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Biomedical subjects

B E Jarrell

Publications and source records attributed to B E Jarrell.

At least 73 records · Page 4Linked to original sources

Use of the isolated perfused kidney model to assess the acute pharmacologic effects of cyclosporine and its vehicle, cremophor EL.

"Nephrotoxicity" secondary to cyclosporine and its clinically used vehicle, Cremophor EL, was examined in the isolated perfused rat kidney model. This model allows the serial determination of renal hemodynamic and tubular functional studies over a 3-hr duration using a normothermic, low hematocrit (13-15%) perfusion system. Initial studies indicated that the addition of small quantities of Cremophor EL resulted in marked renal vasoconstriction with decreased renal blood flow and deterioration in renal tubular function. These effects were highly significant and were of the same magnitude whether or not cyclosporine was present in the system. Cyclosporine was therefore examined after being dissolved in another vehicle, methanol. A 10% (v/v) amount of plasma was necessary in the perfusate to prevent significant adsorption of cyclosporine to the perfusion apparatus. Cyclosporine at concentrations below 100 ng/ml resulted in minor changes in renal hemodynamics. Beginning at 100 ng/ml glomerular filtration rate dropped significantly and renal vascular resistance increased three-fold. Fractional excretion of sodium significantly increased and the urine:plasma inulin ratio significantly decreased. We conclude that the clinically used drug vehicle, Cremophor EL, has significantly adverse effects on renal hemodynamics and tubular function. In addition, CsA causes similar renal toxicity in a dose-dependent fashion. Simultaneous administration of these two nephrotoxic agents could contribute to the high incidence of acute renal failure seen after transplantation. These observations suggest that an alternate vehicle with less renal toxicity might significantly decrease the incidence of this clinical problem.

Animals↗

The periportal collar: a CT sign of liver transplant rejection.

A low-attenuation region around the peripheral portal tracts (periportal collar) was noted on 13 of 43 computed tomographic studies obtained in 17 patients who had undergone 20 orthotopic liver transplantations. This region was then correlated with acute liver transplant rejection. The periportal collar as a sign of rejection has a sensitivity of 1.0, a specificity of 0.86, a negative predictive value of 1.0, and a positive predictive value of 0.62. This sign corresponds histopathologically with the lymphocytic portal infiltration that occurs during acute liver transplant rejection. Though viral hepatitis and nonspecific portal triad edema can also result in a periportal collar, acute liver rejection is strongly suggested when this sign is seen after liver transplantation. Early diagnosis and confirmation of rejection permit faster and more appropriate clinical intervention.

Adolescent↗

Risk of pulmonary embolus with inferior vena cava thrombosis.

The authors have evaluated the risk of pulmonary embolism both as a primary event or as a secondary embolus despite adequate anticoagulation in 39 patients with phlebographically documented inferior vena caval (IVC) thrombosis. Twenty-six of these patients had thrombi characterized as free floating, and 13 had thrombi that were adherent to the IVC wall without a free-floating component. The incidence of initial pulmonary embolism confirmed by either pulmonary arteriography or high probability ventilation-perfusion lung scanning was 50 per cent (13/26) in those patients with free-floating IVC thrombi, but 15 per cent (2/13) in those with closely adherent mural thrombi (P less than 0.05). Pulmonary embolism despite adequate anticoagulation occurred in 27 per cent (7/26) of patients with free-floating clots, but in only 17 per cent (1/8) of cases with adherent thrombi (P greater than 0.05). These data strongly suggest that patients with documented free-floating inferior vena caval thrombi are at a significant risk for pulmonary embolism as an initial event and perhaps also as a recurrent embolus, even in the presence of adequate anticoagulation. When such thrombi are identified, the overall incidence of pulmonary embolus is high and conventional anticoagulant treatment with heparin may not be sufficient.

Heparin↗

Anaesthetic technique for transvenous pulmonary embolectomy.

Transvenous pulmonary catheter embolectomy is being used as a method of treatment for patients suffering from massive pulmonary embolism. The anaesthetic management of these patients can be complex. Presented is a case of transvenous pulmonary embolectomy in a patient who also had an intravascular volume deficit secondary to haemorrhage and possible reperfusion oedema. A discussion of appropriate monitoring during procedure follows.

Aged↗

Use of an endothelial monolayer on a vascular graft prior to implantation. Temporal dynamics and compatibility with the operating room.

The temporal sequence of events was examined from initial contact of endothelial cells (ECs) to Dacron until the establishment of a monolayer. Cultured human adult ECs were radiolabeled, seeded onto Dacron, and adherence was quantified after vigorous washing. Firm adherence of 70% of the seeded ECs was seen by 2 hours to untreated Dacron, by 30 minutes to Dacron pretreated with a combination of interstitial type I/III collagen and an amnion-derived basement membrane (Type IV) collagen surface, and by 10 minutes to plasma-coated Dacron. Parallel samples were examined morphologically by scanning electron microscopy (SEM) to evaluate the adherence of ECs to surfaces. ECs seeded onto plain Dacron exhibited limited adherence, while cells on plasma-treated Dacron exhibited limited cell-cell associations. On basement membrane-treated Dacron, by 30 minutes the ECs exhibited a flat attenuated morphology, completely covering the graft surface. This time-frame is compatible with most vascular procedures, making an immediately endothelialized graft feasible.

Arterial Occlusive Diseases↗

Adverse effect of splenectomy on the survival of patients with more than one kidney transplant.

Risk factors associated with death were identified in a cohort of patients who received 2 or more kidney transplants. Data on 19 variables were collected by chart review on 774 patients who received allografts between 1973 and 1980 at any one of 3 hospitals in Philadelphia. 124 of the patients received two or more transplants and were followed for a minimum of 1.5 years. Modified life table analyses of single variables indicated that 7 factors--splenectomy, donor source, age, transplant hospital, number of HLA mismatches, donor sex, and survival time of the prior graft--were significantly related to patient survival. Using all 19 variables, the proportional hazards model was fit to the data. The characteristics most related to survival were splenectomy (P less than .001), donor source (P = .0022), and age (P = .0015). The other 4 factors that were significant on univariate analysis were not significant in this multivariate analysis. The relative risk of death was 5.5 for patients who had had a splenectomy compared with those who had not had a splenectomy. Patients who had received more than one transplant were compared with patients who had received only one transplant, and a subset of recipients of primary transplants who returned to dialysis after primary graft failure. Survival of patients who had received one transplant was approximately the same as that of the retransplanted population. When the proportional hazards model was fit to the populations that received one transplant and compared with the model for the retransplanted group, only age and donor source were common to all three models. The effect of splenectomy on survival was significant for the total population of primary transplant recipients but had no effect on the survival of the subset of recipients whose kidney grafts had failed and were returned to hemodialysis. Infection accounted for 45% of the deaths among splenectomized, retransplanted patients. A higher percentage of septic deaths occurred in patients whose grafts were functioning at the time of death when compared with patients who had returned to dialysis after secondary graft failure. Although retransplantation alone is not associated with an increased mortality, retransplantation in splenectomized patients carries a high risk of death.

Adult↗

Use of freshly isolated capillary endothelial cells for the immediate establishment of a monolayer on a vascular graft at surgery.

Endothelial seeding of vascular graft surfaces may lead to a less thrombogenic surface. We examined the feasibility of using microvessel endothelial cells derived from human fat for seeding purposes. Human fat was treated with collagenase for 24 minutes, washed, and purified in a Percoll gradient separation. This yielded 1.25 +/- 0.45 X 10(6) cells/gm of fat. After a 1-hour incubation on plasma-coated Dacron, 2.8 +/- 1.5 X 10(4) cells remained firmly adherent to the surface. When exposed to flow for 2 hours at a shear stress of 0 to 80 dyne/cm2, between 50% and 100% of the initially adherent cells remained adherent. Statistical analysis of this data failed to demonstrate a strong relationship between the number of adherent cells and the shear rate. Scanning electron microscopy demonstrated endothelial cells in various stages of attachment to the plasma-coated Dacron. Although most cells were still round and only focally attached to the surface, some cells were maximally flattened, forming cell-to-cell contact. Because of the high cell yield and the firm adherence characteristics, we conclude that microvessel endothelial cells may offer the possibility for confluent endothelial cell seeding of a graft at the time of surgical implantation without the need for cell culture.

Adipose Tissue↗

A method for protection of the left hepatic duct during right hepatic trisegmentectomy.

Right hepatic trisegmentectomy which removes the right lobe and the medial segment of the left lobe is necessary to remove completely lesions which extend beyond the true right lobe of the liver. The procedure has been described in detail in excellent reviews. We describe a technique of bile duct preservation during right trisegmentectomy. This is accomplished by cannulating the left hepatic duct with a Silastic catheter which is introduced through the stump of the right hepatic duct. This technique allows palpation of the duct during the dissection. With positive identification, the numerous small branches to the medial segment of the left lobe can be ligated safely. A completion cholangiogram through the catheter is always done to identify and repair any extensive bile duct leaks. Finally, the technique can be adapted for use in other resections, such as left trisegmentectomy by simply cannulating the appropriate duct.

Bile Ducts, Intrahepatic↗

Transvenous catheter pulmonary embolectomy.

Acute cardiovascular collapse in the hospitalized patient is associated with a high mortality rate and remains a therapeutic dilemma. Survival could be improved in the subgroup of patients with massive pulmonary thromboembolism if prompt surgical intervention is undertaken. This report presents the cases of two patients with cardiovascular collapse who survived transvenous catheter pulmonary embolectomy (herein described in detail). This procedure can be performed in any hospital with angiographic facilities and personnel trained in the technique. In our opinion it is the procedure of choice in patients with refractory cardiovascular collapse from massive pulmonary thromboembolism.

Catheterization↗

Endothelialization of human collagen surfaces with human adult endothelial cells.

Artificial vascular grafts are currently used to restore blood flow to ischemic tissue. Although the long-term patency of large diameter grafts is relatively acceptable, small diameter (less than 4 mm) grafts exhibit poor long-term patency rates. One technique to create a nonthrombogenic surface on artificial prostheses has been to seed with endothelial cells derived from autologous vessels. We have examined the interaction of human adult endothelial cells with the natural collagen surfaces presented by human amnion. Scanning electron microscopic evaluation revealed that human adult endothelial cells adhered rapidly to both the basement surface (collagen types IV and V) and interstitial surface (collagen types I and III) of amnion. However, the adherence of cells was significantly greater on the basement membrane surface. In addition, human adult endothelial cells rapidly formed close cell-to-cell interactions on basement membrane as compared with cells seeded onto the interstitial surface. These results suggest that seeding of endothelial cells onto artificial surfaces will be facilitated if the surface simulates the natural basement membrane to which endothelial cells natively adhere.

Adult↗

Adult human endothelial cell compatibility with prosthetic graft material.

We have developed a system for the in vitro evaluation of the interaction of human adult endothelial cells (HAEC) with prosthetic vascular graft material. HAEC, isolated from adult human iliac veins, proliferated vigorously in culture for approximately 70 population doublings. The large number of HAECs produced permitted high-density seeding of prosthetic grafts. Samples of prosthetic material were immobilized on a plastic ring and were used either untreated or coated with extracellular matrix, fibronectin, or plasma. HAEC were seeded at high density and adherence was evaluated by light and electron microscopy after a 2-hr incubation. While essentially no HAEC adhered to untreated grafts, treatment of grafts with either extracellular matrix, plasma, or fibronectin resulted in dramatic adherence of HAEC. The highest density of HAEC adherence was observed on collagen-coated Dacron grafts, and was equal to the cell density observed in confluent monolayers of HAEC grown on gelatin-coated tissue culture plastic. This study demonstrates a method capable of determining HAEC-graft biocompatibility prior to the use of an in vivo system.

Adult↗

Pulmonary tumor microembolism.

Pulmonary tumor microembolism is usually recognized as a slowly progressive syndrome of dyspnea and pulmonary hypertension in a patient with an established diagnosis of malignant disease. We have reported an extremely unusual case in which the pulmonary tumor microembolism syndrome occurred in a patient without prior history of malignancy. Further, no primary tumor could be found on postmortem examination. Clinicians should be aware that this potentially treatable entity may affect a wider spectrum of patients than has been previously recognized.

Dyspnea↗

Suprarenal placement of vena caval filters: indications, techniques, and results.

Preferred treatment for thromboembolism when heparin fails or is contraindicated is infrarenal inferior vena cava (IVC) interruption. In the present study suprarenal Greenfield filters were placed in 11 patients in whom routine infrarenal IVC interruption would have been inadequate therapy. As identified by IVC venography, nine patients, including two patients with renal vein thrombi and proteinuria, had partially attached IVC thrombi extending to or above the orifices of the renal veins. One patient had multiple life-threatening pulmonary emboli (PE) on anticoagulation therapy without a known source of emboli and a large patent ovarian vein, and another had an ovarian vein thrombus. Five patients (45%) had a contraindication to heparin therapy, and five (45%) had recurrent PE on anticoagulants. In follow-up (range 3 to 26 months, mean 12.3 months) there has been no documented or suspected recurrent PE, change in renal function, or peripheral edema. There were two deaths secondary to malignancy. IVC patency was demonstrated in all patients studied. Eight patients continue to receive anticoagulants. Based on our clinical experience, our data suggest that suprarenal filter placement is indicated in the following situations: (1) recurrent thromboemboli despite anticoagulation therapy with IVC thrombi extending to or above the renal veins, renal vein thrombosis, previous IVC interruption, or a large patent left ovarian vein or (2) documented perirenal IVC thrombi when anticoagulation therapy is contraindicated. The results of this study indicate that when thromboemboli originate at or above the level of the renal veins in the IVC, suprarenal IVC filter placement is effective therapy.

Adult↗