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B Kaplan

Publications and source records attributed to B Kaplan.

At least 91 records · Page 5Linked to original sources
PubMed2001

Interaction of mycophenolate mofetil and HLA matching on renal allograft survival.

INTRODUCTION: The importance of HLA matching for renal transplantation outcomes has been appreciated for several decades. It has been hypothesized that as pharmacologic immunosuppression becomes stronger and more specific, the impact of HLA matching may be vanishing. Mycophenolate Mofetil (MMF) has been demonstrated to both decrease acute rejection and improve three-year graft survival. It is possible that with new immunosuppressive regimens containing MMF the relative effect of HLA matching may be altered. To determine the relative impact of HLA matching in patients on MMF we undertook an analysis of the United States Renal Transplant Data Registry (USRDS). METHODS: All primary, solitary renal transplants registered at the USRDS between January 1995 and June 1997, on initial immunosuppression that included either MMF or AZA were followed until June 1998. Primary study end points were graft and patient survival. Kaplan-Meier analysis was performed to compare AZA vs. MMF treated patients by HLA mismatch. Cox proportional hazard models were used to investigate the interaction between HLA mismatch and AZA versus MMF therapy on the study endpoints. All multivariate analyses were corrected for 13 potential confounding pretransplant variables including intention to treat immunosuppression. RESULTS: A total of 19,675 patients were analyzed (8,459 on MMF and 11,216 on AZA). Overall three year graft survival was higher in the MMF group when compared to the AZA group (87% vs. 84% respectively P<0.001). For both AZA and MMF three-year graft survival improved with fewer HLA donor-recipient mismatches. Comparing zero antigen mismatches to six antigen mismatches, the relative improvement was comparable for both patients on AZA (92.4% vs. 80.6%) and MMF (95.2% vs. 82.9%). By Cox proportional hazard model the relative risk for graft loss decreased significantly in both the AZA and MMF treated patients with increased HLA matching. CONCLUSION: The use of MMF does not obviate the benefits of HLA matching, while HLA matching does not minimize the benefits of MMF on long term graft survival. Our study would suggest that HLA matching and MMF therapy are additive factors in decreasing the risk for renal allograft loss.

Azathioprine↗
PubMed2001

Gender differences in the risk for chronic renal allograft failure.

BACKGROUND: Despite the known differences in immunological reactivity between males and females, no differences in graft survival have been described among renal transplant recipients with regard to gender. To address this paradox, we analyzed data from 73,477 primary renal transplants collected in the US Renal Data System database. METHODS: Logistic regression and Cox proportional hazard models were used to investigate the primary study end points, graft loss secondary to acute rejection (AR) or chronic allograft failure (CAF). CAF was defined as graft loss beyond 6 months, not attributable to death, recurrent disease, acute rejection, thrombosis, infection, noncompliance, or technical problems. The models adjusted for 15 covariates including immunosuppressive regimen, and donor and recipient characteristics. RESULTS: The overall 8-year graft and patient survivals were significantly better in female renal transplant recipients compared with male recipients. However graft survival censored for death was not significantly different by gender. By multivariate analysis, females had a 10% increased odds of AR (OR=1.10, CI 1.02-1.12), but conversely a 10% lower risk of graft loss secondary to CAF (RR=0.9, CI 0.85-0.96). The risk for CAF increased significantly with increasing age for both males and females, but this effect was greater for males than for females (P<0.001). CONCLUSION: Although female renal transplant recipients have a similar death censored graft survival compared with males, there are important differences in immunological behavior. Females have a higher risk of AR while having a decreased risk of graft loss secondary to CAF.

Chronic Disease↗
PubMed2001

The impact of simultaneous pancreas-kidney transplantation on long-term patient survival.

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) ameliorates the progression of microvascular diabetic complications but the procedure is associated with excess initial morbidity and an uncertain effect on patient survival when compared with solitary cadaveric or living donor renal transplantation. We evaluated mortality risks associated with SPK, solitary renal transplantation, and dialysis treatment in a national cohort of type 1 diabetics with end-stage nephropathy. METHODS: A total of 13,467 adult-type 1 diabetics enrolled on the renal and renal-pancreas transplant waiting list between 10/01/88 and 06/30/97 were followed until 06/30/98. Time-dependent mortality risks and life expectancy were calculated according to the treatment received subsequent to wait-list registration: SPK; cadaveric kidney only (CAD); living donor kidney only (LKD) transplantation; and dialysis [wait-listed, maintenance dialysis treatment (WLD)]. RESULTS: Adjusted 10-year patient survival was 67% for SPK vs. 65% for LKD recipients (P=0.19) and 46% for CAD recipients (P<0.001). The excess initial mortality normally associated with renal transplantation and the risk of early infectious death was 2-fold higher in SPK recipients. The time to achieve equal proportion of survivors as the WLD patients was 170, 95, and 72 days for SPK, CAD, and LKD recipients, respectively (P<0.001). However, the adjusted 5-year morality risk (RR) using WLD as the reference and the expected remaining life years were 0.40, 0.45, and 0.75 and 23.4, 20.9, and 12.6 years for SPK, LKD, and CAD, respectively. There was no survival benefit in SPK recipients > or =50 years old (RR=1.38, P=0.81). CONCLUSIONS: Among patients with type 1 DM with end-stage nephropathy, SPK transplantation before the age of 50 years was associated with long-term improvement in survival compared to solitary cadaveric renal transplantation or dialysis.

Adult↗
PubMed2001

Evaluating informatics applications--clinical decision support systems literature review.

This paper reviews clinical decision support systems (CDSS) literature, with a focus on evaluation. The literature indicates a general consensus that clinical decision support systems are thought to have the potential to improve care. Evidence is more equivocal for guidelines and for systems to aid physicians with diagnosis. There also is general consensus that a variety of systems are little used despite demonstrated or potential benefits. In the evaluation literature, the main emphasis is on how clinical performance changes. Most studies use an experimental or randomized controlled clinical trials design (RCT) to assess system performance or to focus on changes in clinical performance that could affect patient care. Few studies involve field tests of a CDSS and almost none use a naturalistic design in routine clinical settings with real patients. In addition, there is little theoretical discussion, although papers are permeated by a rationalist perspective that excludes contextual issues related to how and why systems are used. The studies mostly concern physicians rather than other clinicians. Further, CDSS evaluation studies appear to be insulated from evaluations of other informatics applications. Consequently, there is a lack of information useful for understanding why CDSSs may or may not be effective, resulting in making less informed decisions about these technologies and, by extension, other medical informatics applications.

Decision Support Systems, Clinical↗
PubMed2001

Evaluating informatics applications--some alternative approaches: theory, social interactionism, and call for methodological pluralism.

A review of evaluation literature concerning CDSSs indicates that randomized controlled clinical trials (RCTs) are the 'gold standard' for evaluation. While this approach is excellent for studying system or clinical performance, it is not well suited to answering questions concerning whether systems will be used or how they will be used. Because lack of use of CDSS has been of concern for some years, other evaluation research designs are needed to address those issues. This paper critiques RCT and experimental evaluation approaches and presents alternative approaches to evaluation that address questions outside the scope of the usual RCT and experimental designs. A wide range of literature is summarized to illustrate the value of evaluations that take into account social, organizational, professional, and other contextual considerations. Many of these studies go beyond the usual measures of systems performance or physicians' behavior by focusing on 'fit' of the system with other aspects of professional and organizational life. Because there is little explicit theory that informs many evaluations, the paper then reviews CDSS evaluations informed by social science theories. Lastly, it proposes a theoretical social science base of social interactionism. An example of such an approach is given. It involves a CDSS in psychiatry and is based on Kaplan's 4Cs, which focus on communication, control, care, and context. Although the example is a CDSS, the evaluation approach also is useful for clinical guideline implementation and other medical informatics applications. Similarly, although the discussion is about social interactionism, the more important point is the need to broaden evaluation through a variety of methods and approaches that investigate social, cultural, organizational, cognitive, and other contextual concerns. Methodological pluralism and a variety of research questions can increase understanding of many influences concerning informatics applications development and deployment.

Attitude↗
PubMed2001

Differential influence of azathioprine and mycophenolate mofetil on the disposition of basiliximab in renal transplant patients.

Pharmacokinetic sampling was performed in two multicenter trials in which basiliximab (anti-CD25 monoclonal antibody) was administered with triple immunosuppression consisting of cyclosporine microemulsion, corticosteroids, and either azathioprine or mycophenolate mofetil. Blood samples were collected over 12 wk post-transplant from 31 azathioprine-treated and 66 mycophenolate mofetil-treated patients. Empirical Bayes estimates of each patient's basiliximab disposition parameters were derived and the duration of CD25 saturation was estimated as the time over which serum concentrations exceeded 0.2 microg/mL as confirmed by flow cytometry measurements. Basiliximab clearance was 29+/-14 mL/h when coadministered with azathioprine and 18+/-8 mL/h with mycophenolate mofetil. Both were significantly lower compared with a clearance of 37+/-15 mL/h from a previous study of basiliximab with dual therapy (p<0.001). As a consequence of the lower clearance of basiliximab, the durations of CD25 saturation were prolonged in the presence of azathioprine (50+/-20 d; range, 13--84) and mycophenolate mofetil (59+/-17 d; range, 28--94) compared with dual therapy (36+/-14 d; range, 12--91). A total of 27 acute rejection episodes occurred during the first 6 months in the two studies. Durations of CD25 saturation were not different in these patients compared with those who remained rejection-free in each study. A single patient among 57 who were screened developed anti-idiotype antibodies to basiliximab. The average duration of CD25 saturation was prolonged by 39 and 64% in the presence of azathioprine and mycophenolate mofetil, respectively. This graded effect was also observed for basiliximab clearance and may be due in part to a differentially reduced humoral response to basiliximab. Nonetheless, the range of CD25 saturation durations and basiliximab clearances did not extend outside the range when basiliximab was used with dual therapy in the absence of these agents. Hence, no dosing adjustment is deemed necessary when basiliximab is used in triple immunosuppressive therapy including either azathioprine or mycophenolate mofetil.

Antibodies, Anti-Idiotypic↗
PubMed2001

Effects of epidermal growth factor in artificial tear on vitamin C levels of corneal wounded eye tissues.

PURPOSE: To investigate the effect of artificial tear (AT) solution and epidermal growth factor (EGF) treatment on the cornea and aqueous humour ascorbic acid (AA) levels of full-thickness corneal wounded eyes. METHODS: The effect of EGF on the AA levels of aqueous humour and corneal wound tissue was determined in full-thickness corneal wounded rabbit eyes on the seventh post-operative day. There were three groups: untreated controls, AT-treated controls and an EGF+AT-treated experimental group (n = 6 in each group). Corneal wounded eyes were topically treated with 5 microl AT or 5 microl EGF in AT (1 mg/l EGF in AT prepaaration which contained 3.0% carbopol 940) twice daily for 6 days after operation. The wound strengths were also measured on the seventh post-operative day as a measure of wound healing. Statistical analysis was carried out using the Mann-Whitney U-test by Statview program. RESULTS: The wound strengths of corneas, and AA levels of wound tissues and aqueous humour, increased significantly following AT and EGF treatment (p < 0.05). CONCLUSION: In the corneal wounded eye, aqueous humour serves as a source of vitamin C and there may be a relation between EGF treatment in AT and AA levels of corneal wounded eye tissues.

Animals↗
PubMed2001

Real-time intraoperative ultrasound guidance: the transrectal approach.

OBJECTIVE: To assess the role of real-time transrectal ultrasound guidance in complicated gynecologic procedures. DESIGN: In 1998-99, real-time guidance with transrectal ultrasound was utilized in our department to assist the gynecologic surgeon in two procedures: completing the evacuation of the uterine cavity after identification of uterine wall perforation during first trimester termination of pregnancy, and drainage of infected vaginal vault hematoma following hysterectomy. RESULTS: The technique was applied for 11 patients, six abortions and five infected hematomas. All the procedures were completed without any further complications and the patients were discharged on the following day. Follow-up was uneventful. CONCLUSIONS: On-line intraoperative transrectal ultrasound can effectively provide real-time assistance to the gynecologic surgeon during complicated pelvic procedures.

Abortion, Induced↗
PubMed2001

Exponentially increased risk of infectious death in older renal transplant recipients.

BACKGROUND: The benefit of renal transplantation for patients with end-stage renal disease (ESRD) has been well documented. This benefit is seen throughout all age ranges of patients. However, it has been documented that older renal transplant recipients are at increased risk for death because of infectious causes when compared with younger recipients. The present study addresses whether this increased risk merely parallels an age-related increase in infectious mortality or is reflective of a particular vulnerability in older renal transplant recipients. METHODS: Patients wait-listed and transplanted between 1988 and 1997 were analyzed utilizing the United States Renal Data System (USRDS) database. The primary study end point was patient death secondary to infection. Secondary end points included death secondary to cardiovascular cause and malignancy. Cox-proportional hazard models were utilized with all pertinent variables. RESULTS: Death related to infectious cause increased exponentially in transplanted patients with increasing age (slope = 2.90.34x), while it increased linearly (slope = 1.9x + 8.6) with increasing age for those patients on the waiting list. Overall mortality increases with age were equal between the wait-listed and transplanted groups. CONCLUSIONS: The overall survival benefit of transplantation is maintained in the older age groups. However, renal transplantation is associated with an increased risk for infectious death beyond the expected age-related increased risk in patients on the renal transplant waiting list. This may have an impact on future immunosuppressive regimens in this population.

Adult↗
PubMed2001

Longitudinal assessment of everolimus in de novo renal transplant recipients over the first post-transplant year: pharmacokinetics, exposure-response relationships, and influence on cyclosporine.

OBJECTIVE: Our objective was to characterize the steady-state pharmacokinetics of everolimus and cyclosporine (INN, ciclosporin) when coadministered in de novo kidney allograft recipients during the first year after transplantation. METHOD: This study was a multicenter randomized double-blind study of 101 patients who were randomly assigned 1:1:1 to receive everolimus tablets at doses of 0.5 mg, 1 mg, or 2 mg twice daily with cyclosporine and prednisone. Blood sampling for the pharmacokinetics of everolimus and cyclosporine was performed on day 1, on weeks 1, 2, 3, and 4, and on months 2, 3, 6, 9, and 12. Everolimus dose-proportionality and stability over time were assessed in the context of linear regression and ANOVA models. Everolimus exposure-response relationships between area under the blood concentration-time curve (AUC) and changes in platelets, leukocytes, and lipids were explored with the median-effect model. Potential differences in cyclosporine dosing and pharmacokinetics at different levels of everolimus exposure were assessed in the context of ANOVA. RESULTS: Everolimus steady state was reached on or before day 7, with a median 3-fold accumulation of drug exposure compared with that after the first postoperative dose. Both steady-state maximum concentration and AUC were dose proportional over the full dose range when assessed on day 1, as well as for the full duration of the study at steady state. There was evidence for longitudinal stability in AUC of everolimus during the course of the study. The interindividual pharmacokinetic variability for AUC was 85.4% and intraindividual, interoccasion variability was 40.8%. Age (range, 17-69 years), weight (range, 49-106 kg), and sex (65 men and 36 women) were not significant contributors to variability. There was an increasing incidence of transient thrombocytopenia (< or =100 x 10(9)/L) with increasing everolimus AUC (P = .03). Cyclosporine doses, trough concentrations, and AUC exhibited similar temporal patterns during the course of the study regardless of the co-administered everolimus dose level (P = .13, .82, and .76, respectively). CONCLUSIONS: Everolimus exhibited dose-proportional, stable exposure during the first post-transplant year. For a 4-fold range of everolimus doses there were no differential effects on cyclosporine dosing or pharmacokinetics.

Administration, Oral↗
PubMed2001

Neuropsychological effects of prefrontal slow rTMS in normal volunteers: a double-blind sham-controlled study.

Recent reports have suggested that repetitive transcranial magnetic stimulation (rTMS) is effective in major depression. Unlike ECT, rTMS does not involve a seizure and is associated with minimal side-effects, including cognitive difficulties. However, the effect of rTMS on cognitive functioning has not been systematically evaluated. This study was designed to examine the neuropsychological effects of slow rTMS in normal volunteers. Forty-six normal volunteers were randomly assigned to receive one session of right (N = 16) or left prefrontal (N = 15), or sham (N = 15) rTMS at 1 HZ. Patients were assessed before and after stimulation by a computerized neurospychological battery. All three groups showed significant improvement over time in processing speed (reaction time) and efficiency (correct responses per unit of time). However, no time by group interaction was found for any of the neuropsychological tests. These findings suggest that a single session of slow rTMS does not interfere with neurospychological functioning in normal volunteers, supporting clinical reports of no adverse cognitive effects.

Adult↗
PubMed2001

An economic and quality-of-life assessment of basiliximab vs antithymocyte globulin immunoprophylaxis in renal transplantation.

BACKGROUND: Immunosuppressive therapy with cyclosporin A has substantially improved clinical outcomes for renal transplantation. Whether basiliximab (a chimeric monoclonal antibody) demonstrates economic and quality-of-life advantages over other induction therapies has not yet been shown. METHODS: A multi-centre open-label clinical trial was conducted among renal transplant recipients in the US, in which patients were randomized into two induction therapy regimens: basiliximab and antithymocyte globulin (ATG) as part of a quadruple immunosuppressive regimen. Medical resources used and a EuroQol visual analogue scale (VAS) rating of quality of life were collected prospectively for the 135 dosed subjects for a period of 1 year post-treatment. We analysed the differences between treatment groups in 1-year costs and 1-year quality-adjusted survival. We also conducted a post hoc analysis of outcomes among the subgroup of patients identified as high risk. RESULTS: A significant difference was observed in first-year post-treatment costs (basiliximab, $45857; ATG, $54729; difference, $8872 (95% CI, $1169 to $16573). The savings from basiliximab can be attributed to the less expensive induction therapy (basiliximab, $2378; ATG, $8670; difference, $6292 (95% CI, $5165 to $7419)) and other savings during the initial hospitalization totalling $2609. One-year quality-adjusted survival was the same in both groups (basiliximab, 81.5; ATG, 81.1; difference, 0.45 (95% CI, -5.9 to 6.8)). The results of the post hoc analysis of the 48 high-risk patients were comparable to the analysis of all patients. CONCLUSIONS: These results demonstrate lower first-year post-treatment costs in renal-transplant recipients receiving basiliximab compared to ATG with no differences in quality-adjusted survival. The results also suggest similar differences among high-risk subjects.

Antibodies, Monoclonal↗
PubMed2001

Immunosuppression in elderly renal transplant recipients: are current regimens too aggressive?

Renal transplantation is an accepted and successful treatment modality in elderly patients with end-stage renal disease. In comparison with maintenance dialysis, transplantation has been shown to confer a mortality benefit as well as improvements in quality of life in older individuals with end-stage renal disease. Despite this, overall outcomes of renal transplantation in elderly individuals have, in general, been less successful than those of younger renal transplant recipients. Largely, this has been due to the particular vulnerability of elderly patients to the immunosuppressive medications used in renal transplantation. This review article covers these issues in some detail and briefly discusses some of the pharmacokinetic, pharmacodynamic, physiological and immunological differences between younger and older transplant recipients. Elderly renal transplant recipients have both a higher rate of patient death and allograft loss censored for death. Upon multivariate analysis, age of the recipient is strongly associated with allograft loss independent of other known factors. Acute rejections are less frequent in older individuals; however the consequence of a rejection if it occurs is negative for long-term graft survival. On the other hand, death by infection is vastly increased in older versus younger renal transplant recipients. In general, the pharmacokinetics of the immunosuppressive agents are little affected by age, but the tolerance to these agents seems to decrease with increasing age. Elderly renal transplant recipients present a very difficult clinical challenge. As the elderly become an ever-increasing segment of the renal transplant population, new and innovative immunosuppressive strategies will have to be considered and applied.

Aged↗
PubMed2001

Role of anti-interleukin-2 receptor antibodies in kidney transplantation.

From the early 1960s, the mainstay of immunosuppression for kidney transplantation has been corticosteroids. Since then, many new drugs have been developed to maintain the renal allograft. Current maintenance immunosuppression commonly consists of corticosteroids, antiproliferative agents and calcineurin inhibitors (e.g. cyclosporin). More recently, antihuman antibodies, either monoclonal or polyclonal, have been developed to use for induction at the time of transplantation or to treat rejection. With the advances in molecular technology, a new class of antihuman antibodies [the anti-interleukin-2 receptor (IL-2R) antibodies] has emerged that incorporate a murine antigen-binding site on to a human immunoglobulin backbone. Such methodology creates antihuman antibodies with high affinity for the epitope and with prolonged serum antibody half-lives. Interleukin-2 and its receptor are central to lymphocyte activation and are the main targets of calcineurin inhibitors. In addition, the anti-IL-2R antibodies inhibit a key target in immune activation. Daclizumab and basiliximab have been shown to significantly reduce the incidence of acute rejection in kidney transplantation. Since these anti-IL-2R antibodies are well tolerated and since calcineurin inhibitors are intrinsically nephrotoxic, anti-IL-2R antibodies have been used in an attempt to avoid cyclosporin after transplantation. Data from clinical trials seem to indicate that the addition of an anti-IL-2R antibody is not sufficient to warrant complete withdrawal of calcineurin inhibitors for more than a very short period after transplantation. A more promising role for anti-IL-2R antibodies may be in renal transplant recipients with delayed graft function (DGF). Recent data on the use of either low-dose calcineurin inhibitors or sirolimus (rapamycin) in conjunction with the anti-IL-2R antibodies for patients with DGF showed no increased risk of acute rejection. Long-term graft survival with use of these low-dose calcineurin inhibitor protocols has yet to be established.

Animals↗
PubMed2001

Micro-method to isolate and purify amyloid proteins for chemical characterization.

The amyloidoses represent a heterogeneous group of disorders characterized by the pathologic deposition as fibrils of at least 20 different precursor molecules. To establish definitively the specific type of amyloid protein contained in fibrillar deposits, such material must be extracted, purified, and subjected to amino acid sequence analysis. Heretofore, the chemical identification of amyloid components has required gram quantities of tissue. Given the often-limited amounts of sample available, e.g., that derived from diagnostic needle biopsies, we have developed a micro-method to isolate and purify amyloid from minute tissue specimens. The procedure involves micro-extraction of the amyloid with subsequent purification by SDS-PAGE, electroblotting onto PVDF membranes, excision and elution of amyloid protein-related bands, and reversed phase HPLC. Chemical and immunologic studies of isolated amyloid components have demonstrated the purity achieved with this technique and have provided information on the molecular mass, heterogeneity, and immunoreactivity of the amyloid. Further, using this methodology, it has been possible to obtain sufficient material for amino acid sequencing and thus to establish unequivocally the chemical and molecular composition of the fibrillar deposits. Our microtechnique has clinical import and also is applicable to analyses of the amyloid found in experimental small animal models of these disorders.

Amino Acid Sequence↗
PubMed2001

Removal of basiliximab by plasmapheresis.

Basiliximab is a chimeric monoclonal antibody directed against the alpha chain of interleukin-2 (IL-2) receptors. Given its expected volume of distribution (plasma volume), therapeutic plasmapheresis may be expected to lower serum Basiliximab levels. A 20-mg dose of Basiliximab was given before plasmapheresis. Blood and pheresis fluid samples were obtained to monitor Basiliximab levels. A total of three blood samples were drawn: the first was obtained 4 hours before, the second sample immediately before commencement, and the third 2 hours after cessation of plasmapheresis. A fourth sample was obtained from the removed plasma. There was an appreciable reduction in Basiliximab concentration levels after plasmapheresis. From the change in serum concentration after plasmapheresis, approximately 64.6% of circulating Basiliximab was removed. Plasmapheresis removes substantial amounts of Basiliximab. Therefore, supplemental Basiliximab should be given after plasmapheresis to maintain the desired duration of IL-2R saturation.

Antibodies, Monoclonal↗