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Biomedical subjects

I Dawidson

Publications and source records attributed to I Dawidson.

At least 55 records · Page 3Linked to original sources
PubMed1989

Prevention of acute cyclosporine-induced renal blood flow inhibition and improved immunosuppression with verapamil.

Pretreatment with calcium antagonists such as verapamil (VP) and isradipine prevents CsA-induced decrease in renal microcirculation in mice. Recently, in posttransplant cadaver renal transplant (CRT) recipients, we demonstrated a CsA-induced 70% reduction in renal parenchymal diastolic blood flow velocity (PDBFV). Using duplex Doppler scanning, this randomized study of forty CRT patients examines the effect of pretreatment with VP on renal blood flow velocity and posttransplant function. Patients with initially low PDBFV (less than 8.0 cm/sec) who received VP therapy prior to administration of CsA experienced prompt restoration of flow, and continued to improve during CsA administration. With CsA alone, PDBFV diminished from 8.9 +/- 2.4 (SD) to 5.3 +/- 2.7 cm/sec (P less than 0.002). Although blood CsA levels were significantly higher at 1, 4, and 7 days (68, 184, and 235 ng/ml, respectively), after CsA induction, during VP treatment than in control patients (39, 105, and 156 ng/ml, respectively) (P less than 0.001), with the same daily doses of CsA, serum creatinines at day 7 were lower during VP treatment (1.28 +/- 0.44 vs. 1.66 +/- 0.44 mg%) than in controls (P less than 0.01). When the glomerular filtration rate was less than 45 ml/min on day 1. VP-treated patients showed greater improvement in GFR at day 7 by 34.1 +/- 10.9 ml/min compared with the 18 +/- 13 ml/min in controls (P less than 0.02). Only 3 of the 22 VP patients had rejection episodes within 4 weeks, versus 10 of the 18 recipients randomized to no drug (P less than 0.005). We conclude that VP is beneficial in CRT because it improves renal blood flow characteristics and prevents CsA-induced inhibition of blood flow. VP also ameliorates CsA-induced acute nephrotoxicity, and is associated with improved immunosuppression and fewer early rejections.

Cyclosporins↗
PubMed1988

Cryopreserved human fetal pancreas: a source of insulin-producing tissue?

Human fetal pancreata (HFP) were obtained from dilatation and extraction aborted fetuses of 11-18 weeks' gestation. The pancreas was excised under sterile conditions and kept in culture medium at 4 degrees C, prior to stepwise digestion into 50- to 150-micron fragments. The fragmented pieces were allowed to sediment by gravity, then transferred to tissue culture for 24-48 h, and cryopreserved. The freeze-thaw protocol used stepwise equilibration with dimethyl sulfoxide, nucleation of the sample at -10 degrees C, and a slow cooling rate of 0.25 degrees C/min to -40 degrees C, followed by submersion in liquid nitrogen (-196 degrees C). Rapid thawing at 300 degrees C/min from -196 degrees C was employed. Both fresh and frozen-thawed HFP fragments appeared viable as judged by light and electron microscopy, and secreted insulin in a perifusion system upon stimulation with glucose (28 mM) and theophylline (10 mM) or glucose (2.8 mM) and theophylline (10 mM). Six patients with Type I insulin-dependent diabetes mellitus, already requiring immunosuppression for a kidney transplant, had intraportal injection of 20 cryopreserved-thawed and pooled HFP fragments. Up to the 1-year post-transplant follow-up, there has been no evidence of in vivo insulin or C-peptide production. The usefulness of cryopreserved human fetal pancreata as a source of insulin-producing tissue for diabetic patients, therefore, remains to be demonstrated.

Abortion, Spontaneous↗
PubMed1988

Confirmation of the utility of fine needle aspiration biopsy of the renal allograft.

Allograft immunobiologic theory would predict that analysis of immunocompetent cells infiltrating the renal transplant would be most instructive. Recently a new aspiration biopsy technique has been developed to permit such analysis in patients which can be safely and repetitively performed. The clinical utility of such a technique has been tested utilizing a randomized prospective trial in which an aspirate was obtained every other day from the third post-operative day until discharge. Analysis included examination of adequacy criteria and the capacity of pathologic diagnosis to corroborate clinical diagnosis from coded specimens. Ninety-six aspirates from 21 consenting transplant recipients were obtained and analyzed. In 94 instances a clinical diagnosis could be made; 80 aspirates fulfilled adequacy criteria. We found the technique to be highly sensitive (greater than or equal to 90%) and highly specific (greater than or equal to 90%) for the clinical diagnoses of acute allograft rejection, post-operative acute renal failure, cyclosporine toxicity, and normal function. We conclude that the fine needle aspiration technique is an important adjunct to analysis of clinical renal transplantation and offers a major advantage to the clinical scholar in understanding transplant biology.

Acute Kidney Injury↗
PubMed1988

Deleterious effects of stroma-free hemoglobin used as resuscitative fluid for rats with ischemic intestinal shock.

This study examined the effect of modified stroma-free Hgb solution (SFHS) as a resuscitative fluid for rats in an ischemic intestinal shock model. The experiments compared the effect of SFHS with two other resuscitative fluids: lactated Ringer's solution (RL) and 3% albumin in RL. The control group received no fluids. After the induction of shock, the resuscitative solution was given iv over a 6-h period. RL and albumin in RL resulted in long-term (greater than 7 days) survival in 15 of 16 animals. All animals in the control group and six of eight animals in the SFHS-treated group died within 24 h. Hct was used to estimate changes in intravascular volume. All control animals became hemoconcentrated and exhibited a 50% loss in plasma volume. The failure of SFHS to improve significantly the survival in rats compared to the controls is surprising in view of the fact that the SFHS had the same oncotic pressure as the albumin-containing solution and identical volumes were administered.

Albumins↗
PubMed1988

Protection against cyclosporine-induced impairment of renal microcirculation by verapamil in mice.

Fluorescence microscopy was used to examine the effect of cyclosporine (CsA) infusion on renal subcapsular (cortical) blood flow in 53 living mice, using FITC-dextran (MW: 156,000) as a fluorescent marker. CsA (8-19 mg/kg body weight) given i.v. for 1 min induced complete inhibition of blood flow. A complete standstill of flow was also obtained during a continuous infusion with a rate of 0.8-2 mg/kg/min. With lower infusion rates (0.15-0.23 mg/kg/min), blood flow was partially impaired. In all experiments, the decrease in flow occurred after a 15-25 min delay, suggesting a CsA metabolite or exhaustion of a protective mechanism as the causative agent. Pretreatment with an alpha-blocking agent, phentolamine (1.0 mg/kg), did not prevent the CsA-induced inhibition of blood flow. In contrast, pretreatment with a calcium antagonist, verapamil (0.3-0.4 mg/kg), prevented the impairment of blood flow at low (0.15-0.23 mg/kg/min), and partially at higher (0.8-2.4 mg/kg/min) rates of CsA infusion. Clinical studies are warranted to explore the role of calcium antagonists in the prevention of posttransplant acute cyclosporine-induced nephrotoxicity.

Animals↗
PubMed1988

Studies of the isolation and viability of human islets of Langerhans.

Pancreas obtained from 34 adult human cadaver organ donors was divided into proximal and distal segments, and the duct to each segment was cannulated. Collagenase was injected into the proximal duct of 7 glands and into the distal duct of 7 others; the duct of the opposite segment was perfused with collagenase. The pancreas was then dispersed by teasing, trituration, and passage through filters. Perfused proximal and distal segments released 1461 +/- 287 and 2728 +/- 797 islets/g (+/- SEM) versus 710 +/- 149 (P less than 0.05) and 1950 +/- 636 after injection. Twenty other pancreases were perfused with collagenase warmed rapidly to 39 degrees C (n = 4) or warmed slowly to 37 degrees C (n = 6) or 39 degrees C (n = 10): the yield was 1625 +/- 632, 1320 +/- 116, and 2009 +/- 277 islets/g respectively. Total yields from the latter were 76 X 10(3) large (greater than 100 microns) and 85 X 10(3) small (less than 100 microns) islets with recoveries of 61% and 42%, respectively, after Ficoll density gradient purification. Histology showed highly purified islets. Perifusion with glucose elicited a biphasic release of insulin with the mean response (microU/islet/min) rising to a first peak of 0.5 and constant second phase secretion of 0.25, followed by a return to baseline. Reduced response was observed for islets from pancreas stored greater than 6 hr and tissue obtained from multiple centers. Less insulin was produced by freshly isolated islets, islets less than 100 microns, and after Ficoll separation. Secretion was similar for islets derived from proximal or distal segments. Perfusion of collagenase via the ducts of human pancreas improves islet isolation and Ficoll gradient separation yields highly purified islets. Important factors influencing insulin secretion are the source of donor tissue, cold storage of pancreas, Ficoll purification, islet size, and tissue culture.

Cell Separation↗
PubMed1988

In vivo fluorescence microscopy of kidney subcapsular blood flow in mice. Effects of cyclosporine, (NVA2)-cyclosporine, and isradipine, a new calcium antagonist.

The subcapsular kidney microcirculation in mice was observed through a fluorescence microscope, recorded on videotape, and examined for response to infusions of cyclosporine A (CsA) and cyclosporine G (CsG). Coded video recordings were evaluated by a semiquantitative method. CsA infusion (1.6 +/- 0.4 mg/kg/min) induced a nearly complete inhibition of the subcapsular blood flow. At lower infusion rates (0.46 +/- 0.2 mg/kg/min), the blood flow inhibition was less pronounced. CsG infusions at corresponding rates induced significantly less inhibition. Pretreatment with a new calcium antagonist, isradipine (18-20 micrograms/kg bwt), completely prevented the CsA-induced impairment of subcapsular microcirculation. The calcium antagonist, however, did not improve blood flow when administered after induction of inhibition by CsA (16.8 +/- 2.5 mg/kg), emphasizing the importance of pretreatment. This study suggests hypoperfusion due to vasoconstriction as an important pathophysiologic mechanism for CsA-induced nephrotoxicity. CsG, when given at corresponding rates, induced less inhibition of the blood flow. Pretreatment with a calcium antagonist, isradipine, completely prevented a CsA-induced inhibition of blood flow, suggesting a potential value in the prevention of CsA-induced nephrotoxicity.

Animals↗
PubMed1987

Intravascular volumes and colloid dynamics in relation to fluid management in living related kidney donors and recipients.

This study examines our current perioperative fluid regimen in relation to body fluid compartments, intravascular volumes, and early kidney function in 17 kidney transplant recipients and their living related donors. Donors were given 0.5 g/kg of 10% dextran-40 during surgery and electrolyte solutions averaging 3032 ml/24 h. Recipients were randomized to receive albumin or dextran-40 infusions and given 0.5 g/kg during surgery. Electrolyte and 5% glucose infusions averaged 5580 ml/24 h, to match the urinary output. Total intravascular albumin (TIA) and total intravascular dextran (TID) were calculated from the plasma concentrations and plasma volume (PV). Mean preoperative PV in the donors was 44.5 ml/kg. The TIA loss of 0.37 g/kg was balanced by a TID of 0.27 g/kg, and PV increased to 46 and 49 ml/kg at 3 and 34 h after surgery, respectively. In recipients, the preoperative volume of extracellular water correlated linearly to the total body water and PV, as well as to the urine flow the first 24 h after transplantation. No difference was found in urine volume, serum creatinine, or PV expansion between recipient patients receiving albumin or dextran-40. Twelve patients with immediate urinary onset had blood volume (BV) and PV of more than 70 and 45 ml/kg, respectively, in sharp contrast to five patients with delayed urinary onset, who had lower BV and PV values. A fall in TIA of 0.9 g/kg at 3 h corresponded to a PV loss of 18 ml/kg and was only partially replaced by the 0.5 g/kg of intraoperative colloids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗