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Biomedical subjects

R Didlake

Publications and source records attributed to R Didlake.

At least 19 recordsLinked to original sources

Composite dialysis access grafts.

Hemodialysis access devices constructed of expanded polytetrafluoroethylene (ePTFE) require a maturation period of seven to 14 days before cannulation. Percutaneously placed dual-lumen catheters can be used for temporary access during this interval but are associated with significant short and long term complications. Access devices constructed of Plasma-TFE (pl-TFE) (Atrium, Hollis) conduits have been reported to tolerate cannulation immediately after placement, but long term patency is inferior to that of conventional ePTFE. To combine the immediate access advantages of pl-TFE and the long term patency of ePTFE, composite grafts were constructed, which consisted of 10 to 12 centimeters of pl-TFE and the remainder of ePTFE. The pl-TFE segment was made available for immediate access and the ePTFE segment after an appropriate maturation period. Thirty percent of composite grafts were cannulated on the day of placement and 83.8 percent were cannulated within 72 hours. No complications of early access of the pl-TFE segment occurred. These grafts were compared with a cohort of conventional ePTFE grafts for the occurrence of thrombosis, infection and pseudoaneurysm. No significant differences were noted. Event-free patency of the two groups was equal (327.7 versus 346.3 days, p = 0.282). Patency after an initial thrombotic episode was slightly better in the composite group. We conclude that composite dialysis access grafts can be cannulated immediately after placement and demonstrate long term performance at least equal to that of conventional ePTFE grafts. Use of the composite graft concept should be considered when immediate dialysis is needed and to avoid the use of temporary access catheters.

Arteriovenous Shunt, Surgical↗

Outpatient vascular access surgery: impact of a dialysis unit-based surgical facility.

The present report describes a novel approach to vascular access surgery based on the philosophy that a readily available operating room, staffed by nurses familiar with the unique problems of dialysis patients and their therapy, would reduce dialysis delays and maintain the quality of surgical care. Based on a 28-month experience with more than 1,000 access cases, we conclude that a traditional surgical setting is not necessary for either quality access graft placement or the management of access complications.

Age Factors↗

Choice of anesthetic technique for needle localized breast biopsy.

General anesthesia has been recommended to increase the accuracy and safety of needle localized biopsy (NLB). The authors' NLB experience was reviewed to determine whether the method of anesthesia affected accuracy, yield, complication rate, or cost. All biopsies were performed in a standard operating room using either local anesthesia (Group 1, n = 14), local anesthesia with an anesthesiologist present (Group 2, n = 14), or general anesthesia (Group 3, n = 10). The mean operative times were 54, 59, and 56 minutes for Groups 1, 2, and 3, respectively. In groups 1 and 2, 100 per cent of the specimen radiographs showed the target lesion had been excised, although one biopsy was indeterminate. Among Group 3 two target lesions could not be identified on specimen radiographs and one was indeterminate. There was one malignancy in Group 1 compared with four malignancies in Group 2 and two in Group 3. The average hospital bill was $1,172 for Group 1, $1,418 for Group 2, and $1,488 for Group 3. Anesthesiologists' fees added an additional $224 to Groups 2 and 3. NLB can be performed using local anesthesia without sacrificing accuracy or yield, increasing operative time, or increasing complication rate; the cost is significantly less than with general anesthesia.

Adult↗

Mirizzi's syndrome. An uncommon cause of biliary obstruction.

An uncommon cystic-duct anomaly characterized by a course parallel to the common hepatic duct or contained in a sheath with the common hepatic duct over a significant distance can allow cystic-duct stones to occlude the common hepatic duct by extrinsic pressure. This condition is appropriately referred to as Mirizzi's syndrome. One such case is described in the present study. Recognition of this and other biliary anomalies is critical to safe operative management of calculous biliary disease.

Adult↗

Attenuation of ischemic renal injury with fructose 1,6-diphosphate.

Fructose 1,6-diphosphate (FDP) has been shown to attenuate tissue injury associated with ischemia and shock by enhancing the anaerobic carbohydrate utilization and by inhibiting oxygen-free-radical generation by the neutrophils. Previously, we have reported that FDP prevents ischemic renal failure if administered prior to the ischemic insult. The present study was designed to determine whether this agent could prevent renal damage when administered during the postischemic reperfusion period. Rats were subjected to 30 min of bilateral renal artery occlusion and infused with FDP (350 mg/kg body wt) beginning 10 min after release of the renal artery clamps. Control rats received an equal volume of glucose/saline solution. A third group of rats were sham operated. Twenty-four hours after injury, BUN, creatinine, and fractional sodium excretion values were less in FDP-treated rats than in control rats (P less than 0.001, P less than 0.005, and P less than 0.001, respectively) and not different from values observed in sham-operated rats. Inulin clearance was greater (P less than 0.001) in FDP-treated rats than in control rats (665 +/- 38 microliters/min/g kidney wt). Renal histology was also better preserved in the FDP-treated group. These data suggest that FDP infused after the initiation of an acute ischemic insult provides significant, but not complete, functional and histologic protection from renal damage.

Animals↗

Prolongation of heterotopic heart allograft survival by local delivery of continuous low-dose cyclosporine therapy.

The effectiveness of local versus systemic low-dose CsA (2 mg/kg/day) therapy delivered by osmotic pump for a 14-day continuous infusion was examined in the rat model. Systemic subtherapeutic CsA treatment of WFu recipients either by oral gavage or intravenously using an osmotic pump resulted in quick rejection of BUF heart allografts within a median survival time (MST) of 8 days in comparison with untreated controls (MST = 7 days). In contrast, direct local subtherapeutic CsA delivery to BUF heart allografts produced significantly (P less than 0.01) prolonged heart allograft survivals up to MST of 40 days. Splenic T cells, isolated on days 10 to 12 from locally immunosuppressed WFu recipients, revealed a nonspecifically reduced proliferative response toward alloantigens. Coculture experiments demonstrate that these T cells have the capacity to inhibit normal T cell proliferative responses in a nonspecific fashion either by their suppressor function or more likely by carrying CsA to the culture plate. In contrast, T cells isolated from WFu recipients three weeks after transplantation and tested in vitro demonstrated the presence in alloantigen specific T suppressor cells that coincided with a decreased frequency of alloantigen-specific T cytotoxic cells and may explain the extended heart allograft survival beyond the time of CsA delivery. CsA therapy delivered directly to the graft resulted in high CsA levels within the heart graft (1108 ng/0.1 g) but subtherapeutic levels in other tissues. These results demonstrate that local drug delivery is effective in inhibiting the rejection process within the graft itself, as manifested by prolonged heart allograft survival. Further, subtherapeutic CsA therapy facilitates development of Ts cells that may be responsible for the survival of heart allografts beyond the CsA delivery time.

Animals↗

The synergistic effect of total-lymphoid irradiation with extracted donor alloantigen in inducing transplantation unresponsiveness.

The synergistic effect of total lymphoid irradiation with KCl-extracted donor type antigen (H-Ag) was examined in the rat cardiac graft model. TLI therapy alone of 10, 16, and 20 Gy achieved by a 2 Gy daily treatment of WFu recipients produced modest prolongation of BUF heart survival to median survival times (MST) of 11, 26, and 30 days, respectively, in comparison with normal control (MST = 6). The TLI immunosuppressive effect was significantly potentiated with donor H-Ag when combined with 16 (greater than 100 days) but not with 10 or 20 Gy TLI therapy. This effect was specific: 16 Gy TLI treated recipients of BUF hearts rejected their grafts in a MST of 27 days when treated with third-party BN H-Ag. The state of unresponsiveness was transferable to 6 Gy total-body-irradiated WFu recipients of BUF hearts with 60 x 10(6) purified T cells isolated from TLI/H-Ag-treated rats (greater than 100) but not from normal controls (MST = 6). In vitro analysis of nontransplanted WFu rats 1-4 weeks after completion of 16 Gy TLI therapy alone demonstrated a nonspecifically reduced MLR proliferative response as well as the presence of potent nonspecific suppressor cells (NSC). By 3 or even 6 months post-TLI, W3/25- NSC displayed persistent suppressive activity and inhibited normal proliferative response to alloantigens. Limiting dilution assay revealed that the frequency of T cytotoxic cells (fTc) was severely decreased to 1:63111 at one day and to 1:16488 at one week postirradiation in comparison with normal control (1:2551). At 3 and 6 months the fTc of 1:2301 and 1:2040, respectively, approximated normal levels. These combined in vivo and in vitro results demonstrate that 16 Gy TLI therapy induces an unresponsiveness mediated by NSC and that the administration of donor type H-Ag facilitates the generation of potent regulatory T cells capable of inducing prolonged heart allograft survival.

Animals↗

Ability of 3M KC1-extracted histocompatibility antigen to potentiate the immunosuppressive effect of cyclosporine to prolong the survival of heterotopic rat cardiac allografts.

A soluble histocompatibility antigen preparation (HAg) derived by 3M KCl extraction of donor spleen cells has been shown to prolong rat renal allografts in CsA-treated hosts. In the present study, the effect of combined soluble antigen-CsA treatment on cardiac allograft survival was studied in WFu hosts grafted with BUF hearts. Cardiac allograft survival was prolonged in WFu recipients treated with both BUF HAg and CsA compared with survival time in untreated controls or controls treated with HAg or CsA alone. In addition, experiments were performed to test the antigenicity of the HAg extract. BUF extract given sc to WFu hosts before grafting specifically sensitized the hosts to BUF grafts, as shown by the accelerated rejection of BUF grafts but not third-party grafts. Assays to determine the major histocompatibility antigenic determinants present in the extract showed that class I and class II determinants were present.

Animals↗

The protective effect of hepatic dysfunction on vascularized allograft survival.

Recent studies have demonstrated that hepatic dysfunction, induced by experimental biliary ligation (EBL), impairs lymphocytic responsiveness to PHA stimulation in vitro and to cellular antigens in vivo. This suppression appears to be selective for T-cell mechanisms while B-cell-mediated functions remain intact. The purpose of this study was to determine whether coexisting hepatic insufficiency could exert a protective effect on vascularized or nonvascularized allograft survival in the transplanted recipient. Female Wistar-Furth (Rtlw) 225 g rats were assigned randomly to three groups: EBL, sham operation (Sham) and normal control (NC). Fourteen days following operation animals received heterotopic cardiac or skin allografts from Buffalo (Rtlb) donors. Cardiac and skin graft survival was determined daily, rejection was confirmed histologically, and technical failures were omitted from analysis. Allograft survival was expressed as median survival time +/- SEM. Serum total bilirubin (mean +/- SEM) was significantly elevated at Day 14 in EBL animals compared to Sham and NC groups (15.1 +/- 1.0 vs 0.1 +/- 0 and 0.2 +/- 0.1 mg/dl, respectively, P less than 0.01). Median cardiac allograft survival time by Probit was 10.6 +/- 2.6 vs 5.6 +/- 0.7 and 6.0 +/- 0.9 days, respectively (P less than 0.03). Skin graft survival (mean and range) was similar in all groups. These results demonstrate that EBL in the rat suppresses T-cell function and significantly prolongs vascularized allograft survival, but not skin allograft survival across the Rtl histocompatibility barrier. The mechanism whereby coexisting hepatic dysfunction exerts a protective effect on vascularized allograft survival warrants further investigation.

Animals↗

Donor-specific antigen and cyclosporine in rat islet allografts.

Combination therapy with one dose of 3 M KCl extracted donor-soluble antigen (Ag) and a short course of cyclosporine (CsA) has proven to prolong the survival of kidney allografts by enhancing specific T-suppressor populations. This regimen is tested in rat islet allografts in this study (Lewis to ACI). A 3-day perioperative course of 10 mg/kg/day CsA on Days -1, 0, and 1 did not prolong graft survival (MST = 10.7 +/- 2.5 days vs 9.4 +/- 1.2 days in controls). When this course of CsA therapy was combined with a single dose of donor antigen on Day -1, the survival time was prolonged slightly but significantly (MST = 14.0 +/- 5.8 days). Three cycles of a 3-day course of CsA therapy at 7-day intervals, a total of nine doses of 10 mg/kg/day CsA, were effective in delaying rejection of islet allografts (MST = 26.4 +/- 30.3). Moreover, combined therapy with donor antigen and three cycles of a 3-day course of CsA prolonged the survival of islet allografts (MST = 57.7 +/- 51.4 days) with 50% of recipients still normoglycemic at 60 days after transplantation. These findings indicate that the combination therapy of donor antigen with a short course of CsA has a powerful effect to prevent the rejection of islet allografts, as shown in kidney allografts, in rats.

Animals↗

Protection from ischemic renal injury by fructose-1,6-diphosphate infusion in the rat.

Fructose-1,6-diphosphate (FDP) improves survival in experimental shock. To determine if FDP would protect against single organ damage, rats pretreated with an intravenous infusion of 5% FDP were subjected to 30 minutes of bilateral renal artery occlusion. Controls received an equal volume of a dextrose and sodium chloride solution. Renal function and histology were examined in all groups 24 hours after the insult. Following ischemia, FDP-treated rats had inulin clearances (FDP 897 +/- 129 vs control 349 +/- 59 microliter/min/100 gm BW; P less than 0.01) and solute excretion rates (FDP 6,386 +/- 1,346 vs control 2,602 +/- 396 mOsm/kg/min/100 gm BW; P less than 0.05) greater than control and not different (P-NS) from sham-operated rats. Renal histology was better preserved in the FDP-pretreated group. Thus, pretreatment with FDP provides histologic and functional protection from an ischemic renal insult.

Animals↗

Chronic granulocytic leukemia after renal transplantation.

Chronic granulocytic leukemia (CGL) developed in a 31-year-old man after he underwent a third renal transplant. The leukemia was initially controlled with azathioprine sodium and prednisone therapy, but eventually it entered blast cell crisis. This was controlled with an adult acute lymphocytic leukemia protocol with an excellent response. Despite discontinuing treatment with azathioprine and with the use of busulfan to control the peripheral WBC count, the patient maintained stable renal function for one year following treatment of the blast cell crisis and subsequently died of sepsis. We suggest that CGL after renal transplantation is similar to that observed in the general population and can be treated with the usual chemotherapeutic agents for the disorder without sacrificing renal function.

Adult↗