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Biomedical subjects

B A Lucas

Publications and source records attributed to B A Lucas.

At least 37 records · Page 2Linked to original sources
PubMed1989

T10B9.1A-31 anti-T-cell monoclonal antibody: preclinical studies and clinical treatment of solid organ allograft rejection.

T10B9.1A-31 is an immunoglobulin Mk (lgMk), CD3b class, murine monoclonal antibody. It is not itself mitogenic, but it partially blocks mitogenesis produced by concanavilin-A, phytohemagglutinin, and a soluble antigen cocktail and is lytic for human peripheral blood T lymphocytes (PB-T) in the presence of fresh autologous human complement and rabbit complement. It reacts with a monomorphic epitope found on all mature PB-Ts that modulates in vitro and in vivo with the CD3/T-cell antigen receptor (TCR) complex, but unlike OKT3, which reacts with CD3 proteins, T10B9.1A-31 reacts with an epitope of the TCR alpha/beta heterodimer. Immunoprecipitation of HPB-ALL with T10B9.1A-31 or OKT3 revealed that T10B9.1A-31 does not react with the 20-to 26-kd polypeptides that compose CD3, and T10B9.1A-31 failed to bind to the PEER cell, which is CD3 gamma/delta positive, TCR alpha/beta negative. Phase 1 clinical trials demonstrated that T10B9.1A-31 caused a rapid decrease in PB-Ts and no toxic effects other than fever, chills, rigors, and transient hypotension. These side effects were absent in methylprednisolone (MP)-pretreated patients. Phase II studies revealed that T10B9.1A-31 reversed steroid refractory acute rejection in three of five renal allografts treated with cyclosporine (CyA) and prednisone (P) maintenance immunosuppression, reversed steroid and polyclonal antisera refractory rejection in three cardiac allograft recipients receiving CyA/P, and attenuated acute rejection in three of three renal patients receiving baseline azathioprine/prednisone (AZA/P) when used as primary therapy. Rerejection was not seen when patients received CyA baseline immunosuppression but was seen in patients maintained on AZA/P OKT3 was efficacious in treating rejection following T10B9.1A-31 therapy. Side effects of T10B9.1A-31 appears to reverse acute rejection crisis effectively in renal and cardiac transplantation with a low incidence of rerejection in CyA-maintained patients and with fewer, milder side effects. Sequential therapy with OKT3 is possible because OKT3 and T10B9.1A-31 are of different isotypes and idiotypes.

Animals↗
PubMed1989

The impact of purposeful sharing by HLA matching in the South Eastern Organ Procurement Foundation (SEOPF).

A voluntary system was created to foster early sharing of well-matched organs between like-minded renal transplantation programs. In the two historic periods 1982-85 and 1985-86, sharing programs (Category I & II) and nonsharing programs (Category III) had similar graft survival. In the study period 1986-88, graft survival improved in Category I and II programs and was unchanged in Category III programs. Highly sensitized recipients in sharing programs had an incremental gain of 15.0%, patients receiving multiple grafts 12.6%. Grafts derived from local donors and transplants in less sensitized patients also were improved but for less obvious reasons. The implementation of this study was followed by a slight decrement in delayed graft function. It is our conclusion that early graft sharing can result in improved overall early graft survival.

Graft Survival↗
PubMed1988

Colonic complications of renal transplantation.

Colonic complications of renal transplantation occur in 1.9 per cent of the cases. In our series of 587 consecutive renal transplants recipients 3 (0.51 per cent) had colonic complications, including 2 with ischemic colitis and 1 with pseudomembranous colitis. A review of 8 large series describing 2,539 additional renal transplant patients revealed 55 with significant colonic complications. The most common complication was ischemic colitis, which occurred in 29 patients, followed by diverticulitis in 17, pseudomembranous colitis in 5, appendicitis in 3, hemorrhagic proctitis in 1, a disrupted appendiceal stump in 1 and fecal impaction in 1. Etiological factors that may be important in the development of these colonic complications are uremia, blood volume redistribution, immunosuppressive therapy, antibiotic therapy, irradiation and previous retroperitoneal surgery.

Adult↗
PubMed1988

Organ sharing for good HLA-A,B, and DR matching improves cadaver renal graft survival in SEOPF: retrospective and prospective studies considering delayed graft function, race, center effects, cyclosporine, and other factors.

1. HLA matching is associated significantly with factors including CsA use, ALS use, recipient race, prior graft loss, presensitization, preservation time and most strongly, with organ sharing. However, HLA match is not directly associated with delayed graft function. 2. By univariate and multivariate analyses, good HLA matching provides significant benefits in graft survival regardless of CsA use, organ source or other potentially confounding factors. 3. HLA-A,B, and DR matching have independent and essentially equivalent benefits on graft survival in CsA-treated patients, whereas HLA-A,B matching has a greater benefit in non-CsA-treated patients. 4. Organ sharing, per se, provides no direct detrimental effect on graft survival by univariate or multivariate analysis. 5. By multivariate and univariate analyses, shared/well-matched kidneys provide significantly better graft survival than local/poorly matched kidneys. 6. Delayed graft function is associated in a complex relationship with organ sharing, prior graft failure, presensitization, and CsA use. 7. The increased rate of delayed graft function associated with organ sharing is overcome by the benefit of good HLA matching. 8. Since April 1986, purposeful organ sharing at SEOPF centers for good HLA matching has been associated with improved graft survival, especially in patients at high risk due to presensitization or prior graft failure.

Actuarial Analysis↗
PubMed1987

Identification of donor factors predisposing to high discard rates of cadaver kidneys and increased graft loss within one year posttransplantation--SEOPF 1977-1982. South-Eastern Organ Procurement Foundation.

From 1977 to 1982, the South-Eastern Organ Procurement Foundation (SEOPF) conducted a prospective study to determine the fate of all cadaver kidneys retrieved by member institutions. During the study period, 6152 kidneys were retrieved, 1264 being discarded. Donor factors predisposing to wastage included AB and A blood groups, donor age greater than 30, hospitalization greater than 3 days, serum creatinine greater than 2.0 mg%, average systolic blood pressure less than 80, last-hour urine output less than 100 ml, proteinuria, heart not beating at time of nephrectomy, and kidneys not removed en bloc. Donor factors affecting graft survival rate at one year include age, length of hospitalization, last-hour urine output, and changing serum creatinine. The data suggest that certain donor kidneys are less likely than others to be transplanted depending on donor characteristics and retrieval practices. Furthermore, some of these factors have a negative impact on long-term success when kidneys are transplanted.

Adolescent↗
PubMed1986

The influence of uremia and immunosuppression on an animal model for ischemic colitis.

Up to 1 percent of renal transplant recipients have been reported to develop ischemic colitis. Immunosuppressive agents and uremia have been implicated in the development of this complication, but their exact relationship remains unclear. A rat model was developed to determine the effects of uremia alone and in combination with immunosuppression on the development of ischemic colitis. Seventy-six animals were included in the study. Uremia and ischemic colitis were induced surgically. The immunosuppressive agents azathioprine and methylprednisolone were administered for 72 hours after a colonic segment was devascularized in chronically uremic rats. One-way analysis of variance (ANOVA) showed that uremia potentiates colonic ischemia significantly (4.09 cm2 vs 1.25 cm2, P less than 0.03). The addition of parenteral steroids (methylprednisolone) or azathioprine alone and in combination did not potentiate or reduce this ischemic process in uremic animals. Each of these factors alone is commonly present in the renal transplant population and can contribute to the development of potentially fatal ischemic colitis.

Animals↗
PubMed1985

Prospective DR matching for first cadaver donor renal allografts and retransplantation.

From January 1981 through 1983 80 cadaver donor renal allografts were transplanted at a single center utilizing prospective HLA-DR matching. All patients received at least two blood transfusions prior to transplantation. One year actual allograft survival of 77% for initial grafts and 57% for retransplantation was observed. When there was no DR mismatch the results were 84% and 80% respectively. Only 6% of no-DR-mismatch initial grafts were lost to rejection or patient death. These significantly better results were associated with decreased incidence of acute rejection episodes with transplants well matched for DR. Matching for A and B locus antigens conveyed no benefits in this series. Use of prospective DR matching for donor/recipient selection also resulted in efficient transplantation. Patients receiving initial grafts waited an average of 3.9 months while retransplanted patients waited an average of 13.5 months after being entered on the waiting list. The data suggest that if all transplant centers would preferentially share kidneys regionally on the basis of DR matching, nearly all patients could receive timely allografts with no DR mismatch and good results at one year with conventional immunosuppressive therapy.

Acute Disease↗
PubMed1984

The efficacy of patient-controlled analgesia in patients recovering from flank incisions.

We report on 13 patients undergoing flank incisions in whom the postoperative pain was managed with a patient-controlled analgesia device. An initial group of 7 patients was used to determine the optimal injection dose for each patient and to examine variability in narcotic requirement during the postoperative course. A progressive decrease in narcotic need was noted during the postoperative course with patient-controlled analgesia, resulting in excellent patient acceptance, no postoperative complications and no drug-seeking behavior. A second group of 10 patients was randomized prospectively to receive either patient-controlled analgesia or a standard regimen of intramuscular morphine sulfate. Based on nursing observations, an analgesia and sedation scale was developed that compared the 2 groups. Analysis of a questionnaire evaluating subjective perception of postoperative pain revealed significantly less pain, less sedation and greater activity among patients randomized to patient-controlled analgesia (95 per cent confidence limit).

Adolescent↗
PubMed1984

The detrimental effects of delayed graft function in cadaver donor renal transplantation.

Data collected prospectively on over 3800 cadaveric renal transplants performed between June 1977 and July 1982 by the 41 member institutions of the South-Eastern Organ Procurement Foundation were analyzed to determine the influence of delayed graft function (DGF) on patient and graft outcome. Approximately 35% of first graft recipients and 47% of regrafted patients were found to have DGF, as determined by the necessity for dialysis at one week posttransplant. First-graft recipients with DGF tended to include more black recipients, patients with higher peak levels of panel reactive antibody (PRA), less use of antilymphocyte serum (ALS) posttransplant, slightly longer organ preservation times and the more frequent use of organs by ice alone. Multivariate (Cox) regression analysis considering DGF simultaneously with ten other potentially confounding variables showed a highly significant association between DGF and overall graft loss from all causes (P less than 10(-5], irreversible graft rejection (P less than 0.001) as well as patient death (P = 0.012). The differences in graft survival between first graft recipients with DGF (n = 961) versus those without DGF (n = 1769) at one and four years posttransplant were 46% +/- 2 vs. 60% +/- 1 and 28% +/- 3 vs. 40% +/- 2, respectively. The detrimental effect of DGF was highly significant irrespective of the source of donor organs or the type of preservation used. For first transplant recipients who recovered good graft function by one month following DGF (n = 564), there was a significant decrease in eventual graft survival, as compared with patients who had graft function at one month but no prior history of DGF (n = 1407; P = 0.008). However, patients with history of DGF who had good graft function at six months (n = 361) showed no significant difference in longer-term graft survival when compared with similar patients with good graft function at six months but no history of DGF (n = 912). Interestingly, first transplant recipients with DGF were found to have significantly better graft survival if they had received bilateral native nephrectomy at least one month prior to transplantation. These results indicate that delayed graft function following cadaver donor renal transplantation provides a significant risk for eventual graft and patients survival that is principally manifested during the first six months posttransplant. In addition, patients who recover graft function following DGF appear to also remain at higher risk for early graft loss, while pretransplant bilateral native nephrectomy may afford some protection against the detrimental effects of DGF.

Female↗
PubMed1983

Complications associated with preoperative radiation therapy and Iodine-125 brachytherapy for localized prostatic carcinoma.

Twenty-five consecutive patients with localized adenocarcinoma of the prostate treated with 1,050 rad preoperative radiation therapy and Iodine-125 seed brachytherapy arreviewed. Significant long-term postoperative complications included radiation cystitis (12%), radiation proctitis (4%), genital and leg edema (12%), stress incontinence (8%), total incontinence (4%), and impotence (26%). Complications occurred in 75 per cent of patients who received additional postoperative radiation. Improved staging with CT scan, lymphangiography, and Chiba needle biopsy of any possibly abnormal lymph nodes provided excellent preoperative staging with only 1 patient (6%) upstaged at surgery to Stage D1.

Adenocarcinoma↗
PubMed1983

Cutaneous stimulation of the bladder in multiple sclerosis: a case report.

We report on the use of transcutaneous electrical nerve stimulation to improve bladder emptying in a multiple sclerosis patient with a hypotonic bladder. Urodynamic testing demonstrated decreased bladder capacity, earlier first sensation and increased bladder pressure during trials of stimulation.

Adult↗
PubMed1983

The medullary pyramid index: an objective assessment of prominence in renal transplant rejection.

Prominence of the medullary pyramids at sonography has been considered a sign of renal transplant rejection. A search of the literature reveals no previously published objective assessment of this phenomenon. Medullary pyramids of 67 normal kidneys, 53 nonrejecting transplanted kidneys, and 71 transplanted kidneys in rejection were measured. The area of the pyramid was related to the thickness of the overlying renal cortex by a "medullary pyramid index" (MPI): MPI (formula; see text) The median MPI was 4.17 for normal kidneys, 6.0 for nonrejecting transplanted kidneys, and 7.50 for transplanted kidneys in rejection. The results are significantly different (P = 0.0001) for all possible pairs. Overlap between rejection and nonrejection distributions is, however, considerable, rendering the discriminatory value of an individual observation quite low (0.69). Prominence of the medullary pyramids is therefore of very limited predictive value in the determination of transplant rejection in an individual patient.

Graft Rejection↗
PubMed1982

Effect of alternate-day prednisone on plasma lipids in renal transplant recipients.

While numerous groups have reported high prevalences of plasma lipid abnormalities in their renal transplant recipients, we have been unable to confirm this finding. We have suggested that the routine use of alternate-day steroids (ADS) in our patients may be responsible. To test that hypothesis, a prospective controlled trial of equal total dose ADS versus daily steroids (DS) was conducted. Four months after transplant and before entering the trial, transplant study patients had significantly higher serum cholesterol (243 +/- 9 mg/dl) than either normal controls (cholesterol 200 +/- 7 mg/dl, alpha = 0.01) or hemodialysis patients (cholesterol 211 +/- 9 mg/dl, alpha = 0.01). They also had higher serum triglyceride than controls (129 +/- 7 mg/dl vs. 98 +/- 8 mg/dl, alpha = 0.01). After randomization to DS or ADS and 1 year of further followup study, the ADS group had a significant decrease in both serum triglyceride (139 +/- 9 to 100 +/- 7 mg/dl, P less than 0.01) and cholesterol (251 +/- 16 to 220 +/- 9 mg/dl, P less than 0.05) while the DS group's serum triglyceride and cholesterol values remained unchanged. Serum triglyceride and cholesterol in the ADS group had decreased to values that were not significantly different from 41 normal healthy controls. Dose spacing per se, and not the use of a lower total dose of prednisone, appears to result in a lower prevalence of abnormal plasma lipids after successful renal transplantation.

Adolescent↗