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Biomedical subjects

R W Hobson

Publications and source records attributed to R W Hobson.

At least 91 records · Page 5Linked to original sources
PubMed1993

Death associated with asymptomatic carotid artery stenosis: long-term clinical evaluation. VA Cooperative Study 167 Group.

PURPOSE: As part of a prospective clinical trial on the efficacy of carotid endarterectomy in patients with asymptomatic carotid artery stenosis, we studied the risk factors for death in 444 male patients. METHODS: At entry to the trial, patients were judged to be healthy enough to be randomized to operative intervention and were judged to be free of any disease that would preclude a minimal 5-year life expectancy after randomization. RESULTS: Patients were treated with aspirin and optimal medical care and were monitored for an average of 4 years. Combined mortality rate was 37% (9% per year) for the medical group (38%) and surgical group (35%). Eight factors were identified that were significantly associated with increased mortality rates: coronary artery disease (p = 0.044), history of angina (p = 0.047), congestive heart failure (CHF) (p = 0.012), abnormal electrocardiography results at entry (p = 0.005), peripheral vascular disease (p = 0.019), claudication (p = 0.044), diabetes (p = 0.008), and history of hypertension (p = 0.044). The increase in risk indicated by the odds ratios (OR) were moderate (OR < 2.00) for each of the clinical risk factors except for CHF. Sixteen of 27 patients (59%) with a history of CHF at entry to the study died during follow-up (OR = 2.67). Arteriographic predictors of increased mortality rates included bilateral carotid artery stenosis and intracranial vascular disease (ICVD). With bilateral stenosis, 42% (80 of 190 patients) died compared with 33% (83 of 252 patients) with unilateral stenosis (p = 0.062). With ICVD, 43% (56 of 130 patients) died compared with 34% (107 of 314 patients) of those without ICVD (p = 0.073). Multivariate analysis demonstrated that three risk factors were significantly associated with an increased risk of death: diabetes, abnormal electrocardiography results, and claudication. Patients with two or three of these risk factors demonstrated annual mortality rates of 11.3% and 13%, respectively. This was significantly higher than patients with none of these risks (OR = 2.95 and OR = 4.06, respectively). CONCLUSION: Adult male patients with high-grade asymptomatic carotid artery stenosis demonstrate a mortality rate of 37% at a mean follow-up of 4 years. Although age was not a risk for increased mortality rates in this population, diabetes, abnormal electrocardiography results, and claudication were significant. Patients with two or three of these risk factors were at high risk of death and may require aggressive treatment of their concurrent medical diseases.

Aged↗
PubMed1993

Influence of aspirin in the management of asymptomatic carotid artery stenosis. VA Cooperative Study Group on Asymptomatic Carotid Stenosis.

PURPOSE: Aspirin therapy is recommended commonly for symptomatic extracranial carotid artery occlusive disease. However, its role in the management of asymptomatic carotid artery stenosis has not been reported previously. METHODS: In 11 clinical centers during the period 1983 to 1991, 444 adult male patients with significant asymptomatic carotid artery stenosis (> or = 50% arteriographically) were randomized to receive optimal medical management including aspirin plus carotid endarterectomy (n = 211) or optimal medical management alone (n = 233). At the conclusion of the study (mean follow-up time 47.9 months), at the time of a patient's death, or at occurrence of a neurologic end point, 16% of patients (n = 72) were not taking any aspirin, 51% (n = 226) had been converted to receiving enteric-coated aspirin, and only 33% (n = 146) were taking plain aspirin (27% at reduced dosage). Among patients from the medical group, 37 (16%) of 233 were not taking any aspirin and formed the basis for this retrospective analysis of the group for which no control population was available. RESULTS: Mortality rates in this group were not significantly different for patients not taking aspirin as compared with the rates for those taking aspirin, although patients not taking aspirin had a higher incidence of myocardial infarction (27%) as compared with patients taking aspirin (8%), p < 0.05. The incidence of ipsilateral neurologic events for patients not taking aspirin as compared with that for patients who were taking aspirin, respectively, was as follows: stroke, 13.5% and 8.7%, p > 0.05; stroke and transient ischemic attack, 37.8% and 17.3%, p < 0.05. No significant differences were observed in stroke severity scores for patients taking or not taking aspirin. CONCLUSION: These data suggest that patients with significant asymptomatic carotid artery stenosis who are intolerant of aspirin have a higher incidence of neurologic events than those patients able to tolerate the drug.

Aspirin↗
PubMed1993

Arterial intimal flaps: a comparison of primary repair, aspirin, and endovascular excision in an experimental model.

The optimal management for traumatic arterial intimal injuries is unresolved. Three therapeutic options were compared in an experimental model employing a standard intimal flap created in 51 canine superficial femoral arteries. Group 1 (14 arteries) underwent resection with end-to-end repair. Group 2 (19 arteries) received acetylsalicylic acid (ASA) and observation only. Group 3 (21 arteries) underwent endovascular excision of the flap with angioscopic guidance. Control intimal flaps (18 arteries) were created and observed without further intervention. Patency in group 1 (primary repair) and group 2 (ASA) was 100%; the patency in both was significantly (p < 0.05) greater than in the controls, which was 67%. Patency in group 3 (endovascular excision) was 79%. Residual luminal defects were observed in only 8% of the arteries repaired primarily, but in 76% of the aspirin-treated arteries. Residual luminal defects following endovascular excision were present in 53% of the arteries remaining patent. Although resection and primary repair (group 1) provided better results than observation alone (control), addition of ASA (group 2) also sustained patency. However, a high incidence of residual intimal defects occurred, the natural history of which is unknown. While endovascular excision (group 3) may become a feasible alternative, current technology provided inferior patency with frequent residual intimal defects. These results suggest that observation alone supplemented with antiplatelet medication (ASA) may be adequate treatment, but longer follow-up is necessary for confirmation.

Angioscopy↗
PubMed1992

The arterial wall response to intimal injury in an experimental model.

Repair of occult arterial injuries is advocated to prevent thrombosis, arteriovenous fistula, and pseudoaneurysm formation. However, recent clinical series describe the healing of arterial intimal injuries and recommend nonoperative therapy. To investigate the arterial wall response to intimal injury, we created intimal flaps in 46 canine femoral arteries. The intimal flaps were imaged by arteriography, angioscopy, and intravascular ultrasound acutely, and at one and three weeks and five months post-injury. Lumen area was measured using caliper techniques (arteriography) and computerized video planimetry (angioscopy, intravascular ultrasound). Intimal and medial thickness were measured by intravascular ultrasound prior to harvest for histologic evaluation by light microscopy. Analysis of 32 patent arteries was performed after exclusion of 14 thrombosed arteries. Residual lumen area (mm2) correlated closely among the imaging modalities at one week (8.7 +/- 1.1, 7.3 +/- 2.0, 6.9 +/- 1.8), three weeks (4.2 +/- 0.9, 2.9 +/- 1.0, 2.7 +/- 0.8), and five months (5.3 +/- 0.9, 5.0 +/- 0.5, 5.0 +/- 0.9). Maximal intimal and medial thickness occurred three weeks post-injury, coincident with the maximal reduction in lumen area. Although intimal injuries can cause acute and delayed arterial thromboses, observation may be appropriate in selected cases. The evaluation of those patients chosen for nonoperative therapy should extend beyond three weeks, as this is the time of maximal arterial wall response with a continued potential for adverse clinical events.

Analysis of Variance↗
PubMed1992

Adverse effects of aspirin in the treatment of asymptomatic carotid artery stenosis. The VA Cooperative Asymptomatic Carotid Artery Stenosis Study Group.

We prospectively analyzed adverse effects of aspirin in a multicentered cooperative study undertaken to determine the role of endarterectomy in the treatment of asymptomatic carotid artery stenosis. Persons with active peptic ulcer disease or known intolerance to aspirin were excluded from the study. Patients initially received 650 mg aspirin twice daily. After a 54-month recruitment period, 444 patients in 11 centers were followed up for as many as 8 years (mean 47.9 +/- 27.9 months). Patients intolerant to 650 mg aspirin twice daily could be switched to enteric-coated aspirin or "low-dose" aspirin (80 to 325 mg daily). At the conclusion of the study, we performed a cross-sectional analysis of aspirin usage and complications. Overall, there were 757 episodes reported wherein adjustments in study medications were made, including cessation and change in formulation or dosage. At the conclusion of the study, at the time of death, or at occurrence of a neurologic end point, 16% of patients were off medication entirely, 51% had been converted to enteric-coated aspirin, and only 33% were taking regular aspirin with 27% of those having been placed on a reduced dosage. Adverse reactions were ascertained from 4954 patient visit records. In all there were a total of 837 adverse reactions reported, or one in every 5.9 visits. The most frequently reported reaction was heartburn or stomach pain for which 372 episodes were reported in 184 (42%) patients. Nausea or vomiting occurred on 79 occasions in 58 patients, and bloody stools were reported 52 times in 41 patients. We conclude that high-dose aspirin therapy for asymptomatic carotid artery stenosis is poorly tolerated and that adverse reactions even to low-dose enteric-coated aspirin are common even in patients screened for aspirin intolerance.

Aged↗
PubMed1992

Infrapopliteal arterial injury: prompt revascularization affords optimal limb salvage.

Sixty-nine limbs with infrapopliteal arterial injuries were evaluated in 68 patients. Thirty-five (50%) cases were complicated by acute limb-threatening ischemia. Management consisted of revascularization (26 limbs), ligation (15 limbs), fasciotomy only (2 limbs), observation (18 limbs), and primary amputation (8 limbs). Penetrating injuries (n = 35) had a 33% incidence of ischemia and a reduced frequency of associated injury. One delayed amputation (3%) was required. In contrast, blunt injuries (n = 34) had a 68% incidence of ischemia and a greater frequency of associated injury. There were 20 amputations in the blunt group, including eight primary amputations performed in limbs with profound ischemia, complex open fractures, severe soft-tissue damage, and neural injury. Observation or ligation of single arterial injuries resulted in no early amputations. Associated local injuries in both groups included fracture or ligamentous disruption (64%), severe soft-tissue damage (32%), and nerve dysfunction (36%). In both groups, 15 of 35 ischemic limbs were salvaged by prompt revascularization (11 penetrating and four blunt injuries). Aggressive revascularization with autogenous repair or bypass is recommended for management of penetrating trauma. Though a good outcome will be achieved in some patients with combined blunt trauma and infrapopliteal arterial injury, the probability of delayed amputation and prolonged disability must be consciously integrated into the decision to pursue limb salvage. The prognosis for blunt injury complicated by arterial ischemia is poor; thus the severity of associated local and remote injuries will affect the results of revascularization program.

Adult↗
PubMed1992

Comparison of multicenter study designs for investigation of carotid endarterectomy efficacy.

BACKGROUND: Our report summarizes and compares the characteristics of six prospective, multicenter, randomized clinical trials of carotid endarterectomy underway in North America and Europe. SUMMARY OF REVIEW: Three trials are designed to evaluate the safety and efficacy of endarterectomy in patients with asymptomatic carotid artery stenosis. The other three trials enroll patients who have had transient ischemic attacks or a minor cerebral infarction in the distribution of the randomized artery. Considered together, these six clinical trials span the range of candidates for carotid endarterectomy. The inclusion and exclusion criteria, methodology, and statistical considerations of each study are detailed in tables. CONCLUSIONS: The results from these trials will be helpful in resolving some of the questions surrounding endarterectomy, provided the similarities and differences in the study designs are considered when interpreting the results.

Carotid Arteries↗
PubMed1991

Carotid endarterectomy for asymptomatic carotid stenosis: a ten-year experience with 120 procedures in a fellowship training program.

Performance of carotid endarterectomy for asymptomatic carotid stenosis has been restricted during recent years because of concern of reported complications in as high as 10-15% of patients, as well as limited long-term data on stroke protection. During the last 10 years, we have studied immediate and long-term results of carotid endarterectomy for asymptomatic disease in 120 patients. Operations were performed by a clinical vascular fellow with a staff surgeon in attendance in 113 (94%) cases with the remainder performed by the staff surgeon. Patients' mean age was 66 years; 82% were men. Risk factors included hypertension (56%), smoking (52%), coronary artery disease (32%), diabetes (24%), and hypercholesterolemia (6%). Arteriographic severity of stenoses was 80-99% in 74%, 60-79% in 22%, and 40-59% in 4% of cases. Postoperative complications included two transient neurological events (1.7%). No permanent strokes or deaths occurred. Using the life table method, cumulative stroke rate was 4.5% for ipsilateral events and 7.3% for contralateral events, confirming the high degree of stroke protection afforded by carotid endarterectomy in this population. Since these results were accomplished in a fellowship training program, we regard adequacy of this experience as the most influential factor in accomplishing this record. Surgeons who are unable to achieve comparable results should consider abandonment of the procedure or an extended period of additional training.

Aged↗
PubMed1991

Leukocyte activation in ischemia-reperfusion injury of skeletal muscle.

Polymorphonuclear leukocyte (PMN) participation in the pathophysiology of the reperfusion injury following skeletal muscle ischemia has become recognized. We measured the activation of PMNs as evidenced by production of superoxide anion (O2-) in the isolated canine gracilis muscle preparation of ischemia-reperfusion injury. PMNs were isolated from the gracilis muscle venous effluent and central venous blood after 6 hr of bilateral gracilis ischemia and 1 hr of reperfusion in five dogs. Baseline samples were obtained prior to ischemia from the central venous circulation. Liberation of O2- from PMNs and from PMNs stimulated by opsonized zymosan was determined by measuring ferricytochrome reduction. Results are expressed as nanomoles of O2- produced/2 x 10(6) PMN +/- SEM. O2- production by unstimulated cells was increased from 0.33 +/- 0.15 nmole in the baseline samples to 0.96 +/- 0.08 nmole in the central venous sample (P less than 0.01). With stimulation by zymosan, production increased from 10.3 +/- 1.4 nmole in the baseline samples to 15.2 +/- 1.1 nmole in the central venous sample (P less than 0.05) and to 15.5 +/- 0.9 nmole in the gracilis venous sample (P less than 0.01). These increases in superoxide production were not seen in the three sham-operated animals. Mean infarct size determined by planimetry was 55%. O2- produced by PMNs from central venous blood correlated with infarct size (r = 0.934, P = 0.02). These data imply that PMNs are activated by muscular ischemia, and the degree of activation is directly related to the extent of the muscle infarction.

Animals↗
PubMed1991

A prospective evaluation of arterial intimal injuries in an experimental model.

The management of arterial intimal defects remains controversial because of uncertainty concerning their natural history. We developed an experimental canine model to prospectively evaluate posterior wall intimal flaps in the superficial femoral artery. Arterial intimal flaps were constructed in 20 anesthetized dogs (40 arteries) and evaluated by arteriography, and angioscopy, and intravascular ultrasound. Postoperative patency rates at 1 (n = 20) and 3 weeks (n = 20) were compared with a control group of ten animals (n = 20, arteriotomy without intimal flap). Acute thromboses occurred in five experimental arteries with thromboses of eight additional experimental arteries at followup. Control patency was 100%, while experimental group patencies were 75% (p less than 0.05) at 1 week and 60% (p less than 0.009) at 3 weeks. All thrombosed arteries had intimal flaps with greater than 75% luminal stenosis. We conclude that intimal injuries cause arterial thromboses acutely and during subsequent followup. Intimal flaps with stenosis greater than 75% as determined arteriographically are at greatest risk for thrombosis. Angioscopy and intravascular ultrasound characterize arterial intimal defects and may delineate injuries requiring surgical or endovascular repair.

Angiography↗
PubMed1991

A new model for studying ischemia-reperfusion injury in hamster cheek pouch.

The cheek pouch was prepared as a single layer and attached to a two-piece Lucite chamber that was filled with bicarbonate buffer (pH 7.35, equilibrated with 95% N2-5% CO2). Two microcirculatory areas were circumscribed in the cheek pouch by equilateral triangular chambers. Each chamber was made of 90-microns thick Mylar sheet (2 mm wide, 18 mm long). A cover slip was used as the chamber top. Ischemia was induced by applying pressure to the cover slip. The experimental area was reperfused after 1 h of ischemia by releasing the pressure. The other area served as control. One hour of reperfusion after 1 h of ischemia caused a significant increase in the number of leukocytes adhering to postcapillary venules (PCVs) per 100 microns vessel length in the ischemic area relative to the values in the control area (7.8 +/- 2.5 vs. 3.7 +/- 1.3, respectively, for PCVs 10-19.9 microns diam; and 10.9 +/- 2.8 vs. 6.2 +/- 1.8 for PCVs 20-29.9 microns diam; P less than 0.01 for both comparisons). The results demonstrate the adequacy of the model to investigate leukocyte adhesion to endothelium in ischemia-reperfusion. Because blood flow is maintained in most of the pouch, our model should also be useful for identifying possible interactions between ischemic and nonischemic areas in the microcirculation.

Animals↗
PubMed1991

The influence of arachidonic acid metabolites on leukocyte activation and skeletal muscle injury after ischemia and reperfusion.

Derivatives of arachidonic acid have been found to play a role in the reperfusion injury of various tissues. These compounds have a broad spectrum of activity, including modulation of white blood cell response to injured tissue. This study was designed to determine the effect of thromboxane and lipoxygenase derivatives on the local and systemic response to ischemia and reperfusion of skeletal muscle. Fifteen dogs were separated into three groups and subjected to gracilis muscle ischemia followed by 2 hours of reperfusion. One group served as controls, one group was treated with OKY-046 (a thromboxane synthetase inhibitor), and one group was treated with diethylcarbamazine (a lipoxygenase inhibitor). White blood cell activation as measured by superoxide anion production, and eicosanoid levels were measured both in the gracilis venous effluent and central venous circulation. These results were compared to infarct size in the gracilis muscle. OKY-046 significantly reduced thromboxane production in both the central venous (102 +/- 30 to 31 +/- 9 pg/ml, p less than 0.05) and gracilis samples (107 +/- 22 to 25 +/- 6 pg/ml, p less than 0.005). This was accompanied by a reduced white cell activation in the central venous blood (15 +/- 1 to 10 +/- 1 nmol O2-, p less than 0.05), but did not affect infarct size or white cell activation in the gracilis. Conversely, diethylcarbamazine significantly reduced both white cell activation (16 +/- 1 to 10 +/- 1 nmol O2-, p less than 0.005) and infarct size in the gracilis muscles (61.6% +/- 4.5% to 28.5% +/- 8.6%, p less than 0.01), as well as reduced systemic white blood cell activation.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Intravascular ultrasonography: validation studies and preliminary intraoperative observations.

Intravascular ultrasonography is emerging as an important imaging modality to assess the presence, distribution, and extent of atherosclerotic vascular disease. To determine the accuracy and clinical utility of intravascular ultrasonography, a flexible catheter-based system was used to generate two-dimensional, cross-sectional vascular images. In 23 arteries of 11 sheep 206 in vivo images demonstrated an echo-free lumen surrounded by three distinct concentric acoustic transitions corresponding to intima, media, and adventitia. Ultrasound measurements of lumen diameter and area correlated significantly with those of corresponding arteriographic measurements obtained by use of digital calipers (r = 0.91, r = 0.86). To evaluate clinical feasibility, intraoperative images (n = 160) were obtained in 10 patients undergoing vascular bypass or hemodialysis access procedures. The images depicted luminal configuration and arterial wall morphologic characteristics. Measurements of lumen diameter and lumen area correlated closely with corresponding intraoperative arteriography (r = 0.81, r = 0.79). The ultrasound images demonstrated arterial stenoses, intimal hyperplasia, intraluminal thrombus, polytetrafluoroethylene graft material, and anastomotic sites. We conclude that flexible catheter-based ultrasonography produces images that accurately demonstrate arterial wall architecture, lumen diameter, and area. Intraoperative application can produce images that provide unique information thus expanding the clinical potential of ultrasonography as a guidance system for vascular procedures.

Animals↗
PubMed1991

Endovascular management of arterial intimal defects: an experimental comparison by arteriography, angioscopy, and intravascular ultrasonography.

To determine the feasibility of the endovascular management of intimal defects while comparing the accuracy of arteriography with angioscopy and intravascular ultrasonography, we developed an in vivo model of arterial intimal flaps. In 10 superficial femoral arteries of five anesthetized mongrel dogs, intimal flaps were constructed and then imaged by arteriography, angioscopy, and intravascular ultrasound. A flexible microbiopsy forceps was used to remove each intimal flap under angioscopic guidance. Arteriographic lumen diameters were measured and cross-sectional areas calculated. Corresponding measurements by angioscopy and intravascular ultrasound with reduction in luminal area at the flap were obtained by use of computerized planimetry. Uniplanar arteriography identified 60% (6/10) of the intimal flaps, whereas angioscopy and intravascular ultrasound demonstrated 100%. Lumen diameter (in millimeters) measured by arteriography (3.4 +/- 0.6) correlated significantly with measurements by angioscopy (3.5 +/- 0.5, r = 0.77) and intravascular ultrasound (3.5 +/- 0.6, r = 0.96). Similarly, lumen area (square millimeters) by arteriography (9.2 +/- 2.9) correlated with measurements by angioscopy (8.9 +/- 2.2, r = 0.82) and intravascular ultrasound (8.6 +/- 2.7, r = 0.91). Reduction in lumen area by the flap by angioscopy (37 +/- 7%) and intravascular ultrasound (33 +/- 8%) also correlated significantly (r = 0.72). The intimal flaps were removed successfully in all 10 arteries as confirmed by arteriography, angioscopy, and intravascular ultrasound. We conclude that the endovascular management of intimal defects is possible. Additionally, angioscopy and intravascular ultrasound accurately evaluate lumen diameter and area while providing direct assessment of intimal defects.

Animals↗
PubMed1990

Sustained benefit of temporary limited reperfusion in skeletal muscle following ischemia.

Limiting the rate of reperfusion blood flow following prolonged ischemia in skeletal muscle has been shown beneficial. However, the persistence of this benefit with reinstitution of normal blood flow remains undefined. We investigated the role of temporary limited reperfusion on ischemia-reperfusion injury in an isolated gracilis muscle model in six anesthetized dogs. Both gracilis muscles were subjected to 6 hr of ischemia followed by 2 hr of reperfusion. Reperfusion blood flow was limited for the first hour in one gracilis muscle to its preischemic rate followed by a second hour of normal reperfusion (LR/NR). The contralateral muscle underwent 2 hr of normal reperfusion (NR/NR). Muscle injury was quantified by technetium-99m pyrophosphate (TcPyp) uptake and by histochemical staining using triphenyltetrazolium chloride (TTC) with planimetry of the infarct size. Capillary permeability was evaluated by muscle weight gain. Results are reported as the mean +/- SEM: [table: see text] These data demonstrate a sustained benefit from temporary limited reperfusion. This methodology should be considered in the surgical management of the acutely ischemic limb.

Animals↗