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R W Hobson

Publications and source records attributed to R W Hobson.

At least 73 records · Page 4Linked to original sources
PubMed1995

Diminished mononuclear cell function is associated with chronic venous insufficiency.

PURPOSE: With clinical progression of chronic venous insufficiency (CVI), dermal infiltration of mononuclear cells increases. Because these cells regulate chronic inflammatory responses and modulate wound healing, cellular dysfunction could explain alterations in wound healing with CVI. The purpose of this study was to determine whether monocytes in patients with CVI are dysfunctional. METHODS: Mononuclear cell function was measured as the degree of proliferation in response to a mitogenic challenge. Fifty patients were separated into four groups: group 1, 14 patients with normal limbs; group 2, 10 patients with class 2 CVI; group 3, 15 patients with active venous ulcers; group 4, 11 patients with healed venous ulcers and current evidence of lipodermatosclerosis. Duplex scanning and air plethysmography correlated with the clinical classification of CVI. Systemically circulating monocytes and lymphocytes were obtained by antecubital venipuncture from groups 1 to 4. Cells were cultured in the presence of staphylococcal enterotoxins A, B, C1, D, and E (mitogens) at 1, 8, 31, and 125 micrograms/well on the basis of previous dose-response experiments. Phytohemagglutinin (PHA), 5 micrograms/well, served as a control mitogen. The dose-response curves indicated that 8 micrograms/well elicited the greatest degree of cell proliferation. Proliferative responses at 8 micrograms/well were analyzed for statistical significance among groups 1 to 4. Comparisons among groups were performed by use of the nonparametric Mann Whitney U post tests and a one-tailed unpaired t test. Results were considered significant at p < or = 0.05. RESULTS: Proliferative responses to PHA indicate that lymphocytes and monocytes from patients with CVI are not globally depressed. However, patients in group 2 did not exhibit the same degree of proliferation to PHA as did groups 1, 3 and 4. Proliferative responses between groups 2 and 1 (44.38 +/- 43.9 vs 118.87 +/- 27.1, p < or = 0.05) and groups 2 and 3 (44.38 +/- 43.9 vs 105.95 +/- 60.99, p < or = 0.05) were significant. Challenges with staphylococcal enterotoxin A and B reveal significant diminution of proliferative responses in groups 2 (42.73 +/- 11.55, p < or = 0.05) and 3 (45.57 +/- 9.1, p < or = 0.05) and groups 3 (36.81 +/- 6.9, p < or = 0.05) and 4 (35.04 +/- 7.5, p < or = 0.05), compared with staphylococcal enterotoxin A controls (68.68 +/- 9.9) and staphylococcal enterotoxin B controls (66.25 +/- 13.56), respectively. A trend of diminished mononuclear cell function with progression of CVI was observed with staphylococcal enterotoxins B, C1, D, and E, strongly suggesting biologic significance. Furthermore, patients with lipodermatosclerosis uniformly exhibited the poorest proliferative responses. CONCLUSIONS: Deterioration of mononuclear cell function is associated with CVI. A trend of diminishing proliferative responses with clinical disease progression is observed and suggests biologic significance. The decreased capacity for mononuclear cell proliferation in response to various challenges may manifest itself clinically as poor and prolonged wound healing.

Aged↗
PubMed1995

Inhibition of nitric oxide synthase attenuates primed microvascular permeability in the in vivo microcirculation.

PURPOSE: Changes in microvascular permeability play a critical role in the inflammatory sequence of tissue injury leading to leakage of proteins and subsequent edema. Primed responses induced by topical applications of platelet-activating factor (PAF) and histamine greatly increase microvascular permeability and mimic inflammation. We assessed the role of nitric oxide (NO) by use of 1-NG-monomethyl arginine (1-NMMA, a NO synthase inhibitor), on the primed microvascular permeability. We also explored the role of mast cells and a leukocyte adhesion complex by use of cromolyn sodium and 1B6 (a monoclonal antibody), respectively. METHODS: Forty anesthetized hamsters were separated into five groups: group 1 (n = 5) received no intervention; group 2 (n = 5) received topical 10(-9) mol/L PAF and 10(-6) mol/L histamine at a 5-minute interval; group 3 (n = 5 at each dose) received PAF/histamine and 1-NMMA (at 10(-5) mol/L or 10(-6) mol/L); group 4 (n = 5 at each dose) received cromolyn sodium plus PAF/histamine; group 5 (n = 5) received 1B6 plus PAF/histamine. We examined the cheek pouch with intravital videomicroscopy under fluorescent epiillumination. We quantified microvascular permeability to fluorescein isothiocyanate-dextran 150 with computer-assisted images analysis on the basis of integrated optical intensity (IOI) measurements. RESULTS: The mean (+/- SEM) IOI of the control group was 8.7 +/- 5.2, whereas the group primed with PAF and histamine was 62.4 +/- 10.8. The 1-NMMA (10(-5) mol/L and 10(-6) mol/L) abolished the changes in microvascular permeability (p < 0.05) yielding IOI values of 8.0 +/- 1.6 and 10.9 +/- 2.8, respectively. Cromolyn sodium and 1B6 did not significantly attenuate the primed response to PAF and histamine. CONCLUSION: Inhibition of NO synthase attenuates primed macromolecular extravasation in vivo. Our results indicate that NO is involved in the primed reaction of PAF and histamine, causing increases in microvascular permeability. Our study suggests a role for NO in the microcirculatory changes observed in ischemia-reperfusion injury and shock.

Animals↗
PubMed1995

L-type calcium channel blockers modulate the microvascular hyperpermeability induced by platelet-activating factor in vivo.

PURPOSE: Platelet-activating factor (PAF) is a potent phospholipid mediator of the microvascular dysfunction associated with ischemia-reperfusion injury. Because changes in cytosolic-free Ca2+ concentration are essential in PAF cellular signaling, we formulated the hypothesis that blockade of Ca2+ entry may inhibit the PAF-induced microvascular dysfunction. METHODS: To investigate this hypothesis two L-type calcium channel blockers, verapamil and nifedipine, were applied to the hamster cheek pouch before the topical PAF challenge was undertaken. Permeability was assessed by measurement of the plasma clearance of fluorescein isothiocyanate dextran, 150,000 mol wt. The arteriolar diameter was measured simultaneously to evaluate the effects of L-type calcium channel blockers on PAF-induced vasoconstriction. RESULTS: Baseline clearance was 498.7 +/- 225.0 nl/60 min/gm (mean +/- SE). PAF at 10(-8) mol/L (n = 5) increased clearance to 3753.8 +/- 572.8 nl/60 min/gm (p < 0.01). Pretreatment with verapamil (2 mg/kg; n = 5) significantly reduced the increase in permeability caused by 10(-8) mol/L PAF (1909.1 +/- 620.2 nl/60 min/gm; p < 0.05). Nifedipine (5-10(-6) mol/L; n = 5) also significantly attenuated the impact of 10(-8) mol/L PAF (2037.2 +/- 427.5 nl/60 min/gm; p < 0.05). Neither verapamil nor nifedipine affected PAF-induced vasoconstriction. CONCLUSION: The significant inhibition of the increase in permeability by the L-type calcium channel blockers suggests that these compounds may be useful in the management of PAF-induced hyperpermeability.

Animals↗
PubMed1995

Guidelines for carotid endarterectomy. A multidisciplinary consensus statement from the ad hoc Committee, American Heart Association.

BACKGROUND AND PURPOSE: Indications for carotid endarterectomy have engendered considerable debate among experts and have resulted in publication of retrospective reviews, natural history studies, audits of community practice, position papers, expert opinion statements, and finally prospective randomized trials. The American Heart Association assembled a group of experts in a multidisciplinary consensus conference to develop this statement. METHODS: A conference was held July 16-18, 1993, in Park City, Utah, that included recognized experts in neurology, neurosurgery, vascular surgery, and healthcare planning. A program of critical topics was developed, and each expert presented a talk and provided the chairman with a summary statement. From these summary statements a document was developed and edited onsite to achieve consensus before final revision. RESULTS: The first section of this document reviews the natural history, methods of patient evaluation, options for medical management, results of surgical management, data from position statements, and results to date of prospective randomized trials for symptomatic and asymptomatic patients with carotid artery disease. The second section divides 96 potential indications for carotid endarterectomy, based on surgical risk, into four categories: (1) Proven: This is the strongest indication for carotid endarterectomy; data are supported by results of prospective contemporary randomized trials. (2) Acceptable but not proven: a good indication for operation; supported by promising but not scientifically certain data. (3) Uncertain: Data are insufficient to define the risk/benefit ratio. (4) Proven inappropriate: Current data are adequate to show that the risk of surgery outweighs any benefit. CONCLUSIONS: Indications for carotid endarterectomy in symptomatic good-risk patients with a surgeon whose surgical morbidity and mortality rate is less than 6% are as follows. (1) Proven: one or more TIAs in the past 6 months and carotid stenosis > or = 70% or mild stroke within 6 months and a carotid stenosis > or = 70%; (2) acceptable but not proven: TIAs within the past 6 months and a stenosis 50% to 69%, progressive stroke and a stenosis > or = 70%, mild or moderate stroke in the past 6 months and a stenosis 50% to 69%, or carotid endarterectomy ipsilateral to TIAs and a stenosis > or = 70% combined with required coronary artery bypass grafting; (3) uncertain: TIAs with a stenosis < 50%, mild stroke and stenosis < 50%, TIAs with a stenosis < 70% combined with coronary artery bypass grafting, or symptomatic, acute carotid thrombosis; (4) proven inappropriate: moderate stroke with stenosis < 50%, not on aspirin; single TIA, < 50% stenosis, not on aspirin; high-risk patient with multiple TIAs, not on aspirin, stenosis < 50%; high-risk patient, mild or moderate stroke, stenosis < 50%, not on aspirin; global ischemic symptoms with stenosis < 50%; acute dissection, asymptomatic on heparin. Indications for carotid endarterectomy in asymptomatic good-risk patients performed by a surgeon whose surgical morbidity and mortality rate is less than 3% are as follows. (1) Proven: none. (As this statement went to press, the National Institute of Neurological Disorders and Stroke issued a clinical advisory stating that the Institute has halted the Asymptomatic Carotid Atherosclerosis Study (ACAS) because of a clear benefit in favor of surgery for patients with carotid stenosis > or = 60% as measured by diameter reduction. When the ACAS report is published, this indication will be recategorized as proven. (2) acceptable but not proven: stenosis > 75% by linear diameter; (3) uncertain; stenosis > 75% in a high-risk patient/surgeon (surgical morbidity and mortality rate > 3%), combined carotid/coronary operations, or ulcerative lesions without hemodynamically significant stenosis; (4) proven inappropriate: operations with a combined stroke morbidity and mortality > 5%.

Aspirin↗
PubMed1994

The significance of calf muscle pump function in venous ulceration.

PURPOSE: Patients with clinically evident chronic venous insufficiency were evaluated to relate the degree of insufficiency and calf muscle pump dysfunction to venous ulceration. METHODS: Sixty-nine limbs in 55 patients with chronic venous insufficiency by Society for Vascular Surgery/International Society for Cardiovascular Surgery Classification were compared in three groups: classes 1 and 2 with no history of ulceration (19 limbs); class 3 with healed ulceration (20 limbs); and class 3 with active ulcers (30 limbs). Air plethysmography measurements of outflow fraction, venous volume, venous filling time, venous filling index, ejection fraction, ejection volume, residual volume fraction, and residual volume were made. In 62 of the 69 limbs, color-flow duplex ultrasonography was used to determine the pattern of reflux. RESULTS: The outflow fraction was normal in 84%, 75%, and 77% of nonulcerated, healed, and ulcerated limbs. The venous filling index was abnormal in most limbs (nonulcerated 95%, healed 90%, ulcerated 98%) but not significantly different among groups. Differences in calf muscle pump function were significant. Ulcerated limbs had significantly poorer ejection fractions (p = 0.0002) and greater residual volume fractions (p = 0.0006) than nonulcerated or healed limbs. By ultrasonography, deep and superficial vein incompetence was present in most limbs and was not statistically different among groups. Although venous insufficiency was not measurably different among groups, limbs with active venous ulcers had significantly poorer calf muscle pump function than those with healed ulcers or with no history of ulceration. CONCLUSION: Venous insufficiency is necessary but not sufficient to cause ulceration, and a deficiency of the calf muscle pump is significant to the severity of venous ulceration.

Adult↗
PubMed1994

Platelet-activating factor modulates microvascular transport by stimulation of protein kinase C.

To investigate the possible involvement of protein kinase C (PKC) in platelet-activating factor (PAF)-stimulated microvascular responses, PKC inhibitors, sphingosine (SPH), 1-(5-isoquino-linylsulfonyl)-3-methylpiperazine (iso H-7), and calphostin C, were applied topically to the hamster cheek pouch, and PAF-elicited changes in microvascular permselectivity and arteriolar constriction were evaluated. Pretreatment with 10(-6) M SPH, 10(-5) M SPH, or 10(-10) M iso H-7 significantly reduced 10(-7) M PAF-induced increase in fluorescein isothiocyanate-Dextran 150 clearance (2,677.3 +/- 397.3, 2,985.3 +/- 350.7, and 2,689.3 +/- 256.0 vs. 4,784.0 +/- 474.7 nl.60 min-1.g-1, respectively). Calphostin C at 10(-7) M attenuated 10(-8) M PAF-induced increase in clearance (2,156.9 +/- 353.3 vs. 3,841.6 +/- 260.9 nl.60 min-1.g-1). Permeability changes were also measured by integrated optical intensity (IOI). Pretreatment with 10(-6) M SPH, 10(-5) M SPH, or 10(-10) M iso H-7 attenuated the maximal increment in IOI induced by 10(-7) M PAF (2,024.0 +/- 364.4, 1,690.0 +/- 525.2, and 2,432.8 +/- 655.3 vs. 4,255.9 +/- 695.6 U, respectively). Direct stimulation of PKC by phorbol dibutyrate increased clearance in dose-dependent fashion. Similarly, activation of PKC with phorbol myristate acetate increased IOI values. The PAF-induced arteriolar constriction was not blocked by the PKC inhibitors. Our results suggest that PKC represents a biochemical pathway involved in the PAF modulation of microvascular permeability but not of arteriolar constriction.

Animals↗
PubMed1994

Cardiac prognosis of patients with carotid stenosis and no history of coronary artery disease. Veterans Affairs Cooperative Study Group 167.

BACKGROUND AND PURPOSE: Patients with carotid stenosis have a high frequency of asymptomatic coronary artery disease (CAD). The purpose of this study of patients with asymptomatic carotid stenosis was to test the hypothesis that patients without a history of CAD have the same cardiac prognosis as patients with a history of CAD. METHODS: Men enrolled in the Department of Veterans Affairs study on the efficacy of carotid endarterectomy for asymptomatic carotid stenosis underwent a baseline cardiac evaluation (history, physical examination, and electrocardiogram) to document previous angina or myocardial infarction. Patients were randomized to medical therapy alone or medical therapy and carotid endarterectomy. Medical therapy consisted of aspirin 650 mg twice daily and treatment of risk factors. All episodes of angina, myocardial infarction, or sudden death during follow-up (average of 47.9 months) were recorded. RESULTS: Of 444 men enrolled in the study, 200 (45%) had a history of CAD. During the study 86 (43%) of 200 patients with CAD and 81 (33%) of 244 patients without a history of CAD had cardiac ischemic events (P = .03). In patients without a history of CAD, the first cardiac event was myocardial infarction or sudden death in 45 patients (56%). Factors that were independently associated with cardiac events in patients without a history of CAD were diabetes (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.15 to 3.97), intracranial occlusive disease (OR, 2.13; 95% CI, 1.13 to 4.02), and peripheral vascular disease (OR, 2.04; 95% CI, 1.14 to 3.66). Forty-two percent of patients with two of these factors and 69% of patients with all three factors had cardiac events. CONCLUSIONS: Men with carotid stenosis and no history of CAD have a lower rate of cardiac events than men with carotid stenosis who have a history of CAD. However, a subgroup of patients with carotid stenosis and no history of CAD who have coexistent intracranial occlusive disease, diabetes, or peripheral vascular disease have a risk of cardiac events similar to that of patients with a history of CAD.

Aged↗
PubMed1994

Randomized clinical trial results define operative indications in symptomatic and asymptomatic carotid endarterectomy patients.

Randomized clinical trials on the efficacy of carotid endarterectomy have assisted in the selection of patients for operative intervention. Three such trials involving symptomatic carotid stenosis have confirmed the value of endarterectomy in patients with stenoses 70% or greater. Patients with recent transient ischemic attack or nondisabling stroke should be referred for noninvasive testing. If the patient's stenosis exceeds a threshold level (50% to 70% diameter-reducing lesion), arteriography should be performed and prompt endarterectomy scheduled, rather than antiplatelet therapy, as the primary means of treatment. Furthermore, the results of one clinical trial on asymptomatic stenosis have demonstrated benefits for operative intervention in reducing neurologic events (transient ischemic attack plus stroke). These data require additional confirmation in the analysis of stroke alone, which should be available within the next year from another clinical trial. These trials help to define indications for operation, and the thorough knowledge of their results has become essential to our practices.

Carotid Stenosis↗
PubMed1994

4. Current status of operative treatment for asymptomatic carotid stenosis.

OBJECTIVE: To determine the natural history of asymptomatic carotid stenosis and the effect of prophylactic carotid surgery on neurologic morbidity and mortality. DESIGN: A prospective, randomized, cooperative study, with a mean follow-up of 47.9 months. SETTING: Ten Veterans Administration hospitals across the United States. PATIENTS: The study comprised 436 patients who were divided into two groups: group 1, patients with symptomatic unilateral carotid disease, who were treated with carotid endarterectomy, and had contralateral asymptomatic stenosis; group 2, patients with significant asymptomatic carotid disease. Carotid stenosis was confirmed by arteriography, which demonstrated at least 50% stenosis, measured by comparing the least transverse diameter of the stenosis on lateral arteriography. INTERVENTIONS: Ocular plethysmography, duplex scanning and arteriography; carotid endarterectomy and acetylsalicylic acid or acetylsalicylic acid alone. RESULTS: The 436 patients were randomized between nonoperative (medical) (233) and operative (surgical) (211 procedures on 203 patients) groups. In the surgical group, the 30-day mortality was 1.9% and the permanent neurologic morbidity was 2.4%, for a combined stroke and death rate of 4.3%. The incidence of neurologic events was 8% in the surgical group compared with 20.6% in the medical group, for an absolute reduction in risk of 12.6% (p < 0.001). CONCLUSION: Carotid endarterectomy, combined with optional medical management, can reduce the incidence of ipsilateral neurologic events in high-risk men with arteriographically confirmed asymptomatic carotid stenosis.

Aspirin↗
PubMed1993

Efficacy of carotid endarterectomy for asymptomatic carotid stenosis. The Veterans Affairs Cooperative Study Group.

BACKGROUND: The efficacy of carotid endarterectomy in patients with asymptomatic carotid stenosis has not been confirmed in randomized clinical trials, despite the widespread use of operative intervention in such patients. METHODS: We conducted a multicenter clinical trial at 11 Veterans Affairs medical centers to determine the effect of carotid endarterectomy on the combined incidence of transient ischemic attack, transient monocular blindness, and stroke. We studied 444 men with asymptomatic carotid stenosis shown arteriographically to reduce the diameter of the arterial lumen by 50 percent or more. The patients were randomly assigned to optimal medical treatment including antiplatelet medication (aspirin) plus carotid endarterectomy (the surgical group; 211 patients) or optimal medical treatment alone (the medical group; 233 patients). All the patients at each center were followed independently by a vascular surgeon and a neurologist for a mean of 47.9 months. RESULTS: The combined incidence of ipsilateral neurologic events was 8.0 percent in the surgical group and 20.6 percent in the medical group (P < 0.001), giving a relative risk (for the surgical group vs. the medical group) of 0.38 (95 percent confidence interval, 0.22 to 0.67). The incidence of ipsilateral stroke alone was 4.7 percent in the surgical group and 9.4 percent in the medical group. An analysis of stroke and death combined within the first 30 postoperative days showed no significant differences. Nor were there significant differences between groups in an analysis of all strokes and deaths (surgical, 41.2 percent; medical, 44.2 percent; relative risk, 0.92; 95 percent confidence interval, 0.69 to 1.22). Overall mortality, including postoperative deaths, was primarily due to coronary atherosclerosis. CONCLUSIONS: Carotid endarterectomy reduced the overall incidence of ipsilateral neurologic events in a selected group of male patients with asymptomatic carotid stenosis. We did not find a significant influence of carotid endarterectomy on the combined incidence of stroke and death, but because of the size of our sample, a modest effect could not be excluded.

Adult↗
PubMed1993

Refinements in the ultrasonic detection of popliteal vein reflux.

Color-flow and duplex ultrasonography were used to determine the optimal method for documenting venous valvular reflux. Popliteal veins were examined in 10 normal limbs and 11 limbs with clinical evidence of chronic venous insufficiency (CVI). Peak reflux velocity (spectral) and duration of reflux (spectral and color) were measured with the patient in supine and standing positions, with manual and pneumatic compression applied sequentially to thigh and calf. Manual and pneumatic compression produced equivalent reflux velocity and duration. In normal limbs peak reflux velocity was always less than 22 cm/sec, with a mean reverse flow duration of 0.3 sec +/- 0.03 (SEM). In limbs with CVI, reflux velocity varied widely among protocols. Reflux duration and velocity were greater in the supine position than in the standing position for both normal limbs and limbs with CVI (p < 0.04). Duration was significantly increased for thigh versus calf compression in normal limbs (p < 0.001) but decreased in limbs with CVI (p < 0.003). Methods that used thigh compression or supine position were less capable of discriminating normal limbs from limbs with CVI. Standing calf compression provided the greatest rates of sensitivity (91%), specificity (100%), and accuracy (95%). Compared with spectral Doppler scanning, color-flow ultrasonography produced a consistently shorter reflux duration (p < 0.001). In limbs with CVI with a mean spectral duration of 2.5 sec +/- 0.2 (SEM), mean color Doppler duration was 0.7 sec shorter. Our results demonstrate that popliteal vein incompetence is identified optimally by reflux duration after standing calf compression; adequate manual compression is sufficient to identify reflux; color-flow Doppler ultrasonography may underestimate reflux duration.

Adult↗