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Impaired red cell deformability in peripheral vascular disease.

By means of a recently developed technique, red-cell deformability was measured in 44 patients with peripheral vascular disease and in 44 age and sex matched normal control subjects. 28 patients had intermittent claudication and 16 rest pain or gangrene. The ability of the red cells to deform was significantly reduced in patients and significantly less in patients with rest pain or gangrene than in those who only had intermittent claudication. A reduction in red-cell deformability by retarding blood-flow through the microcirculation may be an important factor in states of peripheral vascular insufficiency.

Aged↗

The clinical utility of a six-minute walk test in peripheral arterial occlusive disease patients.

OBJECTIVES: To determine the test-retest reliability of the distance covered and the steps taken to complete a 6-minute walk test by peripheral arterial occlusive disease (PAOD) patients with intermittent claudication. To determine the relationship between the total distance and steps covered during the 6-minute walk test and clinical measures of PAOD severity. DESIGN: Cross-sectional design. SETTING: The Claude Pepper Older Americans Independence Center at the University of Maryland at Baltimore. PARTICIPANTS: Sixty-four PAOD patients between the ages of 45 and 88 years (age = 68 +/- 7 years, ankle/brachial index (ABI) = .61 +/- .19) were recruited from the Vascular Clinic at the Baltimore Veterans Affairs Medical Center and from radio and newspaper advertisements. MEASUREMENTS: Patients were assessed on a 6-minute walk test and a treadmill graded exercise test. A second 6-minute walk test was administered approximately 1 week later. Patients also were characterized in regard to blood pressure in the arms and legs, ABI, anthropometry, body composition, and physical activity. RESULTS: The distances walked during the two 6-minute walk tests were similar (350 +/- 78 m vs 360 +/- 73 m), resulting in a high reliability coefficient (R = .94) and a low coefficient of variation (10.4%). The total steps taken during the 6-minute walk test also were similar (562 +/- 113 steps vs 587 +/- 107 steps), resulting in a high reliability coefficient (R = .90) and a low coefficient of variation (11.7%). Furthermore, the 6-minute walking distance correlated with the distances to onset (r = .346, P = .007) and with maximal claudication pain (r = .525, P < .001) during the treadmill test as well as with ABI (r = .552, P < .001). CONCLUSION: The 6-minute walk test yields highly reliable measurements, which are related to the functional and hemodynamic severity of PAOD, in patients with intermittent claudication.

Aged↗

Clopidogrel has no effect on D-dimer and thrombin-antithrombin III levels in patients with peripheral arterial disease undergoing peripheral percutaneous transluminal angioplasty.

OBJECTIVE: Coagulation activation markers are significantly elevated in patients with peripheral arterial disease compared with healthy controls. The more severe the disease, the higher the markers. Increased coagulation activation may contribute to the disease process and the risk of complications in patients with peripheral arterial disease, particularly after endovascular intervention. Animal studies have shown that clopidogrel significantly inhibits coagulation activation. The aim of this study was to determine whether combination of aspirin and clopidogrel affects thrombin-antithrombin III and D-dimer in patients with intermittent claudication undergoing angioplasty, compared with aspirin alone. METHODS: This was a double blind, randomized placebo-controlled trial conducted in a vascular unit in a tertiary referral center. One hundred thirty-two patients with intermittent claudication were randomized to clopidogrel and aspirin or placebo and aspirin, with a loading dose 12 hours before endovascular intervention. D-dimer and thrombin-antithrombin III (TAT) levels were measured using enzyme-linked immunosorbent assay at baseline, 1 hour before, and 1 hour, 24 hours, and 30 days after intervention in 103 patients who underwent endovascular intervention. RESULTS: There was a significant rise in D-dimer levels at 1 hour and 24 hours after angioplasty in both groups (placebo group: 63.69, 141.45, 122.18 ng/mL; clopidogrel group: 103.79, 159.95, 134.69 ng/mL), but no difference between the two groups (P = .514). Similarly there was a significant rise in TAT levels at 1 hour after angioplasty in both groups (placebo group: 2.93, 6.16 microg/L; clopidogrel group: 3.39, 5.27 microg/L), with no significant difference between the two groups (P = .746). CONCLUSION: Endovascular intervention results in a significant increase in TAT and D-dimer. The addition of clopidogrel to aspirin has no effect on TAT and D-dimer before or after endovascular intervention.

Adolescent↗

Pentoxifylline (Trental)--a new drug for the treatment of peripheral chronic occlusive arterial disease.

Pentoxifylline (Trental), a xanthine analog, was evaluated for tolerance, safety and efficacy in the treatment of chronic arterial disease in a pilot study. Evaluation was performed in 35 cases. Twenty patients (Fontaine stage II or stage III severity) were given pentoxifylline in a daily dose of 1200 mg (Trental 400 t.i.d.) and 15 patients were given placebo for a period of eight weeks, respectively. Pentoxifylline was significantly more effective than the placebo in increasing both the initial and absolute claudication distance (ICD and ACD) in patients with peripheral chronic occlusive arterial disease (COAD). The subjective parameters such as paresthesias, muscular cramps and sensation of heaviness in the legs paralled the course of walking parameters. These results support the hypothesis that pentoxifylline in doses of 400 mg (slow release tablets) t.i.d. enhances blood flow via reducing blood viscosity and improving red cell flexibility in patients with intermittent claudication due to COAD. Pentoxifylline is thus regarded as a promising drug for the treatment of circulatory ischemic disorders, especially in intermittent claudication. It was well tolerated with minimal untoward effects.

Administration, Oral↗

Managing PAD with multiple platelet inhibitors: the effect of combination therapy on bleeding time.

PURPOSE: Patients with lower-extremity peripheral arterial disease (PAD) face a high risk of cardiovascular morbidity and mortality. Platelet inhibition (PI) significantly reduces this risk. Combination PI is common and increasingly indicated in patients with PAD; however, the effect on platelet function has not been objectively evaluated. Aspirin (ASA), clopidogrel (Clop), and cilostazol (Cilo) are the three most commonly used PI drugs in patients with PAD. A prospective, sequential evaluation of platelet function using the template bleeding time (BT) was performed for PAD patients taking these medications singly and in combination. METHODS: Twenty-one patients with PAD, averaging 65.9 years of age, were studied. Patients were placed on sequential two-week regimens of the following therapies: washout (no PI), ASA (325 mg daily), ASA + Cilo (100 mg twice daily), washout, Cilo, Cilo + Clop (75 mg each day), washout, Clop, Clop + ASA, and Clop + ASA + Cilo. At the end of each phase, trained personnel measured the BT. RESULTS: Baseline bleeding time for the group was 4.29 +/- 1.69 minutes. ASA (BT = 6.64 +/- 3.52) and Clop (BT = 10.17 +/- 5.4) significantly prolonged bleeding time (P < 0.01); however, no significant effect was observed with Cilo alone (BT = 5.41 +/- 2.69). Combined treatment with ASA + Clop (BT = 17.39 +/- 4.59) had a more pronounced effect on BT compared with either agent alone (P < 0.01). The addition of Cilo to either ASA (BT = 8.3 +/- 4.27) or Clop (BT = 12.7 +/- 7.46) or the combination of ASA + Clop (BT = 17.92 +/- 4.69) did not prolong BT. CONCLUSION: All patients with PAD require platelet inhibition, and many require pharmacotherapy for intermittent claudication. The platelet inhibitors aspirin and clopidogrel are used for the reduction of ischemic events. They significantly prolong bleeding time individually and to a greater extent in combination. Cilo is used to improve walking distance in patients with intermittent claudication. When Cilo is added to ASA, Clop, or the combination of the two, there is no additional increase in bleeding time. Therefore, Cilo can be used in combination with other platelet inhibitors without an additional effect on platelet function as reflected by the bleeding time.

Aged↗

Epidemiology and pathophysiology of lower extremity peripheral arterial disease.

Peripheral arterial disease (PAD), a major cause of disability, loss of work, and lifestyle changes in the United States, is defined as obstruction of blood flow into an arterial tree excluding the intracranial or coronary circulations. PAD is mostly silent in its early stages, but when lesion obstruction exceeds 50%, it may cause intermittent claudication with ambulation. Further disease progression typically leads to rest pain or frank tissue loss. However, some patients may remain asymptomatic with severe disease because of extensive collateralization in the lower extremity. Estimates of the prevalence of intermittent claudication vary by population, from 0.6% to nearly 10%; the rate increases dramatically with age. Approximately 20% to 25% of patients will require revascularization, while fewer than 5% will progress to critical limb ischemia. Limb loss, although rare, is associated with severe disability and an overall poor prognosis, with 30% to 40% mortality in the first 24 months after limb loss. As with coronary artery disease, the most common cause of symptomatic obstruction in the peripheral arterial tree is atherosclerosis, a systemic inflammatory process in which cholesterol-laden plaque builds up in the artery and eventually blocks the lumen. Typical risk factors include age, gender, diabetes, tobacco abuse, hypertension, and hyperlipidemia.

Age Factors↗

[Drug treatment strategies for peripheral obliterative arteriopathy].

Peripheral arterial disease of the lower limbs is a manifestation of atherosclerosis, and may also affect other vascular territories such as the coronary and cerebral arteries. Progressive narrowing of the vessels up to total occlusion can present as intermittent claudication or pain at rest, with or without cutaneous lesions. Patients with intermittent claudication are at a low risk of amputation, and the symptom has to be regarded as a warning signal for myocardial infarction and stroke. Nevertheless, if the patient's walking distance is too limited to allow a near-normal life, symptomatic treatment to improve quality of life should be considered. Treatment may consist of walking exercise, surgical or interventional radiological revascularisation, or, in some cases, administration of vasoactive drugs. Antiplatelet agents should be administered in an attempt to limit disease progression and prevent cardiac and cerebrovascular complications, together with active measures to reduce established risk factors such as smoking, diabetes, hyperlipidaemia, and arterial hypertension. The presence of pain at rest indicates that a lower limb is jeopardised, especially when the criteria for critical ischaemia have also been met. These criteria include the presence of chronic (lasting for more than 2 weeks) symptoms of ischaemia at rest and a systolic blood pressure less than 50 mm Hg or 30 mm Hg at the ankle or big toe, respectively. In such a situation, revascularisation should be attempted whenever possible. If this is not possible or if the procedure has failed, prostacyclin administered intravenously for days or weeks is an alternative. After revascularisation, early reocclusion may be prevented by administering anticoagulants and late reocclusion by antiplatelet agents, in conjunction with eradication of risk factors. In all situations, therapeutic decision-making should be undertaken in a multidisciplinary setting and should include the following: specialists in angiology (an internist) and interventional radiology; a vascular surgeon; an orthopaedic surgeon, if necessary; and diabetes and infectious disease specialists.

Arterial Occlusive Diseases↗

Vitamin E and cardiovascular disease.

Randomized clinical trials of the effects of Vitamin E on complaints of intermittent claudication and angina pectoris are reviewed, and their methodological shortcomings are considered. Mechanisms by which Vitamin E might act in cardiovascular disease are discussed. The evidence about the possible pharmacological actions of Vitamin E supports the need for randomized clinical trials. It is concluded that Vitamin E may have a positive effect, especially in intermittent claudication.

Angina Pectoris↗

[Pharmacotherapeutical action on arteriosclerotic vascular diseases with benzarone (author's transl)].

We report the results of a pilot study to evaluate the therapeutical efficiency of Benzarone in a time span of four weeks in 11 male patients with intermittent claudication. Numerous experimental data indicate that there was a statistically significant increase of painless walking distance and a statistically significant decrease of plasma uric acid, cholesterol and triglycerides. Coagulation analyses furthermore show an increase of the factor VIII activity and the plasminogen levels. For the first time, positive results were shown with Benzarone in patients with intermittent claudication.

Arteriosclerosis↗

Sirolimus for below the knee lesions: mid-term results of SiroBTK study.

OBJECTIVES: To assess the safety and efficacy of sirolimus-eluting stents (SESs) in the treatment of severe intermittent claudication and critical limb ischaemia with "below-the-knee" lesions, unsuitable for surgery. BACKGROUND: Limited published evidence suggests that drug-eluting stents may offer significant improvements in the treatment of infrapopliteal lesions. METHODS: Thirty consecutive patients with either severe intermittent claudication or critical limb ischemia (CLI), category 3-6 of Rutherford classification, and multivessel disease of infrapopliteal arteries (> or = 2 vessels) were treated with SES. Sixty-two arteries were treated with 106 SES. Mean age was 73.9 years, 77% of patients were male and 36% diabetic. The primary endpoint was clinical improvement and healing of ulcers at short term (1 month) and mid term (7.7 months). The secondary endpoint was primary vessel patency rate (angiographic or duplex assessment). All patients received clopidogrel (75 mg daily) or ticlopidine (150 mg daily) for 2 months or longer. RESULTS: Angiographic and procedural success was achieved in all patients. At 7 months (7.7 +/- 5.8), it was necessary to amputate 1 toe in one patient and 1 mid-foot in another. Limb salvage was obtained in 100% of patients. Other events were: two cardiac deaths unrelated to CLI, one stroke with hemiparesia, one initial reperfusion syndrome, one contralateral CLI, and three recurrent homolateral claudication cases. All surviving patients had a mid-term clinical improvement with 97% of primary patency (56 patent arteries on 58 arteries). CONCLUSION: Treatment of "below-the-knee" lesions with SES may provide an alternative treatment for patients with CLI.

Adult↗

Calf muscle adaptation to peripheral vascular disease.

130 muscle biopsies were taken from the gastrocnemius of 82 patients with different degrees of peripheral vascular disease (PVD) and 19 normal controls for histochemical analysis, and 30 patients and 7 controls for biochemical analysis of "aerobic" and "anaerobic" enzymes. The results showed that the gastrocnemius of patients with PVD did not adapt by increasing its "aerobic" potential as previously suggested. Histochemical studies showed that the cross-sectional area of both Type 1 and Type 2 muscle fibres became smaller than those from age-matched controls in the presence of PVD, and in some cases biopsies from both legs confirmed that this trend was greater in those limbs with increasing evidence of PVD. There is also some evidence to suggest a decrease in absolute capillary numbers per muscle fibre. The biochemical assays confirmed decreased levels of aerobic enzymes with increasing evidence of PVD as judged by ankle systolic pressure, and those patients with intermittent claudication showed some evidence of increased anaerobic enzyme levels in comparison to both the normal controls and those with rest pain. Patients with PVD do not adapt to ischaemia/anoxia by increasing their aerobic capability, but show signs of muscle atrophy probably due to reduced mobility. Training regimes may benefit patients with intermittent claudication by reversing these changes.

Adaptation, Physiological↗

Free versus pedicled omental grafts for limb salvage in Buerger's disease.

BACKGROUND: Buerger's disease is a disabling and progressive disease that affects young smokers with a variable and unpredictable course. Free or pedicled omental transfer are the possible modes of management for these patients, and these modes are compared in the present study. METHODS: Of the 43 patients who had Buerger's disease who were treated at the Department of Surgery, Jawahar Lal Nehru (JLN) Hospital, Ajmer, between January 1990 and December 1995, 15 patients underwent application of free omental grafts (group A); 28 patients underwent pedicled omental transplantation (group B). The clinical results obtained with the use of either technique were compared. RESULTS: There were no statistically significant differences in the relief of intermittent claudication (80% vs 82%), rest pain (82% vs 91%), coldness (83% vs 87%), discolouration (80% vs 82%), ulceration (75% vs 78%) and post-amputation ulcer healing (75% vs 86%) in the two groups (P > 0.05); but the time taken for the relief of intermittent claudication, rest pain and coldness was significantly less in group B. Major amputations were not required in both the groups. CONCLUSIONS: These findings suggest that the ultimate clinical benefits obtained with the use of either free or pedicled omental grafts in patients with Buerger's disease are similar, supporting a possible local action of the omentum.

Adult↗

Muscle enzyme adaptation in patients with peripheral arterial insufficiency: spontaneous adaptation, effect of different treatments and consequences on walking performance.

1. The activities of phosphofructokinase (PFK), citrate synthetase (CS), lactate dehydrogenase (LDH), 3-hydroxyacyl-CoA dehydrogenase (ACDH) and cytochrome-c oxidase(Cyt-ox) in the calf muscle tissue were compared in subjects with intermittent claudication (n = 38) and controls (n = 20). The activities of CS, ACDH and Cyt-ox were increased and the activity of Cytox was positively correlated to the maximal walking distance (MWD) in the patients. 2. Thirty-three patients with intermittent claudication were randomized to three treatment groups: (1) operative surgery, (2) operative surgery supplemented with physical training and (3) physical training alone. Before and after 6-12 months of treatment, symptom-free walking distance (SFWD), MWD, ankle-brachial blood pressure quotient (ankle index), maximal plethysmographic calf blood flow (MPBF) and the activities of PFK, CS, LDH, ACDH and Cyt-ox were measured. 3. SFWD and MWD increased in all three groups. Ankle index and MPBF increased in groups 1 and 2, but were unchanged in group 3. The activities of Cyt-ox and CS decreased with operation, but the activity of Cyt-ox was further augmented with training in group 3. Overall, the change in ankle index explained 80-90% of the variability in walking performance. In a separate analysis, the increased activity of Cyt-ox in group 3 was positively correlated to, and explained 31% of the variability in, the improvement in SFWD. 4. These findings indicate that both physical activity and a reduced calf blood flow are necessary conditions for the enzymatic adaptation to take place. A causal relationship between metabolic adaptation in the muscle tissue and walking performance is suggested.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

Cystic adventitial disease of the popliteal artery--a case of young boy.

Cystic adventitial disease (CAD) of the popliteal artery (PA) is rare but one of the well-recognized causes of intermittent claudication. Now more than 200 case reports are available in the world, but there are only 6 cases younger than 15 years old. In this paper, we report a case of 14-year-old boy with CAD of the PA found by intermittent claudication. On examination, the pulses were not palpable below the right popliteal artery, and the angiography demonstrated about 1.5 cm-long obstruction of the right PA. We operated a resection of a cyst with artery, and replaced the autovein graft (V. saphena magna). Cyst contained mucoid degeneration-like ganglion. Two weeks after operation, the angiography showed no stenotic lesion, and follow-up at 4 years showed no symptoms.

Adolescent↗

The inflammatory response to upper and lower limb exercise and the effects of exercise training in patients with claudication.

PURPOSE: We have previously shown that a program of upper limb exercise training can induce significant improvements in walking distance in patients with claudication. This study assessed whether upper limb exercise avoids the systemic inflammatory responses associated with lower limb exercise and also whether the inflammatory response to acute lower limb exertion is modified by a program of supervised exercise training. METHODS: Fifty-two patients with stable intermittent claudication were randomized into two groups who underwent 6 weeks of supervised upper (n = 26) or lower (n = 26) limb cardiorespiratory exercise training. A parallel control group (n = 15) was provided with lifestyle advice only. Neutrophil activation markers (CD11b and CD66b) and plasma levels of von Willebrand factor (marker of endothelial damage) in response to an acute bout of sustained upper and lower limb exercise were assessed before and after the period of training. Plasma levels of soluble E-selectin (marker of endothelial activation) were also determined before and after the training period. RESULTS: An acute bout of sustained lower limb exercise significantly increased the intensity of CD11b and CD66b expression by peripheral blood neutrophils in all groups, whereas upper limb exercise had no effect. Resting neutrophil expression of CD11b and CD66b and circulating von Willebrand factor levels were unaffected by the training program, as were the inflammatory responses to an acute bout of sustained upper and lower limb muscular work, despite the fact that both training programs significantly increased walking distances. CONCLUSIONS: These findings indicate that upper limb exercise training programs may offer certain advantages over currently prescribed lower limb programs. Our results show that exercising nonischemic muscles in a way that promotes improved cardiorespiratory function and walking capacity can avoid the potentially deleterious systemic inflammatory responses associated with lower limb exertion in patients with stable intermittent claudication.

Adult↗

[Clinical aspects of the narrow spinal canal].

Not infrequently the lumbosacral root-compression syndrome is due to stenosis of the lumbal spinal canal. The clinical symptoms, usually emerging in the middle-aged, may be characterized by either simple radicular pain with or without neurological deficit or by exercise-dependent transient functional disturbance of the cauda equina, namely, the so-called neurogenic intermittent claudication (NIC). In most cases, NIC is due to mechanical compression of the cauda fibers as a result of extension of the patient's lumbar spine. In some patients, exercise-induced ischemic radiculopathy is assumed to be the main factor. Differential diagnosis must take into account true intermittent claudication, certain rare myopathies (if the exercise-dependent pain is the main feature), and certain transient disturbances in spinal cord function (if a motor and/or sensory deficit arises during the NIC attack).

Cauda Equina↗

[Peripheral arterial occlusive disease. Symptoms, basic diagnosis and staged therapy].

Intermittent claudication or rest pain are typical symptoms of peripheral arterial occlusive disease (PAOD) affecting the lower limbs. The pain is localized one level below that of the occlusion. Initial investigations should determine skin temperature and color, pulse status, stenotic sounds and Doppler occlusive pressures. If intermittent claudication is present, angiography of the pelvis and legs then follows. Treatment is stage-dependent: while in stages I and IIa conservative treatment such as cessation of smoking, administration of acetylsalicylic acid and walking training suffices, stages IIb and higher require invasive measures extending from PTA to amputation of gangrenous parts of the limb.

Amputation, Surgical↗

[Validation of a French translation of the Edinburgh claudication questionnaire among general practitioners' patients].

OBJECTIVES: Intermittent claudication is one of the clinical symptoms of peripheral arterial disease (PAD). The presence of PAD is a high risk marker of cardiac events and stroke. The PAD screening can be enhanced by the use of questionnaires. The Edinburgh Questionnaire presents in its English version better diagnostic performances compared to the Rose (WHO) Questionnaire. The aim of this study is to precise the performances of the French version of the Edinburgh Questionnaire among a population consulting general practitioners. METHODS: Four centers instructed 10 general practitioners each to the measurement of ankle pressure with a Doppler stethoscope. The physicians administrated the Questionnaire to 10 consecutive consultants in a same day, and measured the pressure on posterior tibial, dorsalis pedis and humeral arteries. With a second questionnaire they collected data concerning age, weight, height, and the presence of major risk factors. The same protocol was repeated a second day on new patients. The diagnosis of PAD was based on an ankle-arm index lower than 0.85 for at least on limb. RESULTS: The population studied consisted of 727 subjects (351 females and 376 males). The mean age was at 58.3 +/- 16.1 years (ranging from 18 to 83.3 years). The sensitivity of the Questionnaire is at 47% (95% CI: 32.3-61.7%), the specificity at 98.8% (95% CI: 97.5-99.4%), the positive and negative predictive values are respectively at 73.3% (95% CI: 54.1-87.7%) and 94.8% (95% CI: 94.7-97.6%). Among this population of general practitioners consultants, the prevalence of a low ankle-arm index under 0.85 is at 6.7%. DISCUSSION: The French version of the Edinburgh Questionnaire maintains the very good specificity of the English version. The lower sensitivity could be explained by the choice of the gold standard, namely the ankle-arm index which includes asymptomatic patients with authentic PAD. The use of this Questionnaire can be recommended for the screening of this disease as well as in epidemiological studies.

Adolescent↗