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E K Sullivan

Publications and source records attributed to E K Sullivan.

48 records · Page 3Linked to original sources

Renal transplantation and chronic dialysis in children and adolescents: the 1993 annual report of the North American Pediatric Renal Transplant Cooperative Study.

The 1993 North American Pediatric Renal Transplant Cooperative Study annual report summarizes data voluntarily contributed by 82 participating centers on 3,223 pediatric patients who received 2,819 renal transplants from January 1987 through January 1993 and 999 independent courses of dialysis from January 1992 through January 1993. In addition to updating information regarding trends and outcomes in pediatric renal transplantation presented in previous annual reports, 1st-year registry data are presented regarding current practices and trends in chronic dialysis therapy for children and adolescents in North America. Living donor graft (LDG) survival rate was 90% at 1 year, 85% at 2 years and 75% at 5 years post transplant. Cadaver graft (CG) survival rates were 76%, 71% and 62% at 1, 2 and 5 years post transplant, respectively. Overall mortality post transplantation continues to be low (CG 6.8%, LDG 4%), mortality remains high in young infants. The dialysis cohort was generally younger than the transplantation cohort. In all age groups, peritoneal dialysis was utilized in the majority of pediatric patients and the overall incidence of peritonitis was 1 episode per 8.2 patients months. External percutaneous catheters were utilized as the predominant chronic hemodialysis access in the study, and access site infections ranged from 6.9% at 1 month to 13.5% at 6 months.

Adolescent↗

Steady improvement in renal allograft survival among North American children: a five year appraisal by the North American Pediatric Renal Transplant Cooperative Study.

From 1987 through 1994, the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) has enrolled 1641 cadaver donor transplants. For this study, we have analyzed one and two year graft survival by annual cohorts for the years 1987 through 1991. For the 1987 cohort one and two year graft survival was 72% and 65%, respectively, and for the 1991 cohort it was 83% and 78%, respectively. Using a proportional hazards model, and comparing the 1987 cohort to the 1991 cohort, the relative risk for graft failure was 1.40 (P = 0.02). Analysis of practice patterns revealed the following changes which may have been associated with this improved graft survival: (1) use of T cell induction antibody, 38% in 1987 and 67% in 1991 (P < or = 0.001); (2) the increased use of cyclosporine (CsA) post-transplant: in 1987, 87% were maintained on CsA at day 30 compared to 97% in 1991 (P < 0.001); (3) the mean higher daily maintenance CsA dose at 12 months post-transplant which in 1987 was 6.5 mg/kg compared to 7.5 mg/kg in 1991 (P = 0.03); (4) the decreased use of random transfusions, 54% receiving > 5 transfusions in 1987 compared to 37% in 1991 (P < 0.001); and (5) decreased use of younger cadaver donors between 1987 and 1991 (P < 0.001).

Antibodies, Monoclonal↗

A heat shock-responsive domain of human HSF1 that regulates transcription activation domain function.

Human heat shock factor 1 (HSF1) stimulates transcription from heat shock protein genes following stress. We have used chimeric proteins containing the GAL4 DNA binding domain to identify the transcriptional activation domains of HSF1 and a separate domain that is capable of regulating activation domain function. This regulatory domain conferred heat shock inducibility to chimeric proteins containing the activation domains. The regulatory domain is located between the transcriptional activation domains and the DNA binding domain of HSF1 and is conserved between mammalian and chicken HSF1 but is not found in HSF2 or HSF3. The regulatory domain was found to be functionally homologous between chicken and human HSF1. This domain does not affect DNA binding by the chimeric proteins and does not contain any of the sequences previously postulated to regulate DNA binding of HSF1. Thus, we suggest that activation of HSF1 by stress in humans is controlled by two regulatory mechanisms that separately confer heat shock-induced DNA binding and transcriptional stimulation.

Amino Acid Sequence↗

Posttransplant deaths and factors that influence the mortality rate in North American children.

Of 2457 patients in the North American Pediatric Renal Transplant Cooperative Study registry who were followed for 5481 patient-years after the index transplantation, we observed 136 deaths, for an average annual rate of 24.8 deaths per 1000 patient-years. Death resulted primarily from infection (n = 55, 40%), cardiovascular causes (n = 28, 21%), hemorrhage (n = 16, 12%), and malignancies (n = 9, 7%). Cadaver-donor source was associated with greater mortality (6.7%) than a living-donor source (4.0%) (P < 0.005). Recipients aged 0-1, 2-5, 6-12, and 13-17 years old had mortality rates of 17.5, 8.0, 3.6, and 4.5%, respectively (P < .001). Mortality rates increased substantially when examined by recipient and cadaver donor ages (mortality rates of up to 45%), the greater the concordance between young donor and recipient ages. Interestingly, acute tubular necrosis and graft failure less than 30 days after transplantation (GH30) were each associated with markedly elevated mortality rates. (The risk ratio for ATN was 3.1 [P < 0.001] and for GF30 it was 6.4 [P < 0.001].) Mortality after transplantation was also affected by the underlying renal disease, with high mortality rates observed for oxalosis (n = 21, 33.3%), congenital nephrotic syndrome (n = 79, 15.2%), pyelo/interstitial nephritis (n = 54, 11.1%), and Drash syndrome (n = 14, 21.4%). When the joint effect of these risk factors was examined in a Cox proportional hazards model, young recipient age (0-1 years old) and GF30 were significant (P < .001) risk factors of mortality for recipients of living-donor organs. For recipients of cadaver kidneys, young recipient age--0-1 years old (P < .001) and 2-5 years old (P = .002)--ATN (P = .029), and GF30 (P < .001) were all significant risk factors. Recipient age is the major determinant of increased mortality after renal transplantation. Avoidance of acute tubular necrosis by reducing cold time and preventing early graft failure by better matching techniques in this vulnerable population may improve the mortality rate.

Adolescent↗

Subregion analysis of the rat femur: a sensitive indicator of changes in bone density following treatment with thyroid hormone or bisphosphonates.

Measurement of bone mineral density (BMD) by dual X-ray absorptiometry (DXA) is a precise and accurate way to assess changes in BMD due to a variety of causes. However, the degree of bone loss may vary depending on the skeletal site examined. We postulated that interventions that change bone density would have a different effect on an area rich in trabecular bone, such as the distal femur, than on other subregions of the femur. Male Sprague-Dawley rats (325-350 g) were treated with triiodothyronine (T3), a bisphosphonate (pamidronate), or placebo for 21 days and then sacrificed. Ex vivo BMD of the proximal, distal, mid and total femur were measured by DXA. We found that mean BMD of hyperthyroid rats was significantly lower than controls at all femoral subregions. However, the difference in mean BMD between hyperthyroid and control rats was greatest at the distal femur (8.6%). In rats treated with bisphosphonate, mean BMD was significantly higher than controls at the proximal, distal, and total femur. The difference in mean BMD between controls and rats treated with bisphosphonate was greatest at the distal femur (31.8%). Furthermore, pamidronate (APD)-treated rats had lower mean mid-femur BMD than controls. We conclude that changes in BMD after treatment with bisphosphonate or T3 are greatest at the distal femur subregion, and that treatment with bisphosphonate may cause a slight reduction in mid-femur BMD. Future studies examining changes in BMD in the rat femur after interventions that alter mineral metabolism should include subregion analysis.

Absorptiometry, Photon↗

The Advanced Glaucoma Intervention Study (AGIS): 1. Study design and methods and baseline characteristics of study patients.

Medical therapy has been the standard initial treatment for open-angle glaucoma. When some visual field has been lost and maximum tolerated and effective medical therapy does not succeed in controlling the disease, the patient is considered to have advanced glaucoma, and the first of a potential sequence of surgical treatments is usually indicated. Little is known about the long-term course and prognosis of advanced glaucoma or about the long-term effectiveness of sequential surgical treatments in controlling the disease and preventing vision loss and blindness. The Advanced Glaucoma Intervention Study was designed to study, in advanced glaucoma, the long-term clinical course and prognosis, and, in a randomized trial, the comparative outcomes of two sequences of surgical treatments. Toward these goals, 789 eyes in 591 patients were enrolled at 11 clinical centers between 1988 and 1992. Follow-up will continue until 1996. Eyes were randomly assigned to one of two sequences of surgical treatments. One sequence begins with argon laser trabeculoplasty (ALT), is followed by trabeculectomy, an incisional surgical filtering procedure, should ALT fail to control the disease, and by a second trabeculectomy should the first trabeculectomy fail. The other sequence begins with trabeculectomy, is followed by ALT should the trabeculectomy fail, and by a second trabeculectomy should ALT fail. The main outcome of interest is visual function (visual field and visual acuity). Other important outcomes are intraocular pressure, complications of surgery, time to treatment failure, and extent of need for additional medical therapy. We present in this paper the rationale, objectives, design and methods of the study, and the baseline characteristics of study patients and eyes.

Adult↗

Pre-emptive renal transplantation in children: report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

Of 2213 primary transplants reported to NAPRTCS between 1/1/87 and 10/31/92, 581 (26.3%) were performed without prior dialysis. The rate of pre-emptive transplantation (PET) differed by donor source, 35.7% LD and 16.1% CD (p < 0.001); gender, 29.6% male and 21.1% female (p < 0.001); race, 30.1% white, 16.1% black, 19.5% hispanic, and 20.2% other (p < 0.001); recipient age, 0-1 yr 18.7%, 2-5 yr 27.9%, 6-12 yr 30.5%, and 13-17 yr 22.8% (p < 0.001). The graft survival rate was significantly better for both the LD (p < 0.01) and CD (p = 0.01) grafts in the pre-emptive group; however, the differences were not significant after adjustment for other variables. The major reasons for pre-emptive transplantation were the parents' desire to avoid dialysis and the recommendation of the nephrologist/surgeon. The data indicate that pre-emptive transplantation does not adversely impact on transplant outcome and that the desire to avoid dialysis is the primary motivating factor.

Adolescent↗

Parenteral pamidronate prevents thyroid hormone-induced bone loss in rats.

Pamidronate (APD) is a bisphosphonate that prevents bone loss from a variety of causes. We studied the role of APD in preventing thyroid hormone-induced bone loss. A total of 32 rats were assigned to one of four treatment groups: (1) -APD/triiodothyronine (-T3), (2) -APD/+T3, (3) +APD/-T3, or (4) +APD/+T3. In the first of two studies, the rats received APD for the first week and T3 for the second week, and then their blood was analyzed for alkaline phosphatase and osteocalcin. Alkaline phosphatase and osteocalcin were significantly higher (p < 0.05) in hyperthyroid rats (-APD/+T3, 3.9 +/- 0.25 mukat/liter and 23 +/- 1.6 nM, respectively) than in control animals (2.53 +/- 0.28 mukat/liter and 18.3 +/- 1.4 nM, respectively). Hyperthyroid rats pretreated with APD (+APD/+T3) had levels of alkaline phosphatase and osteocalcin no different from controls. In a second study, rats were divided into the same four groups, except they received APD/placebo and T3/placebo concomitantly for 3 weeks. At the end of the study, bone mineral density (BMD) of the femur, spine, and whole body was measured by dual-energy x-ray absorptiometry, and the calcium content of the femora was measured directly. In hyperthyroid rats (-APD/+T3) BMD was significantly lower than in controls in the spine (0.201 +/- 0.004 versus 0.214 +/- 0.002 g/cm2, p < 0.05) and femur (0.204 +/- 0.003 versus 0.218 +/- 0.002, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗

Maintenance dialysis in North American children and adolescents: a preliminary report. North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

During 1992 the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) began to develop a pediatric Dialysis Patient Data Base by collecting data on pediatric patients who had received either hemodialysis (HD) or peritoneal dialysis (PD), or both, at a participating NAPRTCS center. This preliminary report describes study methods and contains detailed, though short-term observations reported by 64 of 87 NAPRTCS centers on 762 patients who were < 21 years of age at enrollment and who received treatment between January 1, 1992 and September 15, 1992. In these 762 patients, a total of 810 independent courses of dialysis therapy were identified (PD = 534 [65.9%]; HD = 276 [34.1%]). Patients age groupings showed a significantly greater proportion of PD patients among younger age groups. Automated peritoneal dialysis was used by about 75% of registered PD patients at one and six months after registration. A total of 196 peritonitis episodes were reported, yielding a peritonitis rate of one episode every 7.1 patient-months. Ten percent of PD catheters were replaced, primarily for mechanical malfunction and leaks. Percutaneous catheters were used for vascular access in about one-half of the HD patients, with the remainder almost equally divided between arteriovenous fistulae and grafts. Vascular access revision was reported in 28% of HD patients, with about one-third of these revisions performed to create a more permanent access. Recombinant human erythropoietin therapy was used in 89% of PD and 94% of HD patients at six months. Recombinant human growth hormone therapy was used in 9% of PD and 5% of HD patients at six months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Cyclosporine dosing and its relationship to outcome in pediatric renal transplantation.

The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) contains information on more than 2,000 pediatric renal transplants performed since 1987. We reviewed the NAPRTCS database to determine the long-term trends in cyclosporine dosing for pediatric recipients of renal transplants and to determine whether there is a relationship between cyclosporine doses and graft outcome. More than 90% of all patients in the NAPRTCS registry received cyclosporine as initial therapy, with a slightly higher percentages of cadaver donor recipients than living-related donor recipients. Cyclosporine doses is all patients decreased from a median of 9 mg/kg/day at one month following transplant to 4.3 mg/kg/day at 36 months. Cyclosporine doses were generally higher in younger patients, particularly during the first year following transplantation. The relationships between cyclosporine doses and both rejection episodes and graft losses were assessed. Between 6 months and 36 months following transplantation, patients who had first rejection episodes or lost their grafts had lower median cyclosporine doses than those who did not. Proportional hazards regression analysis of the risk of having a first rejection episode more than one year after the transplant indicated that the cyclosporine dose was negatively correlated with risk of rejection (RR = 0.9, P = 0.02). We conclude that cyclosporine doses are routinely decreased following renal transplantation in children. Lower doses of cyclosporine are associated with rejection episodes, particularly late rejections. Cyclosporine doses of pediatric recipients of renal transplants should not be tapered.

Adolescent↗

Hospitalization in children during the first year after kidney transplantation.

Length of hospital stay post-renal transplant was investigated in 2171 North American pediatric patients. Hospitalization for those surviving one year with a functioning graft was 28.8 versus 36.0 days (P < 0.05) for living donor (LD) compared with cadaveric donor (CAD) recipients during the first year post-transplant. Significantly prolonged hospital stays were recorded for LD recipients who (a) were less than one-year-old, (b) were receiving prophylactic ALG/OKT3, and (c) had a history of prior dialysis, and for CAD recipients who (a) were non-White and (b) received kidneys with cold ischemic times over 24 hours. In period II (2 to 6 months post-transplant), 51% and 68% of LD and CAD recipients, respectively were hospitalized while the corresponding values were 27% or 31% in period III (7 to 12 months post-transplant). Hospitalization was due mainly to graft loss or rejection episodes. Prolonged hospital stay coupled with poor graft survival might help to determine which aspects of the clinical practice of transplanting children warrant changes.

Child↗