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Disrupted in schizophrenia 1 (DISC1) is a multi-functional scaffolding protein that has been associated with neuropsychiatric disease. The role of DISC1 is to assemble protein complexes that promote neural development and signaling, hence tight control of the concentration of cellular DISC1 in neurons is vital to brain function. Using structural and biochemical techniques, we show for we believe the first time that not only is DISC1 turnover elicited by the ubiquitin proteasome system (UPS) but that it is orchestrated by the F-Box protein, FBXW7. We present the structure of FBXW7 bound to the DISC1 phosphodegron motif and exploit this information to prove that disruption of the FBXW7-DISC1 complex results in a stabilization of DISC1. This action can counteract DISC1 deficiencies observed in neural progenitor cells derived from induced pluripotent stem cells from schizophrenia patients with a DISC1 frameshift mutation. Thus manipulation of DISC1 levels via the UPS may provide a novel method to explore DISC1 function.

A large, retrospective database analysis was conducted to evaluate the long-term outcomes of patients who received enteric-coated mycophenolate sodium (EC-MPS) versus mycophenolate mofetil (MMF) maintenance immunosuppression at the time of discharge.

The laparoscopic donor nephrectomy has revolutionized the living donation process for kidney transplantation. Because this surgery is elective and altruistic and smoking has been associated with greater technical difficulty and increased risk for postoperative complications for other types of surgeries, the potential risk of smoking must be addressed with regard to surgical complications. We reviewed 221 laparoscopic kidney donors with known smoking status. Forty-two (19) were smokers, 39 (18) were former smokers, and 140 (63) were nonsmokers. Important donor demographics were similar between groups. There was no difference between the 3 groups for mean operative time (4.5 h vs. 4.6 h vs. 4.4 h), median or mean length of stay (2 days for all groups), estimated blood loss (173±137 mL vs. 209±184 mL vs. 188±198 mL), narcotic use (0.57±0.48 mgkg vs. 0.49±0.26 mgkg vs. 0.53±0.36 mgkg of total 4 morphine equivalents), or postoperative complications. Smoking status does not seem to impact perisurgical patient outcomes in patients undergoing laparoscopic nephrectomies.

BACKGROUND: Posttransplant bone disease is a well recognized and under-treated problem. The use of protocols within other populations has been shown to improve recognition and treatment of common disease states, but outcome studies involving the use of protocols within transplant patients are lacking.OBJECTIVE: To compare the appropriate screening for and the prevention and treatment of osteopenia and osteoporosis in transplant patients before and after a bone health protocol was implemented.METHODS: A retrospective analysis in a single institution was designed to determine whether the development and implementation of a comprehensive bone health protocol impacted disease outcomes in posttransplant kidney and simultaneous kidney—pancreas patients.RESULTS: There were 132 patients in the historical control group and 76 in the treatment group. The groups were well matched, with no statistically significant differences noted for any of the baseline characteristics that were compared, including the modifiable and nonmodifiable risk factors known to put a patient at increased risk for osteopenia or osteoporosis. Significantly more patients in the treatment group received proper screening and prevention compared with the historical control group (p < 0.001). Although more patients in the treatment group received proper bone disease treatment, this did not reach statistical significance (81% vs 66%; p < 0.22). Additionally, the dual energy X-ray absorptiometry scans were performed, on average, 19 days earlier in the treatment group, although this also did not achieve statistical significance (p = 0.149).CONCLUSIONS: The multidisciplinary development and implementation of a comprehensive bone health protocol improves the screening and prevention of osteopenia and osteoporosis within kidney and pancreas transplant recipients.TRASFONDO: La enfermedad ósea luego de un transplante de órganos es un problema conocido y que no es tratado adecuadamente. La utilización de protocolos en otras poblaciones ha demostrado mejorar el reconocimiento y tratamiento de enfermedades comunes pero no hay suficientes estudios de los resultados del uso de protocolos en pacientes con transplante de órganos.

Heparin-induced thrombocytopenia (HIT) type II is an immunologically mediated reduction in platelets that increases the risk of arterial or venous thrombosis. It has been reported in up to 5% of patients receiving unfractionated heparin. Unlike other thrombocytopenic coagulopathies, HIT is associated with a high risk of thromboembolic events if not treated with an appropriate anticoagulant alternative. Diagnosis is dependent on assessment of platelet reduction, identification of previous heparin exposure, detection of thrombotic complications and evaluation of laboratory assays. HIT has been well described in surgical patient populations; however, the abdominal organ transplant population is an exception. HIT should be included in the differential diagnosis of patients presenting with thrombocytopenia after transplantation in order to prevent or treat thrombotic complications that can pose a risk to patient or graft survival.

Heparin-induced thrombocytopenia (HIT) type II is an immunologically mediated reduction in platelets that increases the risk of arterial or venous thrombosis. It has been reported in up to 5% of patients receiving unfractionated heparin. Unlike other thrombocytopenic coagulopathies, HIT is associated with a high risk of thromboembolic events if not treated with an appropriate anticoagulant alternative. Diagnosis is dependent on assessment of platelet reduction, identification of previous heparin exposure, detection of thrombotic complications and evaluation of laboratory assays. HIT has been well described in surgical patient populations; however, the abdominal organ transplant population is an exception. HIT should be included in the differential diagnosis of patients presenting with thrombocytopenia after transplantation in order to prevent or treat thrombotic complications that can pose a risk to patient or graft survival.

Cerulenin has been shown to reduce body weight and hepatic steatosis in murine models of obesity by inhibiting fatty acid synthase (FAS). We have shown that attenuating intrahepatocyte lipid content diminished the sensitivity of ob/ob mice to ischemia/reperfusion injury and improved survival after liver transplantation. The mechanism of action is by inhibition of fatty acid metabolism by downregulating PPARα, as well as mitochondrial uncoupling protein 2 (UCP2), with a concomitant increase in ATP. A short treatment course of cerulenin prior to I/R injury is ideal for protection of steatotic livers. Cerulenin opens the potential for expanding the use of steatotic livers in transplantation.

Cerulenin has been shown to reduce body weight and hepatic steatosis in murine models of obesity by inhibiting fatty acid synthase (FAS). We have shown that attenuating intrahepatocyte lipid content diminished the sensitivity of ob/ob mice to ischemia/reperfusion injury and improved survival after liver transplantation. The mechanism of action is by inhibition of fatty acid metabolism by downregulating PPARα, as well as mitochondrial uncoupling protein 2 (UCP2), with a concomitant increase in ATP. A short treatment course of cerulenin prior to I/R injury is ideal for protection of steatotic livers. Cerulenin opens the potential for expanding the use of steatotic livers in transplantation.

Sirolimus (SRL) rescue in kidney-pancreas transplantation has not been well described. We reviewed 112 KPTxs performed at our institution between December 3, 1995 and June 27, 2002. All patients received antibody induction, tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids. In 35 patients, SRL was substituted for MMF for the following reasons: acute rejection (AR) of kidney or pancreas despite adequate TAC levels, MMF intolerance, increasing creatinine levels, and TAC-induced hyperglycemia. Three-year kidney and pancreas graft survivals were 97% and 90%, respectively. Of 10 patients who were switched to SRL because of AR, one kidney failed because of antibody-resistant AR, and one kidney developed borderline AR; the other eight patients remain AR-free. AR developed in seven other patients despite therapeutic SRL levels; six had TAC levels less than 4.5 ng/mL. The mean creatinine levels overall and for the group with increasing creatinine remained stable. All patients who were switched to SRL for TAC-induced hyperglycemia or MMF intolerance improved. Kidney-pancreas transplant recipients can be safely switched to SRL with excellent graft and patient survival.

The influence of ethnicity on outcome of simultaneous pancreas-kidney transplantation (SPK) is poorly defined. After excluding technical failures, we retrospectively reviewed 96 consecutive SPKs (63 Caucasians [C], 33 African-Americans [AA]). All patients received antibody induction, tacrolimus, mycophenolate mofetil, and steroids. One-, 3-, and 5-year actuarial patient survival was similar between C (98%, 95%, 87%) and AA (90%, 90%, 81%), p=NS. One-, 3-, and 5-year kidney graft survival was similar between C (98%, 86%, 81%) and AA (85%, 85%, 78%), p =NS. One-, 3-, and 5-year pancreas graft survival was significantly worse in AA (71%, 68%, 46%) than in C (90%, 85%, 81%), p = 0.008. The cumulative incidence of kidney and pancreas acute rejection (AR) was higher in AA compared with C. Distribution of kidney and pancreas rejection grade was similar between C and AA. AA experienced more pancreas graft losses from early death with functioning graft, AR, and late chronic rejection. The higher incidence of AR and resistance to currently employed induction, maintenance, and antirejection immunosuppression therapies in AA may account for their inferior pancreas graft survival. More aggressive immunosuppression strategies may improve pancreas graft survival in AA but may be associated with increased morbidity and mortality. Further study is warranted.

A synthetic LDL (sLDL) has been prepared by combining a lipid microemulsion with amphipathic peptides containing the apoprotein B receptor domain. The biological properties of sLDL have been investigated using the U937 in vitro cell proliferation assay. sLDL exhibits a concentration dependent and saturable stimulation of U937 proliferation. By utilizing different amphipathic peptides, variable proliferation is achieved, indicating a specific interaction between sLDL and the U937 LDL receptor are possible. U937 proliferation is reduced by the addition of an anti-LDL receptor antibody, indicating that sLDL is assimilated via the LDL receptor pathway.The behavior of sLDL mimics that of native LDL, and this approach represents a viable technique for the production of an sLDL particle on a large scale for research and general application.

The current disparity of viable organs and patients in need of a transplant has been an impetus for innovative measures. Live donor renal transplantation offers significant advantages compared with cadaveric donor transplantation: increased graft and patient survival, diminution in incidence of delayed graft function, acute tubular necrosis (ATN), and reduction in waiting time. Notwithstanding these gains live donors continue to be underutilized and account for only approximately one quarter of all renal transplants performed in the United States. It has been felt that inherent disincentives to live donation have slowed its growth. These include degree and duration of postoperative pain and convalescence, child care concerns, cosmetic concerns, and time until return to full activities and employment. In an attempt to curtail the disincentives to live donation, laparoscopic live donation (laparoscopic donor nephrectomy; LDN) was developed. The purpose of this study was to compare the results of our first 25 laparoscopic nephrectomies (performed over a 10-month period from September 1998 through July 1999) with the previous 25 standard open donor nephrectomies (ODNs) completed over the past 3 years. We conducted a retrospective review of all donor nephrectomies and recipient pairs performed over the past 3 years. End points included sex, operative time, length of stay, immediate and long-term renal function, and willingness to donate. There were no differences in demographics of the ODN versusthe LDN group. The average length of stay was 2.48 ± 0.72 days for the LDN versus4.08 ± 0.28 days for the ODN. ODN and LDN have comparable short- and long-term function with no delayed graft function and no complications. Growth of living donor transplant has increased from 16 per cent of all kidney transplants performed in 1995 to 23 per cent in 1999. We conclude that LDN is a viable alternative to the standard donor operation. LDN has had a positive impact on the donor pool by minimizing disincentives to live donation. With the initiation of our laparoscopic program the number of LDNs has increased. Presently the live donor pool is the most viable alternative to significantly increase the number of kidneys for transplantation.

Extracellular polymeric material (EP), comprising the matrix of Candida albicans biofilms, was isolated and its composition was compared with that of EP obtained from culture supernatants of planktonically grown (suspended) organisms. Both preparations consisted of carbohydrate, protein, phosphorus and hexosamine, but biofilm EP contained significantly less total carbohydrate (41%) and protein (5%) than planktonic EP. It also had a higher proportion of glucose (16%) and contained galactose, suggesting that it might possess components unique to biofilms. To investigate whether the EP matrix plays a role in the resistance of biofilms to antifungal agents, susceptibility profiles of biofilms incubated statically (which have relatively little matrix) were compared with those for biofilms incubated with gentle shaking (which produce much more matrix material). Biofilms grown with or without shaking did not exhibit significant differences in susceptibility to any of the drugs tested, indicating that drug resistance is unrelated to the extent of matrix formation. However, biofilms formed on two different types of polyvinyl chloride catheter, obtained from different manufacturers, showed differences in susceptibility to amphotericin B, suggesting that drug resistance may arise as a result of highly specific, surface-induced gene expression.

The cAMP-specific phosphodiesterase family 4, subfamily D, isoform 3 (PDE4D3) is shown to have FQF and KIM docking sites for extracellular signal-regulated kinase 2 (ERK2) (p42(MAPK)). These straddle the target residue, Ser(579), for ERK2 phosphorylation of PDE4D3. Mutation of either or both of these docking sites prevented ERK2 from being co-immunoprecipitated with PDE4D3, ablated the ability of epidermal growth factor to inhibit PDE4D3 through ERK2 action in transfected COS cells, and attenuated the ability of ERK2 to phosphorylate PDE4D3 in vitro. The two conserved NH(2)-terminal blocks of sequence, called upstream conserved regions 1 and 2 (UCR1 and UCR2), that characterize PDE4 long isoforms, are proposed to amplify the small, inherent inhibitory effect that ERK2 phosphorylation exerts on the PDE4D catalytic unit. In contrast to this, the lone intact UCR2 region found in PDE4D1 directs COOH-terminal ERK2 phosphorylation to cause the activation of this short isoform. From the analysis of PDE4D3 truncates, it is suggested that UCR1 and UCR2 provide a regulatory signal integration module that serves to orchestrate the functional consequences of ERK2 phosphorylation. The PDE4D gene thus encodes a series of isoenzymes that are either inhibited or activated by ERK2 phosphorylation and thereby offers the potential for ERK2 activation either to increase or decrease cAMP levels in cellular compartments.

A 59‐year‐old black man who received a cadaveric renal transplant 15 months earlier developed subcutaneous nodules on his right upper extremity that were identified as phaeohyphomycosis caused by Exophiala jeanselmei. The man was admitted 4 weeks later with a swollen left arm and had Nocardia asteroidesin this area and in the apex of his left lung. He was treated with surgical excision, and itraconazole, imipenem‐cilastatin, and trimethoprimsulfamethoxazole. With the potential presence of more than one microorganism in an immunocompromised patient, it is important to identify and differentiate them correctly to direct appropriate therapy.

Reports on renal graft outcome after kidney‐alone (KA) and simultaneous pancreas‐kidney (SPK) transplants have focused on graft survival instead of function. The aim of this study is to compare renal graft outcome after KA and SPK using graft function and survival as the measures of outcome. The records of 102 transplants performed in type I diabetics from 10/90 to 9/96 were reviewed (SPK 42, KA 60). Serum creatinine (Cr) and calculated glomerular filtration rate (GFR) were used as estimates of graft function. Cr were similar in SPK and KA on day 3 (4.8±2.9 vs. 4.8 2.8 mg/dl, P=0.9) and day 7 (2.5±1.8 vs. 3.0±2.5 mg/dl, P=0.3). GFR was higher KA at 6 months (5718 vs. 5112 ml/min, P = 0.08), 1 yr (55±23 vs. 51±11 ml/ min, P = 0.4) and 3 yr (60±22 vs. 42±16 ml/min, P=0.03). Kidney graft survival was similar in KA and SPK at 1 and 5 yr (87% vs. 89% and 44% vs. 47%, P=0.8). Immunologic failure of the renal graft occurred more frequently in SPK (58% vs. 48%, P = 0.04) whereas death with function was more common in KA (33% vs. 17%, P = 0.04). In KA, risk factors for failure of the renal graft included acute rejection (P 0.008, relative risk or rr = 3.4) and African American recipient (P 0.06, rr = 2.8). In SPK, risk factors included donor age > 40 yr (P 0.05, rr = 5.3) and African American donor (P = 0.03, rr = 4.5). Logistic regression analysis revealed the following risk factors for GFR <50 ml/min at 1 yr: acute rejection (P = 0.03, rr = 2.2) and Cr> 3 mg/dl on day 7 (P=0.06, rr = 2.3). In conclusion, although renal graft survival was similar after KA and SPK, better graft function was observed in KA at 3 yr. Assessment of renal graft function allows us to evaluate outcome from a different perspective than graft survival, and these two measures of outcome complement each other.

OBJECTIVE: To review data supporting the hypothesis that syndrome X plays a major role in the pathogenesis of coronary artery disease (CAD), and the effects of lifestyle factors and pharmacologic interventions on insulin, other metabolic parameters, and outcomes.DATA SOURCES: MEDLINE (January 1966–August 1997) and Current Contents database searches identified applicable English-language experimental trials, epidemiologic studies, reviews, and editorials.STUDY SELECTION AND DATA EXTRACTION: Studies that were included addressed the role of insulin resistance and hyperinsulinemia in the pathogenesis of CAD or the effects of lifestyle factors and pharmacologic interventions on metabolic parameters and outcomes.DATA SYNTHESIS: The main characteristics of syndrome X are hyperinsulinemia and insulin resistance. These result in secondary syndrome X features, including hyperglycemia, increased very-low-density lipoprotein concentrations, decreased high-density lipoprotein cholesterol, and hypertension. Insulin resistance is worsened by obesity, and insulin has been shown to contribute to the development of hypertension. Other studies demonstrate that smoking adversely affects glucose and insulin concentrations. Animal studies have linked hyperinsulinemia and atherogenesis. These animal data have been confirmed by several large prospective and population studies that have identified associations between hyperinsulinemia and CAD.CONCLUSIONS: Strong evidence links insulin resistance and hyperinsulinemia to CAD. Lifestyle modifications play an important role in decreasing cardiovascular risk, and clinicians should strongly encourage such changes. Clinicians must also carefully consider the effects of antihypertensive, antihyperglycemic, and antidyslipidemic agents on patients' metabolic profiles when choosing appropriate therapeutic regimens. However, outcome data on many potentially beneficial agents, including calcium antagonists, α1-adrenergic antagonists, angiotensin-converting enzyme inhibitors, metformin, acarbose, and troglitazone, are not yet available.OBJETIVO: Repasar (1) datos apoyando la hipótesis de que el Síndrome X tiene un papel principal en la patogénesis de la enfermedad de la arteria coronaria (EAC) y (2) los efectos de factores del estilo de vida e intervenciones farmacológicas sobre insulina, otros parámetros metabólicos, y resultados.FUENTES DE INFORMACIÓN: Investigaciones de MEDLINE y Current Contents identificaron pruebas experimentales, estudios epidemiológicos, revisiones, y editoriales aplicables en el idioma inglés.SELECCIÓN DE FUENTES DE INFORMACIÓN: Los estudios incluídos discutieron el rol de la resistencia a insulina e hiperinsulinemia en la patogénesis de EAC, o los efectos de factores del estilo de vida e intervenciones farmacológicas en los parámetros metabólicos y resultados.SÍNTESIS: Las características principales del Síndrome X son hiperinsulinemia y resistencia a insulina. Esto resulta en características del Síndrome X secundarias incluyendo hiperglicemia, aumento en las concentraciones de lipoproteina de muy baja densidad, disminución en la lipoproteina colesterol de densidad elevada, e hipertensión. La resistencia a insulina es agravada por obesidad, y se ha demostrado que la insulina contribuye al desarrollo de hipertensión. Otros estudios demuestran que el fumar afecta adversamente las concentraciones de glucosa e insulina. Estudios en animales han conectado la hiperinsulinemia con aterogénesis. Estos datos en animales han sido confirmados por varios estudios prospectivos y de población grandes que han identificado asociaciones entre hiperinsulinemia y EAC.CONCLUSIONES: Existe fuerte evidencia conectando la resistencia a insulina e hiperinsulinemia con EAC. Modificaciones en el estilo de vida tienen un papel importante en la disminución del riesgo cardiovascular y los médicos deben fomentar firmemente tales cambios. Los médicos también deben considerar cuidadosamente los efectos de agentes antihipertensivos, antihiperglicémicos, y antidislipidémicos en los perfiles metabólicos de los pacientes al seleccionar regímenes terapéuticos apropiados. Sin embargo, datos sobre los resultados de muchos agentes potencialmente beneficiosos, incluyendo los antagonistas de calcio, antagonistas adrenérgicos α-1, inhibidores de la enzima convertidora de angiotensina, metformina, acarbosa, y troglitazona no están disponibles aún.OBJECTIF: Réviser (1) les données supportant l'hypothèse selon laquelle le Syndrome X joue un rôle majeur dans la pathogénèse de la maladie coronarienne et (2) l'effet des modifications aux habitudes de vie ou des interventions pharmacologiques sur l'insuline, et d'autres paramètres métaboliques, ainsi que sur les résultats cliniques.REVUE DE LITTÉRATURE: Des recherches dans les banques de données MEDLINE et Current Contents ont permis d'identifier les études cliniques et épidémiologiques pertinentes, de même que les articles de revue, et les éditoriaux publiés en anglais.SÉLECTION DES ÉTUDES ET DE L'INFORMATION: Les études choisies discutent de l'influence de la résistance à l'insuline et de l'hyperinsulinémie sur la pathogénèse de la maladie coronarienne ou de l'effet des changements aux habitudes de vie ou des interventions pharmacologiques sur les paramètres métaboliques et les résultats cliniques.RÉSUMÉ: Les caractéristiques principales du Syndrome X sont l'hyperinsulinémie et la résistance à l'insuline. Ceci produit les caractéristiques secondaires du Syndrome X soit, l'hyperglycémie, l'élévation des concentrations de lipoprotéines de très faible densité, la chute des concentrations de lipoprotéines de haute densité et l'hypertension. La résistance à l'insuline est aggravée par l'obésité et on a démontré que l'insuline contribue au développement de l'hypertension. D'autres études ont démontré que le tabagisme altère défavorablement les concentrations d'insuline et de glucose. Des études animales ont établi un lien entre rhyperinsulinémie et l'athérogénèse. Ces données animales ont été confirmées par quelques grandes études prospectives de population qui ont démontré une association entre l'hyperinsulinémie et la maladie coronarienne.CONCLUSIONS: Il est évident que la résistance à l'insuline et l'hyperinsulinémie sont liées à la maladie coronarienne. Les modifications aux habitudes de vie jouent un rôle important dans la diminution du risque de maladie cardiovasculaire et les cliniciens devraient fortement encourager ces mesures chez leurs patients. Au moment de choisir le régime thérapeutique approprié, les cliniciens doivent également considérer les effets des agents antihypertenseurs, hypoglycémiants, et hypolipémiants sur le profil métabolique du patient. Toutefois, la confirmation des résultats cliniques n'est toujours pas disponible avec plusieurs agents potentiellement bénéfiques soit, les bloqueurs des canaux calciques, les α1-bloqueurs, les inhibiteurs de l'enzyme de conversion de l'angiotensine, la metformine, l'acarbose, et le troglitazone.

Complexes of the chlorides and bromides of manganese(II), iron(II), cobalt(II), nickel(II), copper(II) and zinc(II) with isoniazid (INH) have been prepared and studied by means of their magnetic susceptibilities, infrared and electronic spectra. All of the complexes have octahedral structures with the exception of the zinc complexes and the chloro- complexes of manganese and iron which are tetrahedral. The chloro- complex of copper is square planar.

Complexes of isonicotinic acid have been prepared with the bromides and chlorides of cobalt(II), nickel(II) and copper(II) and also with the chlorides of manganese(II) and iron(II). These complexes have been characterized by analysis, vibrational and electronic spectra and magnetic moments. The compounds have octahedral polymeric structures.

Complexes of 2-aminopyrimidine with the chlorides, bromides and iodides of cobalt(II), zinc(II) and also with the chlorides and bromides of manganese(II), nickel(II) and copper(II) have been prepared. The chloride complex of iron(II) was also obtained. The stereochemical configurations of the complexes were deduced using spectral and magnetic properties. The decomposition of the complexes was studied by thermogravimetry and differential thermal analysis.

A series of complexes has been prepared with the halides of cobalt(II), nickel(II), copper(II) and 2-,3-,4-ethylpyridine. The compounds were essentially all octahedral with the exception of those formed between 2-ethylpyridine and the cobalt(II) halides. The stereochemical configurations were deduced using spectral and magnetic properties. The decomposition of the complexes was studied by thermogravimetry and differential thermal analysis.

Neoral was replaced with a generic cyclosporine formulation on our hospital formulary. We compared outcomes for de novo kidney transplant recipients who either received Gengraf (n88) or Neoral (n100) in a single-center, retrospective review. As compared to patients who received Neoral, patients who received Gengraf were significantly more likely to have an acute rejection episode (39% vs. 25%, P0.04), more likely to have a second rejection episode (13% vs. 4%; P0.03), or to have received an antibody preparation to treat acute rejection (19% vs. 8%; P0.02). Patients treated with Gengraf had a higher degree of intrapatient variability for cyclosporine trough concentrations as determined by %CV (P<0.05). The incidence of acute rejection at 6 months posttransplant was significantly higher in patients who received Gengraf compared to Neoral. A larger, prospective analysis is warranted to compare these formulations of cyclosporine in de novo kidney transplant recipients.

Cardiotoxicity due to tacrolimus is documented infrequently in the medical literature. Sinus bradycardia associated with intravenous tacrolimus occurred in a 15‐year‐old orthotopic liver transplant recipient. The mechanism of this adverse effect is unknown; however, it does not appear to be concentration dependent, and in this patient it resolved on changing to oral therapy. Practitioners should be aware that intravenous administration of tacrolimus may be associated with adverse cardiac events including sinus bradycardia.

BACKGROUND: The University HealthSystem Consortium (UHC) conducted a benchmarking study to assess members’ compliance with published guidelines for prevention of fungal infections in hematopoietic stem cell transplant (HSCT) recipients. METHODS: Adult HSCT patients were evaluated by retrospective chart review of cases discharged between 01/01/04 and 06/30/05. Data collected included demographics, use of prophylaxis (px), and outcomes. Patients were classified as high or low risk for fungal infection according to NCCN and CDC guidelines. RESULTS: Thirteen UHC member hospitals submitted a total of 242 HSCT cases. Patient characteristics and administration of antifungal therapy are shown in Table 1. 57% (137/242) of patients were classified as high risk for fungal infection. Overall, 85% (205/242) of patients received antifungal px. Compliance with national guideline directed antifungal px was 54%. Of patients who did not receive px, 59% (22/37) were high-risk. 32% (7/22) of these patients required empiric antifungal therapy, 29% (2/7) had a confirmed fungal infection and 1 of these patients died. Of patients who received antifungal px, 44% (90/205) were classified as low risk. 6.7% (6/90) went on to require empiric therapy and 2 died. 84.4% of patients had fluconazole as at least one of their prophylactic agents, and 34% of patients received prophylactic antifungals that provided coverage for both Aspergillus and Candida species. 5.4% (13/242) of HSCT recipients died during the target hospitalization. 76.9% (10/13) of these patients were high risk. 61.5% (8/13) had signs/symptoms of a suspected or definitive fungal infection at the time of death (6 were high risk). CONCLUSION: Most HSCT patients did not receive appropriate fungal px based on current guidelines. Failure represented both under and over utilization of px. Further study is required to explain poor adherence to current guidelines. Table 1: Patient Characteristics by Degree of Risk High Risk (n=137) Low Risk (n=105) % (n) % (n) *ABX = broad spectrum antibiotics Chemotherapy prior to admission 53.3% (73) 61.9% (65) Radiation prior to admission 23.4% (32) 17.1% (18) Allogeneic Transplant 75.9% (104) 17.1% (18) Cytomegalovirus disease 11.7% (16) 6.7% (7) GVHD 15.3% (21) 1.0% (1) Mucositis 55.5% (76) 7.6% (8) Systemic corticosteroids 63.5% (87) 44.8% (47) Fever unresponsive to >4 days of ABX 19.0% (26) 12.4% (13) Neutropenia during antifungal therapy 39.4% (54) 27.6% (29) History of Aspergillus infection 3.6% (5) 0.0% (0) Antifungal therapy: Prophylaxis 83.9% (115) 85.7% (90) Failed prophylaxis 21.2% (29) 5.7% (6) Empiric therapy 25.4% (32) 10.5% (11) Definite treatment 6.6% (8) 0.0% (0)

BACKGROUND: The University HealthSystem Consortium (UHC) conducted a benchmarking study to assess members' compliance with published guidelines for prevention of fungal infections in hematopoietic stem cell transplant (HSCT) recipients.