolysis and produce inflammatory cytokines such as interleukin -1, tumor necrosis factor α, asnd interferon γ ( (5) Ferrara J.L. Deeg H.J. Graft-versus-host disease. N Engl J Med. 1991; 324: 667-674 Crossref PubMed Scopus (1154) Google Scholar ). Clinical manifestations can include dyspigmentation, erythema, and scleroderma of the skin; increased liver function tests; oral mucositis or sicca; ocular sicca; esophagitis; enteritis; and bronchiolitis obliterans ( (6) Przepiorka D. Anderlini P. Saliba R. Cleary K. Mehra R. Khouri I. Huh Y.O. Giralt S. Braunschweig I. van Besien K. Champlin R. Chronic graft-versus-host disease after allogeneic blood stem cell transplantation. Blood. 2001; 98: 1695-1700 Crossref PubMed Scopus (172) Google Scholar ).

Anesthetic Considerations for Bariatric Surgery

According to the National Institutes of Health, obesity is a major health problem with clearly established health implications, including an increased risk for coronary artery disease, hypertension, dyslipidemia, diabetes mellitus, gallbladder disease, degenerative joint disease, obstructive sleep apnea, and socioeconomic and psychosocial impairment (1). The risk of developing one or more of these obesityrelated conditions is based on body mass index (BMI), with 25–30 kg/m 2 being low risk and 40 kg/m 2 being very high risk (2). The prevalence of obesity in the 18- to 29-yr-old group increased from 12% in 1991 to 18.9% in 1999 (3). Bariatric surgery encompasses a variety of surgical weight loss procedures used to treat morbid obesity. Obesity is clinically expressed in terms of BMI or Quetelet’s index (4), which is derived by dividing weight by the square of height to estimate the degree of obesity. Thus, BMI body weight (kg)/height 2 (m 2 ). Morbid obesity is a BMI more than 35 kg/m 2 , and super morbid obesity is BMI more than 55 kg/m 2 . The indications for surgical treatment of severe obesity, as outlined in the 1991 National Institutes of Health Consensus Development Conference Panel, include an absolute BMI more than 40 kg/m 2 or BMI more than 35 kg/m 2 in combination with lifethreatening cardiopulmonary problems or severe diabetes mellitus (1). Patients seeking surgical weight loss must have proven attempts at medically supervised weight loss. Documentation of loss of 5% to 10% excess body weight or weight gain after at least 6 mo of diet modification, exercise, and medical therapy or nonimprovement in comorbid conditions during this period indicates failure. Studies have shown that weight loss of 5%–10% of initial body weight improves glucose intolerance and Type II diabetes, hypertension, and dyslipidemia (5–7). The average expenditure is approximately $7000 per year per patient on weight loss programs and equipment. Unfortunately, long-term weight loss is the exception, and most patients regain weight, sometimes more than they initially lost.

Long-term venous complications after full-size and segmental pediatric liver transplantation.

To assess the long-term incidence of venous complications, including portal vein and hepatic vein stenoses, in both whole cadaveric and reduced-size cadaveric and living related liver transplants in a pediatric population, and to assess the therapeutic modalities in the treatment of these lesions. A shortage in appropriate-sized liver grafts for pediatric patients led to the use of segmental liver grafts, which became the predominant graft used in 325 of 600 (54%) transplants at the authors' institution. To assess the long-term impact of this strategy, the authors examined the incidence of late (>90 days) venous complications and the efficacy of all therapeutic interventions. Six hundred pediatric liver transplants were performed in 325 patients, with reduced-size or split (RSS; n = 207), living related (LRD; n = 118), or full-size cadaveric grafts (FS; n = 275) from 1988 to 2000. All transplants identified with late portal vein or vena caval stenoses or thromboses from a cohort of 524 grafts with survival greater than 90 days were reviewed for demographics, symptoms, therapeutic intervention, recurrence, morbidity, and mortality. Fifty lesions were identified in 49 patients (38 portal vein and 12 hepatic vein-cava stenoses). Sex distribution was similar between portal vein and hepatic vein to cava, as was the mean patient age. Portal vein stenoses occurred in 32 LRD, 3 RSS, and 3 FS, while hepatic vein-cava stenoses occurred in 2 LRD, 8 RSS, and 2 FS. In the 38 portal vein stenoses, 9 had prior perioperative portal vein and/or 5 hepatic artery thrombectomies. Portal vein stenoses were identified after bleeding (17/38), ascites (6/38), increased liver function tests (6/38), splenomegaly (5/38), or screening ultrasound (4/38). Portal vein stenosis was associated most often with cryopreserved vein for portal conduits. Excluding conduits, the incidence of late portal vein complications was reduced to 1%. Lesions became symptomatic at a mean of 50.8 +/- 184.2 months posttransplant. All patients underwent venous angioplasty with a 66% (25/38) success rate, while 7 of 25 required further angioplasty and stenting. In the 13 unsuccessful angioplasties, 8 required surgical shunts for complete portal vein thrombosis. Recurrence occurred in 9 patients: all were amenable to stenting. Nine patients (24%) eventually died of sepsis (4) and surgical deaths at shunt or retransplant (5). Hepatic vein-cava stenoses occurred after a mean of 37.2 +/- 35.2 months, presenting with ascites (n = 10), increased liver function tests (n = 2), and splenomegaly (n = 2). All patients were diagnosed by venogram and managed by balloon dilatation alone (n = 6) or stented (n = 4), with an 80% (10/12) success, with two late recurrences amenable to repeat angioplasty or stenting. Long-term survival was 80% at 1 year. The use of segmental grafts without venous conduits is not associated with a significant rate of long-term venous complication. When late venous complications do occur, venous angioplasty and stenting are both a safe and effective management modality. If necessary, venous angioplasty may be repeated with the placement of a stent. When this is required, care must be taken to place the stent in a position where the metallic object will not interfere with future surgical manipulations should retransplantation be necessary.

Prospective, Pilot, Open-Label, Short-Term Study of Conversion to Leflunomide Reverses Chronic Renal Allograft Dysfunction

Leflunomide (LEF) is a synthetic isoxazole derivative with anti-inflammatory and antiviral properties, which has been reported to prevent acute rejection and delay progression of chronic allograft nephropathy (CAN) in animal models. We performed a pilot, crossover trial in 22 renal transplant recipients who were converted from azathioprine (AZA) or mycophenolate mofetil (MMF) to LEF in an effort to slow progression of renal dysfunction [deteriorating renal function (n = 5), cyclosporine (CyA) nephrotoxicity (n = 4) or biopsy-proven CAN (n = 13)]. Baseline maintenance immunosuppression consisted of CyA, AZA or MMF and prednisone. Six-month postconversion patient and graft survival was 100% and 91%, respectively. Mean serum creatinine 6months preconversion was 2.2 +/- 0.6mg/dL, at initiation was 3.0 +/- 1.1 mg/dL, and 6 months postconversion was 2.8 +/- 1.3 mg/dL. The rate of change in serum creatinine was 35 +/- 39%/6 months preconversion and -5 +/- 21%/6 months postconversion to LEF (p = 0.003). Two patients discontinued LEF for diarrhea and myalgia. No readmissions, increase in liver function tests, infections or acute rejection episodes occurred. Mean CyA levels did not change, 146 +/- 72 ng/ mL pre-LEF vs. 132 +/- 51 ng/mL post-LEF, p = NS. Conversion to LEF reversed progression of chronic renal allograft dysfunction with minimal toxicity.

Long-term chemotherapy of HIV-associated Kaposi's sarcoma with liposomal doxorubicin

The aim of this study was to examine the outcome, adverse events and clinical complications of long-term chemotherapy with pegylated liposomal doxorubicin (PegLiposomal DOX) for human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS) in the pre-highly active antirectroval therapy (HAART) era. A phase II study over a 4-year period in a tertiary care university hospital was carried out. 52 acquired immunodeficiency syndrome (AIDS)-patients with advanced KS received long-term chemotherapy (71±51 weeks) with a mean of 22.8±18.2 cycles and a mean cumulative liposomal doxorubicin dose of 456±364 mg/m2 (120–1040 mg/m2). Tumour burden, duration and dosage of PegLiposomal DOX, adverse events, opportunistic infections, immunological parameters and HIV load were measured. A complete (10%) or partial response (56%) was achieved while on chemotherapy. 10 patients (19%) showed stable disease. Tumour progression was observed in 8 patients (15%). Importantly, chemotherapy with PegLiposomal DOX was also successful after previous cytostatic therapy with bleomycin and vincristine. The most common adverse events included leucopenia, neutropenia, anaemia, and increased liver function tests. 34 patients (65%) developed new opportunistic infections and 29 patients (56%) died during the study period. To conclude, pegylated liposomal doxorubicin is a safe and effective drug for long-term chemotherapy of advanced (AIDS) KS without adverse effects on CD4 cell counts and HIV viral load.

Effect of treatment with divalproex sodium and lorazepam in residents of long-term-care facilities with dementia-related anxiety or agitation: retrospective chart review

Objective: The aim of this study was to compare the efficacy and safety of divalproex sodium with those of lorazepam in residents of long-term-care (LTC) facilities who had documented diagnoses of dementia with agitation or anxiety. Background: Anxiety and agitation are frequent behavioral complications of Alzheimer's disease that increase the costs and emotional stress associated with caring for these patients. Methods: LTC facilities in New Jersey and Pennsylvania were identified for 60 days of retrospective medical chart review. Patients with documented dementia and behavioral disturbances were screened to identify the use of divalproex sodium or lorazepam. Diagnoses of dementia with agitation or dementia with anxiety were confirmed through physicians' notes on history and physical examinations. Data collected included dose, drug blood levels, adverse events, and efficacy. The chart review did not control for other medications that might cause anxiety or agitation. Because this was a retrospective study, there was no random allocation of patients for statistical analysis. A MEDLINE® search was done on the effects of benzodiazepines in the elderly. Results: The charts of 146 patients (81, lorazepam; 65, divalproex sodium) in 60 long-term-care facilities were reviewed. Behavioral improvement occurred in 25 patients (30.9%) treated with lorazepam, compared with 37 patients (56.9%) treated with divalproex sodium ( P < 0.05). Weight loss (50.6%) and falls (40.7%) were the most common adverse events in the lorazepam-treated group; lorazepam was discontinued in 7 patients (8.6%) because of adverse events. Weight gain in 32 patients (49.2%) was the most common adverse event in the divalproex sodium group. There was 1 fall (1.5%) in the divalproex sodium group, and no patient required discontinuation of divalproex sodium treatment. Increased liver function test values in 7 divalproex sodium—treated patients (10.8%) were transient and did not require discontinuation of treatment. Conclusions: Despite being short term and small, the present study suggests that divalproex sodium may be more effective and safer than lorazepam for the treatment of agitation or anxiety related to dementia in LTC facility residents. Larger, longer-term controlled studies are recommended to further assess these results.

Safety and Efficacy of Total Dose Iron Dextran Administration in Patients on Home Renal Replacement Therapies

To determine the safety and efficacy of intravenous total dose iron (TDI) replacement in patients treated with home renal replacement therapy. Prospective open-label study on end points in the population studied. Institutional outpatient home dialysis program. The study included 20 end-stage renal disease (ESRD) patients, performing chronic peritoneal or home hemodialysis, with iron deficiency defined as ferritin < 100 ng/mL and/or an iron saturation < 20%. The total dose of iron dextran was calculated and infused at a rate not exceeding 6 mg/min. Hemoglobin, hematocrit, iron studies, and liver function tests (LFTs) were obtained before and 3 to 4 weeks after TDI infusion. Hematocrit of patients failing to achieve an increase in Hct over this period was re-examined 2 to 4 weeks later looking for a delayed response. Primary end points for efficacy were changes in Hct, ferritin, and iron saturation. Toxicity was measured as reported immediate and delayed symptoms and elevated transaminases and/or alkaline phosphatase levels. A median iron dose of 1000 mg (range, 325-1500 mg) was administered. The infusions were generally well tolerated. Clinical adverse effects were seen in 2 patients weighing less than 50 kg. No increase in LFT results was seen. Hematocrit increased 2.2% (95% CI, 0.5%-3.9%) from 29.0% to 31.2% (p = 0.01) within 4 weeks of infusion. Significant increases also occurred in iron saturation (from 13% to 22%, p = 0.001) and ferritin (from 234 to 305 ng/mL, p = 0.008). Among the 9 patients who did not respond with a significant increase in Hct, 2 had a delayed response, increasing the overall response from 63% at 4 weeks to 71%, 8 weeks after TDI. Inadequate erythropoietin dosing and low-grade infectious/inflammatory disorders may have contributed to a poor response in several patients. Total dose iron is a safe and effective means of restoring iron and erythropoietic response in ESRD patients weighing more than 50 kg who receive their renal replacement therapy at home.

GANCICLOVIR PROPHYLAXIS IS MORE EFFECTIVE THAN INTRAVENOUS IMMUNOGLOBULIN(IVIG) IN PREVENTING CYTOMEGALOVIRUS (CMV) DISEASE IN RENAL TRANSPLANT RECIPIENTS

605 CMV disease is the most important infectious complication in renal transplantation that is associated with increased morbidity and mortality. We compared the effectiveness of two different prophylactic protocols(Ganciclovir vs IVIG) against CMV disease in renal transplant recipients. Sixty-nine renal transplant recipients at risk of developing CMV disease were identified retrospectively. These were CMV- recipients of CMV + donor kidneys (R-D+) and CMV + recipients of either CMV + (R+D+) or CMV-(R+D-) donor kidneys who received immunosuppression with antilymphocyte globulin. Patients received either IVIG(n=42) or Ganciclovir (n=30) prophylaxis. IVIG (GAMMAR, ARMOUR, Kankakee, IL) dose was 500mg/kg at weeks 1, 2, and 4 post transplant, then 250mg/kg wks 6 and 8. Ganciclovir was given during hospital stay and in conjunction with antilymphocyte therapy at a dose of 2.5mg/kg every 1-3 days depending on serum creatinine. All patients received Acyclovir 600-3200 mg/day depending on weight and serum creatinine for 12 weeks post transplant. CMV disease was defined as CMV + buffy coat plus any 2 combinations: Leukopenia<3000 mm3, fever > 38 °C for > 3 days, increased liver function tests, tissue involvement on biopsy (renal, bronchial, etc.) Incidence of CMV disease was as follows: TableThese data demonstrate that Ganciclovir is more effective than IVIG in the prevention of CMV disease in high risk renal transplant patients (R-D+).