PubMed Health⌕ Search

Biomedical subjects

B A Lucas

Publications and source records attributed to B A Lucas.

At least 19 recordsLinked to original sources
PubMed1999

CD40 expression on graft infiltrates and parenchymal CD154 (CD40L) induction in human chronic renal allograft rejection.

BACKGROUND: CD40-CD154 (CD40L) costimulatory signaling plays a pivotal role in the effector mechanisms of transplant graft rejection. In animal models, CD40-CD154 blockade induces long-term graft acceptance concurrent with an absence of chronic rejection (CR) lesions. Given the critical importance of CD40-CD154 interactions in the development of chronic transplant allograft rejection, the relevance of in situ CD40 and CD154 expression was assessed in human chronic renal allograft rejection. METHODS: The expression of CD40, CD154, CD68, and T-cell receptor (TCR)alpha/beta was analyzed by immunohistochemistry. Serial cryostat sections of snap-frozen core renal allograft biopsies were obtained from 30 renal transplant patients. Biopsy specimens received diagnoses of CR (N = 23) according to the Banff classification and were compared with controls (N = 7) consisting of stable allografts and normal kidney tissue. RESULTS: Striking CD40 staining of graft cellular infiltrates (P = 0.016) was observed in renal allografts with CR compared with controls. The CD40+ cellular infiltrates in CR were predominantly TCR alpha/beta + T cells and some CD68+ macrophages. These findings were contrasted by the low-level CD40 expression detected in glomeruli and tubules of CR and controls. However, glomerular induction of CD154 was observed in CR allografts (P = 0.028) as compared with controls. CD154 immunoreactivity was demonstrated on glomerular endothelial, epithelial, and mesangial cells. Moderate CD154 expression was detected on tubular epithelial cells, and only weak CD154 immunoreactivity was observed on the infiltrates in isolated CR cases. CONCLUSION: In human chronic renal allograft rejection, CD40 is expressed on graft-infiltrating cells of the T cell and macrophage compartments. CD154 expression is induced on glomerular and tubular epithelial cells during CR, demonstrating another novel source of CD154 expression. The data substantiate the potential contributory role of an interaction between CD40+ graft-destructive effector T cells and macrophages with CD154+ renal allograft parenchymal cells in the development of chronic renal allograft rejection.

Antigens, CD↗
PubMed1998

Improving the request process to increase family consent for organ donation.

The greatest impediment to organ donation is refusal of family consent. This study examined the impact of 3 modifiable elements of the donation request on family consent rates: (1) decoupling (i.e., the family understands and accepts brain death before discussion of organ donation is begun); (2) the procurement coordinator participates in the request for consent; and (3) donation is requested in a quiet, private place. Data on the request process were collected prospectively for 707 medically suitable potential donors who had been referred to 3 organ procurement organizations. The average rate of consent for donation was 62.2%. Higher consent rates were independently associated with the 3 characteristics studied. These components were summarized in the Request Process Scale. Multivariate regression analyses indicated that consent rates can be as high as 74% when all 3 process elements are present. Hospitals and organ procurement organizations should incorporate these elements into their standard of practice when requesting organ donation.

Adolescent↗
PubMed1997

Treatment of renal allograft rejection with T10B9.1A31 or OKT3: final analysis of a phase II clinical trial.

BACKGROUND: Treatment of acute renal allograft rejection with the monoclonal antibody (mAb) OKT3 has been shown to be superior to treatment with polyclonal antisera. To date, only OKT3 has demonstrated consistent efficacy in reversing rejection crisis. METHODS: From 1989 to 1993, a phase II trial comparing the mAb T10B9.1A31 (T10B9) with OKT3 for treatment of acute cellular rejection in renal allograft recipients was done at the University of Kentucky. We collected data from 178 patients potentially eligible to enter the study; 48 never rejected, 9 refused, 13 could not be biopsied, 16 received methylprednisolone, and 11 received antithymocyte globulin or OKT3. Altogether, 81 patients entered the study, 76 of whom were able to be evaluated. Patients with biopsy-confirmed acute rejection were randomly assigned to T10B9 or OKT3 for at least 10 days. RESULTS: Demographically, there was no difference between the T10B9 or OKT3 cohorts. Actuarial graft survival at 4 years was 87% for patients receiving T10B9, 79% for those receiving OKT3, and 89% for those receiving both mAbs (P=0.55). Patient survival at 4 years was 94% for T10B9, 100% for OKT3, and 89% for both mAbs (P=0.45). Mean creatinines of the cohorts were no different at 1, 6, 12, 24, and 36 months. There was less cytokine nephropathy (P<0.001) observed in patients receiving T10B9. Untoward gastrointestinal, neurological, respiratory, and febrile effects were significantly more frequent in the OKT3 cohort after the first dose (day 0) and with later (day 1-9) administration. Cytokine levels (tumor necrosis factor alpha and interferon gamma) measured 2 hr after the first dose were three to six times higher in patients treated with OKT3 than in those treated with T10B9 (P<0.005). Infectious complications were not significantly different, although serious infections occurred only in patients receiving OKT3. No cases of posttransplant lymphoproliferative disorder were seen in either cohort. Human anti-mouse antibody development was as follows: titer 1:100, 30% T10B9, 42% OKT3; titer 1:1000, 3% T10B9, 3% OKT3. There was no cross-reactivity with OKT3 in patients treated with T10B9, and there was only 9.7% cross-reactivity to T10B9 in patients treated with OKT3. CONCLUSIONS: T10B9 provides treatment for renal allograft acute cellular rejection as effective as that of OKT3 with fewer untoward effects, less cytokine release and nephropathy, fewer serious infections, and without increased development of human anti-mouse antibody. The lack of cross-reactivity offers an alternative therapy should the first mAb fail or re-rejection occur. A phase III trial should be initiated in renal allograft recipients, and phase I and phase II trials should be initiated in other solid-organ transplantations.

Adult↗
PubMed1996

Organ donor potential and performance: size and nature of the organ donor shortfall.

OBJECTIVES: To estimate the potential for solid organ donation; to identify modifiable reasons for nondonation. DESIGN: Retrospective medical records review. SETTING: Sixty-nine acute care hospitals in four geographic areas of the United States in 1990, and a stratified random sample of 89 hospitals in three of the same areas and 33 of the same hospitals in 1993. PATIENTS: PATIENTS < or = 70 yrs of age who were brain dead and medically suitable for donation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Standard forms were used to record patient demographic and hospital information. Reasons for nondonation were coded as "not identified," "family not asked," "consent denied," or "other." The main outcome measures were rate of donation and rates of nonidentification, not asking, and nonconsent. Organ donation occurred among 33% (299/916) of medically suitable cases identified in 1990 (95% confidence interval 30% to 36%). Ninety-four potential donors were not identified, 156 were not asked, 326 families denied consent, and 41 potential donors were categorized as "other," including patients who had suffered a cardiac arrest, and medical examiner prohibition of donation. In the 1993 study, organ donation occurred in an estimated 33% of suitable cases. In 1990, rates of donation were highest among patients <50 yrs of age, patients who died of traumatic causes, and non-Hispanic white patients. Logistic regression showed lower odds of donation for African American patients (odds ratio 0.38, 95% confidence interval 0.23 to 0.63) independent of potentially confounding hospital and patient variables (p=.0001). Donation rates did not vary by hospital size or type. CONCLUSIONS: Despite legal and policy initiatives, only one third of potential donors became donors in 1990, with similar results in 1993. Extrapolating the 1990 findings to the United States suggests a pool of 13,700 medically suitable donors per year. Prospective identification and requesting donation in all suitable potential donor cases could lead to 1,800 additional donors per year.

Adolescent↗
PubMed1996

T10B9 (MEDI-500) mediated immunosuppression: studies on the mechanism of action.

The murine IgM anti-human CD3/TCR mAb T10B9 is an effective agent for the reversal of acute cellular renal allograft rejection which offers several advantages over conventional OKT3 therapy. These include reduced morbidity and a more rapid decrease in serum creatinine levels. In the studies presented here comparing T10B9 and OKT3, soluble T10B9 is shown to be a nonactivating anti-T cell mAb. Evidence for its lack of activating potential includes in vitro failure to stimulate PBMC proliferation either alone or in the presence of nonmitogenic doses of phorbol ester, failure to induce the expression of early and late activation antigens and failure to induce IFN-gamma, TNF-alpha, IL-6 or IL-2 release. Analysis of acute renal allograft rejection patient plasma cytokine levels 2 h after the first dose support the hypothesis that T10B9 has reduced immunoactivation activity in vivo. Both TNF alpha and IFN gamma patient plasma levels are significantly reduced in T10B9 as compared to OKT3 therapy. However, T10B9 is capable of cellular signaling as demonstrated by its ability to induce apoptosis and IL-2 release in the human T cell line Sup-T13. Thus T10B9 retains the potent immunosuppressive activity of OKT3 with reduced immunoactivation.

Antibodies, Monoclonal↗
PubMed1995

Initial experience with retroperitoneoscopic nephroureterectomy: use of a double-balloon technique.

OBJECTIVES: To report the initial experience with retroperitoneoscopic nephroureterectomy for symptomatic, end-stage vesicoureteral reflux. METHODS: Two patients underwent a nephroureterectomy by a four-port retroperitoneal laparoscopic approach. In 1 patient, a double-balloon technique was used to dissect the pelvic extraperitoneal space and gain access to the juxtavesical ureter. In the second patient, the distal ureter was mobilized with routine laparoscopic dissection techniques. RESULTS: Operative time was 6 and 5.5 hours, respectively, and mean hospital stay was 4 days. Mean patient follow-up is 17.5 months. CONCLUSIONS: The technique of retroperitoneoscopic nephroureterectomy is in evolution; until now, a major concern has been the inadequate access to the distal ureter through a completely retroperitoneoscopic approach. Described herein is a double-balloon technique that significantly facilitates dissection of the juxtavesical ureter during a retroperitoneal laparoscopic nephroureterectomy.

Adult↗
PubMed1995

Transperitoneal marsupialization of lymphoceles: a comparison of laparoscopic and open techniques.

This 2-center study compares the relative merits of laparoscopic and open surgical internal marsupialization of pelvic lymphoceles. Laparoscopic lymphocelectomy was performed in 12 patients (group 1). The results were compared with open lymphocelectomy performed in 13 contemporary patients (group 2) as well as 13 historical patients (group 3). Operative time was longer in group 1 compared to groups 2 and 3 (194.6 versus 176.9 versus 133.8 minutes, respectively). However, group 1 had a decreased blood loss (23.1 versus 74.6 versus 61.7 ml.), earlier resumption of oral food intake (0.9 versus 2.5 versus 2.1 days), shorter hospital stay (2 versus 6.1 versus 6.3 days) and abbreviated convalescence (2.2 versus 6.9 versus 4.5 weeks) compared to groups 2 and 3. Complications included cystotomy requiring open repair in 1 patient in group 1, prolonged ileus in 1 in group 2, transection of the ureter of a transplant kidney in 1 in group 3 and pneumonitis in 1 in group 3. Lymphocele recurred in no patient in group 1, 4 in group 2 and 3 in group 3. Mean followup in groups 1 to 3 was 12.8, 25 and 54.5 months, respectively. We conclude that laparoscopic lymphocelectomy is effective, results in minimal patient morbidity and allows for a more rapid recovery compared to open surgical lymphocelectomy.

Adult↗
PubMed1994

Use of a stockinette to minimize warm ischemia during renal transplant vascular anastomoses.

Prolonged warm ischemia during renal transplant vascular anastomosis may have a deleterious impact upon allograft function in the immediate post-transplant period. Placing the donor kidney and sterile ice slush in a cotton stockinette obviates renal rewarming during vascular anastomoses. We successfully used this technique in nearly 1,000 patients undergoing renal transplantation. The stockinette facilitates transplant vascular anastomoses by permitting easier handling of the kidney and eliminating warm ischemia during revascularization as documented by continuous core temperature monitoring.

Anastomosis, Surgical↗
PubMed1994

Intraperitoneal drainage of recurrent lymphoceles using an internalized Tenckhoff catheter.

Occasionally, lymphoceles recur after renal transplantation in relatively inaccessible pelvic locations, usually in the setting of a transversely oriented allograft that separates the lymphocele from the peritoneal cavity. Such lymphoceles do not share a common wall with the peritoneal cavity and, therefore, are not manageable by conventional open surgical or laparoscopic drainage techniques. We used an internalized Tenckhoff catheter to drain recurrent lymphoceles into the peritoneal cavity in 3 patients who had undergone prior renal transplantation. No evidence of lymphocele recurrence or catheter-induced septic complications have been noted in our immunocompromised patients up to a mean followup of 5.3 years. Our experience with this alternative management option for the recurrent, inaccessible lymphocele is presented along with a single case report of intractable, recurrent perinephric fluid collection in the nontransplant setting treated by the same technique.

Adult↗
PubMed1994

Laparoscopic live-donor nephrectomy.

Laparoscopic nephrectomy with ablative intent has been performed clinically. The current study aimed to determine whether a physiologically and anatomically intact kidney suitable for transplantation could be harvested laparoscopically. Three weeks after an ablative laparoscopic right nephrectomy, 15 pigs were divided into two groups: the study group (n = 10) underwent a laparoscopic live-donor left nephrectomy of the solitary kidney and conventional autotransplantation; the control group (n = 5) underwent an open live-donor left nephrectomy of the solitary kidney and conventional autotransplantation. All study kidneys underwent laparoscopic in situ hypothermic perfusion. The mean length of the left renal artery and vein were similar in the study and control groups: 3.1 cm and 3.4 cm, respectively, in the study group compared with 2.5 cm and 3.8 cm, respectively, in the control group (P = 0.5). No intraoperative renal vascular injuries or postoperative ureteral complications were noted in either group. Renal histopathologic examination immediately after live-donor nephrectomy and at 1 month post-transplant showed similar findings in the two groups. The mean serum creatinine at 7 and 30 days postoperatively was not significantly different: 2.1 mg/dL and 1.6 mg/dL, respectively, in the study group and 1.7 mg/dL, and 1.4 mg/dL, respectively, in the control group (P = 0.4). We conclude that laparoscopic live-donor nephrectomy can be performed safely and reproducibly in the porcine model.

Adenosine Triphosphate↗
PubMed1993

MMPI Scale 9 changes in incarcerated felons.

This article focuses on the scores of incarcerated male felons on the MMPI clinical subscales 4 and 9 because they are the most frequently elevated for this type of population. Over time, while scores on Scale 4 remained consistent, those on Scale 9 declined significantly. That inmates might become depressed, as a result of the foibles of incarceration, is discussed.

Adult↗
PubMed1992

Treatment of acute cellular rejection with T10B9.1A-31 or OKT3 in renal allograft recipients.

T10B9.1A-31, a nonmitogenic immunoglobulin Mk monoclonal antibody that detects an epitope on the alpha/beta chains of the T cell antigen receptor (TCR alpha/beta), or OKT3, an anti-CD3 mAb, was employed in a randomized double-blind phase II clinical trial to treat biopsy-proven acute cellular renal allograft rejection. Two of the 40 patients initially selected for the protocol were considered to be nonevaluable. Analysis of the remaining 38 patients receiving both living related and cadaveric donor allografts revealed a patient survival of 100% and a graft survival of 97%. Primary rejection reversal was achieved in 18/19 (95%) patients treated with T10B9.1A-31 and in 20/21 (95%) of patients receiving OKT3. The two patients who did not respond to the first mAb responded to the crossover mAb. Rerejection occurred in 3/18 (17%) of patients treated with T10B9.1A-31 and in 3/20 (15%) treated with OKT3. The mean day of rejection reversal was 1.9 +/- 0.7 with T10B9.1A-31 and 3.37 +/- 1.21 with OKT3 treatment. The rise in mean serum creatinine after mAb administration and the mean creatinine on days 1 through 6 were significantly less in patients treated with T10B9.1A-31. Biopsy specimens analyzed for rejection revealed no significant difference between the T10B9.1A-31 and OKT3 cohorts. The mean serum creatinines at 30, 60, 180, and 360 days posttransplantation were the same for both groups. Significantly fewer febrile, respiratory, and untoward effects followed the first dose (day 0) and fewer febrile, gastrointestinal, and neurological side effects occurred with subsequent doses (days 1-9) in patients treated with T10B9.1A-31. Infectious complications occurred in 3/13 patients treated only with T10B9.1A-31, in 9/17 OKT3-treated patients, and in 4/8 patients treated with both mAb. Analysis of human antimouse antibody (HAMA) revealed that the development of HAMA with T10B9.1A-31 was similar to that of OKT3.

Adult↗
PubMed1991

There is an answer to the shortage of organ donors.

From a retrospective review of 32,562 deaths that occurred in 1988 in the service area of Kentucky Organ Donor Affiliates, an area with a population of 3.4 million, 173 potential solid organ donors were identified for a rate of 50.8 donors per million population base. There were only 38 actual solid organ donors from this potential pool. The physician failed to recognize the potential for donation in 29 instances and in 92, the family refused consent for donation. In the second phase of the study, we analyzed 155 consecutive medically suitable organ donor referrals for one year. A specific focus on the process and timing of the request for donation was made in this review. In 143 of these instances (92 per cent), a clear temporal separation of the explanation of death or the certainty of family acceptance of death before the request for donation yielded a donor success in 53 of 82 instances. In contrast, only 11 of 61 instances resulted in a consent when the discussion of death and donation were combined into one discussion with the family (p less than 0.05). From this study, there seemed to be adequate numbers of organs available to provide for the current pool of recipients within the state of Kentucky. Educational assistance and an ongoing individual patient review of each death improved the donor rate during the time frame of this study. It is essential to allow a temporal separation between the explanation of death and the request for organ donation to maximize actual organ donation.

Adolescent↗
PubMed1990

Primary biliary and pancreatic carcinoma after renal transplantation.

Renal transplant recipients have an increased risk of malignancies. We have described a 41-year-old man in whom adenocarcinoma of the gallbladder developed during the first year after renal transplantation. He also had a nonfunctioning pancreatic islet cell tumor during the fifth year after transplantation. He was the first known renal transplant recipient to be a long-term survivor of adenocarcinoma of the gallbladder.

Adenocarcinoma↗