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Improvement of walking distance in patients with intermittent claudication by chronic local therapy with isosorbide dinitrate ointment.

Isosorbide dinitrate ointment (100 mg tid) was directly applied to 30 male patients with stable, documented intermittent claudication on the areas where ischemic pain was experienced. The symptom-free distance walked (DWA) and the maximum distance reached (MDR) basally, after one, three, six, and twelve months were evaluated by means of treadmill stress tests (TSTs) (angle 0 degree-velocity constant/patient). After the basal TST, patients were randomly divided into two groups: placebo group and therapy group (double blind), and a further TST was administered one month later. DWA results were 74 +/- 8 m vs 297 +/- 83 m and MDR results were 163 +/- 22 m vs 506 +/- 86 m in the therapy group (basal vs one month TST: p less than .01) and 94 +/- 24 m vs 96 +/- 15 m and 232 +/- 53 m vs 183 +/- 26 m in the placebo group, respectively (basal vs one month TST: NS). Being confident that a significant placebo effect was absent, the authors opened the trial and treated all patients, repeating further TSTs at three, six, and twelve months. The following results were obtained: DWA was 84 +/- 13 m, 316 +/- 63 m, 374 +/- 55 m, and 452 +/- 61 m; and MDR was 197 +/- 29 m, 431 +/- 59 m, 514 +/- 57 m, and 547 +/- 59 m, respectively, in basal conditions and after three, six, and twelve months of treatment (p less than .01 for all the values for both DWA and MDR vs basal values).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

Capillary supply and muscle fibre types in patients with intermittent claudication: relationships between morphology and metabolism.

There have been previous reports on an increased oxidative capacity in muscle tissue from the diseased legs of patients with intermittent claudication. The present study was designed to correlate metabolic and morphological data and to investigate whether the metabolic adaptive changes in muscle tissue of claudicating legs were also reflected in morphological variables such as capillary supply, fibre type distribution, and fibre area. The activity of cytochrome-c-oxidase in gastrocnemius muscle was determined and the insulin and glucose uptakes were measured across the leg in the basal state and 10 min following intravenous administration of 25 g glucose. The finding of a reduced relative number of Type II B fibres and a reduced ratio Type II B/II A fibre area, as well as an increased capillary supply to Type II A, indicated that the most extensive morphologic changes in muscle tissue of claudicating legs had occurred in Type II fibres. The increased number of capillaries in contact with Type II A fibres in muscle tissue from claudicating legs, compared with muscle tissue from control legs, suggested that the most apparent metabolic changes occurred in this fibre type in the adaptation process of these patients. The more pronounced morphologic and metabolic changes in Type II fibres suggest that these fibres are more intensely activated than Type I fibres during physical activity in claudicating legs. The insulin uptake correlated positively with the number of capillaries per fibre, suggesting that the endothelial surface area is one of the determining factors for insulin uptake. The percentage of Type II B fibres reflected to a certain extent the metabolic adaptation in muscle tissue.

Aged↗

[Intermittent venous claudication].

Intermittent venous claudication develops mostly in young patients after iliac vein thrombosis and subsides promptly in the recumbent position. Plethysmographic assessment of calf volume during treadmill work permits objective diagnosis of the phenomenon remaining frequently unrecognized.

Adult↗

The effect of naftidrofuryl (Praxilene) on intermittent claudication.

In a randomized double-blind controlled trial the effect of naftidrofuryl (Praxilene) 200 mg t.d.s., taken for 6 months, was compared with placebo in intermittent claudication. Whilst there was a significant subjective improvement regardless of age or treatment, patients over 60 on naftidrofuryl experienced a more rapid symptomatic relief than other patients. At six months this age group showed a significant improvement over the placebo group. There was no significnat objective evidence of improvement.

Aged↗

Intermittent claudication and limb-threatening ischemia in systemic lupus erythematosus and in SLE-like disease: a report of two cases and review of the literature.

Intermittent claudication and limb-threatening ischemia caused by occlusion of large and medium-sized arteries are rare manifestations of systemic lupus erythematosus. So far only eight documented cases have been reported, predominantly in young women. In this report two more patients are described. There is no common opinion concerning pathophysiologic mechanism, but immunologic endothelial damage and circulating antibodies to phospholipid probably play a role. The results of medical and surgical treatment are disappointing, and amputation becomes necessary in more than half of the patients.

Adult↗

Controlled trial of propranolol in intermittent claudication.

Seven patients (5 with arteriosclerosis obliterans and 2 with Buerger's disease) completed a two-phase double-blind crossover trial of propranolol in intermittent claudication. Performance was measured on a moving treadmill. In the initial phase, the patients were hospitalized in order to determine an "effective" dose of propranolol. Improvement was noted in all: after 1,600 mg in 5 and after 240 mg and 600 mg in the others. The controlled phase was carried out on an outpatient basis over 8 weeks, the patients receiving propranolol and placebo in a random manner, each for two 2-week periods. Comparison of matched periods of drug and placebo revealed no advantage for propranolol. Patients' performances deteriorated with time. None of the patients evidenced deterioration of occlusive peripheral arterial disease that could be attributed to propranolol, in spite of the high doses used.

Adult↗

Exercise training for intermittent claudication: does it adversely affect biochemical markers of the exercise-induced inflammatory response?

OBJECTIVES: To identify a stable biochemical marker of disease severity in patients with intermittent claudication and to use these findings to assess the effect of therapeutic exercise training. DESIGN: Case-control study: prospective randomised-controlled trial of exercise training. MATERIALS AND METHODS: Plasma fibrinogen, serum amyloid A protein (SAA), C-reactive protein (CRP) and urinary albumin-creatinine ratio (ACR) were measured in 67 claudicants and 15 controls. Twenty-two patients were randomised to supervised exercise training and 17 randomised to observation. Subjects were reviewed at 3, 6 and 12 months. RESULTS: The median (interquartile range) baseline fibrinogen was 3.7 g/l (3.3-4.25) in claudicants and 3.5 g/l (2.9-3.95) in controls (p = 0.045); CRP was 4.7 mg/l (2.2-9.0) and 2.1 mg/l (1.0-2.8), respectively (p < 0.0001); SAA was 72 mg/l (35-132) and 30 mg/l (20-89) (p = 0.0009). Claudicants showed an increased urinary ACR following treadmill exercise (Wilcoxon, p < 0.0001) with no change in controls. Exercise training reduced SAA at 6 months, CRP at 3 months and progressively attenuated the post-exercise increase in ACR. No similar changes were found in controls. CONCLUSIONS: Repetitive low-grade inflammatory events in claudicants lead to elevation of serum acute-phase proteins. Exercise training is associated with symptomatic improvement and reduction inflammatory markers. The concern that exercise has adverse systemic effects therefore seems to be unjustified.

Aged↗

Performance of patients with intermittent claudication undergoing physical training, with or without an aggravation of arterial disease: retrospective cohort study.

PURPOSE: This was a retrospective cohort study aiming to investigate the clinical outcome of patients with intermittent claudication undergoing physical training in whom there was an aggravation of the arterial disease. METHOD: Three hundred and sixty-four patients with claudication who presented with femoropopliteal or tibioperoneal obstructions in at least 1 of the lower limbs and who did not have aortic or bilateral iliac obstructions were included. Forty patients developed new stenoses in previously spared arterial segments (confirmed by duplex scanning), which were proximal to preexisting lesions, and formed the progression group, in contrast to the stable group of patients (n = 324) who did not exhibit this worsening of the disease. Follow-up was 276 and 277 days for stable and progression groups, respectively. All patients underwent an unsupervised program of submaximal walking 4 days a week. Changes in maximal walking distance at a progressive treadmill test were appraised during follow-up, with special interest directed to the periods between admission, diagnosis of arterial worsening, and the end of follow-up. RESULTS: Performance was not significantly different between groups during the entire follow-up period. Furthermore, patients with claudication who evolved with progression of their arteriopathy did not present a reduction of their maximal walking distance in response to the development of new arterial lesions at any time during their follow-up. CONCLUSION: Worsening of the peripheral arterial disease in patients with claudication undergoing physical training, manifested as de novo arterial occlusion in proximal and previously spared segments, does not imply in an impairment of their claudication distance.

Aged↗

Intermittent claudication due to ischaemia of the lumbosacral plexus.

The distinct clinical syndrome of exercise induced ischaemia of the lumbosacral plexus is not a widely known cause for intermittent claudication. Eight patients with the mentioned syndrome were investigated clinically, neurophysiologically, and with imaging techniques. The clinical examination showed a typical exercise induced sequence of symptoms: pain, paraesthesia, and sensory and motor deficits. The underlying vascular conditions were high grade stenoses or occlusions of the arteries supplying the lumbosacral plexus. Spinal stenosis could be excluded in all cases. Five patients received successful interventional radiological therapy. The syndrome can be diagnosed clinically and successful therapy is possible by interventional radiology.

Acute Disease↗

Predictive value of the ankle-brachial index in the evaluation of intermittent claudication.

The purpose of this study was to determine whether the ankle-brachial index (ABI) could be used to predict the prognosis for a patient with intermittent claudication (IC). We studied 611 patients prospectively during 28 months of follow-up. We analyzed the predictive power of using various levels of ABI - 0.30 to 0.70 at 0.05 increments - in terms of the measure's specificity (association with a favorable outcome after exercise rehabilitation therapy) and sensitivity (association with a poor outcome after exercise rehabilitation therapy). We found that using an ABI of 0.30 as a cut-off value produced the lowest margin of error overall, but the predictive power was still low with respect to identifying the patients with a poor prognosis after non-aggressive therapeutic treatment. Further study is needed to perhaps identify a second factor that could increase the sensitivity of the test.

Ankle↗

Isokinetic strength and endurance in peripheral arterial insufficiency with intermittent claudication.

Isokinetic plantar flexor peak torques (PT) and contractional work (CW) of the triceps surae muscle have been measured in 24 patients with peripheral arterial insufficiency and intermittent claudication and in 15 controls. Tests were performed both during non-fatiguing (30-180 degrees/s) and fatiguing (200 repeated plantar flexions at 60 degrees/s) conditions. The electromyographic signals (iEMG) from all three heads of the triceps surae were measured. The patients were significantly weaker (PT) and produced significantly less contractional work (CW) than the controls. In contrast, similar iEMGs of the triceps surae heads indicated similar levels of activation. At 40 contractions the majority of the patients had already given up and the remainder showed significantly greater declines in PT (50%) and CW (55%) than did the controls (13% and 18%, respectively). The decline in muscular excitations was similar in both groups. The ratio CW/iEMG showed a dramatic decline in the patients but was virtually constant in the controls. These results indicate a fatigue of low-frequency type in the patient group. There were close correlations between maximum walking tolerance and total work production.

Aged↗

Intermittent claudication and muscle fiber fine structure: correlation between clinical and morphological data.

Bilaterally obtained muscle biopsies (anterior tibial muscle) from 22 patients with unilateral peripheral arterial insufficiency (intermittent claudication) were qualitatively and quantitatively analyzed by means of enzyme histochemistry and electron microscopy. In a majority of the biopsies from the symptomatic legs, two different patterns of morphological deviations were seen in the abnormal muscles: one suggested primary muscle fiber damage and the other indicated denervation. Biopsies from the asymptomatic legs were often only slightly changed or normal. Significant correlations were found in both legs between the relative number of type 1 (slow twitch, highly oxidative) fibers and the age of the subjects. In symptomatic legs, furthermore, a relation could be demonstrated between the relative number of type 1 fibers and (1) the initial walking tolerance (walking distance covered before pain occurred), (2) duration of symptoms, and (3) occlusion or stenosis at high level (i.e., above the deep femoral artery). Finally, the diameters of both type 1 and type 2 fibers in the symptomatic leg were correlated to the initial walking tolerance. The importance of circulatory disturbances as differential diagnostic points (arteriovasculo-occlusive myopathy) in the diagnosis of neuromuscular diseases is stressed.

Adult↗

The oral glucose tolerance test in men under 55 years of age with intermittent claudication.

Blood glucose at sixty, ninety, and one hundred twenty minutes after a standardized oral glucose load was compared in healthy middle-aged men and patients with intermittent claudication. No difference was found when the authors compared blood glucose at zero and sixty minutes. At both ninety and one hundred twenty minutes, however, they found a relative hypoglycemia in patients with peripheral arteriosclerotic disease in an early stage.

Administration, Oral↗

The diagnosis intermittent claudication. The value of walking test, ankle pressure index and calf plethysmography in relation to the clinical findings.

Three hundred and forty-nine patients with the diagnosis intermittent claudication (IC) based on Rose's questionnaire were all found to have clinical abnormality based on pulse palpation, and/or auscultation in lower abdomen and groin. The diagnosis was in the majority of cases (87-95%) confirmed by standardized walking test (WT), ankle pressure index (AI) and venous occlusion calf plethysmography (VOP). In clinical abnormality based on bruit only in groin, AI and VOP confirmed the diagnosis less frequently than in the other clinical abnormalities (p less than 0.01).

Adult↗

European multicenter study on propionyl-L-carnitine in intermittent claudication.

OBJECTIVES: This study was performed to identify a target population of claudicants for propionyl-L-carnitine treatment. BACKGROUND: Previous studies suggest that the efficacy of propionyl-L-carnitine in intermittent claudication is greater in patients with severe functional impairment than in those with mild walking disability. METHODS: After run-in, 485 claudicant patients were randomized to placebo or propionyl-L-carnitine (1 g bid, p.o.) and then stratified on the basis of maximal walking distance (cutoff point 250 m) and maximal walking distance variability (cutoff point 25%). Treatment lasted 12 months. Walking capacity was assessed by treadmill and quality of life by a questionnaire exploring various aspects of daily life. RESULTS: In the target population, that is, patients who at baseline walked < or = 250 m and showed a maximal walking distance variability < or = 25%, per-protocol analysis showed that the effect of propinyl-L-carnitine was significantly greater than that with placebo for both maximal walking distance and initial claudication distance (ICD). In the intention-to-treat population, maximal walking distance increased by 62 +/- 14% on propionyl-L-carnitine and by 46 +/- 9% (p < 0.05) on placebo, while no difference between treatments was observed for ICD. The beneficial effect of propionyl-L-carnitine was confirmed when data of the target population were pooled with those of patients who at baseline walked < or = 250 m and showed a > 25% maximal walking distance < 50% variability. Actually, maximal walking distance increased by 98 +/- 16% in the propionyl-L-carnitine group and by only 54 +/- 10% in the placebo group (p < 0.01). The corresponding values for ICD were 99 +/- 21% and 51 +/- 8% (p < 0.05). For patients with baseline maximal walking distance > 250 m, no difference between treatments was observed. CONCLUSIONS: Claudicants with maximal walking distance < or = 250 m benefited from the use of propionyl-L-carnitine, with improvement in walking distance and quality of life. However, patients with mild functional impairment (i.e., walking distance > 250 m) showed no response to propionyl-L-carnitine.

Cardiotonic Agents↗

[Long term follow up of patients with intermittent claudication and correlated with the management of risk factors (author's transl)].

The follow-up (3 to 20 years, mean = 8,9 yrs) of 145 patients with intermittent claudication showed the high incidence of tobacco use (86%) hyperlipidemia (43%) elevated blood pressure (45%) and glucose intolerance (30%), two or more of these factors were present in 66% of cases. A statistically significant higher rate of fairly reduced risk factors was noted in 57 patients improved functionally (based on the maximal walking distance on treadmill and arm/ankle systolic pressure ratio) versus 45 functionally impaired patients, and in 55 patients free of CHD, compared with 54 patients with coronary events (p 0.001). A group of 26 patients with cerebro-vascular insufficiency exhibited a higher incidence of non reduced hypertensive cases.

Aged↗

The impact of walking impairment, cardiovascular risk factors, and comorbidity on quality of life in patients with intermittent claudication.

OBJECTIVE: The objective of this study was to assess the impact of walking impairment, cardiovascular risk factors, and comorbidity on quality of life (QOL) in patients with intermittent claudication (IC). MATERIAL AND METHODS: The prospective observational study was conducted in the setting of a vascular outpatient department of a teaching hospital. QOL was assessed in 200 consecutive patients with IC, with a reduced version of the World Health Organization Quality of Life Assessment Instrument-100. The reduced instrument assesses 17 facets of QOL within five domains (Physical and Psychological Health, Level of Independence, Social Relationships, and Environment). Age, gender, degree of IC, risk factors, comorbidity, as recommended by the Society for Vascular Surgery/North American Chapter of the International Society for Cardiovascular Surgery (SVS/ISCVS), and the presence of back, hip, or knee symptoms were analyzed as possible predictors of QOL. Multiple regression analyses were run with each of the QOL facets and domains as dependent variable. A probability value of less than.05 was considered to be statistically significant. RESULTS: Male gender was found to be a predictor of better scores for Energy and Fatigue and for Sleep and Rest. Women had more Negative Feelings. The presence of back, hip, or knee symptoms was a significant predictive value for many aspects of QOL. With more concomitant diseases, patients had lower scores on the facets of Overall QOL and General Health and of Energy and Fatigue and showed more dependence on medication and treatments. The degree of IC, as expressed in the SVS/ISCVS classification, was a statistically significant predictor of QOL on the domain Level of Independence and its facets Mobility, Activities of Daily Living, and Working Capacity and the facets Pain and Discomfort, Sexual Activity, and Transport. Hypertension was the second most important single predictor of QOL in patients with IC. CONCLUSION: QOL in patients with IC is only partially determined by the severity of walking limitation as expressed in the SVS/ISCVS classification. The significant impact of cardiovascular risk factors and comorbidity and the presence of back, hip, or knee symptoms on QOL should be recognized and taken into account in the treatment policy.

Adult↗

[Treatment of severe intermittent claudication: ORACLE-PGE1 short term study. A randomised 40-week study. Evaluation of efficacy and costs].

BACKGROUND: The efficacy and cost of prostaglandin E1 (PGE1) in severe intermittent claudication was studied comparing a long-term protocol (LTP) with a short-term protocol (STP) in a randomised 40-week study. METHODS: Phase 1 was a 2-week run-in phase (no treatment) for both protocols. In LTP, phase 2 was the main treatment phase. Treatment was performed with 2-hour infusions (60 micro g PGE1, 5 days each week for 4 weeks. In phase 3 (4-week interval period), PGE1 was administered twice a week (same dosage). In phase 4 (40 weeks), no PGE1 were used. In STP, phase 2 treatment was performed in two days by a 2-hour infusion (60 micro g PGE1 twice a day in 2 days). The same cycle was repeated every 4 weeks. A treadmill test was performed at inclusion, at the beginning of each phase and at the end of weeks 12, 16, 20 32 and 40. A progressive training plan (walking) and reduction in risk factors plan was used in both groups. RESULTS: Out of the 1276 included patients 1165 completed the study (606 in LTP group; 559 in the STP). Drop-outs were 111. The two groups were comparable in distribution, risk factors and smoking. Intention-to-treat analysis indicated an increase in pain free walking distance (PFWD). The absolute and percent increase in pain-free walking distance (PFWD) was comparable in both LTP and STP groups with a significative increase in TWD at 4 weeks. At 20 and 40 weeks increase was up to 219% in the LTP and 460% in the STP group (p<0.02). Comparable results concerning PFWD were obtained in the two groups. Both treatments were well tolerated. No side effect was observed. Local effects were observed in 8.5% of the treated subjects in the LTP and 4% in the STP. The average cost of the LTP protocol was 8786 Euro. For STP the costs was 946 (10.8% of LTP). For both protocols the cost of the infusion was 24% of the total for the LTP and 35% in the STP. Therefore 75% of the cost is not drug-related. CONCLUSIONS: In conclusion between-group-analysis favours STP considering walking distance and costs. Results indicate good efficacy and tolerability of PGE1 treatment particularly STP.

Alprostadil↗