Increasing the sensitivity of the diagnosis of chronic venous obstruction.
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Adult↗
Biomedical subjects
R M Green
Publications and source records attributed to R M Green.
Thrombolysis with prourokinase versus urokinase: an in vitro comparison.
PURPOSE: Despite advantages demonstrated in vitro, no single thrombolytic agent has been clearly shown to be superior to another in the clinical setting. Prourokinase has recently received attention as a new thrombolytic agent with higher fibrin specificity. The thrombolytic activity of prourokinase, however, remains ill defined. The purpose of this study was to evaluate thrombolysis with prourokinase in comparison to urokinase in vitro. METHODS: We used an in vitro parallel channel perfusion model that simulates catheter-directed thrombolysis in the peripheral arterial system. Radiolabeled thrombi were subjected to 90 minutes of endhole catheter-directed infusion with either prourokinase 5000 IU/ml, urokinase 5000 IU/ml; or 5% dextrose in water at 4 ml/hr. RESULTS: Prourokinase and urokinase were found to be equivalent with respect to thrombolytic effect. Percent lysis was maximal at 90 minutes in both the urokinase and prourokinase groups. Prourokinase and urokinase were found to be equally effective in restoring flow through thrombosed graft segments. CONCLUSION: Prourokinase appears to offer little benefit over urokinase with respect to thrombolytic activity in an in vitro model that closely resembles the clinical setting. If prourokinase is to be accepted as an alternative to urokinase, advantages must relate to differences in fibrin specificity.
Catheterization↗
Regulation of hepatocyte bile salt transporters by endotoxin and inflammatory cytokines in rodents.
BACKGROUND & AIMS: Pathophysiological conditions such as sepsis and hepatitis are mediated by inflammatory cytokines and frequently are associated with cholestasis. The aim of this study was to determine the effect of endotoxin (lipopolysaccharide [LPS]) and cytokine administration on hepatocellular transporters involved in bile salt transport. METHODS: LPS and cytokines were administered to Sprague-Dawley rats or C57BL/6 mice, and the expression and function of hepatocyte transporters involved in bile salt secretion were examined. RESULTS: LPS caused gene expression of the hepatocyte basolateral sodium-dependent taurocholate cotransporter (Ntcp) to decrease by more than 90%. Tumor necrosis factor alpha (TNF-alpha) or interleukin (IL) 1beta also produced a time-dependent decrease in Ntcp messenger RNA levels, whereas IL-6 had no effect. LPS administration resulted in a concordant 90% reduction of basolateral protein expression of the hepatocyte sodium taurocholate cotransporter and markedly diminished sodium-dependent taurocholate uptake. Activity of the hepatocyte basolateral Na+,K+-adenosine triphosphatase (ATPase) was also decreased by 50% in a posttranslational manner after endotoxin treatment. CONCLUSIONS: Endotoxin inhibits hepatocellular sodium-dependent bile salt uptake by decreasing both expression of Ntcp and activity of the Na+,K-ATPase. The effects on Ntcp are mediated via TNF-alpha and IL-1beta. Alterations of these transporters may contribute to the cholestasis of sepsis and inflammation.
Animals↗
Treatment of heparin-induced thrombocytopenia and thrombosis.
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Ancrod↗
A new factor from Escherichia coli affects translocation of mRNA.
Reconstitution of protein synthesis from purified translation factors on ribosomes from Escherichia coli has revealed the requirement for a protein, W, that affects chain elongation and is essential to reconstitute the process (Ganoza, M. C., Cunningham, C., and Green, R. M. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 1648-1652). We report that W has no effect on initiation complex formation by 30 or 70 S ribosomes or on the association of ribosomal subunits, peptide bond synthesis, or binding Ala-tRNA, which is the second amino acid of the coat protein of the MS2 RNA virion. W has a pronounced effect on tripeptide synthesis, and is obligatory for the synthesis of the coat protein or of the hexapeptide encoded by f2am3 RNA. Extracts from a temperature-sensitive mutant of the translocase, EF-G, were purified free of the W protein and were used to score for translocation defects. W is required for binding Ser-tRNA, the third N-terminal amino acid of the MS2 or f2 RNA coat protein to ribosomes bearing fMet-Ala-tRNA, as well as for the ejection of deacyl-tRNA from ribosomes, which occurred concomitant with the binding of the Ser-tRNA. We propose that W functions by ejecting tRNAs from ribosomes in a step that precedes the movement of mRNA during translocation.
Bacterial Proteins↗
Cloning and characterization of a cDNA encoding the specific phosphatidylcholine transfer protein from bovine liver.
A 1917-bp cDNA clone encoding phosphatidylcholine transfer protein (PC-TP) was identified by screening a bovine liver library. Northern blot analysis demonstrated a 2-kb mRNA transcript in bovine liver, and Southern blotting was consistent with a single bovine PC-TP gene which was shown to be present in a diverse group of vertebrates, but not in yeast. Database comparisons revealed the nucleotide sequence of the clone to be unique and unrelated to other cytosolic lipid TP.
Amino Acid Sequence↗
Determinants of bone mass in 10- to 26-year-old females: a twin study.
This cross-sectional twin study aimed to quantify the roles of constitutional and lifestyle factors on bone mass in adolescent and young adult women. Areal bone density (BMD) at the lumbar spine, femoral neck, Ward's triangle, and total hip, total body bone mineral content (BMC), and lean mass and fat mass were measured using dual energy X-ray absorptiometry (DXA) in 215 female volunteer twin pairs (122 monozygotic [MZ], 93 dizygotic [DZ]) aged 10 to 26 years. Height, weight, menarchial history, dietary calcium intake, physical activity, current tobacco use, and alcohol consumption were determined by questionnaire. Mean BMD increased with age to around 16 years, when it reached a plateau. Within-pair differences in BMD at the lumbar spine (expressed as a percentage of the pair mean BMD) were univariately associated with pair differences in menarchial status (14 +/- 3%), height (0.7 +/- 0.1% per cm), weight (0.4 +/- 0.1% per kg), lean mass (1.0 +/- 0.1% per kg), and fat mass (0.5 +/- 0.1% per kg). Only menarchial status, height, and lean mass, however, were independent predictors. At the proximal femoral sites, within-pair BMD differences were associated with within-pair lean mass differences (1.0 to 1.1 +/- 0.2%/kg), and no other factor was significant. The same conclusions applied to within-pair differences in BMD/height. Total body BMC was independently associated with menarchial status, height, lean mass, and fat mass; the effects of the latter two variables were stronger in pairs both premenarchial. After adjusting for constitutional factors, no lifestyle factor was independently predictive. By reducing collinearity, the cotwin method clearly identified that lean mass, not fat mass, was the major independent determinant of bone mass at the hip, both pre- and postmenarche.
Absorptiometry, Photon↗
Bone density determinants in elderly women: a twin study.
This cross-sectional twin study examined the influence of constitutional, lifestyle, and genetic factors on bone mineral density (BMD) in elderly women. BMD, at the lumbar spine, femoral neck, Ward's triangle, total hip, and total forearm, total body bone mineral content (BMC), and lean mass and fat mass were measured using dual energy X-ray absorptiometry in 69 volunteer female twin pairs (37 monozygotic [MZ], 32 dizygotic [DZ]) aged 60-89 years. Height and weight were measured. Medical history and lifetime tobacco and alcohol use were determined by questionnaire. In terms of within-pair differences, lean mass was independently associated with BMD at all sites. In contrast, fat mass was not associated with BMD at any site once allowance had been made for lean mass. Lifetime tobacco use was independently associated with BMD at the lumbar spine, total hip, and forearm. Total body BMC was independently predicted by lean mass, fat mass, tobacco use, and alcohol consumption. Age and the above independently predictive body composition and lifestyle factors accounted for 20-33% of variation in BMD. After allowing for these covariates, MZ and DZ correlations were consistent with about 75% of residual variation in BMD at the nonforearm sites being determined by genetic factors. For total body BMC, the covariates explained 75% of total variation, and genetic factors 76% of the residual variation. Therefore, at the proximal femur and lumbar spine, after taking into account the relation of BMD with lean mass and smoking, genetic factors appear to play a substantial role in explaining variation in BMD in elderly women.
Absorptiometry, Photon↗
Operative management of coexistent aortic disease and horseshoe kidney.
The presence of horseshoe kidney in conjunction with abdominal aortic disease significantly increases the technical difficulty of aortic reconstruction. Preservation of the renal blood supply and collecting system during the surgical procedure is the goal of operative management. The pertinent issues that remain unresolved include the need for specific preoperative studies, the optimal operative approach and the safety of isthmus division. From 1979 to 1994 eight patients with horseshoe kidney underwent operative intervention for aortic disease. Five men and three women who had a mean age of 66 years underwent seven reconstructions for aneurysmal disease and one for aortoiliac occlusive disease. All operations were elective and the transperitoneal approach was used in all cases. In the patients with aneurysmal disease the mean maximal aortic diameter was 7.3 cm. The mean preoperative serum creatinine value was 1.1 mg/dl. Preoperative identification of horseshoe kidney was accomplished in all seven patients with aneurysmal disease but not in the patient with occlusive disease. The anomaly was correctly identified by CT scan in seven of seven (100%) patients, arteriography in two of eight (25%) patients, ultrasonography in two of seven (29%) patients, and renal scan in one patient. In the three patients who underwent intravenous pyelography (IVP) the caliceal system was demonstrated to be completely separate from the isthmus. Renal artery anomalies were present in six (75%) patients; in three (50%) these anomalies could be not visualized on the preoperative arteriogram. Renal revascularization was accomplished by a variety of techniques, including reimplantation of multiple (one patient) and single (four patients) renal arteries and branch grafting to an individual renal artery (one patient).(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Tumor necrosis factor-alpha decreases hepatocyte bile salt uptake and mediates endotoxin-induced cholestasis.
Tumor necrosis factor-alpha (TNF alpha), a cytokine that is produced in a variety of inflammatory diseases associated with cholestasis, is believed to be the primary mediator of the systemic effects of endotoxin. Thus, we have investigated the role of TNF alpha in the pathogenesis of endotoxin-induced cholestasis in intact animals, and in the uptake of taurocholate by cultured hepatocytes. Male Sprague-Dawley rats received either intravenous (IV) endotoxin (7.5 mg/kg) or monoclonal anti-TNF alpha antibody followed by endotoxin. Basal bile flow and bile salt excretion were measured for a 2-hour period, after which all animals received an IV bolus of taurocholate (10 mumol/100 g body weight). Endotoxin decreased basal bile flow by 41% and bile salt stimulated bile flow by 38% (n = 12; P < .01). Basal bile salt excretion was decreased 86% after endotoxin administration. Passive immunization with anti-TNF alpha antibody blocked this endotoxin-associated cholestasis. In addition, rat hepatocytes were isolated and cultured in the presence of either endotoxin (10 micrograms/mL) or TNF alpha (100 ng/mL) for 24 hours. These primary hepatocyte cultures exhibited a dose- and time-dependent, noncompetitive, inhibition of taurocholate uptake. We postulate that TNF alpha is an important mediator of the cholestasis of sepsis.
Animals↗
Evolution of technologies in endovascular grafting.
The safety, efficacy and utility of inserting a vascular prosthesis through the femoral artery and attaching it to a native artery with stents to treat abdominal aortic aneurysms are under various stages of testing around the world. The potential of these endovascular techniques to reduce the morbidity and cost of care is enormous. Many advances in imaging, catheter techniques, delivery systems and the knowledge about aneurysm morphology are responsible for the progress to date. The requirements of an endoprosthesis include a small and flexible delivery system that allows retrograde insertion through the iliofemoral arterial system, secure attachments to normal arterial wall, and a fabric which meets Food and Drugs Administration criteria for strength and durability. Application of this technique to large numbers of patients with aneurysms will probably require the development of a bifurcated prosthesis. The long-term behavior of the aneurysm wall after endoprosthesis insertion will not be known until clinical trials are completed. The development of these techniques will undoubtedly fuel the 'turf battle' between vascular surgeons and interventionalists. Although each group will lay claim to the technology, a cooperative effort to maximize patient benefit seems to be the most appropriate way to insure that the interests of the patients are best served.
Aortic Aneurysm, Abdominal↗
Autogenous venous bypass grafts and limb salvage: 5-year results in 1971 and 1991.
Claims have been made that the increased utilization of arterial reconstruction has not resulted in improved limb salvage. This report compares the results of two series of patients with autogenous venous bypass grafts and examines the institutional trends at a major regional vascular center with these procedures. The two groups of patients underwent operation between 1957 and 1964 (group I) and 1982 and 1985 (group II) respectively. Each patient was followed for a minimum of 5 years or until death. This review showed that the demographics of the population and the nature of the operation changed dramatically over the 20-year period. Patients were older, had more medical co-morbid conditions, more operations were performed for salvage and more to vessels below the knee joint in the latter series. Despite these adverse factors, the 30-day patency rates were significantly better in the later group, 93% versus 76%. Likewise, limb salvage rates were improved both initially and after the 5-year period of observation. The 5-year primary patency, however, was no different between groups I and II, 60% versus 56%. Since both series preceded the use of duplex scanning for graft surveillance, even further improvements in both graft patency and limb salvage rates would be expected in patients currently treated.
Adult↗
Differential mechanisms of failure of autogenous and non-autogenous bypass conduits: an assessment following successful graft thrombolysis.
The advent of graft thrombolysis has provided an objective means for evaluating the etiology of graft occlusion. Over a 10-year period, intra-arterial urokinase (102 cases) or streptokinase (seven cases) was used in 109 infrainguinal conduits (30 autogenous and 79 non-autogenous) that failed 30 days or more after implantation. Thrombolysis was not achieved in 19 additional graft occlusions; these cases were excluded from study because of an inability to define the mechanism of failure. Non-invasive laboratory data were available within 6 months of graft occlusion in 82 (75%) of the cases, with Doppler segmental studies in 80 cases (73%) and duplex ultrasonography studies in 39 cases (36%). Pre-failure non-invasive laboratory abnormalities were detected more frequently in autogenous grafts (21 of 24 patients, 88%), while non-autogenous grafts usually occluded without prior hemodynamic change (11 of 58 patients had abnormalities, 19%) (P < 0.001). Thrombolysis uncovered anatomic defects responsible for thrombosis in 27 (90%) of 30 autogenous grafts compared with only 32 (41%) of non-autogenous conduits (P < 0.001). The most common lesions underlying autogenous graft failure comprised stenoses within the body of the graft (11 cases, 37%), while the most common lesions in failed non-autogenous grafts appeared to be stenoses at an anastomosis (21 cases, 27%). Thus, the mechanisms underlying the late failure of autogenous and non-autogenous grafts differ markedly; autogenous grafts most commonly fail as a result of the gradual development of lesions intrinsic to the graft, while non-autogenous grafts fail precipitously, presumably as a result of some non-anatomic mechanism.
Adult↗
Thrombus formation on polytetrafluoroethylene surfaces: the importance of von Willebrand factor.
The importance of von Willebrand factor (vWf) in the formation of platelet-fibrin thrombi on expanded polytetrafluoroethylene (ePTFE) surfaces was studied in an in vitro system, perfusing non-anticoagulated human blood over ePTFE grafts for 3 min at varying shear rates (100, 500 and 1500/s shear). Platelet (111In) and fibrin (125I) deposition was assessed on ePTFE surfaces in the presence and relative absence of vWf, achieved by use of polyclonal anti-vWf antibody (anti-vWf Ab). A total of 29 perfusions were performed. Increasing shear rate was associated with greater platelet deposition in the presence of vWf (p < 0.001). This shear-dependent rise in platelet deposition was not observed when vWf was blocked by anti-vWf Ab (P < 0.1), confirming the role of vWf in platelet deposition at high shear rates. Fibrin deposition increased with increasing shear rate in the presence of vWf (P < 0.01). Inhibiting vWf abolished the shear-dependent increase in fibrin deposition. These data suggest that vWf plays a critical role in platelet and fibrin thrombus formation on ePTFE surfaces. These effects are particularly important under conditions of high shear rate. These mechanisms may lead to the observed pathologic thrombus formation and platelet-dependent neointimal processes occurring at areas of high shear rate within the anastomotic regions of ePTFE grafts.
Blood Platelets↗
Appropriate frequency of carotid duplex testing following carotid endarterectomy.
BACKGROUND: The value of carotid duplex analysis is well proven for the diagnosis of carotid bifurcation occlusive disease, but its use in the postoperative setting is less well defined. PATIENTS AND METHODS: A series of 281 carotid endarterectomies were performed in 222 patients. A protocol of serial duplex examinations was established, with tests performed at the time of the first postoperative clinic visit and every 6 months thereafter. The goal of postoperative surveillance was to identify critical restenotic carotid lesions of greater than 80% diameter reduction and determine the incidence of subsequent carotid occlusion and neurologic events. RESULTS: Critical restenoses developed in 25 (8.9%) of the arteries and occlusions occurred in 12 (4%). Restenosis occurred with greatest frequency during the first year after operation (5%), but continued to develop with a frequency of approximately 2% per year thereafter. Postoperative carotid occlusions occurred at a rate of approximately 1% per year. Known restenotic lesions progressed to occlusion over a mean duration of 11 months. Stroke was infrequent in patients with critical restenoses (4%) until the lesions progressed to occlusion (33%). CONCLUSIONS: These observations suggest that a protocol of semiannual duplex testing into the late postoperative period may identify critical carotid restenotic lesions prior to the development of carotid occlusion and stroke.
Adult↗
Economic implications of thrombolysis or operation as the initial treatment modality in acute peripheral arterial occlusion.
BACKGROUND: Thrombolytic agents have been used to treat arterial occlusion for almost 40 years. Recently, an investigation of the costs associated with two treatment options for acute peripheral arterial occlusions, thrombolysis and surgical intervention, was completed. The availability of hospital cost data for patients enrolled in the thrombolytic and operative treatment groups provided a basis with which to accurately assess the financial impact of the different treatment strategies, both from a purely financial standpoint and in relation to outcome. METHODS: The patient base was composed of 114 patients with acute limb ischemia of less than 7 days' duration. The patients were randomly assigned to receive urokinase (n = 57) or to undergo an operation (n = 57) as the initial therapeutic intervention. Patients in the thrombolytic group underwent standard intraarterial diagnostic arteriography, and patients with embolic events, in whom complete lysis of all embolic and propagated thrombotic material was achieved, were subsequently treated with heparin and long-term warfarin (Coumadin) therapy. The economic analysis was undertaken after the completion of the trial. Statistical comparisons between groups were made with the Student t test for continuous, normally distributed data. Mortality and limb salvage rates were calculated from Kaplan-Meier curves, appropriate for the censored nature of the data. RESULTS: The total treatment costs did not differ significantly between the two treatment groups ($22,171 +/- $4,959 in the thrombolytic group and $19,775 +/- $5,253 in the operative group). The total hospital charges were similar between the two groups. Overall, the total charges were remarkably similar between the two treatment groups, averaging $40,823 +/- $8,764 in the thrombolytic group and $41,930 +/- $10,398 in the operative group. CONCLUSIONS: An economic analysis of the data confirmed that the total economic impact of thrombolysis approximated that of initial operative therapy. The improved clinical outcome in patients treated with thrombolysis suggests that this modality may be appropriate as the initial therapeutic intervention in the select group of patients seen within the first few hours of an acute peripheral arterial occlusive event.
Acute Disease↗
Outpatient echocardiography as a predictor of perioperative cardiac morbidity after peripheral vascular surgical procedures.
PURPOSE: A variety of preoperative provocative tests have been used to define the risk of cardiac morbidity and mortality after peripheral vascular procedures, including dipyridamole myocardial scintigraphy and dobutamine stress echocardiography. Although highly sensitive, these tests are time-consuming and associated with significant expense. We investigated outpatient echocardiography as a less resource-intensive means of assessing cardiac risk with operation. METHODS: Over a 2-year period 250 consecutive patients underwent outpatient transthoracic echocardiography before elective peripheral vascular operation was performed. The accuracy of the Goldman, Detsky, and the American Society of Anesthesiologists' Physical Status Classification clinical indexes of cardiac risk were assessed with regard to the development of cardiac complications such as unstable angina, myocardial infarction, life-threatening ventricular arrhythmias, severe congestive heart failure, and cardiogenic shock. The accuracy of echocardiographically determined left ventricular ejection fraction was determined at threshold values between 20% and 60%. RESULTS: Perioperative cardiac events developed in 23 (9.2%) of the patients, and nine (3.6%) of the patients died as a result of these complications. Clinical indexes lacked sensitivity in the preoperative prediction of cardiac complications. Receiver operating curve analysis defined a left ventricular ejection fraction of less than 50% as an appropriate threshold for defining patients at high risk, with a sensitivity of 78% and a specificity of 81% in the identification of patients who had cardiac morbidity. The positive predictive value was 27%, and the negative predictive value was 97%. The economic impact of outpatient echocardiography was well below that of dipyridamole myocardial scintigraphy or dobutamine stress echocardiography. CONCLUSIONS: Outpatient echocardiography appears to offer a cost-efficient compromise between clinical criteria alone and provocative cardiac testing such as dipyridamole myocardial scintigraphy and dobutamine stress echocardiography in the preoperative screening of patients undergoing peripheral vascular surgical procedures.
Adult↗
The effects of low-dose radiation on neointimal hyperplasia.
PURPOSE: We sought to determine whether low-dose radiation can inhibit neointimal hyperplasia immediately after balloon injury to the common carotid artery and to assess the extent of endothelial regeneration after treatment. METHODS: Sprague-Dawley rats were subjected to balloon injury to the common carotid artery. Immediately after injury rats were treated with a single dose of iridium 192 radiation at 5 gy, 10 gy, and 15 gy or received no radiation (control). Three weeks after injury and treatment, vessels were harvested and compartment areas were measured on fixed specimens. Scanning and transmission electron microscopy, along with Evans blue dye uptake into injured vessels, was used to assess the effect radiation had on endothelial regeneration. RESULTS: Rats receiving radiation at all three doses demonstrated no intimal thickening when compared with rats that were not treated (at 5 Gy 0.01 +/- 0.01 mm2; at 10 Gy 0.02 +/- 0.01 mm2; at 15 Gy 0.05 +/- 0.02 mm2; with balloon injury/no radiation 0.12 +/- 0.02 mm2; p < 0.01). In addition, the groups that were irradiated had no medial thickening when compared with control rats (at 5 Gy 0.22 +/- 0.02 mm2; at 10 Gy 0.21 +/- 0.02 mm2; at 15 Gy 0.22 +/- 0.07 mm2; with balloon injury/no radiation 0.37 +/- 0.03 mm2; p < 0.01). Endothelial regeneration, evaluated by transmission and scanning electron micrographs along with uptake of Evans blue dye, was significantly greater in animals that received radiation compared with controls. CONCLUSIONS: Low-dose radiation prevents the occurrence of neointimal hyperplasia after balloon injury and may have a future role in vascular grafting.
Animals↗