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A Lo

Publications and source records attributed to A Lo.

At least 19 recordsLinked to original sources

Survey of the prevalence, diagnosis and treatment of dermatological conditions in small animals in general practice.

A survey was made of the prevalence, diagnosis and treatment of dermatological conditions in small animals in general practice in the UK. Out of 3707 small animal consultations in general practice that were observed and recorded, 795 (21.4 per cent) involved animals that had a dermatological problem. In dogs and exotic species, pruritus was the most common presenting sign, accounting for 30 to 40 per cent of the dermatological consultations. In cats, cutaneous swellings were the most common presentation (36 per cent). A diagnosis or recommendation for treatment was made on the basis of the presenting clinical signs and physical examination alone in 576 (72 per cent) of the cases, and various diagnostic tests were performed in the other cases. In dogs, parasitic infestations, bacterial infections and neoplasia accounted for the majority of the diagnoses. In cats, parasites and bacterial infections were the most common. In exotic species, parasites accounted for over 80 per cent of the dermatological diagnoses. In dogs, the most common final diagnoses were otitis, pyoderma, anal sac impaction, flea infestation and atopic dermatitis. In cats, abscesses, flea infestation, and otitis were the most common diagnoses. In exotic species, the most common diagnosis was an unspecified mite infestation. Systemic antibiotics were prescribed in 196 cases (25 per cent), systemic glucocorticoids were prescribed in 162 cases (20 per cent) and treatment with an ectoparasiticide was prescribed in 167 cases (21 per cent).

Animals↗

Isoflurane preconditioning-induced cardio-protection in patients undergoing coronary artery bypass grafting.

BACKGROUND AND OBJECTIVES: Ischaemic preconditioning is commonly regarded as one of the most powerful protective mechanisms against a subsequent lethal ischaemic injury during coronary artery bypass graft surgery but is not practiced routinely. Experimentally, isoflurane, a commonly used volatile anaesthetic agent, provides myocardial protection through a signal transduction cascade that is remarkably similar to the pathways identified in ischaemic preconditioning. The aim of our study was to investigate whether pre-ischaemic administration of isoflurane exerted protection against prolonged ischaemia with functional recovery and reduced necrosis among patients undergoing coronary artery bypass graft surgery. METHODS: Forty patients scheduled for elective coronary artery bypass graft operations were prospectively randomized into the control or isoflurane groups. In the isoflurane group, isoflurane 2.5 minimum alveolar concentration was administered for 15 min followed by a 5-min washout period before aortic cross-clamping. The control group received a time-matched period of isoflurane-free cardiopulmonary bypass. The conduction of anaesthesia and surgery were standardized in all patients. Haemodynamic data, troponin I release and inotropic support were measured and recorded perioperatively. RESULTS: There were no adverse effects related to isoflurane administration. In the isoflurane group, the mean cardiac index after cardiopulmonary bypass was significantly higher than the pre-bypass value (P < 0.05), whereas no difference was found in the control group. At 15 min after cardiopulmonary bypass and 6 h after surgery, the changes in cardiac index and stroke volume index were significantly higher in the isoflurane group than in the control group (P < 0.05). There was a consistently lower release of troponin I in the isoflurane group compared to the control group. Compared to the controls, the mean troponin I level was significantly reduced in the isoflurane group at 24 h after surgery (P = 0.042). CONCLUSIONS: The present results support the preconditioning effect of isoflurane in patients undergoing coronary artery bypass graft surgery as clinically feasible and providing optimal cardiac protection.

Aged↗

Are autoimmune diseases or glomerulonephritis affecting the development of panel-reactive antibodies in candidates for renal transplantation?

Panel-reactive antibodies (PRA) are a major obstacle to kidney transplantation (KTx). It is not completely clear why only some patients develop PRA, whereas others do not. We hypothesized that other factors, such as autoimmune diseases involving the kidney, might be a trigger for PRA development. We reviewed the original diseases that led to renal failure and their possible role in PRA development. Charts of 270 patients on the active waiting list for KTx were reviewed for complete demographics, presence of PRA, peak PRA level, first KTx or retransplantation, original disease, blood transfusions, pregnancy and rejection. Patients were divided into group 1 (PRA >10%) and group 2 (PRA <10%). There was a significantly higher proportion of patients in group 1 with autoimmune diseases than in group 2. The same proportion was found significant for all of the patients as well as for the patients listed for the first KTx (new patients). Previous KTx has significant impact on both class I and II peak PRA levels when compared with new patients who are already sensitized. A subanalysis of retransplantation showed patients with autoimmune disease (54%) have more graft loss due to rejection compared with nonautoimmune disease (43%). There is an association between high PRA level and autoimmune diseases causing renal failure regardless of the previous KTx status. Besides the risk of recurrence, autoimmune disease seems to affect the risk of graft loss due to rejection.

Adult↗

A multicenter analysis of the significance of HLA matching on outcomes after kidney-pancreas transplantation.

The purpose of this study was to determine the influence of HLA matching on outcomes in simultaneous kidney-pancreas transplant (SKPT) recipients in a multicenter trial. From March 1999 to May 2001, a total of 297 SKPT recipients were enrolled in a prospective randomized trial of 2 daclizumab dosing strategies versus no antibody induction in combination with tacrolimus, mycophenolate mofetil, and steroids in SKPT recipients. Subanalyses using both univariate and multivariate models were performed at 1 year to identify factors associated with acute rejection, graft loss, or death. Potential risk factors evaluated were treatment group, African American ethnicity, HLA-A mismatches (MM), HLA-B MM, HLA-DR MM, total HLA MM, surgical technique, cytomegalovirus status of donor and recipient, and delayed graft function (DGF). Univariate analyses revealed that treatment group, HLA-A MM, HLA-B MM, total HLA MM >3, and DGF were significantly associated with acute rejection. These variables were then entered into logistic and Cox regression analyses. HLA-A MM and DGF were the only variables that remained significantly associated with acute rejection in the multivariate model. The relative risk for acute rejection in recipients with HLA-A MM was 1.56 (P = .02). In conclusion, despite contemporary immunosuppression, the degree of HLA MM, particularly HLA-A, and DGF are associated with an increased risk for acute rejection in SKPT recipients at 1 year. Less rejection was noted in patients with 0 MM at all 3 HLA loci and in patients with total HLA-MM <3. However, none of these factors affected short-term patient or graft survival rates.

Antibodies, Monoclonal↗

Inferior late functional and metabolic outcomes in African American simultaneous kidney-pancreas recipients.

The aim of this study was to determine the impact of ethnicity on the major endpoints of a prospective, multi-center, randomized trial of 2 dosing regimens of daclizumab compared with no antibody induction in simultaneous kidney-pancreas transplantation (SKPT). A total of 298 patients were randomized into 3 groups: daclizumab 1 mg/kg/dose every 14 days for 5 doses (Group I, n = 107), daclizumab 2 mg/kg/dose every 14 days for 2 doses (Group II, n = 113), and no antibody induction (Group III, n = 78). All patients received tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids. Thirty-seven patients (12.4%) were African American (AA) and 261 were non-African American (NAA). Demographic and transplant characteristics were comparable between AA and NAA patients. At 3 years, there were no differences in patient, kidney, or pancreas graft survival rates. Rejection rate was similar between AA and NAA. Although mean serum creatinine (SCr) levels at 1 year were comparable between AA and NAA patients (AA 1.5 mg/dL vs NAA 1.3 mg/dL; P = .23), by 3 years AA patients had higher mean SCr levels (AA 2.1 mg/dL vs NAA 1.5 mg/dL; P < .0001) and lower calculated glomerular filtration rate (GFR) (AA 45 mL/min vs NAA 56 mL/min; P = .01). Mean HgbA1C, total cholesterol, and diastolic blood pressure (BP) were higher in AA patients at 3 years, compared with NAA patients. In conclusion, in this study, AA patients had worse late functional and metabolic outcomes after SKPT compared with NAA patients. Further longitudinal follow-up is needed to determine the ultimate impact of these findings on long-term patient and graft survival.

Adult↗

Impact of the metabolic syndrome on long-term outcomes in simultaneous kidney-pancreas transplantation.

The metabolic syndrome (MS) has been implicated as an important nonimmunologic risk factor for chronic renal transplant dysfunction. The aim of this study was to determine the impact of the MS on outcomes in simultaneous kidney-pancreas transplantation (SKPT). Data were available on 241 patients enrolled in a prospective, multicenter randomized study of daclizumab compared with no antibody induction in SKPT. Presence of MS before and after SKPT was defined using NCEP-ATP III (National Cholesterol Education Program Adult Treatment Panel III) criteria. Body mass index (BMI) was used as a surrogate for waist circumference. MS was present in 59% of patients pretransplantation but only in 19% of patients 1 year after SKPT (P < .0001). Demographic and transplant characteristics were well matched for those with MS (MS+) and without MS (MS-) at 1 year. Presence of MS at 1 year was associated with the following changes at 3 years: increased serum creatinine level (1.65 mg/dL MS- vs 2.05 mg/dL MS+; P = .13); decreased modification of diet in renal disease calculated glomerular filtration rate (GFR; 58 mL/min MS- vs 48 mL/min MS+; P = .02); increased HgbA1C level (5.6% MS- vs 6.6% MS+; P < .001); and lower pancreas graft (PG) survival rate (88% MS- vs 71% MS+; P = .01). Linear regression analysis identified MS+ and the subgroup of MS+ without functioning PG at 1 year as independent risk factors for renal dysfunction, whereas MS+ with functioning PG at 1 year was not a risk factor for renal dysfunction. Presence of MS at 1 year is associated with long-term renal dysfunction after SKPT. Efforts to decrease early PG failure may help mitigate against MS-associated renal dysfunction.

Adult↗

A prospective, randomized, multicenter study evaluating the safety and efficacy of two dosing regimens of daclizumab compared to no antibody induction in simultaneous kidney-pancreas transplantation: results at 3 years.

UNLABELLED: This is a report of outcomes at 36 months of a prospective, multicenter study comparing the safety and efficacy of two dosing regimens of daclizumab with no antibody induction in simultaneous kidney-pancreas transplant (SKPT) patients receiving tacrolimus, mycophenolate mofetil, and prednisone. A total of 298 SKPT patients were randomized into one of three groups: daclizumab 1 mg/kg/dose every 14 days for 5 doses (group 1, n = 107); daclizumab 2 mg/kg/dose for 2 doses (group 2, n = 113); and no antibody induction (group 3, n = 78). There were no differences in baseline characteristics among the three groups, and results were analyzed by an intent-to-treat analysis. The incidence of composite events (acute rejection [AR], any allograft lost, or death) at 3 years was 49%, 43%, and 55% in groups 1, 2, and 3, respectively (P = .278). The cumulative incidences of AR were not statistically different among the three groups (P = .178). The mean time to first AR was delayed in groups 2 (288 days) and 1 (245 days) compared to group 3 (145 days, P = .07). There were no differences in patient or allograft survival rates among the three groups, and the rates of serious adverse events, infections, and hospital readmissions were also comparable. Excellent dual graft function in patients with surviving grafts was observed in all three groups at 3 years. CONCLUSIONS: The alternative 2-dose regimen of daclizumab was as safe and effective as the conventional 5-dose regimen compared to no antibody induction in SKPT patients, but no long-term benefits were noted.

Acute Disease↗

Risk factors and outcomes analyses at 36 months of a prospective, randomized, multicenter, trial of daclizumab induction in simultaneous kidney-pancreas transplant recipients.

UNLABELLED: The purpose of this study was to analyze risk factors for acute rejection (AR) and long-term outcomes in simultaneous kidney-pancreas transplant (SKPT) patients enrolled in a prospective, multicenter study of daclizumab (DAC) versus no antibody induction. METHODS: A total of 298 SKPT patients were randomized into three groups and categorized based on an intent to treat analysis, and factors associated with AR and survival were identified using logistic regression and Cox proportional hazards models. RESULTS: There were no differences in patient or allograft survival or rejection rates among the three groups at 36 months follow-up. Delayed (kidney) graft function (DGF) was a risk factor for subsequent kidney AR (odds ratio = 2.79, P = .002). The presence of kidney AR was also a risk factor (hazard ratio [HR] = 3.1, P = .003) for kidney graft loss, whereas risk factors for pancreas graft loss (censored for graft loss within 30 days or death with functioning graft) included pancreas AR (HR = 1.97, P = .012), kidney AR (HR = 1.61, P = .042), CMV serostatus donor +/recipient - (HR = 1.62, P = .026), and HLA-B mismatch (HR = 1.58, P = .01). Kidney graft loss (HR = 5.5, P = .02) was the only predictor of mortality. CONCLUSIONS: At 36 months, no significant differences in outcomes were noted in the three study groups. DGF was the major risk factor for kidney AR, kidney AR was the major risk factor for kidney graft loss, and kidney graft loss was the major determinant of mortality. Prevention of kidney DGF and AR in SKPT recipients may play a pivotal role in optimizing long-term outcomes.

Antibodies, Monoclonal↗

African-American ethnicity is no longer a risk factor for early adverse outcomes in simultaneous kidney-pancreas transplantation with contemporary immunosuppression.

The influence of ethnicity on the outcome of simultaneous kidney-pancreas transplantation (SKPT) is controversial. The aim of this study was to determine the impact of ethnicity on the major endpoints of a prospective, multicenter, randomized trial of two dosing regimens of daclizumab compared to no-antibody induction in SKPT. A total of 297 patients were randomized into three groups: daclizumab 1 mg/kg/dose every 14 days for five doses (group I, n = 107); daclizumab 2 mg/kg/dose every 14 days for two doses (group II, n = 112), and no-antibody induction (group III, n = 78). All patients received tacrolimus, mycophenolate mofetil, and steroids for maintenance immunosuppression. Thirty-seven patients (12.5%) were African-American (AA) and 260 were non-African-American (NAA). Demographics and transplant characteristics were comparable between AA and NAA patients. At 1 year, no differences were seen in patient survival (97% AA, 96% NAA), kidney graft survival (94% AA, 93% NAA), and pancreas graft survival (84% AA, 85% NAA). Rejection rate and incidence of adverse events were similar between AA and NAA subjects. Kidney graft function was comparable between AA and NAA patients at 1 year; however, mean HgbA1C was higher, C-peptide was lower, and oral hypoglycemic use was more common in AA subjects. Thus, in this prospective multicenter study, AA ethnicity was not associated with an increased risk of early adverse outcomes in SKPT. Follow-up will be required to determine whether long-term outcomes remain equivalent, particularly with regard to pancreas graft function.

Adult↗

Does surgical technique influence outcomes after simultaneous kidney-pancreas transplantation?

Since 1995, many centers have switched from bladder to enteric drainage of the exocrine secretions in simultaneous kidney-pancreas transplantation (SKPT). Enteric exocrine drainage may be performed with either systemic (systemic-enteric [S-E]) or portal (portal-enteric [P-E]) venous delivery of insulin. Controversy exists regarding the optimal surgical technique. From March 1999 to May 2001, a total of 297 SKPT patients were enrolled into a prospective, multicenter, randomized, open-label, comparative trial of two daclizumab dosing strategies versus no-antibody induction in combination with tacrolimus, mycophenolate mofetil, and steroids in SKPT recipients. Surgical techniques were center specific. A total of 171 patients (58%) underwent SKPT with S-E drainage, 96 (32%) with P-E drainage, and 30 (10%) with systemic-bladder (S-B) drainage. The two groups randomized to daclizumab induction were similar with regard to surgical technique (64% S-E, 25% P-E, 11% S-B drainage). Demographic and transplant characteristics and immunosuppression were similar among the three groups, except that more patients with P-E drainage did not receive antibody induction. At 6 months, no differences were seen in patient and graft survival rates, surgical complications including pancreas thrombosis, rates of rejection or infection, readmissions, and kidney and pancreas allograft function among the three different surgical techniques. The 6-month results of this multicenter study suggest no significant differences in outcomes in SKPT recipients according to surgical technique.

Antibodies, Monoclonal↗

The impact of delayed graft function of the kidney on the pancreas allograft in simultaneous kidney-pancreas transplantation.

UNLABELLED: It is unclear whether delayed graft function (DGF) of the kidney has any influence on pancreas graft function following simultaneous kidney-pancreas transplantation (SKPT). A subgroup analysis was conducted using data from a multicenter study to determine the impact of DGF of the kidney on pancreas graft function following SKPT. METHODS: Of the 297 SKPT patients, 24 (8%) had DGF of the kidney, defined as the need for dialysis during the first week posttransplant. Clinical parameters including patient and graft survival, incidence of acute rejection, and pancreas and renal function were compared between patients with and without DGF at 1 week, and at 1, 3, 6, and 12 months posttransplant. RESULTS: Demographic and transplant characteristics were similar between the two groups except for longer kidney and pancreas cold ischemia times, more males, and more primary cytomegalovirus (CMV) exposure in the DGF group (P <.05). No differences were seen in patient and graft survival rates, but the incidence of acute renal rejection was higher in patients with DGF (42%) than in those without DGF (15%, P =.001). More patients with DGF (25%) received oral hypoglycemic agents at 1-year posttransplant than in those without DGF (5%, P <.01). At 1 year, the mean serum creatinine was 1.8 mg/dL and 1.4 mg/dL in patients with and without DGF, respectively (P <.01). CONCLUSIONS: Patients with DGF of the kidney had a higher incidence of acute renal rejection and received oral hypoglycemic agents more often during the first year posttransplant compared to those who did not have DGF following SKPT.

Cytomegalovirus Infections↗

Human islet graft function in NOD-SCID mice predicts clinical response in islet transplant recipients.

The purpose of this study was to evaluate the utility of nondiabetic immune-deficient NOD-SCID mouse model in assessing the functional capacity of isolated human islets. We transplanted 2000 islet equivalents obtained from six preparations used for human islet transplantation in three patients under the kidney capsule of groups of 10 mice. Human (Hu) C-peptide and insulin levels were determined following intraperitoneal (i.p.) glucose challenge at days 0, 7, 14, 21, 30, 60, 90, and 120. The Hu C-peptide level >1.5 ng/mL was the threshold for islet function in this model. The first patient did not achieve insulin independence and had minimal (0.5 ng/mL) fasting C-peptide levels that mirrored the low C-peptide levels observed in the mice. After the first infusion, the insulin requirements were reduced by 50% in the second patient. She became insulin free 10 days after her second infusion with a C-peptide level of 3.0 ng/mL, which corresponded to the peak C-peptide level (3.9 ng/mL) observed in the mice. By 150 days' posttransplant, the decline in C-peptide level paralleled the decline observed in mice. Within 2 weeks after the first transplant, insulin dose was reduced by 75% in the third patient, which corresponded to the robust C-peptide production in mice (7.3 ng/mL). Both patient and mice had a delay in islet function following the second infusion. She remained with a C-peptide level of 1.8 ng/mL and insulin free until suffering a rejection episode 3 months later. We observed that human islet graft function in NOD-SCID mice correlated with clinical response in islet transplant recipients.

Animals↗

Renal pathology and clinical presentations of polyomavirus nephropathy in simultaneous kidney pancreas transplant recipients compared with kidney transplant recipients.

INTRODUCTION: The purpose of this study was to describe and compare the renal histopathology and clinical course of simultaneous kidney-pancreas transplant (SKP) recipients with kidney transplant (KT) recipients with polyomavirus nephropathy (PVN). METHODS: Between 1997 and 2002, 20 patients (7 SKP, 13 KT) were diagnosed with PVN. Clinical characteristics and outcomes of PV-N were correlated with histopathologic examinations of renal allograft biopsy and compared between SKP and KT recipients. RESULTS: There were no differences in demographics between SKP and KT recipients with PV-N. The mean time to PVN was 611 (172 to 1174) days posttransplant in SKP and 343 (83 to 720) days posttransplant in KT (P =.05). The serum creatinine at the time of diagnosis was similar between SKP and KT recipients. All patients were treated with reduction in immunosuppression. After a median follow-up of 2 years, the patient survival was 71% in SKP and 100% in KT. Four grafts (57%) were lost owing to PVN in SKP group and three grafts (23%) were lost owing to PVN in the KT group. More patients (43%) in SKP had a history of acute rejection prior to diagnosis of PVN compared to KT (8%) and biopsy-proven tacrolimus nephrotoxicity prior to PVN was more common in SKPT (86%) than in KT (8%) patients (P <.05). SKP patients with evidence of diffuse fibrosis and high total sum scores at time of presentation all subsequently lost their grafts. CONCLUSIONS: SKP recipients with PVN had a worse clinical course than KT recipients.

Humans↗

Effect of donor-recipient cytomegalovirus serologic status on outcomes in simultaneous kidney-pancreas transplant recipients.

Diabetic patients undergoing simultaneous kidney-pancreas transplantation (SKPT) may be at high risk for developing cytomegalovirus (CMV) infection. To study this issue, we analyzed 297 SKPT patients enrolled into a multicenter trial of two daclizumab dosing strategies versus no antibody induction in combination with tacrolimus, mycophenolate mofetil, and steroids. Complete donor (D) and recipient (R) CMV serology values were available in 294 cases and were distributed as follows: 86 (29%) D+/R-. Eighty-six (29%) D+R+; 45 (16%) D-/R+; 77 (26%) D-/R-; CMV antiviral prophylaxis was center specific, but 98% of patients received either ganciclovir or acyclovir. No differences existed in demographic or transplant characteristics or immunosuppressive regimens among the four groups except that more African-American SKPT recipients were CMV positive at transplant (P <.001). At 6 months, no differences were seen in patient and graft survival rates (GSR) and the incidence of acute rejection (AR) among the groups. However, the CMV D+/R- group had a significantly higher incidence of CMV infection/disease (14%) than the other groups collectively (4%, P <.05). Most cases of CMV infection/disease occurred greater than 3 months posttransplant when prophylaxis was discontinued. In the D-/R- group, the pancreas GSR was higher (94% vs 86% in the remaining three groups) and the incidence of AR was lower (16% vs 25% in the remaining three groups, both P =.09). Primary CMV exposure remains a major risk factor for CMV infection/disease, but does not have an adverse impact on short-term outcomes. Conversely, protective CMV seronegative matching may have a beneficial effect on outcomes.

Cytomegalovirus Infections↗

One-year outcomes in simultaneous kidney-pancreas transplant recipients receiving an alternative dosing regimen of daclizumab.

UNLABELLED: The purpose of this study was to compare the safety and efficacy of two dosing regimen of daclizumab with no-antibody induction in simultaneous kidney-pancreas transplant (SKPT) recipients receiving tacrolimus, mycophenolate mofetil, and steroids. METHODS: A total of 297 SKPT patients were enrolled into this prospective, multicenter, randomized, open-label study. The patients were randomized into three groups: daclizumab 1 mg/kg/dose every 14 days for five doses (group I, n = 107), daclizumab 2 mg/kg/dose every 14 days for two doses (group II, n = 112), and no-antibody induction (group III, n = 78). RESULTS: There were no differences in baseline characteristics among the three groups, except for a higher proportion of African-Americans in group II. The incidence of composite events (acute rejection, graft loss, or death) at 1 year was 36.4%, 32.7%, and 48.7% for groups I, II, and III, respectively (P <.05, group II vs group III). The incidence of acute rejection was highest in group III (34.6%) compared to groups I and II (22.4% and 22.1%, respectively, P <.05). The mean time to acute rejection was delayed in group II (96 days) compared to 23 days in group I and 20 days in group III (P <.05). The adverse-event profiles were comparable among the three groups, except for a higher incidence of infection and readmissions in group III. CONCLUSIONS: Daclizumab was safe and effective in reducing the incidence of acute rejection when compared to no induction. The alternative two-dose regimen of daclizumab was as effective as the conventional five-dose regimen and is logistically more desirable.

Antibodies, Monoclonal↗

Mapping of the prostate in endorectal coil-based MRI/MRSI and CT: a deformable registration and validation study.

The endorectal coil is being increasingly used in magnetic resonance imaging (MRI) and MR spectroscopic imaging (MRSI) to obtain anatomic and metabolic images of the prostate with high signal-to-noise ratio (SNR). In practice, however, the use of endorectal probe inevitably distorts the prostate and other soft tissue organs, making the analysis and the use of the acquired image data in treatment planning difficult. The purpose of this work is to develop a deformable image registration algorithm to map the MRI/MRSI information obtained using an endorectal probe onto CT images and to verify the accuracy of the registration by phantom and patient studies. A mapping procedure involved using a thin plate spline (TPS) transformation was implemented to establish voxel-to-voxel correspondence between a reference image and a floating image with deformation. An elastic phantom with a number of implanted fiducial markers was designed for the validation of the quality of the registration. Radiographic images of the phantom were obtained before and after a series of intentionally introduced distortions. After mapping the distorted phantom to the original one, the displacements of the implanted markers were measured with respect to their ideal positions and the mean error was calculated. In patient studies, CT images of three prostate patients were acquired, followed by 3 Tesla (3 T) MR images with a rigid endorectal coil. Registration quality was estimated by the centroid position displacement and image coincidence index (CI). Phantom and patient studies show that TPS-based registration has achieved significantly higher accuracy than the previously reported method based on a rigid-body transformation and scaling. The technique should be useful to map the MR spectroscopic dataset acquired with ER probe onto the treatment planning CT dataset to guide radiotherapy planning.

Algorithms↗

Observations on the use of sirolimus and tacrolimus in high-risk renal transplant recipients.

Sirolimus is the first of a group of mammalian target of rapamycin inhibitors to be introduced for clinical use in the United States. At the University of Tennessee in Memphis, we have evolved strategies for the use of sirolimus in kidney transplant recipients; which utilize the drug as a primary immunosuppressant and exploit its potential for preserving renal function. Conversions from the calcineurins to sirolimusbased immunosuppression established the efficacy of calcineurin-free immunosuppressants in selected high-risk patients. The conversion experience stimulated the design of protocols for primary use of sirolimus. Posttransplant use of sirolimus was associated with low incidence of rejection whether sirolimus was used with low-dose Prograf or in calcineurin-free protocols. Primary use with full-dose Prograf was associated with a high incidence of calcineurin-related nephrotoxicity and was abandoned in our program. Hematologic and lipid side effects were manageable, as was an observed increase in wound-healing problems and lymphocele formation. Continuous modifications of the sirolimus protocols to increase our benefit-to-risk ratio are ongoing and indicate a continued role for the drug in posttransplant immune suppression.

Dose-Response Relationship, Drug↗

Polyomavirus in kidney and kidney-pancreas transplant recipients.

PURPOSE: To report the incidence and clinical characteristics of polyomavirus (PV) nephritis in kidney (KTX) and kidney-pancreas transplant (KPTX) recipients. METHODS: Single center retrospective analysis of all cases of PV nephritis in KTX and KPTX patients transplanted between 1994 and 1999. RESULTS: Thirteen (5 KTX and 8 KPTX) patients (2.1%) had PV nephritis diagnosed on multiple biopsies (n = 22) among 504 KTX and 106 KPTX recipients. The incidence of PV nephritis was higher in cadaver donor transplants (2.6% cadaver vs. 0.7% living donors), after KPTX (1% KTX vs. 7.5% KPTX), in males (3.3% male vs. 0.7% female), and in diabetic patients (4.4% diabetic vs. 0.8% nondiabetic). The mean time to diagnosis of PV nephritis was 18 (range 6-48) months after KTX and 17 (range 9-31) months after KPTX. Three KTX patients and 5 KPTX patients had calcineurin inhibitor toxicity on biopsy prior to developing PV nephritis. Reduction in immunosuppression occurred in 100% of KTX and 63% of KPTX patients. Three patients (23%) developed rejection within 3 months of diagnosis of PV, 1 after a reduction in immunosuppression. Despite multiple antiviral treatment regimens, renal allograft failure requiring dialysis occurred in 60% of KTX and 50% of KPTX patients. All KPTX patients remain insulin independent and 2 were successfully retransplanted with living donor kidneys. 2 patients (15%) died but there was no mortality directly related to the virus. CONCLUSIONS: Polyomavirus nephritis may be increasing in incidence and appears to be unresponsive to either conventional antiviral agents or a reduction in immunosuppression. Most of our cases occurred in male diabetic patients undergoing cadaveric donor transplantation and were preceded by biopsy-proven nephrotoxicity. Further studies are needed to better define the pathogenesis of PV and effective antiviral treatment.

Adult↗