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B E Jarrell

Publications and source records attributed to B E Jarrell.

At least 19 recordsLinked to original sources

The shrinking renal replacement therapy "break-even" point.

BACKGROUND: This study examines the current cost of live donor (LD) transplantation at our institution, and compares it with that of dialysis. METHODS: The study population consisted of 184 consecutive adult recipients of laparoscopically procured LD kidney transplants. Cost-containment measures instituted during this series included elimination of routine postoperative antilymphocyte induction and an accelerated discharge clinical pathway with planned discharge of the recipient on postoperative day (POD) 2. Costs of the transplants to Medicare were estimated from hospital charges, readmission rates, and immunosuppressant usage. These were compared with published costs of dialysis to Medicare in terms of a fiscal transplant-dialysis break-even point. RESULTS: Kaplan-Meier patient and graft survival rates at 1 year were 97 and 93%, respectively. Among patients followed for at least 90 days and treated with no induction and either cyclosporine-mycophenolate mofetil or tacrolimus-mycophenolate mofetil, acute rejection rates were low (27.6 and 13.9%, respectively). In the last 124 patients, 32.3% were discharged by POD 3 and 71.8% by POD 6, with corresponding mean transplant hospital charges (excluding organ acquisition) of $11,873 and $17,350, respectively. The 30-day readmission rate for patients discharged on the accelerated pathway by POD 3 was only 16%. The least expensive subgroup in the present study (30% of patients) was that of patients discharged by POD 6 and not readmitted during the first year; the break-even point with dialysis costs was calculated as 1.7 years after the transplant. CONCLUSIONS: The cost of LD transplants can be safely reduced by elimination of routine postoperative anti-lymphocyte immune induction and by an early discharge clinical pathway. Uncomplicated LD kidney transplants, meaning those with a short length of stay in the hospital after transplantation and no need for readmission within the first year, accrue savings over dialysis within 2 years.

Adolescent

Kidney transplantation at the University of Maryland.

1. The number of kidney transplants performed at the University of Maryland increased yearly from 51 in 1991 to 285 in 1998. Over the past 3 years, the increase in the number of kidney transplants can be ascribed almost exclusively to a marked increase in living donor transplants, from 49 cases in 1995 to 130 cases in 1998; a 160% increase. The increase in our frequency of living-donor kidney transplantation can be attributed to a formal family education program and the availability of the laparoscopic technique for kidney removal. 2. In addition to the availability of the laparoscopic technique, a number of special programs has allowed an increased number of living donor kidney transplants. This includes a special protocol for transplantation of Epstein-Barr virus negative recipients, a protocol for transplantation of patients who have a positive crossmatch with a living donor, as well as, the simultaneous living donor kidney/cadaver pancreas "SPK(LRD/PTA)" program. 3. The one-year graft and patient survival for the entire program was 87.0% and 94.5%, respectively. However, the more recent graft survival rates have markedly increased; Since August 1995, the one-year graft and patient survival was 89.8% and 95.8%, respectively. 4. Improvement in immunosuppression has lead to dramatic improvement in the success rates in living-donor kidney transplants. Despite the omission of antibody-based induction therapy, the one-year graft survival rate using a mycophenolate mofetil/tacrolimus-based immunosuppression protocol was 96.4%. The one-year rejection rate was 8% in Caucasian patients and 14% in African-American patients in this subgroup of living-donor kidney transplant recipients. 5. The data demonstrate that the use of the living-donor transplant option is grossly underutilized. Estimates are presented that more than 11,000 living-donor kidney transplants should be possible in the US yearly.

Black People

Variables affecting birthweight and graft survival in 197 pregnancies in cyclosporine-treated female kidney transplant recipients.

Outcomes from 197 pregnancies in 141 female kidney transplant recipients were analyzed from data collected via questionnaires, hospital records, and phone interviews. All recipients were maintained on cyclosporine (CsA) before and during pregnancy. Of the livebirths, 54% were premature (< 37 wk) and 50% were low-birthweight (LBW) (< 2500 g). The incidence of recipient drug-treated hypertension (HTN) was 56%; preeclampsia, 29%; infections and complications 22%; and rejection during pregnancy and up to 3 mo. post delivery (rej.), 11%. Graft loss within 2 years of delivery occurred in 9% of recipients (GrL < 2). No recipients reported a pregnancy after a postpregnancy graft loss. Mean serum creatinine was reported before, during, and after pregnancy. Mean cyclosporine doses were similar in recipients during and after pregnancy. Data were analyzed by logistic regression using SAS. Outcomes included prematurity, LBW, rej., and GrL < 2. In a case-controlled study comparing a recipient group with graft dysfunction during pregnancy vs. a group with good graft function, there was a trend toward lower mean prepregnancy CsA doses (in mg/kg) in the graft dysfunction group. A decline in recipient graft function during pregnancy is associated with lower newborn birthweights and lower maternal graft survival in cyclosporine treated female kidney recipients. Pregnancy-related infections and complications are associated with rejection and graft loss in this population. Close monitoring of CsA dosing and serum creatinine levels during pregnancy and immediately postpartum is recommended as CsA dosage adjustment may be required.

Case-Control Studies

National Transplantation Pregnancy Registry: analysis of pregnancy outcomes in female liver transplant recipients.

Outcomes from 48 pregnancies in 34 female liver transplant recipients were analyzed. Data were collected via interviews, questionnaires, and hospital records. All recipients were treated with cyclosporine-based immunosuppression except 2 patients treated with FK506 and 2 treated with no immunosuppression. The age at conception was 26.1 +/- 5.9 years (mean +/- SD) with a transplant interval (time from transplantation to conception) of 2.9 +/- 2.5 years. There were 49 outcomes (1 set of twins): miscarriage 9 (18%), therapeutic abortion 4 (8%), and live birth 36 (74%). No stillbirths or ectopic pregnancies were reported. Of the 36 live births, the gestational age was 36.9 +/- 3.5 weeks, the birthweight was 2,604 +/- 698 grams, 39% were premature (< 37 weeks), and 31% had low birthweight (< 2,500 grams). No birth defects or neonatal deaths (< 28 days) were reported. The newborn complication rate was 17% (n = 6), 5% in premature infants. The incidence of drug-treated hypertension was 46%; pre-eclampsia 21%; infectious complications 26%; and Caesarean section 47%. Recipients with hypertension had a higher proportion of premature infants (71%) than normotensive patients (38%) (P = .04 by Fisher's exact test). Acute rejection was diagnosed in 6 pregnancies, 2 of which were ended by therapeutic abortion. Four recipients who continued their pregnancies were treated with increased immunosuppression for rejection, and all delivered livebirths. There were two grafts lost within 6 months of pregnancy. The only maternal death occurred in a patient who required retransplantation for recurrent C hepatitis 3 months afte therapeutic abortion and died 6 months later. The other recipient with graft loss was successfully retransplanted for chronic rejection 6 months after delivery. We draw the following conclusions: (1) female liver transplant recipients can safely undergo pregnancy, although there is a high rate of premature and low birthweight infants; (2) pregnancies in this population should be considered high-risk and require close monitoring of liver function; and (3) altered graft function during pregnancy should be thoroughly investigated.

Adult

National transplantation Pregnancy Registry--outcomes of 154 pregnancies in cyclosporine-treated female kidney transplant recipients.

Outcomes of pregnancies from 115 female kidney transplant recipients maintained on cyclosporine before and during pregnancy were obtained from questionnaires, hospital records, and telephone interviews. The mean age of conception was 29 years with a mean transplant interval of 2.2 years. There were 156 outcomes (2 sets of twins): ectopic 1%, therapeutic abortion 12%, miscarriage 16%, stillborn 2.6%, live birth 68.6%. The incidence of prematurity (< 37 weeks) was 56%, and that of low birthweight (< 2500 g) 49.5%. Complications occurred in 21.7% of newborns, but with only 1 neonatal death. Liveborn infants had a mean gestational age of 35.6 weeks (term 37-42 weeks) and a mean birthweight of 2407 g. The incidence of drug-treated hypertension prior to pregnancy was 51.7%; of diabetes prior to pregnancy, 11.7%; of preeclampsia, 24.8%; and of rejection during pregnancy or within 3 months postdelivery 14.5%. When infants born to women with or without a given risk factor were compared, mothers with pregnancy drug-treated hypertension had significantly lower-birth-weight infants (2250 vs. 2603 g, P = 0.028 by Wilcoxon). Similarly, mothers with prepregnancy creatinine > or = 1.5 mg/dl had smaller infants (2090 vs. 2505 g, P = 0.031 by Wilcoxon). There was a trend toward lower birth-weight in infants of diabetic recipients. Of 107 recipients interviewed, 12(11%) experienced graft loss, 8 associated with graft dysfunction or rejection during pregnancy. There was 1 graft loss during pregnancy due to rejection and 8 grafts were lost within 2 years of the pregnancy. There was one maternal death 4.3 years postpregnancy. For the 8 recipients who lost their graft within 2 years of pregnancy, outcomes included 1 miscarriage and 7 live births. The 7 live births had a mean gestational age of 35.7 weeks and a mean birth-weight of 2194 g. Five of 8 recipients who had graft loss within 2 years of pregnancy were in the drug-treated hypertensive group. Prepregnancy factors that appear to increase the risk to the newborn of a female kidney transplant recipient include maternal drug-treated hypertension, diabetes, and serum creatinine > or = 1.5 mg/dl. More data are needed before specific prepregnancy predictors for maternal graft loss can be determined in this population.

Birth Weight

Microvascular endothelial cell sodding of ePTFE vascular grafts: improved patency and stability of the cellular lining.

Small diameter (< 6 mm) synthetic vascular grafts fail at a clinically unacceptable rate due in large part to their inherent thrombogenicity. The development of a new cellular lining on synthetic vascular grafts would most likely improve the patency rates observed for these grafts in small diameter positions. We have evaluated the use of endothelial cell transplantation to accelerate the formation of a cell lining using microvascular endothelial cells derived from canine falciform ligament fat. This source of fat is histologically similar to human liposuction fat and was isolated using a collagenase digestion technique identical to methods used for human liposuction fat microvessel endothelial cell isolation. The isolated fat endothelial cells were sodded onto 4 mm ePTFE grafts using pressure to force the cells onto the luminal surface. This pressure sodding method permitted cell deposition in less then 3 min. Sodded and control (non-cell-treated) grafts were implanted as interpositional paired grafts using end-to-end anastomoses in the carotid arteries of mixed breed dogs. Each dog therefore received a sodded graft on one side and a control graft on the contralateral side. After 12 weeks of implantation all control grafts were occluded while 86% of the cell-sodded grafts remained patent. Statistical evaluation of the data revealed a significant improvement in patency of cell sodded grafts (McNemar's chi 2 P = .02). Morphological evaluation of grafts explanted at 5, 12, 26, and 52 weeks following implantation revealed the presence of a cell lining on sodded grafts which remained stable for a period of at least one year. This new cell lining exhibited morphologic characteristics of a nonthrombogenic endothelial cell lining. The development of this new intima, evaluated 5 weeks-1 year after implantation, was not associated with a progressive intimal hyperplasia. From these data we conclude that microvessel endothelial cells derived from canine falciform ligament fat can be rapidly isolated using an operating room compatible method. Cell deposition on synthetic grafts is subsequently accelerated using a pressure sodding technique. A cellular lining forms on the inner surface and is associated with a statistically significant improvement in the function of sodded grafts in a canine carotid artery model.

Adipose Tissue

Liposuction-derived human fat used for vascular graft sodding contains endothelial cells and not mesothelial cells as the major cell type.

PURPOSE: Endothelial cell transplantation has been suggested as a method to improve the patency of prosthetic grafts used for vascular reconstruction. A major technical concern of all cell transplantation studies has been the purity of cells in the primary isolate used for subsequent transplantation. Accordingly we have evaluated the cellular constituents of liposuction-derived human fat with immunocytochemistry and scanning electron microscopy. METHODS: Samples of liposuction-derived human fat were processed for immunohistochemistry and subsequently stained for the presence of von Willebrand factor (vWF), alpha-smooth muscle cell actin, cytokeratin (peptide 18), and the endothelial cell-specific marker EN4. We also performed histochemistry studies on the cells derived from this fat after collagenase dispersion of the liposuction far. RESULTS: Immunohistochemistry revealed that 86.1% of the cells in intact, liposuction-derived fat express vWF, whereas 5.7% of the cells exhibited alpha-smooth muscle cell actin, and 1.0% expressed the mesothelial cell-related antigen, cytokeratin peptide 18. Expression of EN4 was found in 89.6% of the cells counted in intact far. After digestion of fat with collagenase and centrifugal separation of adipocytes from vascular and stromal cells, the expression of vWF, alpha-smooth muscle cell actin, and cytokeratin was 77.5%, 5.8%, and 2.1%, respectively. EN4 expression was observed in 74.6% of the isolated cells. Thus most cells present in liposuction-derived fat, even before tissue digestion and cell isolation, were characterized as endothelium. Although other cells common to mesodermally derived tissue were identified (e.g., adipocytes, smooth muscle cells, and mesothelium), they represented a minor fraction of the total cells present. On isolation, the number of cells expressing vWF- and EN4-specific antigens was less than that observed in intact fat. CONCLUSIONS: This finding suggests that a portion of cells reacting with antibodies in situ lose vWF and EN4 staining during the isolation procedure. Unlike omentum, liposuction-derived fat predominantly contains adipocytes and endothelial cells. On digestion of liposuction-derived fat and separation of cells, vascular endothelial cells represent the major cellular component.

Adipocytes

Serum amino acids following human orthotopic liver transplantation.

Our findings indicate that serum amino acid changes after OLT are complex and influenced by multiple factors including sepsis and use of parenteral hyperalimentation with exogenous amino acids. Additional factors which may influence the rate of normalization of amino acids after OLT include the presence of malnutrition (frequently observed before OLT) and the extent of pretransplant portal-systemic shunting. Our results demonstrate that the presence of septic complications and the use of CPN are important determinants of the postoperative levels of several amino acids, including the BCAA/AAA ratio. Our logistic regression model using the BCAA/AAA ratio predicted the occurrence of sepsis after OLT 77% of the time. Prospective assessment and validation of this model is under way.

Amino Acids

Formation of a multilayer cellular lining on a polyurethane vascular graft following endothelial cell sodding.

Small-diameter (less than 6 mm) clinically available vascular grafts often fail due in part to the inherent thrombogenicity of artificial polymers. Transplantation of endothelial cells onto the lumen of these vascular grafts has been suggested as one method to overcome this thrombogenicity. We have developed a compliant polyurethaneurea (PEUU) 4-mm graft with a luminal surface modified by a glow discharge gas plasma. Autologous microvessel endothelial cells were isolated from canine falciform ligament fat, were transplanted onto the luminal surface of the grafts using an intraoperative isolation and sodding technique, and both endothelial-cell-treated and non-cell-treated grafts were placed as bilateral carotid interposition grafts in a canine model. After 5 weeks of implantation, explanted control (non-cell-treated) grafts exhibited a deposition of platelets, white cells and fibrin characteristic of a thrombogenic surface. MVEC sodded grafts exhibited a multicellular lining within but distinct from the lumen of the PEUU graft. The blood-contacting surface of this lining exhibited an antithrombogenic endothelial cell monolayer. We suggest that the PEUU graft supported the initial deposition of MVEC and development of and endothelial cell lining. During the 5 weeks of implantation this lining continued to proliferate and detached from the PEUU graft substratum. The final neocellular lining exhibited a luminal diameter and histological features similar to a native artery.

Animals

A porcine model for adipose tissue-derived endothelial cell transplantation.

The transplantation of endothelial cells represents a technology which has been suggested for applications ranging from improvement in function of implanted vascular devices to genetic therapy. The use of microvascular endothelial cell transplantation has seen increased use both in animal studies as well as clinical use. This report describes our techniques for the isolation and establishment of initial cultures of microvascular endothelial cells derived from porcine fat. A variety of anatomic sites within the pig were evaluated to determine the appropriateness of different sources of fat for endothelial cell isolation. The properitoneal fat was determined to be optimal due to the predominance of endothelium in this tissue and the ease of isolation of microvascular endothelium following collagenase digestion. The study of endothelial cell transplantation in the porcine model is now possible using the methods described for adipose tissue-derived microvessel endothelial cell isolation.

Actins