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Inhibition of adenosine uptake and augmentation of ischemia-induced increase of interstitial adenosine by cilostazol, an agent to treat intermittent claudication.

Cilostazol (Pletal), a quinolinone derivative with a cyclic nucleotide phosphodiesterase type 3 (PDE3) inhibitory activity, was recently approved by the Food and Drug Administration for treatment of symptoms of intermittent claudication (IC). However, the underlying mechanisms of action are not entirely clear. In this study, we showed that cilostazol inhibited adenosine uptake into cardiac ventricular myocytes, coronary artery smooth muscle, and endothelial cells with a median effective concentration (EC50) approximately 10 microM. In vivo, cilostazol increased cardiac interstitial adenosine levels after a 2-min ischemia in rabbit hearts (329 +/- 92% increase vs. 102 +/- 29% ischemia alone). The combination of cilostazol and 2-min ischemia reduced infarction from subsequent 30-min regional ischemia and 3 h of reperfusion (infarct size was 18 +/- 4% vs. 53 +/- 3% in the hearts with 2-min ischemia alone or 48 +/- 2% in the hearts treated with cilostazol alone). In contrast, milrinone had no effect on either adenosine uptake or interstitial adenosine levels. These data show that cilostazol, unlike milrinone, inhibits adenosine uptake, and thus potentiates adenosine accumulation from a 2-min ischemia. Future studies are needed to investigate the role of adenosine in the treatment of IC by cilostazol.

Adenosine↗

Smoking history is related to free-living daily physical activity in claudicants.

PURPOSE: To determine whether smoking history was related to free-living daily physical activity in peripheral arterial occlusive disease (PAOD) patients with intermittent claudication, and whether the effect of smoking history on physical activity level persisted after controlling for group differences in ambulatory function, peripheral circulation, and body composition. METHODS: Patients were separated into three groups: those who never smoked (N = 35), those who had a lower pack-year history of smoking (< or =40 pack-yr; N = 33), and those who had a higher pack-year history (>40 pack-yr; N = 30). Free-living daily physical activity was assessed by activity monitors (an accelerometer and a pedometer) worn on each hip over 2 consecutive weekdays. Patients also were characterized on ambulatory function, peripheral circulation, and body composition because of their relationship with physical activity. RESULTS: A progressive decline (P < 0.001) in free-living daily physical activity with increasing smoking exposure was obtained from the accelerometer in the nonsmokers (482 +/- 36 kcal x d(-1); mean +/- SE), smokers with a lower pack-year history (361 +/- 37 kcal x d(-1)), and smokers with a higher pack-year history (227 +/- 23 kcal x d(-1)). A similar decline was found with the pedometer data (P < 0.001). After controlling for group differences in 6-min walk distance and in calf transcutaneous heating power, group differences in free-living daily physical activity were no longer significant. CONCLUSION: Progressive decrements in free-living daily physical activity with greater levels of smoking exposure in PAOD patients are primarily due to smoking-related impairments in ambulatory function and peripheral circulation.

Aged↗

The treatment of lumbar spondyloptosis or impending lumbar spondyloptosis accompanied by neurologic deficit and/or neurogenic intermittent claudication.

Three patients with complete lumbar spondyloptosis and 8 patients with fourth-degree spondylolisthesis suffering from radicular signs and symptoms are reported. There were 8 female and 3 male patients in the study. A high incidence of neurogenic intermittent claudication was noted in this condition. Decompressive laminectomy and foraminectomy were performed on all patients followed by transabdominal console fusion. Length of follow-up varied from 3 to 17 years, with a mean value of 13.5 years, and results are reported. Radicular signs and symptoms had completely subsided in all cases. Nine of 11 patients are free from signs and symptoms and 2 suffer from residual pain, although less severe than before surgery. All 3 males fathered children after surgery, which is in contrast to the opinion that anterior lumbosacrial fusion is followed by infertility in males. Special attention was given to individuality of remodeling of the lumbosacral junction over the course of time. Solid fusion was obtained in 10 of the 11 patients, while the console fusion collapsed because of failure to follow instructions after surgery in 1 patient.

Adolescent↗

Neurogenic claudication, a delayed complication of a retained bullet.

STUDY DESIGN: A case report is presented of a 31-year-old man who visited the authors' neurosurgical department in 1993, complaining of neurogenic claudication. History revealed a gunshot incident 11 years ago, with a bullet left in situ. OBJECTIVES: To determine whether to operate on patients who have a bullet in situ near the spinal cord without initial neurologic deficits. SUMMARY OF BACKGROUND DATA: In the literature, only four publications report an epidural chronic inflammatory mass as a reaction to a retained bullet, thereby causing delayed neurologic symptoms. Previous to this report, only one case is described of a patient with a bullet lodged in the paravertebral musculature. METHODS: Clinically, the patient had pain radiating from his lower back to both his thighs, provoked by walking, standing, and the Valsalva maneuver. Comparison of radiographs made in 1990 and in 1993 showed the lead bullet still completely intact in 1990, whereas in 1993, a partial disintegration and displacement of the bullet, causing a chronic inflammatory reaction (extraspinal and intraspinal), as well as cyst formation, was seen. Particularly notable was the radiographic feature of a sort of "fallen leaf sign" at the level of L5-S1. RESULTS: The preoperative complaints were still absent 1 year after surgery. CONCLUSIONS: It is argued that with regard to a retained bullet in the vicinity of the spinal canal, the presence or absence of neurologic symptoms should be the guide for further diagnostic procedures. Only if a neurologic deficit develops, which is possible after many years, should surgical intervention be considered, depending on the severity and type of the deficit, as presented in this case report.

Adult↗

Functional improvements following StairMaster vs. treadmill exercise training for patients with intermittent claudication.

BACKGROUND: Although there have been many studies showing that exercise training is beneficial for patients with peripheral vascular occlusive disease (PVOD), there is little research comparing various modes of training. Previous studies showed that exercise tests performed on a StairMaster (StairMaster Sports/Medical Products, Kirkland, WA) produce responses similar to those elicited by treadmill tests. The purpose of this study was to compare these modes of exercise in a training program for patients with PVOD. METHODS: Of the 23 eligible individuals who began the exercise program, 11 did not complete the regimen due to various complications. Thus, 12 patients were randomly assigned to train for 12 weeks on either a StairMaster (n = 6) or a treadmill (n = 6). Patients underwent progressive and single-stage exercise tests on both exercise modalities before and after training. RESULTS: Mean exercise time before the onset of claudication pain for all tests rose significantly after training (P <.01), but greater improvements were seen on the specific training apparatus (i.e., treadmill training resulted in improvement in treadmill exercise performance with less improvement noted when tested on the StairMaster, and vice versa). Exercise time to maximal pain increased for the training apparatus only (P <.01). There were no changes in foot transcutaneous oxygen tension or the ankle-brachial blood pressure index. CONCLUSIONS: Both StairMaster and treadmill training improve the exercise capacity of PVOD patients. The training effect is most apparent for the specific training apparatus, but there is some cross-over improvement to the other exercise modality. Thus, StairMaster training is appropriate and can be part of the exercise prescription for treatment of these patients.

Aged↗

Cigarette smoking shortens the duration of daily leisure time physical activity in patients with intermittent claudication.

PURPOSE: The authors determined (1) whether peripheral arterial occlusive disease (PAOD) patients who smoke have a reduction in either the duration or intensity of daily physical activities compared with nonsmoking patients, and (2) whether group differences in the pattern of physical activity persisted after controlling for potential confounding variables. METHODS: A total of 170 smokers and 201 nonsmokers who had quit smoking for at least 1 year prior to investigation were studied. Physical activity patterns were measured using the Minnesota Leisure Time Physical Activity (LTPA) questionnaire. Patients also were characterized on potential covariates such as demographics, comorbid conditions, cardiovascular risk factors, ambulatory measures, peripheral hemodynamics, and anthropometric measures. RESULTS: The smokers were 37% less physically active than the nonsmokers (87 +/- 90 versus 139 +/- 121 kcal/day; P = 0.027). The reduced total LTPA in the smokers was due to a 28% shorter duration of performing activities (26 +/- 7 versus 36 +/- 22 min/day; P = 0.031), and a 3% lower mean intensity of the activities (3.3 +/- 1.0 versus 3.8 +/- 0.8 kcal/min; P = 0.038). The distance score on the Walking Impairment Questionnaire and the hip circumference were significant covariates of the LTPA measures. After adjusting for these covariates, the total LTPA remained 29% lower in the smokers (P = 0.039), the mean daily duration of LTPA remained 20% lower (P = 0.043), but the mean intensity of LTPA was no longer different between the groups. CONCLUSION: Compared with their nonsmoking counterparts, claudicants who smoke have a reduced total LTPA because they engage in activities of similar intensity for a shorter duration of time.

Adult↗

The treatment mechanism of an interspinous process implant for lumbar neurogenic intermittent claudication.

STUDY DESIGN: The spinal canal and neural foramina dimensions of cadaver lumbar spines were quantified during flexion and extension using magnetic resonance imaging before and after placement of an interspinous process implant. OBJECTIVE: To quantify the effect of the implant on the dimensions of the spinal canal and neural foramina during flexion and extension. SUMMARY OF THE BACKGROUND DATA: Lumbar neurogenic intermittent claudication symptoms are typically exacerbated during extension and relieved during flexion. It is understood that the dimensions of the spinal canal and neural foramen increase in flexion and decrease in extension. The authors hypothesized that an interspinous process implant would significantly prevent narrowing of the canal and foramina in extension and have no significant effect in flexion. METHODS: Eight L2-L5 specimens were positioned to 15 degrees of flexion and 15 degrees of extension using a positioning frame. Each specimen was magnetic resonance imaged with and without an interspinous implant (X STOP) placed between the L3-L4 spinous processes. Canal and foramina dimensions were compared between the intact and implanted specimens using a repeated measures analysis of variance with a level of significance of 0.05. RESULTS: In extension, the implant significantly increased the canal area by 18% (231-273 mm), the subarticular diameter by 50% (2.5-3.7 mm), the canal diameter by 10% (17.8-19.5 mm), the foraminal area by 25% (106-133 mm), and the foraminal width by 41% (3.4-4.8 mm). CONCLUSIONS: The results of this study show that the X STOP interspinous process implant prevents narrowing of the spinal canal and foramina in extension.

Cadaver↗

The smoking habits of men with intermittent claudication.

Smoking habits among 54 male patients with intermittent claudication (IC) and 200 healthy 50-year-old men from the same county have been studied. The prevalence of smokers at the age of 50 was 98% among the IC patients against 46% among the healthy controls. The percentage of heavy smokers and the total tobacco consumptiion were not significantly different in the two groups. However, the percentage of smokers who began to smoke before the age of 15 was significantly higher in IC patients than in the healthy group, 28% to 7%.

Adult↗

Effect of physical training on different categories of patients with intermittent claudication.

The effect of supervised training was studied in 68 patients with intermittent claudication. Maximal walking distance was measured on a treadmill. Eight of the patients had resting pain in the leg when recumbent (group A), 25 had an initial walking distance of less than 500 m (group B), 11 had an initial walking distance of 500--1 000 m (group C), 24 had coronary insufficiency (group D). The study shows that training should be undertaken for at least three months. In some patients with resting pain, training led to relief of pain and surgical treatment was not necessary. Almost all patients without signs of coronary insufficiency increased their walking distance, compared to only 14 of the 24 patients with coronary insufficiency. Walking distance increased significantly in groups B and C and no significant difference was found between patients and proximal or distal arterial stenosis.

Aged↗

Claudication of the cauda equina.

The term "claudication of the cauda equina" is examined. It has arisen from semantic errors, and a belief in ischaemia for which there is no scientific evidence. Its use tends to hamper rather than assist the investigation of patients with obscure pain in the lower limb. A preferable alternative term, "atypical sciatica", is suggested.

Cauda Equina↗

Giant cell arteritis diagnosed following arm claudication.

A patient is described whose initial symptoms, though suggestive of polymyalgia rheumatica, were attributed to psoriatic arthritis, and whose subsequent development of claudication of the left arm led to the biopsy proven diagnosis of giant cell arteritis. Attention is drawn to widespread arterial involvement by giant cell arteritis which, though uncommon, must be considered in all patients with ischemic limb pain. In addition, the consequences of overlooking polymyalgia rheumatica as an early manifestation of giant cell arteritis are outlined.

Aged↗

A meta-analysis of randomized, double-blind, placebo-controlled studies of the effect of buflomedil on intermittent claudication.

A meta-analysis was performed on the results of clinical trials of buflomedil in intermittent claudication. The analysis used results from 744 patients enrolled in ten studies, conducted at 42 centers in seven countries. All studies were randomized, double-blind, placebo-controlled trials which measured improvement in "pain-free" walking distance by treadmill ergometry as the primary measure of efficacy. The meta-analysis results were based on "effect size", a standardized difference in mean response between buflomedil and placebo. Results demonstrated a statistically superior response to buflomedil compared with placebo, indicating that the average buflomedil treated patient was likely to have a greater improvement in walking distance than at least 60% of the placebo treated patients. Results were corroborated using various weighting schemes proportional to study quality ratings and sample sizes.

Double-Blind Method↗

Walking capacity of patients with intermittent claudication during chronic antihypertensive treatment with metoprolol and methyldopa.

In a placebo-controlled double-blind crossover trial, the effect of a 3-week course of treatment with metoprolol (100-200 mg daily) and methyldopa (500-1000 mg daily) on walking capacity on a treadmill with increasing work load was studied in 14 hypertensive patients with intermittent claudication. The walking capacity was not affected by the antihypertensive treatment.

Adult↗

Update on some epidemiologic features of intermittent claudication: the Framingham Study.

During 26 years of surveillance of the Framingham Study Cohort of 5,209 subjects, 176 men and 119 women developed occlusive peripheral arterial disease manifested as intermittent claudication (IC). The incidence increased sharply with age until the age of 75, with about a twofold male predominance at all ages. An incidence of IC comparable to that of angina pectoris was obtained ten years later in life than for angina pectoris. Cigarette smoking, impaired glucose tolerance, and hypertension were powerful predisposing factors. Impaired glucose tolerance was a greater risk in women than in men, and glycosuria carried a greater risk than other indicators of impaired glucose tolerance. Cigarette smoking had about the same impact in men and women, approximately doubling the risk, and the impact was discernible into advanced age. Hypertension increased risk 2.5- to fourfold, respectively, in men and women. A low vital capacity was associated with a substantial excess risk. Electrocardiographic evidence of left ventricular hypertrophy predicted IC in both sexes. Serum cholesterol, relative weight, and hematocrit were weak risk factors. A risk profile made up of the major cardiovascular risk factors was better for predicting IC than for predicting coronary heart disease. Mortality was increased two- to fourfold in men and women, respectively, mainly because of coexistent cardiovascular disease.

Adult↗

Intermittent claudication: factors determining outcome.

Two groups of patients were followed up for four to eight years after first referral or admission to hospital for intermittent claudication (IC) in a study of the natural history of the disease and of factors determining its outcome. In one series of 60 patients, those who stopped or reduced smoking after referral had a much improved prognosis. Thus even after the diagnosis of IC it is extremely important that patients should be encouraged to stop smoking, since this correctable factor appears to be of greater importance in determining outcome than other medical risk factors for the disease that are less amenable to treatment. In the second study, 160 patients were followed up for eight years after first hospital admission. They had a total of 480 hospital admissions and had spent 11 190 days in hospital; their life expectancy after the age of 60 was about half that of the general population. Age, coronary artery disease, cerebrovascular disease, and diabetes were associated with an adverse outcome.

Adult↗

Intermittent claudication: prevalence and risk factors.

Risk factors for intermittent claudication (IC) were studied in 54 patients--that is, all patients with IC on the lists of two general practices--and 108 controls. Smoking was the factor most strongly associated with the development of IC, but systolic and diastolic blood pressures and concentrations of triglyceride, urate, and fibrinogen were all significantly higher among the patients with IC than the controls. The presence of more than one factor appeared to be associated with a multiplicative increase in risk. Cholesterol, an important risk factor for ischaemic heart disease, was not associated with an increased risk of IC. IC was present in about 2% of the men and 1% of the women, who were aged 45-69 years. These findings suggest that IC, a common and disabling manifestation of atheroslcerosis, may be largely preventable.

Aged↗

Place of Achilles tenotomy in the treatment of severe intermittent claudication.

Achilles tenotomy was performed on 66 limbs in 60 patients with severe intermittent claudication and the results were assessed two years later. Early improvement occurred in half of them but decreased to 17% two years postoperatively. Sympathectomy did not influence the result. The postoperative morbidity was 14%, and 21% of limbs were subsequently amputated. The late mortality in the group studied was 8%.

Achilles Tendon↗