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Biomedical subjects

M W Flye

Publications and source records attributed to M W Flye.

At least 163 records · Page 9Linked to original sources
PubMed1989

Detection of focal hepatic masses: prospective evaluation with CT, delayed CT, CT during arterial portography, and MR imaging.

The sensitivities of contrast medium-enhanced computed tomography (CT), delayed CT (DCT), CT during arterial portography (CTAP), and magnetic resonance (MR) imaging for detecting focal liver lesions were prospectively evaluated in eight patients who subsequently underwent hepatic lobectomy or transplantation. Pathologic evaluation of the resected liver specimens demonstrated 37 lesions. The sensitivities were 81% (30 of 37 lesions) for CTAP, 57% (21 of 37 lesions) for MR imaging, 52% (12 of 23 lesions) for DCT, and 38% (14 of 37 lesions) for contrast-enhanced CT. The difference between the sensitivity of CTAP and the sensitivities of the other imaging tests was statistically significant (P less than .004). Of the lesions smaller than 1 cm in diameter, CTAP depicted 61% (11 of 18 lesions), MR imaging 17% (three of 18 lesions), CT 0% (zero of 18 lesions), and DCT 0% (zero of nine lesions). It is concluded that for preoperative detection of focal hepatic masses, CTAP is the most accurate technique available to most radiologists. Patients with primary or secondary hepatic neoplasms who are being considered for hepatic resection should undergo CTAP as part of their preoperative examination.

Adult↗
PubMed1989

Optimization of cryopreservation procedures for rat and human hepatocytes.

1. Rat hepatocytes were cryopreserved using a number of procedures and the viability, attachment, and metabolic activity of the cryopreserved cells were compared to freshly isolated hepatocytes. Several cryopreservation agents (dimethylsulphoxide [DMSO], glycerol, polyvinylpyrrolidone [PVP], dextrans), and combinations of these agents, were examined. Other variables tested included the freezing rate, thawing rate, and the concentration of serum in the freezing medium. 2. Recovery of viable attached cells was optimal using DMSO at concentrations of 10% or higher, a slow stepwise cooling procedure, and a quick thaw. The concentration of serum in the freezing medium (0% to 90%) did not affect cryopreservation results. Using this procedure the recovery of viable hepatocytes was 70%. 3. Levels of hepatocyte ethoxycoumarin-O-deethylase (ECOD) activity did not change following cryopreservation. The rate of decline of ECOD activity with time in culture was similar in freshly isolated and cryopreserved hepatocytes. 4. Hepatocytes isolated from three human livers were cryopreserved and recovered with viabilities similar to those obtained with the rat. A preliminary experiment also showed no loss of metabolic activity in human hepatocytes following cryopreservation.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1989

Trophic factors from pancreatic islets in combined hepatocyte-islet allografts enhance hepatocellular survival.

The purpose of this study was to determine the effect of pancreatic islets on the survival of clusters of rat hepatocytes transplanted across a major histocompatibility barrier into an ectopic site. Aggregates of hepatocytes and pancreatic islets were obtained from Wistar-Furth rats by an automated method of collagenase digestion. Approximately 8000 Wistar-Furth hepatocyte clusters (100 to 300 micron diameter) were transplanted beneath the renal capsule of Lewis rats with or without the addition of 800 pancreatic islets. Recipients received subcutaneous injections of cyclosporine A (CsA): 30 mg/kg on days 0, 1, and 2, 10 mg/kg on days 3 to 7, and 10 mg/kg every other day for days 8 to 28. In the absence of CsA recipient treatment, all the allografts were rejected within 7 days. The combined hepatocyte-islet allografts in recipients treated with CsA showed maintenance of morphologic integrity of both hepatocytes and islet cells 1, 2, and 4 weeks after transplantation, whereas in the absence of pancreatic islets, the hepatocellular aggregates degenerated despite CsA treatment, leaving only a thin rim of hepatocytes immediately adjacent to the renal parenchyma. It can be concluded that in immunosuppressed recipients hepatocyte-islet renal subcapsular allografts survived despite the presence of an intact liver, which indicates a possible role of trophic factors released locally from the islets.

Animals↗
PubMed1989

Hepatic insufficiency after portacaval shunting is prevented by prior intraportal pancreatic islet autotransplantation.

The extrahepatic diversion of essential splanchnic hepatotrophic factors may cause the liver atrophy and insufficiency that follows portacaval shunting. To investigate this, control dogs with end-to-side portacaval shunts (control-PCS, n = 6) were compared with dogs shunted 1 month after intraportal pancreatic islet autotransplantation (islet-Tx-PCS, n = 5). From the distal pancreas of each experimental dog, 1.95 +/- 0.49 X 10(5) islets were isolated by collagenase digestion and retransplanted within 3 hours. Assays of hepatocellular function (caffeine clearance) and hepatic blood flow (indocyanine green), conventional biochemical liver function tests, and glucose, insulin, and glucagon responses to intravenous glucose challenge were measured monthly and when dogs were killed. Four of six control-PCS dogs were killed 32 +/- 9 days after shunting because of more than 20% body weight loss; one control-PCS dog lost only 7% of body weight by day 56 and stabilized. No significant loss of body weight occurred in islet-Tx-PCS dogs (n = 5). Liver function test abnormalities seen in control-PCS dogs were absent in islet-Tx-PCS dogs. Both control-PCS and islet-Tx-PCS indocyanine green half-life measurements were significantly (p less than 0.05) prolonged at all times, indicating equally reduced hepatic blood flow after shunting for both groups. In contrast, islet-Tx-PCS caffeine half-life periods were significantly (p less than 0.05) shorter than in control-PCS dogs and were similar to those in normal dogs, indicating a protective effect of the transplanted islets on hepatocellular function. We conclude that intraportal pancreatic islet autotransplants prevent, by the local release of hepatotrophic factors within the liver, the metabolic abnormalities and loss of hepatic function after PCS.

Animals↗
PubMed1989

Intravenous and portal venous administration of modified donor antigen prolongs rat parathyroid allograft survival.

The effect of pretransplant (day -6) systemic intravenous or portal venous immunization with modified donor antigen combined with cyclophosphamide treatment (75 mg/kg on day -4) on rat parathyroid allograft survival was evaluated. Systemic intravenous preimmunization of Buffalo recipients with 10(8) untreated Lewis donor spleen cells plus cyclophosphamide resulted in 100% accelerated rejection of Lewis parathyroid allografts (mean survival time, 7.3 +/- 0.9 days vs 10.8 +/- 1.1 days for controls). Portal venous administration of untreated cells plus cyclophosphamide reduced accelerated rejection to 40% but could not prolong graft survival (10.8 +/- 2.7 days). Intravenous or portal venous preimmunization with heat-inactivated cells (45 degrees C for 60 minutes) plus cyclophosphamide also did not prolong graft survival, with accelerated rejection occurring in 20% and 40% of recipients, respectively. In contrast, preimmunization by either route with ultraviolet B-irradiated cells (UVB; 12,000 joule/m2) plus cyclophosphamide significantly prolonged graft survival (intravenous = 22.2 +/- 6.0 days and portal venous = 21.4 +/- 7.2 days; p less than 0.005), with no accelerated rejection. Preimmunization with UVB cells combined with cyclophosphamide was synergistic, because neither treatment alone prolonged allograft survival (UVB cell preimmunization only = 10.8 +/- 1.3 days; cyclophosphamide only = 12.6 +/- 2.6 days). The effect of UVB preimmunization was donor specific because third-party Wistar-Furth UVB cells had no effect on Lewis graft survival (12.5 +/- 2.9 days). We conclude that pretreatment with UVB-modified donor antigen plus cyclophosphamide induces allospecific immune hyporesponsiveness and prolongs parathyroid allograft survival.

Animals↗
PubMed1989

Measurement of cyclosporine concentrations in whole blood: HPLC and radioimmunoassay with a specific monoclonal antibody and 3H- or 125I-labeled ligand compared.

We compared cyclosporine concentrations in whole blood as measured by HPLC and by RIA with a monoclonal antibody specific for cyclosporine with 3H- or 125I-labeled cyclosporine ligand. The 3H-RIA kit slightly underestimated cyclosporine concentrations (greater than 600 micrograms/L) in comparison with HPLC. Over a wide range of concentrations, cyclosporine measured with the 125I-RIA kit correlated well with HPLC (slope = 0.99, n = 301, r = 0.98), observed for samples from recipients of kidney, heart, or liver allografts (respective slopes: 1.01, 0.93, and 1.00). The 125I-RIA standard curve was linear to 1000 micrograms of cyclosporine per liter. Inter- and intra-assay CVs for 125I-RIA measurements of cyclosporine were less than or equal to 7%. Evidently, the 125I-RIA kit involving a monoclonal antibody specific for cyclosporine is equivalent to the HPLC assay and can replace it for therapeutic drug monitoring of cyclosporine therapy.

Antibodies, Monoclonal↗
PubMed1989

Concomitant immunosuppression and donor-specific transfusions prior to renal transplantation.

The induction of immunologic unresponsiveness to improve renal allograft survival was attempted in 151 patients by the pretransplant administration of donor-specific whole blood or buffy coat in conjunction with continuous Aza immunosuppression. All donor-recipient combinations were at least one-haplotype disparate and 21 were two-haplotype disparate. Presensitization was present in ten patients and attempts at desensitization were uniformly unsuccessful. Of the 151 nonpresensitized patients, transient sensitization occurred in 3% and permanent sensitization in 7%. Of 140 nonsensitized patients, 135 underwent renal transplantation from the specific blood donor and 56% have never experienced a rejection episode. The allograft survival rate at two years (93%) and seven years (87%) is significantly better (p less than .01) than our historical experience with one-haplotype living-related transplants at two years (68%) and seven years (59%). The low rate of sensitization (7%) has permitted almost all patients to undergo eventual renal transplantation from the specific blood donor. This and the low rate of early rejection (2%) argues for a modification of the immunologic response, perhaps by clonal deletion, rather than a selecting out process as the mechanism for improved allograft survival.

Azathioprine↗
PubMed1988

Use of ricin A-chain to selectively deplete Kupffer cells.

We used the A-chain of the toxin ricin (RTA) as a toxin specific to Kupffer cells in mice. RTA is specifically taken up by the mannose receptor present exclusively in macrophages. Kupffer cells were quantitated by shifts in beta-glucuronidase clearance and microscopic counts of cells which phagocytosed India ink. When compared to saline controls, 20 mg/kg of RTA intraperitoneally (divided over 4 days) or intraportally (single doses) significantly prolonged the t 1/2 half-life of beta-glucuronidase by 270 +/- 37 and 210 +/- 8%, respectively. Kupffer cell numbers were significantly decreased by 27 +/- 8 and 33 +/- 16%. This effect persisted for at least 3 days after toxin administration. Despite effects on Kupffer cell number, minimal histological damage to liver, spleen, lung, and heart was noted. Higher doses of RTA or doses potentiated by ureteral ligation to prevent renal clearance resulted in prohibitive mortalities and histologic liver damage. Doses of Hura crepitans inhibitor, a toxin similar to RTA but not mannose-receptor specific, did not affect Kupffer cell numbers. We conclude that RTA given both intraperitoneally and intraportally at low doses is toxic specifically to Kupffer cells. Kupffer cell numbers can be indirectly measured by beta-glucuronidase clearance.

Animals↗
PubMed1988

Investigation of Doppler waveforms in porcine renal allografts: Doppler-pathologic correlation.

A porcine model was devised to investigate Doppler waveforms in dysfunctional renal allografts. NIH miniature pigs served as allografts donors and recipients. Renal transplantation was effected into the recipient pelvis while the left normotopic kidney was subjected to warm ischemia in order to induce acute tubular necrosis (ATN). Doppler demonstration of allograft arterial occlusion in six animals was confirmed at surgery. Increased pulsatility of intrarenal arterial signals constituted evidence of vascular rejection in two animals. Biopsies confirmed the diagnosis in both cases. Histologic changes of ATN were identified in two native kidneys subjected to ischemia. No waveform or pulsatility alterations were observed in these animals. The porcine model provides for the investigation of allograft Doppler waveforms in a controlled setting with free access to biopsy and operative pathologic correlation.

Animals↗