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Biomedical subjects

J Burdick

Publications and source records attributed to J Burdick.

At least 19 recordsLinked to original sources
PubMed2006

Organ donation and utilization, 1995-2004: entering the collaborative era.

Continued progress in organ donation will help enable transplantation to alleviate the increasing incidence of end-stage organ disease. This article discusses the implementation and effect of the federally initiated Organ Donation Breakthrough Collaborative; it then reviews organ donation data, living and deceased, from 1995 to 2004. It is the first annual report of the Scientific Registry of Transplant Recipients to include national data following initiation of the collaborative in 2003. Prior to that, annual growth in deceased donation was 2%-4%; in 2004, after initiation of the collaborative, deceased donation increased 11%. Identification and dissemination of best practices for organ donation have emphasized new strategies for improved consent, including revised approaches to minority participation, timing of requests and team design. The number of organs recovered from donation after cardiac death (DCD) grew from 64 in 1995 to 391 in 2004. While efforts are ongoing to develop methodologies for identifying expanded criteria donors (ECD) for organs other than kidney, it is clear DCD and ECD raise questions regarding cost and recovery. The number of living donor organs increased from 3493 in 1995 to 7002 in 2004; data show trends toward more living unrelated donors and those providing non-directed donations.

Ethnicity↗
PubMed2005

Exposure data for cosmetic products: lipstick, body lotion, and face cream.

Accurate exposure information for cosmetic products and ingredients is needed in order to conduct safety assessments. Essential information includes both the amount of cosmetic product applied, and the frequency of use. To obtain current data, a study to assess consumer use practices was undertaken. The study included three widely used cosmetic product types: lipstick, body lotion, and face cream. Three hundred and sixty women, ages 19-65 years, who regularly use the products of interest, were recruited at ten different geographical locations within the US. The number of recruits was chosen to ensure a minimum of 300 completes per product type. Subjects were provided with prototype test products, and kept diaries and recorded detailed daily usage information over a two week period. Products were weighed at the start and completion of the study in order to determine the total amount of product used. Statistical analysis of the data was conducted to derive summary distribution of use patterns. The mean and median usage per application, respectively, for the three products was: face cream, 1.22 g and 0.84 g; lipstick, 10 mg and 5 mg; and body lotion, 4.42 g and 3.45 g. The mean and median usage per day for the three products was: face cream, 2.05 g and 1.53 g; lipstick, 24 mg and 13 mg; and body lotion, 8.70 g and 7.63 g. The mean number of applications per day for face cream and lipstick was 1.77 and 2.35, respectively. For body lotion, the mean number of applications per day was dependent on body area, and was 2.12, 1.52, 1.11, 0.95, 0.43, 0.26, and 0.40 for hands, arms, legs, feet, neck and throat, back, and other body areas, respectively. The effect of product preference on use practices was also investigated. This study provides current cosmetic exposure information for commonly used products which will be useful for risk assessment purposes.

Administration, Topical↗
PubMed2004

Augmentation of T-cell apoptosis by immunosuppressive agents.

The regulatory benefit of apoptosis (activation-induced cell death, AICD) in T cells can be influenced by immunosuppressive agents. We examined this for mycophenolate mofetile (MMF, using it's active metabolite, mycophenolate (MPA)) compared with rapamycin (RAPA) and the calcineurin inhibitors (CI) cyclosporin (CYA) and FK506 (FK). Pure T cells from peripheral blood leucocytes (PBL) were stimulated by anti-CD3 plus anti-CD28. Cell division (sequential cohort reduction in carboxyflourescein diacetate succinimidyl ester, CFSE) was used to measure proliferation and determine status of different cell generations without or with added drug at 4 d. Apoptosis was measured by Annexin V staining of activated cells using flow cytometry. We confirmed in this stringent system the inhibition of AICD by CI and showed that RAPA is intermediate and MPA most effective in this potentiation of AICD.

Apoptosis↗
PubMed2001

GenMapDB: a database of mapped human BAC clones.

GenMapDB (http://genomics.med.upenn.edu/genmapdb) is a repository of human bacterial artificial chromosome (BAC) clones mapped by our laboratory to sequence-tagged site markers. Currently, GenMapDB contains over 3000 mapped clones that span 19 chromosomes, chromosomes 2, 4, 5, 9-22, X and Y. This database provides positional information about human BAC clones from the RPCI-11 human male BAC library. It also contains restriction fragment analysis data and end sequences of the clones. GenMapDB is freely available to the public. The main purpose of GenMapDB is to organize the mapping data and to allow the research community to search for mapped BAC clones that can be used in gene mapping studies and chromosomal mutation analysis projects.

Chromosome Mapping↗
PubMed2001

In vitro effects of photodynamic therapy on Aspergillus fumigatus.

Photodynamic therapy is a technique for killing cells with visible light after pretreatment with a photosensitizing agent. We demonstrated significant in vitro fungicidal activity against Aspergillus fumigatus of the photosensitizer Green 2W, activated with 630 nm light. This effect was both inoculum- and light dose-dependent. At a Green 2W concentration of 31.5 mg/L, there was complete killing of 2.7 x 10(1) cfu/mL with a light dose of 110 J/cm(2) and up to 2.7 x 10(6) cfu/mL with a light dose of 385 J/cm(2).

Aspergillus fumigatus↗
PubMed2000

Consensus statement on the live organ donor.

OBJECTIVE: To recommend practice guidelines for transplant physicians, primary care providers, health care planners, and all those who are concerned about the well-being of the live organ donor. PARTICIPANTS: An executive group representing the National Kidney Foundation, and the American Societies of Transplantation, Transplant Surgeons, and Nephrology formed a steering committee of 12 members to evaluate current practices of living donor transplantation of the kidney, pancreas, liver, intestine, and lung. The steering committee subsequently assembled more than 100 representatives of the transplant community (physicians, nurses, ethicists, psychologists, lawyers, scientists, social workers, transplant recipients, and living donors) at a national conference held June 1-2, 2000, in Kansas City, Mo. CONSENSUS PROCESS: Attendees participated in 7 assigned work groups. Three were organ specific (lung, liver, and kidney) and 4 were focused on social and ethical concerns (informed consent, donor source, psychosocial issues, and live organ donor registry). Work groups' deliberations were structured by a series of questions developed by the steering committee. Each work group presented its deliberations to an open plenary session of all attendees. This information was stored and shaped into a statement circulated electronically to all attendees for their comments, and finally approved by the steering committee for publication. The term consensus is not meant to convey universal agreement of the participants. The statement identifies issues of controversy; however, the wording of the entire statement is a consensus by approval of all attendees. CONCLUSION: The person who gives consent to be a live organ donor should be competent, willing to donate, free from coercion, medically and psychosocially suitable, fully informed of the risks and benefits as a donor, and fully informed of the risks, benefits, and alternative treatment available to the recipient. The benefits to both donor and recipient must outweigh the risks associated with the donation and transplantation of the living donor organ.

Health Status↗
PubMed2000

Plasmapheresis and intravenous immune globulin provides effective rescue therapy for refractory humoral rejection and allows kidneys to be successfully transplanted into cross-match-positive recipients.

BACKGROUND: Hyperacute rejection (HAR) and acute humoral rejection (AHR) remain recalcitrant conditions without effective treatments, and usually result in graft loss. Plasmapheresis (PP) has been shown to remove HLA- specific antibody (Ab) in many different clinical settings. Intravenous gamma globulin (IVIG) has been used to suppress alloantibody and modulate immune responses. Our hypothesis was that a combination of PP and IVIG could effectively and durably remove donor-specific, anti-HLA antibody (Ab), rescuing patients with established AHR and preemptively desensitizing recipients who had positive crossmatches with a potential live donor. METHODS: The study patients consisted of seven live donor kidney transplant recipients who experienced AHR and had donor-specific Ab (DSA) for one or more mismatched donor HLA antigens. The patients segregated into two groups: three patients were treated for established AHR (rescue group) and four cross-match-positive patients received therapy before transplantation (preemptive group). RESULTS: Using PP/IVIG we have successfully reversed established AHR in three patients. Four patients who were cross-match-positive (3 by flow cytometry and 1 by cytotoxic assay) and had DSA before treatment underwent successful renal transplantation utilizing their live donor. The overall mean creatinine for both treatment groups is 1.4+/-0.8 with a mean follow up of 58+/-40 weeks (range 17-116 weeks). CONCLUSIONS: In this study, we present seven patients for whom the combined therapies of PP/IVIG were successful in reversing AHR mediated by Ab specific for donor HLA antigens. Furthermore, this protocol shows promise for eliminating DSA preemptively among patients with low-titer positive antihuman globulin-enhanced, complement-dependent cytotoxicity (AHG-CDC) cross-matches, allowing the successful transplantation of these patients using a live donor without any cases of HAR.

Adult↗
PubMed2000

Surface and bulk modifications to photocrosslinked polyanhydrides to control degradation behavior.

A unique class of surface-eroding polyanhydrides was developed and explored for use in medical applications requiring high-strength biomaterials (e.g., orthopedics). In particular, dimethacrylated anhydride monomers were synthesized that photopolymerize quickly to render densely crosslinked polymer networks that degrade from the surface only by hydrolysis of labile anhydride linkages. Previous research on these materials has shown that the rate of hydrolysis of the degradable linkages is dependent on the hydrophobicity of the network composition. This article demonstrates the versatility in controlling the degradation process and resulting cellular response in these materials through the incorporation of new chemistries and the formation of polymer-polymer composite structures. Specifically, the rate of mass loss was controlled by the addition of hydrophobic linear polymers [e.g., poly(methyl methacrylate)] or monovinyl monomers based on hydrophobic natural components (e.g., cholesterol, steric acid). In addition, a newly established photografting method was used to modify the network surface chemistry with cholesterol- and stearic acid-based polymer grafts to control the degradation front and cellular interactions at the polymer-tissue interface. Finally, a porogen leaching method was used to form porous polyanhydride constructs, which can be subsequently filled with osteoblasts photoencapsulated in a hydrogel, as potential synthetic allograft materials for tissue engineering bone.

Anhydrides↗
PubMed2000

Laparoscopic live donor nephrectomy: the recipient.

BACKGROUND: Laparoscopic live donor nephrectomy offers advantages to the donor in terms of decreased pain and shorter recuperation. Heretofore no detailed analysis of the recipient of laparoscopically procured kidneys has been performed. The purpose of this study was to determine whether laparoscopic donor nephrectomy had any deleterious effect on the recipient. METHODS: A retrospective review was conducted of all live donor renal transplantations performed from January 1995 through April 1998. The control group received kidneys procured via a standard flank approach (Open). Rejection was diagnosed histologically. Creatinine clearance was calculated using the Cockroft-Gault formula. RESULTS: A total of 110 patients received kidneys from laparoscopic (Lap) and 48 from open donors. One-year recipient (100% vs. 97.0%) and graft (93.5% vs. 91.1%) survival rates were similar for the Open and Lap groups, respectively. A similar incidence of vascular thrombosis (3.4% vs. 2.1%, P=NS) and ureteral complications (9.1% vs. 6.3%, P=NS) were seen in the Lap and Open groups, respectively. The incidence of acute rejection for the first month was 30.1% for the Lap group and 31.9% for the Open group (P=NS). The rate of decline of serum creatinine level in the early posttransplantation period was initially greater in the Open group, but by postoperative day 4 no significant difference existed. No difference was observed in allograft function long-term. The median length of hospital stay was 7.0 days for both groups. CONCLUSIONS: Laparoscopic live donor nephrectomy does not adversely effect recipient outcome. The previously demonstrated benefits to the donor, and the increased willingness of individuals to undergo live kidney donation, coupled with the acceptable outcomes experienced by recipients of laparoscopically procured kidneys justifies the continued development and adoption of this operation.

Acute Disease↗
PubMed1999

Reduced intrapatient variability of cyclosporine pharmacokinetics in renal transplant recipients switched from oral Sandimmune to Neoral.

Sixty-six renal transplant patients maintained on Sandimmune, the traditional formulation of cyclosporine, participated in an open-label, sequential trial to compare intrapatient variability in drug exposure before and after a switch to Neoral. Three 12-hour cyclosporine pharmacokinetic profiles were obtained over approximately 6 weeks while patients were receiving Sandimmune. Patients were then switched to Neoral, with the dose adjusted as necessary to maintain target trough blood cyclosporine concentrations. At approximately 4 and 6 weeks postconversion, 2 additional pharmacokinetic profiles were obtained. Key pharmacokinetic variables analyzed were area under the concentration-time curve (AUC), maximum concentration (Cmax), and predose trough concentration (C0). Intrapatient variability in drug exposure for dose-normalized mean AUC, Cmax, and C0 was significantly reduced with Neoral, with 50 (76%), 57 (86%), and 45 (68%) patients experiencing reduced variability in AUC, Cmax, and C0, respectively (P < 0.001). Additionally, the total exposure to cyclosporine was more predictable from the trough level of cyclosporine with Neoral; the relationship between AUC and C0 was 0.81 for Neoral at both pharmacokinetic profiling time points but ranged from 0.49 to 0.69 for the 3 Sandimmune time points. The large reductions in intrapatient variability of pharmacokinetic variables for cyclosporine provided by Neoral indicate an improvement in the consistency of drug exposure, which may translate into important clinical benefits.

Adult↗
PubMed1999

Lymphocyte suppression by rolipram with other immunosuppressive drugs.

Pentoxifylline, a nonselective phosphodiesterase inhibitor, has immunomodulatory activity in vitro and in vivo and potentiates the suppressive effects of glucocorticoids and cyclosporine on lymphocyte proliferation in vitro. Since phosphodiesterase isotypes 3 and 4 predominate in lymphocytes, the authors measured the suppressive effect of rolipram alone and in combination with low concentrations of methylprednisolone and calcineurin enzyme inhibitors, compared to that of pentoxifylline on mitogen-stimulated lymphocyte proliferation. The percent inhibition of 3H-thymidine incorporation by both 10(-5) and 10(-8) mol/L concentrations of rolipram were significantly greater than that by both 10(-4) mol/L pentoxifylline and 10(-8) mol/L methylprednisolone. The percent inhibition by the combination of 10(-5), but not 10(-6), mol/L rolipram and methylprednisolone was significantly greater than that by 10(-4) mol/L pentoxifylline and methylprednisolone. Potentiation of the suppressive effects of cyclosporine and tacrolimus by rolipram was less consistent. Measurement of cell culture supernatant concentrations of interferon gamma and interleukin-10 indicate that one of the mechanisms underlying the immunosuppressive activity of rolipram is a significantly disproportionate inhibition of the proinflammatory cytokine, interferon gamma.

Adult↗
PubMed1998

Baseline glomerular size as a predictor of function in human renal transplantation.

BACKGROUND: Nonimmune mechanisms have been implicated in chronic renal allograft injury. In experimental studies, a strong correlation exists between glomerular size and the degree of glomerular sclerosis that develops after subtotal nephrectomy. Therefore, we assessed the impact of glomerular maximal planar area (MPA) in baseline biopsy specimens of human renal allografts on later graft function. METHODS: The MPA was measured, by point counting and by computer planimetry, in postperfusion biopsy specimens from 96 allograft kidneys from nonhypertensive donors that had functioned for at least 2 years. Clinical data were analyzed throughout a follow-up period averaging 7.46+/-2.46 years. RESULTS: Both methods produced equivalent estimates of MPA. MPA proved to be a strong predictor of late renal allograft function, with a significant correlation (P = 0.02 to P < 0.01) between MPA at baseline and later serum creatinine level and creatinine clearance, beginning at 6 months after transplantation and persisting through follow-up. Creatinine level at discharge and occurrence of rejection were also independent predictors, whereas donor age, gender and race, cold ischemia time, cadaveric versus living donor, delay in initial function, and HLA mismatch did not predict clinical outcome. CONCLUSION: Larger glomeruli at baseline, measured by a simple point-counting technique, provide an early predictor of risk for late allograft dysfunction and may identify a subpopulation of patients in whom treatment to prevent/ameliorate glomerular enlargement and/or hypertension may be efficacious.

Adolescent↗
PubMed1998

Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple Therapy Study Group.

BACKGROUND: Monoclonal antibodies that block the high-affinity interleukin-2 receptor expressed on alloantigen-reactive T lymphocytes may cause selective immunosuppression. Daclizumab is a genetically engineered human IgG1 monoclonal antibody that binds specifically to the alpha chain of the interleukin-2 receptor and may thus reduce the risk of rejection after renal transplantation. METHODS: We administered daclizumab (1.0 mg per kilogram of body weight) or placebo intravenously before transplantation and once every other week afterward, for a total of five doses, to 260 patients receiving first cadaveric kidney grafts and immunosuppressive therapy with cyclosporine, azathioprine, and prednisone. The patients were followed at regular intervals for 12 months. The primary end point was the incidence of biopsy-confirmed acute rejection within six months after transplantation. RESULTS: Of the 126 patients given daclizumab, 28 (22 percent) had biopsy-confirmed episodes of acute rejection, as compared with 47 of the 134 patients (35 percent) who received placebo (P=0.03). Graft survival at 12 months was 95 percent in the daclizumab-treated patients, as compared with 90 percent in the patients given placebo (P=0.08). The patients given daclizumab did not have any adverse reactions to the drug, and at six months, there were no significant differences between the two groups with respect to infectious complications or cancers. The serum half-life of daclizumab was 20 days, and its administration resulted in prolonged saturation of interleukin-2alpha receptors on circulating lymphocytes. CONCLUSIONS: Daclizumab reduces the frequency of acute rejection in kidney-transplant recipients.

Acute Disease↗
PubMed1998

Pentoxifylline potentiates in vitro lymphocyte suppression by glucocorticoids and immunosuppressive drugs.

Pentoxifylline, which has immunomodulatory effects in addition to its better known rheologic effects, might potentiate the effectiveness of traditional immunosuppressive drugs. We therefore studied the suppressive effect of pentoxifylline in combination with clinically relevant concentrations of prednisolone, methylprednisolone, cyclosporine, tacrolimus, rapamycin, and mycophenolic acid on mitogen-stimulated lymphocytes from 29 patients with glomerular diseases. Inhibition of lymphocyte proliferation obtained with 10(-7) and 10(-8) mol/L concentrations of the glucocorticoids and with 300 ng/mL cyclosporine was significantly increased when each was combined with 5, 25, or 50 microg/mL of pentoxifylline. The additive inhibitory effect of pentoxifylline in combination with 10(-7) mol/L glucocorticoids was inversely proportional to the inhibitory effect of the 10(-7) mol/L concentration of glucocorticoid alone, suggesting that the less sensitive the patient's cells, the greater the potentiation by pentoxifylline. The greatest degree of potentiation by pentoxifylline occurred when combined with the lower (10(-8) mol/L) concentration of glucocorticoids. Pentoxifylline also significantly increased lymphocyte suppression in combination with 150 and 300 ng/mL concentrations of cyclosporine, 5 ng/mL of tacrolimus, 2.5 x 10(-7) mol/L mycophenolic acid, and 10 ng/mL of rapamycin. These in vitro results suggest that pentoxifylline might have steroid-sparing effects and contribute to improved clinical outcomes from immunosuppressive treatment of renal diseases.

Adult↗
PubMed1997

Local impact of 1995 changes in the renal transplant allocation system.

In 1995, changes to the United Network for Organ Sharing renal allocation system eliminated points for certain HLA matches, increased points for waiting time and for pediatric patients, and extended the mandatory share rule to include the zero-antigen mismatch. We analyzed data, from the period December 1993 to August 1996, on 393 donors, 348 kidney-only cadaveric transplants, and 615 patients ranked first or second on the allocation lists generated for each donor, to assess the effect of the changes in the point system. There was an appreciable (46%) but not significant increase in the frequency of transplants occurring under the mandatory share rule, with a greater relative increase seen in African-Americans than in Caucasians. Recipients of transplants not falling under the mandatory share rule had an increased average waiting time but no increase in sensitization or HLA mismatch, whereas patients ranked at the top of the allocation list had higher levels of sensitization but no increase in waiting time. There was an appreciable increase in the percentage of transplants occurring in African-Americans. Of the various changes we observed, only those involving the mandatory share rule could be attributed to changes in the allocation system, whereas others paralleled changes in the composition of our local waiting list.

Black People↗
PubMed1996

A multicenter trial of FK506 (tacrolimus) therapy in refractory acute renal allograft rejection. A report of the Tacrolimus Kidney Transplantation Rescue Study Group.

A multicenter trial was conducted to evaluate the efficacy and safety of tacrolimus in the treatment of refractory renal allograft rejection. Renal transplant recipients experiencing biopsy-proven recurrent acute allograft rejection were eligible if the current rejection episode was refractory to corticosteroids. A total of 73 patients were enrolled, of whom 59 (81%) had previously received at least one course of antilymphocyte antibody as rejection therapy. One-year follow-up was available in 93% of patients. Median time to tacrolimus rescue therapy was 75 days after transplantation (range, 18-1448 days). Therapeutic responses to tacrolimus included improvement in 78% of patients, stabilization in 11%, and progressive deterioration in 11%. The risk of experiencing progressive deterioration was related to the pretacrolimus serum creatinine level: serum creatinine < or = mg/dl, 3%; 3.1-5 mg/dl, 16% (P < 0.04); > 5 mg/dl, 23% (P < 0.02). Twelve-month (from the time of initiation of tacrolimus therapy) actuarial patient and graft survival rates were 93% and 75%. Graft loss occurred in 19 patients (25%) at a median time of 108 days. Fourteen episodes of recurrent rejection were diagnosed in 10 patients (14%), at a median time of 101 days. Eleven episodes of recurrent rejection were treated (three patients underwent transplant nephrectomy), with resolution achieved in nine patients. Antilymphocyte antibody therapy was not used to treat recurrent rejection. Serum creatinine values improved during tacrolimus therapy: median serum creatinine level before tacrolimus, 3.2 mg/dl; median at 1 year after tacrolimus, 1.8 mg/dl. Twelve infections were documented in 11 patients (15%), including cytomegalovirus infection in three patients (4%). Posttransplant lymphoproliferative disorder was diagnosed in a single patient. Tacrolimus whole blood levels averaged 15.0 +/- 9.9 ng/ml at day 7 of tacrolimus therapy and 9.4 +/- 5.1 ng/ml at 1 year, and were consistent among individual centers. Treatment outcome did not correlate with tacrolimus blood levels. The most commonly observed adverse events were neurological and gastrointestinal. Seventy-four percent of patients received tacrolimus for at least 1 year. Tacrolimus therapy was discontinued in 18% of patients for rejection (11% for progressive, unrelenting rejection, and 7% for recurrent rejection). Tacrolimus therapy was discontinued in 8% of patients due to adverse events. In conclusion, tacrolimus rescue therapy provides (1) prompt, effective reversal of refractory renal allograft rejection, (2) good long-term renal allograft function, (3) a low incidence of recurrent rejection, and (4) an acceptable safety profile in renal allograft recipients experiencing refractory rejection.

Acute Disease↗