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Biomedical subjects

J C Stanley

Publications and source records attributed to J C Stanley.

At least 19 recordsLinked to original sources
PubMed1992

Adhesion and incorporation of lacZ-transduced endothelial cells into the intact capillary wall in the rat.

Use of the capillary bed of skeletal muscle as an in vivo recipient site to transplant autologous endothelial cells that have undergone gene transfer ex vivo has considerable potential as a technique of somatic gene therapy. Here we document a previously unrecognized capacity of endothelial cells to adhere and incorporate spontaneously into confluent endothelial cell monolayers in vitro and in vivo. This spontaneous adhesion and incorporation of endothelial cells enabled us to seed lacZ-transduced endothelial cells into the wall of skeletal muscle capillaries of the hindlimb of the rat. Certain transduced endothelial cells became incorporated within the capillary wall, whereas others remained within the capillary lumen where they formed focal, electron-dense, contacts with host endothelium. lacZ expression in the capillary bed was documented for up to 1 month after transplantation. Use of the intact capillary bed of skeletal muscle as an in vivo recipient site for transduced, autologous endothelial cells holds promise as a strategy for somatic gene therapy to treat various genetic and acquired human diseases.

Animals↗
PubMed1992

Papaverine effects on PGI2 and TXA2 release from the canine vascular wall.

Operative manipulation of blood vessels might lead to spasm, thereby destroying the endothelial cell function: the spasm can be prevented by the vasodilator papaverine. To study if this was mediated via the prostanoid pathway the following investigation was undertaken: canine jugular veins and carotid arteries were dissected with or without papaverine. Vessel segments were then perfused with Hank's balanced salt solution for five times 15 min. Prostacyclin was measured as the stable degradation product 6-keto-PGF1 alpha and thromboxane as TXB2, by radioimmunoassay. Control arterial segments' 6-keto-PGF1 alpha release was initially 129.5 + 20.1 pg/mm2/15 min, and 29.7 + 10.4 after 60 min (p less than 0.05 vs initial value) and responded to arachidonic acid (AA) with an increase to 139.2 +/- 23.1 pg/mm2/15 min (p less than 0.05). Segments treated with papaverine had the same release as the controls. In venous segments there was a lower initial release (p less than 0.05) from segments given papaverine than from controls, but this was more likely an effect of papaverine on the assay. There was no difference in release of prostacyclin from segments given papaverine in the perfusate compared to controls when using 125I tracer. When using 3H tracer including absorption of free antigen to dextran coated charcoal, papaverine displaced the free tracer giving artificially low values. There was no effect of papaverine given intraoperatively on the TXB2 release, neither from arteries nor from veins. In another experiment the vessel wall tension was examined and the cyclooxygenase inhibitor diclofenac did not inhibit the vasodilating effect of papaverine.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Renal revascularization for recurrent pulmonary edema in patients with poorly controlled hypertension and renal insufficiency: a distinct subgroup of patients with arteriosclerotic renal artery occlusive disease.

Recurrent pulmonary edema in patients with poorly controlled hypertension and renal insufficiency appears to be a marker of bilateral renal artery occlusive disease. The effectiveness of renal revascularization to prevent recurrent pulmonary edema in this distinct subgroup with renal artery occlusive disease was analyzed in 17 consecutive patients treated at the University of Michigan Hospital between 1984 and 1990. Their mean preoperative blood pressure was 207/110 mm Hg, and mean serum creatinine clearance was 3.8 mg/dl. Pulmonary edema occurred despite evidence of normal ventricular function in 65% of these patients. Bilateral renal artery occlusive disease affected 94% of the patients, and 54% had an occluded renal artery. Renal revascularization was accomplished by iliorenal bypass (41%), aortorenal bypass (29%), endarterectomy (24%), and transluminal angioplasty (6%). Contralateral nephrectomy (41%) and concomitant aortic reconstruction (24%) were also required frequently. No postoperative deaths occurred, and no patient had early postoperative pulmonary edema. Control of hypertension was improved in all patients, two of whom were discharged from the hospital on no antihypertensive medications. Two of the three patients requiring dialysis before operation were able to discontinue dialysis after operation. Late follow-up (mean, 2.4 years) revealed hypertension to be cured in one patient (6%), and improved in 16 patients (94%). Pulmonary edema occurred in one patient during late follow-up. Late follow-up showed renal function (mean creatinine, 1.7 mg/dl) to be improved in 77%, stable in 12%, and worse in two patients; one required dialysis. A single episode of pulmonary edema in a patient with poorly controlled hypertension and renal insufficiency should prompt consideration of this clinical syndrome and early diagnostic angiography.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Dose-response relationships for neostigmine antagonism of vecuronium-induced neuromuscular block in adults and the elderly.

We have studied the dose-response relationship for neostigmine in 36 adult (ages 18-50 yr) and 36 elderly (ages > 70 yr) subjects during antagonism of neuromuscular block induced by vecuronium. All patients received vecuronium 0.08 mg kg-1 and neuromuscular block was monitored mechanomyo-graphically using the train-of-four (TOF) mode of stimulation. Six patients of each age group were allocated randomly to receive neostigmine 5, 15, 25, 35 or 45 micrograms kg-1 or saline at 10% recovery of T1 (first response in the TOF). TOF ratios were recorded continuously over the next 10 min and the values at 1-min intervals from 5 min onwards were used to construct the dose-response relationships. There was a significant difference (P < 0.05) in the time to spontaneous recovery of T1 to 10% between the adults (24 (SD 5.5) min) and the elderly (33 (7.8) min). Dose-response curves for neostigmine were parallel in the two age groups, but those for the elderly were significantly to the right of the curves for the adults. This suggests an apparently lesser relative potency of neostigmine, or the requirement of a larger dose, in the elderly for attaining antagonism of a moderately intense vecuronium block at the same time as in adults.

Adolescent↗
PubMed1992

High-level expression of recombinant human tPA in cultivated canine endothelial cells under varying conditions of retroviral gene transfer.

Successful genetic transduction of endothelial cells (EC) provides a theoretic means of increasing luminal secretion of tissue-type plasminogen activator (tPA) and lessening arterial and venous thrombotic processes. To identify the duration and number of retroviral exposures for an optimal tPA expression, enzymatically derived adult canine jugular venous EC were subjected to different exposure regimens using an amphotropic murine retroviral vector, MFG, containing the human tPA gene. Human tPA antigen secretion and its functional activity were determined at 2 days (subconfluent cells) and 14 days (confluent cells) after retroviral exposure. High-level secretion of human tPA was detected among transduced EC in all experimental groups. No secretion of human tPA occurred in control EC exposed to media alone. At 2 days after transduction, no significant differences in tPA secretion rates occurred among the different exposure regimens. At 14 days, the 12-hour X two-exposure group exhibited higher tPA secretion rates than all other exposure regimens (analysis of variance, p < 0.05). All exposure groups at 14 days exhibited significantly higher tPA secretion compared with those at 2 days (analysis of variance, p < 0.05). The presence of retroviral sequences in the genome of transduced EC was confirmed by Southern blot analysis. At 14 days, increased EC numbers were observed in vector-exposed wells compared with controls. Human tPA functional activity paralleled tPA antigen secretion. Genetically modified canine EC are capable of high levels of constitutive expression of human tPA after relatively short exposures to a retroviral vector containing the reporter gene. Increased cell number of tPA-transduced EC in culture suggests that tPA also may have other biologically important effects. These results support the efficacy of MFG-tPA gene transfer as a means of genetically modifying EC fibrinolytic activity and establishes the potential of this technology in vivo.

Animals↗
PubMed1992

Clinical evaluation of doxacurium chloride.

Doxacurium was administered to 50 adult patients for determination of potency (n = 10), onset and duration of clinical relaxation (n = 40). Cumulative dose-response showed the ED95 to be 33.24 micrograms.kg-1 (95% confidence limits 27.4-39.3). Doxacurium 33 micrograms.kg-1 was then administered to four groups of 10 patients each who had anaesthesia maintained with either fentanyl-droperidol or halothane and nerve stimulation carried out with single-twitch stimulation at 0.1 Hz or train-of-four stimulation at 2 Hz every 12 s. The onset and duration showed wide individual variation. The mean (SD) times to occurrence of maximal block were 8.5 (4.6), 6.1 (1.9), 6.7 (1.8) and 4.7 (1.3) min in the single twitch-fentanyl, train-of-four--fentanyl, single twitch-halothane and train-of-four--halothane groups respectively, although it ranged from 3.4 to 13.1 min in individual patients. The mean (SD) durations of clinical relaxation (recovery of single twitch or first response in train-of-four to 25%) were 65 (22.8), 52 (21.7), 70 (33.4) and 72 (21.0) min respectively with individual values ranging from 31 to 103 min. Although halothane administration increased the duration of clinical relaxation and train-of-four stimulation accelerated the onset of effect, the changes due to these were not significant. There were no adverse effects on heart rate or indirectly measured arterial pressure.

Adult↗
PubMed1992

Time-related effects of heparin sulfate on regional and systemic anticoagulation.

Optimal timing of vascular clamping to anticoagulation during cardiovascular surgical procedures is poorly defined. This study uses a canine model to determine the effectiveness of three different methods of heparin administration. Heparin sulfate (150 IU/kg) was administered by: injection into the jugular vein 5 minutes before infrarenal aortic clamping (Group 1), injection into the terminal aorta immediately after infrarenal aortic clamping (Group 2), and injection into the jugular vein immediately after infrarenal aortic clamping (Group 3). Thrombin clotting times and partial thromboplastin times were measured in venous blood from the upper and lower extremities before (baseline) heparin administration, and 1, 3, and 5 minutes following heparin administration. Activated clotting times were assessed in lower extremity blood at baseline, and at 1 and 5 minutes after heparin injection. Significant differences existed between groups in both upper and lower extremities. Systemic anticoagulation occurred within 1 minute after intravenous heparin administration in Groups 1 and 2 in the lower extremity, and Groups 1 and 3 in the upper extremity. Delayed anticoagulation in the lower extremity was noted with systemic injection after aortic clamping in Group 3, and after regional intra-aortic administration in the upper extremity of Group 2 subjects. Complete anticoagulation was noted by 5 minutes in all groups in both the upper and lower extremities. These results suggest that the safe time period between heparin administration and vascular clamping varies with the route and the timing of its administration. Intravenous administration prior to aortic cross-clamping provided adequate anticoagulation in this canine model in both the upper and lower extremity blood after 1 minute of heparin circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Heparin-mediated reductions of the toxic effects of protamine sulfate on rabbit myocardium.

Protamine sulfate causes direct myocardial suppression when used to reverse heparin anticoagulation. Protamine's excessive positive charge accompanying its surface arginine groups appears to be responsible for this toxicity. This study was designed to assess the hypothesis that negatively charged heparin given after protamine exposure may enhance the recovery of protamine-induced myocardial dysfunction. Isolated rabbit hearts (n = 20) were perfused with physiologic saline solution at 80 to 90 mm Hg containing high dose protamine, 250 micrograms/ml, until heart contraction essentially ceased (baseline). Hearts were then randomly reperfused for 15 minutes with either physiologic saline solution (group I, n = 10) or heparin plus physiologic saline solution (group II, n = 10) at a dose of 0.1 IU/1.0 microgram of previously administered protamine. Developed left ventricular blood pressure, heart rate, pulmonary artery PaO2, contractility (+dp/dt), oxygen extraction (AvO2), oxygen consumption (VO2), and rate x pressure product were assessed. A protective, beneficial response accompanied heparin administration (group II) in all functions assessed except blood pressure. Maximum changes, comparing group I with II, were heart rate (beats/min) -72 versus -1, p less than 0.001; +dp/dt -64% versus -51%, p less than 0.01; PaO2 +86% versus +9%, p less than 0.001; AvO2 -37% versus -4%, p less than 0.001; VO2 -50% versus -28%, p less than 0.008; and rate x pressure product -73% versus -51%, p less than 0.001. These data suggest a separation of protamine's hemodynamic effects (blood pressure) and metabolic effects (VO2). Furthermore, these data support the tenet that heparin is able to markedly lessen the toxic myocardial effects of protamine.

Animals↗
PubMed1992

Quantitative increases in surgical house officer clinical activity as the basis for increased work loads in a university hospital.

BACKGROUND: House officer (HO) work loads, particularly work hours, have been the subject of considerable controversy. The hypothesis of this study was that a disproportionate work burden has been placed on HOs in teaching hospitals because of increased obligatory clinical activities and increased educational expectations. METHODS: Factors directly and indirectly affecting care of surgical patients were related to individual HO efforts at the University of Michigan from 1981 to 1991. Data regarding clinical activity and support services were abstracted for analysis from hospital year-end reports, personnel rosters, and educational logs and correlated with the number of surgical HOs. RESULTS: The total numbers of HOs in the Department of Surgery were relatively constant (122 +/- 4) throughout the study interval. Increases that occurred in annual hospital admissions (7615 to 10,651), discharges (7909 to 11,176), clinic visits (53,251 to 86,111), total operations (6789 to 16,526), and operating room hours (24,175 to 62,429) were significant (r greater than 0.9; p less than 0.001 in each category). The acuity of inpatient hospital care increased twofold, as measured by a case mix index, and was accompanied by a 125% increase in the number of surgical intensive care unit beds. During the study period, department of surgery faculty increased 49% (59 to 88), clinical nursing staff increased 118% (821 to 1794), hospital administrative staff increased 59% (2086 to 3320), and hospital support staff increased 53% (4134 to 6342). The number of students in each University of Michigan Medical School class, a group that might defray certain HO work loads, decreased significantly by 16% (226 to 189) during this time (r = -0.76; p less than 0.02). CONCLUSIONS: Disproportionate increases in work demands have been placed on surgical HOs compared with other health care team members during the past decade. Calculated work loads increased from 91.2 hr/wk/HO in 1981 to 110.9 hr/wk/HO in 1991. Balancing the increasing service activities with educational needs of surgical HOs remains a substantial challenge to be addressed by educators.

Employee Performance Appraisal↗
PubMed1991

The role of an endothelial cell lining in limiting distal anastomotic intimal hyperplasia of 4-mm-I.D. Dacron grafts in a canine model.

The effect of an endothelial cell (EC) lining on intimal hyperplasia at the distal anastomosis of Dacron grafts was assessed in a canine model. Enzymatically derived autologous EC were used to seed 14 to 17 cm long, 4 mm I.D., knitted Dacron aortoiliac grafts implanted in an end-to-side manner in six dogs (Group I). Unseeded grafts were similarly implanted in six control dogs (Group II). All animals received acetylsalicylic acid (325 mg po qd) 24 h prior to graft placement and for 2 weeks postoperatively. Distal anastomotic intimal hyperplasia (AIH) and luminal surface EC coverage were quantitated at the conclusion of a 16-week study period. Patency for Group I and Group II grafts were 90% and 55%, respectively (p = 0.07). Maximum AIH, defined as the maximum reduction of luminal cross-sectional area at the distal anastomosis, was not significantly different between Group I (13.1 +/- 8.0%) and Group II (15.1 +/- 7.3%) conduits. However, AIH was inversely related to the extent of luminal EC coverage (r = -0.6, p less than 0.05), thus greater endothelialization was associated with decreased AIH. These data support the idea that EC coverage of the luminal surface of prosthetic vascular grafts may limit the development of AIH.

Animals↗
PubMed1991

Increased prostacyclin and adverse hemodynamic responses to protamine sulfate in an experimental canine model.

Prostanoid activity was correlated with the hemodynamic effects of protamine sulfate reversal of heparin in 24 dogs undergoing three different pretreatment regimens: Group I (n = 8) received saline, Group II (n = 8) received the thromboxane synthetase inhibitor U63,557A (30 mg/kg), and Group III (n = 8) received indomethacin (10 mg/kg). Pretreatment substances were administered as 5-min intravenous infusions 20 min before anticoagulation with intravenous heparin (150 IU/kg). Protamine sulfate (1.5 mg/kg) was subsequently given as a 10-sec intravenous infusion 30 min after heparin had been administered. Hemodynamic data, as well as prostacyclin (PGI2) and thromboxane (TxA2) activity in aortic, venous, and pulmonary artery blood samples, were assessed over a 30-min time period following protamine administration. Group III indomethacin pretreatment provided the most protection from declines in blood pressure, heart rate, cardiac output, venous oxygen saturation, oxygen consumption, and elevations in pulmonary pressures and was accompanied with actual declines in PGI2. Group II U63,557A pretreatment was associated with the most severe hemodynamic changes and the greatest increase in PGI2 (+576%). Elevated PGI2 correlated with hypotension at 1 and 3 min (P less than 0.01), as well as pulmonary artery pressure declines at all times following protamine reversal. TxA2 changes did not correlate with hemodynamic changes. Protamine's adverse hemodynamic responses were attenuated with cyclooxygenase blockade by indomethacin, but were worsened with selective TxA2 blockade with U63,557A. Excess arachadonic acid precursors in the latter setting may increase PGI2 production. This study, for the first time, raises the possibility that PGI2 contributes to the adverse effects accompanying protamine reversal of heparin anticoagulation.

Animals↗
PubMed1991

Absence of complement-mediated events after protamine reversal of heparin anticoagulation.

Protamine reversal of heparin anticoagulation is associated with adverse hemodynamic effects that may be attenuated with protamine pretreatment (PP). This study assesses the role of complement activation during these phenomena in adult cardiac surgery patients. Sixteen individuals undergoing cardiopulmonary bypass were given intravenous normal saline or protamine (2 mg/kg) as a randomized pretreatment prior to undergoing heparin anticoagulation (400 IU/kg), coronary artery revascularization, and subsequent reversal of the anticoagulated state with protamine (4 mg/kg). Blood pressure, pulmonary artery diastolic pressure (PAD), heart rate, and cardiac output (CO) were measured during and after pretreatment, prior to heparin reversal by protamine, and for 10 min after reversal. Total hemolytic complement (CH50), C3 conversion to C3b, C3a/C5a, platelet count, and white blood cell count (WBC) were also measured at the same time periods. No significant correlation existed between complement activation and hemodynamic events, as might have been evident by decreased CH50, increased C3 conversion to C3b, or elevations in C3a/C5a levels. PP significantly prevented the CO decrease occurring at 1 and 3 min following heparin reversal by protamine (-0.8 and -1.4 liters/min vs 0.1 and -0.2 liters/min, P less than 0.05 and P less than 0.01, respectively). Reversal hypotension was less with PP, although PAD fell equally in both groups. WBC decreases after heparin reversal were less after PP (-25% vs -7%, P = 0.06). These data support the conclusion that, contrary to earlier reports, adverse hemodynamic and hematologic responses accompanying protamine reversal of heparin anticoagulation do not appear to be correlated with activation of complement. In fact, those patients having the greatest C3a generation exhibited the least hemodynamic changes.

Adult↗
PubMed1991

Effect of controlled hemorrhage on tissue and serum cefazolin clearance.

Effects of blood loss on tissue and serum antibiotic levels were investigated in 30 New Zealand white rabbits. Studies were conducted over a 3.5-hr period after intravenous administration of cefazolin, 30 mg/kg, in control animals (Groups I and IV, n = 5 each) and animals having 50% (Groups II and V, n = 5 each) or 100% (Groups III and VI, n = 5 each) of their blood volume removed and replaced with either Ringer's solution (Groups I, II, and III) or rabbit whole blood (Groups IV, V, and VI) sufficient to maintain central venous pressures at baseline levels. Periodic samples of retroperitoneal fat, iliac artery, and serum were assayed for cefazolin concentration by disc diffusion. Decreased tissue antibiotic levels were observed in animals undergoing 100% blood replacement (Groups III and VI) compared to controls (Groups I and IV) in both fat (P less than or equal to 0.01) and artery (P less than or equal to 0.01) at 90 min. Decreased antibiotic serum half-life accompanying hemorrhage existed when comparing Group II to I (P less than or equal to 0.05), Group III to I (P less than or equal to 0.01), and Group IV to V (P less than or equal to 0.01). The increased antibiotic clearance related to blood loss in this study justifies reassessment of intraoperative dosing intervals. More frequent dosing may be required to maintain stable tissue and serum antibiotic levels during substantial operative hemorrhage.

Animals↗
PubMed1991

Vascular fellowships and laboratory research.

Research activity has assumed an increasingly important role in the education of vascular surgeons and appears to exceed that of other graduate training programs. Laboratory research experience is an integral part of 42 (71%) of the 59 current vascular surgery training programs approved by ACGME-Residency Review Committee. Among existing laboratory experiences, 18 (43%) are fully integrated with research programs in the preclinical basic sciences. Laboratory experience in 30 programs (58%) precedes the obligatory 12-month clinical training program and is 1 year in duration.

Fellowships and Scholarships↗
PubMed1991

Suggested standards for reporting on arterial aneurysms. Subcommittee on Reporting Standards for Arterial Aneurysms, Ad Hoc Committee on Reporting Standards, Society for Vascular Surgery and North American Chapter, International Society for Cardiovascular Surgery.

The literature on arterial aneurysms is subject to potential misinterpretation because of inconsistencies in reporting standards. The joint councils of the Society for Vascular Surgery and the North American Chapter of the International Society for Cardiovascular Surgery appointed an ad hoc committee to address this issue. This communication, prepared in response to the need for standardized reporting, defines and classifies arterial aneurysms and recommends standards for describing the causes, manifestations, treatment, and outcome criteria that are important when publishing data on aneurysmal disease.

Aneurysm↗
PubMed1991

Clinical characteristics and surgical management of vascular complications in patients undergoing cardiac catheterization: interventional versus diagnostic procedures.

The purpose of this report is to define the clinical characteristics and outcome of surgical management of vascular complications after interventional cardiac catheterization and to contrast them to those after diagnostic cardiac catheterization. From October 1985 to December 1989, 101 patients were treated for 106 vascular complications after 1866 interventional and 5046 diagnostic cardiac catheterizations at the University of Michigan Medical Center. Interventional catheterizations resulted in 69 vascular complications in 64 patients (frequency 3.4%). The most common interventions included coronary angioplasty (34), of which 10 required percutaneous partial cardiopulmonary bypass, intraaortic balloon pump placement (14), and aortic valvuloplasty (11). Interventional catheter-related complications included hemorrhage (33), arterial thrombosis (18), pseudoaneurysm formation (12), catheter embolization (2), thromboembolism (2), as well as arteriovenous fistula, pseudoaneurysm, and arterial dissection (1 each). Fifteen of these 69 patients (24%) had suffered acute myocardial infarction just before their catheterization. Surgical repair was performed under local anesthesia in 70% of patients. Major vascular reconstructions were required in 9% of patients. Three percent of the involved lower extremities had to be amputated because of complications occurring after arterial puncture. Eight percent of the patients incurring vascular complications after interventional procedures died after operation. Diagnostic catheterizations resulted in 37 vascular complications in 37 patients (frequency 0.7%). In contrast to diagnostic cardiac catheterization, vascular complications after interventional cardiac catheterization occurred more frequently, were most often due to hemorrhage at the vascular access site, and occurred in high-risk, critically ill patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗