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Clyde F Barker

Publications and source records attributed to Clyde F Barker.

9 recordsLinked to original sources
PubMed2003

The use of non-heart-beating donors for isolated pancreatic islet transplantation.

Recent improvements in isolated islet transplantation indicate that this therapy may ultimately prove applicable to patients with type I diabetes. An obstacle preventing widespread application of islet transplantation is an insufficient supply of cadaveric pancreata. Non-heart-beating donors (NHBDs) are generally not deemed suitable for whole-organ pancreas donation and could provide a significant source of pancreata for islet transplantation. Isolated pancreatic islets prepared from 10 NHBDs were compared with those procured from 10 brain-dead donors (BDDs). The success of the isolation for the two groups was analyzed for preparation purity, quality, and recovered islet mass. The function of NHBD and BDD islets was evaluated using in vitro and in vivo assays. On the basis of the results of this analysis, an NHBD isolated islet allograft was performed in a type I diabetic. The recovery of islets from NHBDs was comparable to that of control BDDs. In vitro assessment of NHBD islet function revealed function-equivalent BDD islets, and NHBD islets transplanted to non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice efficiently reversed diabetes. Transplantation of 446,320 islet equivalents (IEq) (8,500 IEq/kg of recipient body weight) from a single NHBD successfully reversed the diabetes of a type I diabetic recipient. Normally functioning pancreatic islets can be isolated successfully from NHBDs. A single donor transplant from an NHBD resulted in a state of stable insulin independence in a type I diabetic recipient. These results indicate that NHBDs may provide an as yet untapped source of pancreatic tissue for preparation of isolated islets for clinical transplantation.

Adult↗
PubMed2003

Insulin independence following isolated islet transplantation and single islet infusions.

OBJECTIVE: To restore islet function in patients whose labile diabetes subjected them to frequent dangerous episodes of hypoglycemic unawareness, and to determine whether multiple transplants are always required to achieve insulin independence. SUMMARY BACKGROUND DATA: The recent report by the Edmonton group documenting restoration of insulin independence by islet transplantation in seven consecutive patients with type 1 diabetes differed from previous worldwide experience of only sporadic success. In the Edmonton patients, the transplanted islet mass critical for success was approximately more than 9,000 IEq/kg of recipient body weight and required two or three separate transplants of islets isolated from two to four cadaveric donors. Whether the success of the Edmonton group can be recapitulated by others, and whether repeated transplants using multiple donors will be a universal requirement for success have not been reported. METHODS: The authors report their treatment with islet transplantation of nine patients whose labile type 1 diabetes was characterized by frequent episodes of dangerous hypoglycemia. RESULTS: In each of the seven patients who have completed the treatment protocol (i.e., one or if necessary a second islet transplant), insulin independence has been achieved. In five of the seven patients only a single infusion of islets was required. To date, only one recipient has subsequently lost graft function, after an initially successful transplant. This patient suffered recurrent hyperglycemia 9 months after the transplant. CONCLUSIONS: This report confirms the efficacy of the Edmonton immunosuppressive regimen and indicates that insulin independence can often be achieved by a single transplant of sufficient islet mass.

Adult↗
PubMed2003

Magnetic resonance-defined periportal steatosis following intraportal islet transplantation: a functional footprint of islet graft survival?

There is growing interest in more widespread application of isolated islet transplantation for the treatment of type 1 diabetes; however, the sequelae of long-term islet residence within the liver are unknown. We report herein a consequence of intraportal islet transplantation, specifically the development of periportal hepatic steatosis apparently induced by the local secretion of insulin within the liver.

Follow-Up Studies↗
PubMed2002

Comparison of open, laparoscopic, and hand-assisted approaches to live-donor nephrectomy.

BACKGROUND: Minimally invasive donor nephrectomy has become a favored procedure for the procurement of kidneys from live donors. The optimal minimally invasive surgical approach has not been determined. In the current work, we compared the outcome of kidneys procured using the traditional open approach with two minimally invasive techniques: the standard laparoscopic procedure and a hand-assist procedure. METHODS: The function of live-donor kidneys procured by open versus minimally invasive procedures was compared (procedures compared were the traditional open donor nephrectomy [ODN], the standard laparoscopic [LAP] approach, and the hand-assisted [HA] laparoscopic technique). The length of donor operation, donor length of stay in the hospital, surgical complications, and cost of hospitalization for three groups of patients were assessed in a series of 150 live-donor nephrectomies. RESULTS: We found that both minimally invasive procedures yielded kidney allografts with excellent early function and a minimum of complications in the donor. The open procedure was associated with a reduced operative time but increased donor length of stay in the hospital. Resource utilization analysis revealed that both minimally invasive techniques were associated with a slight increase in costs compared with the open procedure, despite a shorter hospital stay. CONCLUSIONS: Minimally invasive donor nephrectomy is safe and effective for procuring normally functioning organs for live-donor transplantation. Of the two minimally invasive approaches examined, the hand-assisted technique was found to afford a number of important advantages, including facilitating teaching of residents and students, that it is more readily mastered by transplant surgeons, and that it may provide an additional margin of safety for the donor.

Adult↗
PubMed2002

Intrathymic islet transplantation in the canine: I. Histological and functional evidence of autologous intrathymic islet engraftment and survival in pancreatectomized recipients.

BACKGROUND: Although an attractive alternative to daily insulin therapy, allogeneic pancreatic islet transplantation has yielded suboptimal results in clinical trials, in contrast to islet allotransplantation in animal models, which have demonstrated consistent success. The successful transplantation of isolated islets to the thymus, with a single concomitant dose of antilymphocyte serum, has been demonstrated in rodents, and more significantly, such intrathymic islet allografts have been shown to induce recipient tolerance toward subsequent extrathymic donor strain islet allografts. Intrathymic islet autotransplantation has been pursued, as a prelude to studies of allogeneic IT islet transplantation and tolerance induction, in canine, porcine, and non-human primate models, to assess the large animal thymus as a site capable of supporting a viable islet graft. However, little functional or histological evidence has established definitive survival of islets transplanted within the thymus of a phylogenetically advanced species, which may be requisite to tolerance induction. This study describes the successful intrathymic autotransplantation of isolated islets using a canine model. METHODS: Purpose-bred juvenile dogs, aged 4-6 months, underwent partial (n=4), or total pancreatectomy (n=11), and transplantation of autologous islets. The pancreas (or pancreatic limb) was distended with collagenase solution, and digested using a modification of the semiautomated system of Ricordi. Islets were purified by discontinuous gradient centrifugation, using Euroficoll (ficoll in Euro-Collin's kidney preservation solution). Partially pancreatectomized canines underwent IT transplantation of purified autologous islets (8000+/-4000 IEs), and were killed 8 weeks posttransplant. Totally pancreatectomized canines underwent transplantation of autologous islets to the liver (via portal vein embolization, n=5, IPO group) or the thymus (via direct IT injection, n=6, IT group), and were serially evaluated for a period of 8 weeks posttransplant to assess fasting blood glucose (FBG), serum insulin (SI) levels, and i.v. glucose tolerance (IVGTTs). K values (defined as the %-decrease/minute of the log(e) of blood glucose values) were calculated from IVGTT results. RESULTS: After autotransplantation in this cohort of animals, five of five IPO, and three of six IT islet recipients, remained normoglycemic (mean FBG< or =250 mg%) immediately posttransplant, and all recipients exhibited significantly elevated SI levels compared to apancreatic controls (n=10, followed 72 hr postpancreatectomy). Normal k values (=-1.1) were observed in two of five IPO, and in one of six IT recipients, 8 weeks after transplantation, and thymic tissue insulin content was increased compared to non-islet-bearing thymi (93.7+/-48.6 ng/g tissue vs. 0.7+/-0.4 ng/g tissue). At 8 weeks posttransplantation thymi from both partially and totally pancreatectomized animals were resected and processed for histological examination. Microscopic analysis of islet-bearing thymi revealed positive staining for islet-specific hormones (insulin and glucagon) within all IT recipients., Identification of islets within thymi of hyperglycemic IT recipients was problematic as islet beta cells were highly degranulated as a result of the recipients glycemic state. CONCLUSIONS: These results indicate that autologous islets, transplanted to the canine thymus, engraft, function, and survive for up to 8 weeks after islet autotransplantation to the canine thymus and establish the feasibility of intrathymic islet transplantation in a phylogenetically advanced animal model. The ability of islets to survive within the thymic environment for a period of at least 8 weeks after transplantation suggests that the successful induction of specific unresponsiveness secondary to intrathymic transplantation will not be impaired or limited by the inability of a viable islet mass to survive within the thymus for a sufficient period.

Animals↗
PubMed2002

Elimination of maternally transmitted autoantibodies prevents diabetes in nonobese diabetic mice.

The influence of maternally transmitted immunoglobulins on the development of autoimmune diabetes mellitus in genetically susceptible human progeny remains unknown. Given the presence of islet beta cell-reactive autoantibodies in prediabetic nonobese diabetic (NOD) mice, we abrogated the maternal transmission of such antibodies in order to assess their influence on the susceptibility of progeny to diabetes. First, we used B cell-deficient NOD mothers to eliminate the transmission of maternal immunoglobulins. In a complementary approach, we used immunoglobulin transgenic NOD mothers to exclude autoreactive specificities from the maternal B-cell repertoire. Finally, we implanted NOD embryos in pseudopregnant mothers of a non-autoimmune strain. The NOD progeny in all three groups were protected from spontaneous diabetes. These findings demonstrate that the maternal transmission of antibodies is a critical environmental parameter influencing the ontogeny of T cell-mediated destruction of islet beta cells in NOD mice. It will be important to definitively determine whether the transmission of maternal autoantibodies in humans affects diabetes progression in susceptible offspring.

Animals↗
PubMed2002

Durability of benefits of endovascular versus conventional abdominal aortic aneurysm repair.

PURPOSE: Endovascular abdominal aortic aneurysm (AAA) repair is reported to result in less initial patient morbidity and a shorter hospital length of stay (LOS) when compared with conventional AAA repair. We sought to examine the durability of this result during the intermediate follow-up interval. METHODS: The records of all admissions for all patients who underwent AAA repair during a 26-month interval were reviewed. RESULTS: Three hundred thirty-seven (337) patients underwent procedures to repair AAAs (163 open and 174 endovascular). Endovascular procedures were performed with a variety of devices (Talent, 108; Ancure, 36; AneuRx, 26; Zenith, 2; and Cordis, 2) and configurations (141 bifurcated and 33 aortomonoiliac). The mean follow-up period was 10.6 months (endovascular repair) and 12.3 months (open repair). LOS did not significantly vary by device (P =.24 to P =.92) or configuration (P =.24). The initial median LOS for procedures was significantly shorter (P =.009) for endovascular repairs (5 days) than for open procedures (8 days). However, the patients who underwent endovascular repair were more likely to be readmitted during the follow-up interval when compared with patients who underwent open procedure. The readmission-free survival rate after AAA repair at 12 months was 95% for patients for open AAA repair versus 71% for patients for endovascular repair (P <.001). If the total hospital days were compared, including the initial and all subsequent AAA-related admissions, there was no significant difference for mean LOS for patients who underwent endovascular versus open AAA procedures (11 days versus 13.6 days; P =.21). The patients for endovascular AAA repair most commonly needed readmission for treatment of endoleak (n = 31), wound infection (n = 12), and graft limb thrombosis (n = 9). Although women had similar LOS to men for endovascular repair (P =.44), they had longer initial LOS for open AAA repair (15 versus 10 days; P =.03). After endovascular repair, women were more likely than men to be readmitted by 12 months (51% versus 71% readmission-free survival rate; P =.03) and they had longer LOS on readmission (13.2 versus 5.2 days; P =.006). No gender differences were identified for patients after open AAA repair regarding readmission-free survival rate (P =.09) or LOS on readmission (P =.98). CONCLUSION: Although initial LOS was shorter for the patients who underwent endovascular as compared with conventional AAA repair, this advantage was lost during the follow-up interval because of frequent readmission for the treatment of procedure-related complications, chiefly endoleak. These readmissions frequently involved the performance of additional invasive procedures. Gender differences existed regarding LOS and the likelihood of complications after open and endovascular AAA repair.

Aged↗
PubMed2002

Potential impact of therapeutic warfarin treatment on type II endoleaks and sac shrinkage rates on midterm follow-up examination.

OBJECTIVE: Successful endovascular aortic aneurysm repair depends on exclusion and spontaneous thrombosis of the aneurysm sac. The need for chronic postoperative anticoagulation therapy could limit the applicability of this technology with delay or prevention of sac thrombosis resulting in endoleak formation and altered remodeling of the aneurysm sac. The purpose of this study was the determination of whether chronic therapeutic anticoagulation therapy with warfarin was associated with an increased incidence rate of early or delayed postoperative endoleaks or altered rates of reduction in aneurysm sac maximum diameter. METHODS: Two hundred thirty-two consecutive patients underwent abdominal aortic endografting during a 32-month period. The data were recorded prospectively with a current mean follow-up period of 18 months. The patients with endoleaks identified with 30-day postoperative computed tomographic scan angiograms subsequently underwent selective arteriography to characterize the source. The patients who underwent chronic warfarin therapy that resulted in a therapeutic internationalized normalized ratio comprised the study group. The control group was defined as all the patients with healthy coagulation profiles. RESULTS: Thirty-six patients (15%) were undergoing warfarin therapy after surgery, and their conditions were chronically maintained with a therapeutic international normalized ratio. Forty-three patients (18%) had endoleaks on 30-day computed tomographic scan angiographic results. There were 39 patients with type II endoleaks and four patients with type I endoleaks. None of the type I endoleaks occurred in patients who were undergoing warfarin therapy, and all endoleaks were repaired with either proximal or distal covered extensions. At 30 days, seven patients (19.4%) undergoing chronic warfarin therapy had type II endoleaks as compared with 36 controls (18.4%; P =.798). Four patients had delayed type II endoleaks develop, two in the control group and two in the warfarin group (P =.3). Ten control individuals (31%) had spontaneous resolution of type II endoleaks develop, whereas spontaneous endoleak thrombosis was not observed in the warfarin group (P =.33). Aneurysm sac remodeling assessed with mean percent reduction in maximum sac diameter at 12 months revealed a statistical difference between the control group (17.5%) and the warfarin group (7.6%; P =.04). CONCLUSION: Warfarin treatment is not associated with an increase in the incidence rate of early or delayed postoperative endoleaks. However, the rate of reduction in maximum aneurysm sac diameter after aortic endografting is slower in patients who undergo therapeutic warfarin therapy at 1-year follow-up examination, a statistically significant difference from the control group. In addition, type II endoleaks may be less likely to undergo spontaneous thrombosis in patients who undergo warfarin therapy.

Anticoagulants↗