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Restless legs syndrome: confirmation of linkage to chromosome 12q, genetic heterogeneity, and evidence of complexity.

BACKGROUND: Genes are involved in the etiology of restless legs syndrome, a common sensorimotor disorder. OBJECTIVES: To replicate and to further characterize our previously reported chromosome 12q linkage results. DESIGN: Family linkage study. SETTING AND PARTICIPANTS: A total of 276 individuals from 19 families have been examined using a selection of markers spanning the identified candidate interval on chromosome 12q. RESULTS: Two-point analyses of individual pedigrees indicated that 5 kindreds were consistent with linkage to chromosome 12q. When considering these 5 pedigrees along with the family in which linkage was originally reported, we observed a maximum 2-point logarithm-of-odds score of 5.67 (at theta = 0.10; for marker D12S1636; autosomal recessive) and a maximum multipoint logarithm-of-odds score of 8.84 between the interval defined by markers D12S326 and D12S304. Furthermore, our results also suggest the presence of heterogeneity in restless legs syndrome as linkage was formally excluded across the region in 6 pedigrees. Interestingly, significantly higher periodic leg movements during sleep indices were observed for all probands with restless legs syndrome from linked families. CONCLUSIONS: These results support the presence of a major restless legs syndrome-susceptibility locus on chromosome 12q, which has been designated as RLS1, and also suggest that at least one additional locus may be involved in the origin of this prevalent condition.

Chromosome Mapping↗

Leg function after radiotherapy for Ewing's sarcoma.

Twenty-nine patients with Ewing's sarcoma of the lower extremity who survived for two or more years following therapy (5000 rad locally and systemic chemotherapy) were studied to assess functional status of the affected leg. Twenty-two of twenty-nine were alive and were reexamined; the deceased patients were evaluated by record review. Twenty-two of the twenty-nine had serial radiographs, which were reviewed to assess growth change induced by radiation. The living patients were divided on the basis of clinical examination into four functional groups with Group I comprising patients with minor functional limitations and leg length discrepancy 1.5 cm or less. Group II patients had moderate functional limitations with 2.5-cm leg-length discrepancy or less. Group III patients had severe functional limitations with up to 4-cm leg length discrepancy. Group IV patients had severe complications, sufficient enough to warrant amputation. Thirteen of twenty-two patients were classified as functional Group I, five as Group II, three as Group III, and one as Group IV. Radiographic changes in growing bone did not correlate with functional results. Although a femoral fracture and an age less than 16 years at diagnosis were found to be less favorable prognostic factors for the functional treatment result, these results show that neither femoral location nor young age justify primary amputation for Ewing's sarcoma of the lower leg extremity.

Adolescent↗

Interventions for varicosities and leg oedema in pregnancy.

BACKGROUND: Leg oedema from venous insufficiency is not dangerous but it can cause women symptoms such as pain, feelings of heaviness, night cramps and paraesthesiae. Leg oedema can be a sign of pre-eclampsia when associated with raised blood pressure or proteinuria. OBJECTIVES: The objective of this review was to assess the effects of treatment to relieve the symptoms associated with varicosity in pregnancy and to reduce leg oedema. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register. SELECTION CRITERIA: Randomised trials of any form of treatment for varicosity or leg oedema in pregnancy. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. MAIN RESULTS: Three trials of three different treatments were included. A total of 115 women were involved. In one trial, two thirds of women given rutoside capsules in the last three months of pregnancy noted an improvement in symptoms compared with only one third given placebo (odds ratio 0.30, 95% confidence interval 0.12 to 0.77). They had a decrease in ankle circumference at 36 weeks' gestation after eight weeks of treatment, while women given placebo had a small increase. In one trial, women with ankle oedema had a small non-significant reduction in lower leg volume when treated with external pneumatic intermittent compression for 30 minutes. Fifty minutes immersion in water at 32 degrees Celsius resulted in greater diuresis and fall in blood pressure than 50 minutes bedrest. REVIEWER'S CONCLUSIONS: Rutosides appear to relieve symptoms of venous insufficiency in late pregnancy. However it is not known if the drug is safe in pregnancy. External pneumatic compression appears to reduce ankle swelling. Immersion in water for 50 minutes results in diuresis and fall in blood pressure. It is not known for how long these changes are sustained nor whether they are of any benefit.

Edema↗

Oral zinc for arterial and venous leg ulcers.

BACKGROUND: Leg ulcers affect up to 1 per cent of people at some time in their life. Management includes care of the ulcer using dressings and treatment of underlying medical problems such as malnutrition, lack of minerals, vitamins, poor blood supply or infection. OBJECTIVES: To assess the effectiveness of oral zinc in healing arterial or venous leg ulcers. SEARCH STRATEGY: Searches of 19 databases, hand searching of journals and conference proceedings from 1948 onwards, and examination of bibliographies. The company manufacturing zinc sulphate tablets was asked for references to relevant trials. SELECTION CRITERIA: Randomised controlled trials comparing oral zinc sulphate with placebo or no treatment in patients with arterial or venous leg ulcers. There was no restriction on date or language. The main outcome measure used was complete healing of the ulcers. Trials were eligible for inclusion if they measured ulcer healing objectively, by time to complete healing, proportion of ulcers healed during the study, or healing rates of ulcers. DATA COLLECTION AND ANALYSIS: All data extraction and assessment of trial quality were done by both authors independently. MAIN RESULTS: There were six eligible trials. All are small and serum zinc was measured at baseline or during the trial in 4 trials. Overall there is no evidence of a beneficial effect of treatment with zinc sulphate on the number of ulcers healed at the end of the trials. There is some evidence that oral zinc might have a beneficial effect on healing of venous ulcers in people with a 'low' serum zinc level at baseline. REVIEWER'S CONCLUSIONS: Overall, oral zinc sulphate does not appear to aid healing of leg ulcers, although it might be beneficial in those with venous leg ulcers and low serum zinc. Further research is needed to ascertain the serum zinc concentration below which treatment with zinc might be beneficial, and the dose required. [This abstract was prepared centrally]

Administration, Oral↗

Circadian rhythm of restless legs syndrome: relationship with biological markers.

Recently, it was suggested that the intensity of restless legs syndrome (RLS) symptoms may be modulated by a circadian factor. The objective of this study was to evaluate, during a 28-hour modified constant routine, the nycthemeral or circadian variations in subjective leg discomfort and periodic leg movements (PLMs) and to parallel these changes with those of subjective vigilance, core body temperature, and salivary melatonin. Seven patients with primary RLS and seven healthy subjects matched for sex and age entered this study. Although the symptoms were more severe in patients than in controls, a significant circadian variation in leg discomfort and PLM (p < 0.01) was found for both groups. In both groups, the profiles of leg discomfort and PLM were significantly correlated with those of subjective vigilance, core body temperature, and salivary melatonin. However, among these variables, the changes in melatonin secretion were the only ones that preceded the increase in sensory and motor symptoms in RLS patients. This result and those of others studies showing that melatonin exerts an inhibitory effect on central dopamine secretion suggest that melatonin might be implicated in the worsening of RLS symptoms in the evening and during the night.

Adult↗

Treatment of spider leg veins with the KTP (532 nm) laser--a prospective study.

BACKGROUND AND OBJECTIVES: Spider leg veins are telangiectasias located intracutaneously. This condition poses a cosmetic problem. STUDY DESIGN/PATIENTS AND METHODS: The purpose of this study was to determine what influence the KTP (532 nm) laser has on spider leg veins dependent on the vascular diameter and to what extent the skin has been affected. Seventy female patients were treated in three laser sessions. Analysis was done 30 weeks after the last laser treatment session. RESULTS: Fifty-six patients completed the study. In group 1 (vascular diameter < or = 0.6 mm), spider leg veins were no longer visible in 33%; in 40%, a decrease in vascular diameter could be observed; in 27%, no change in size occurred. In group 2 (vascular diameter 0.7-1.0 mm), laser-treated spider leg veins were visible in all patients. Hyperpigmentation occurred in 13 patients. CONCLUSIONS: The KTP (532 nm) laser is an effective for treating spider leg veins having a vascular diameter under 0.7 mm.

Adolescent↗

Comparison and sequential study of long pulsed Nd:YAG 1,064 nm laser and sclerotherapy in leg telangiectasias treatment.

BACKGROUND AND OBJECTIVES: Millisecond pulsed 1,064 nm Nd:YAG lasers have been developed for the treatment of leg telangiectasias. To date there have been very few side by side comparison studies of laser versus the gold standard sclerotherapy in treating small leg veins. This study aims to compare a long pulsed Nd:YAG laser with contact cooling to sclerotherapy for treating small diameter leg telangiectasias by evaluating objective and subjective clinical effects. STUDY DESIGN/PATIENTS AND METHODS: Fourteen patients were selected with leg telangiectasias ranging from 0.5 to 2 mm at four comparable sites. One site was treated with long pulsed Nd:YAG alone, the second received sclerotherapy alone, the third laser then sclerotherapy, and the last one sclerotherapy then laser. The patients were followed up at 3 months after the last treatment. Photographs were taken pre-operatively and at 3 months after the last session. They were used for objective and comparative analysis. Statistical analysis was performed using Friedman's test controlling for subject. RESULTS: Improvement was tabulated from the photographic assessment on an improvement scale from 0 (no change) to 4 (greater than 75% clearing). There were clinical improvements in the laser group than sclerotherapy without statistical significance. Side effects were minimal and included hyperpigmentation. CONCLUSIONS: This pilot study demonstrates that the Smartepil LS long pulse Nd:YAG 1,064 nm laser can yield results similar to sclerotherapy in the treatment of small leg telangiectasias. Combination of both methods could increase response to treatment.

Case-Control Studies↗

Alternating leg muscle activation during sleep and arousals: a new sleep-related motor phenomenon?

We describe a quickly alternating pattern of anterior tibialis activation, recorded during nocturnal polysomnography in 16 patients. Polysomnography, usually for sleep-disordered breathing, included surface electromyograms over the anterior tibialis of each leg. Cases were identified from approximately 1,500 studies reviewed in the course of standard clinical care. Patients were 12 men and 4 women (mean age, 41 +/- 15 years; range, 12-70 years). Brief activation of the anterior tibialis in one leg alternated with similar activation in the other leg. Activations occurred at a frequency of approximately 1 to 2 Hz, each lasted between 0.1 and 0.5 seconds, and sequences of alternating activations usually lasted between several and 20 seconds. The phenomenon occurred in all sleep stages but particularly during arousals. Ten of the 16 patients had periodic leg movements during sleep at a rate >/= 5.0 per hour, and 12 of the 16 patients were taking antidepressant medication. Alternating leg muscle activation (ALMA) during sleep, at this relatively high frequency, may be a newly described phenomenon. We speculate that ALMA could represent transient facilitation of a spinal central pattern generator for locomotion, perhaps due to serotonergic effects of antidepressant medication.

Adolescent↗

Home-based leg strengthening for older adults initiated through private practice.

BACKGROUND: Leg strength correlates with functional ability in the frail elderly, many of whom can be reached through a private practice setting. The purpose of this study was to demonstrate the feasibility of physician-prescribed, home-based, clinic-monitored, high-intensity leg-strengthening treatment among elderly patients with a variety of medical problems. METHODS: Twenty-two elderly patients with a variety of chronic medical conditions were invited to participate during regularly scheduled office visits if they had difficulty rising from a chair and an unsteady, cautious gait (age 85.1 +/- 5.7, 14 female). Physical therapists (PT) instructed patients to lift ankle weights at home, three times per week. Patients visited PT five times over a 12-week period. Weights were increased at each visit. RESULTS: Patients' one-repetition maximum increased (right leg 13 to 21 lb, P = 0.00; left leg 15 to 22 lb, P = 0.00). Patients also improved in habitual (18 to 12 s, P = 0.01) and tandem (38 to 26 s, P = 0.00) 20-foot walking times and sit-to-stand time (5 to 3 s, P = 0.01). CONCLUSION: The primary care physician can initiate a home-based leg-strengthening program that is practical for and well tolerated by the frail elderly.

Aged↗

Is there a relationship between femoral anteversion and leg torsion?

In this study, the association between increased femoral anteversion and external torsion of the leg was investigated by computed tomography in adults. In a control group of 15 women, the anteversion angle of the femoral neck measured 11 degrees +/- 9 degrees and 12 degrees +/- 9 degrees for the right and left sides, respectively. The external torsion of the leg was 40 degrees +/- 8 degrees and 39 degrees +/- 10 degrees, respectively. The patient group consisted of 16 women who were evaluated for clinical symptoms related to increased femoral anteversion. In this group, the femoral anteversion was 31 degrees +/- 7 degrees and 33 degrees +/- 7 degrees for the right and left sides, respectively, and the external torsion of the leg was 35 degrees +/- 10 degrees and 33 degrees +/- 12 degrees, respectively. There were no correlations between the degree of femoral anteversion and the degree of external torsion of the leg. This study indicates that in cases of increased femoral anteversion, compensatory external torsion of the leg does not develop regularly during growth.

Adult↗

A quantitative assessment of scintigraphy of the legs using 201Tl.

201Tl perfusion scintigraphy of the legs was evaluated to define intermittent claudication quantitatively, based on Sapirstein's indicator fractionation principle. After intravenous injection of 201Tl with or without exercise, the distribution of the radiotracer throughout the body was obtained using the whole blood scanner. Regional blood flow of cardiac output for three segments of the leg was estimated as a regional fractional uptake (rFU) distributed in these segments compared with the whole body distribution. The validity of the principle was confirmed by a comparative study with 99mTc-MAA (r = 0.979). Normal rFUs (%) for each section at rest and after stress, respectively, were 5.49 +/- 0.69 and 19.40 +/- 2.04 (whole leg); 3.57 +/- 0.49 and 12.26 +/- 1.91 (thigh); 1.59 +/- 0.34 and 6.58 +/- 0.61 (calf). The rates of rFU change from the state of rest to stress (delta rFU) in normals were 3.41 +/- 0.45 (whole leg), 3.44 +/- 0.61 (thigh), and 4.30 +/- 1.03 (calf). Although rFU was within normal limits in patients with arteriosclerosis obliterans (ASO) and thromboangitis obliterans (TAO), delta rFU of the whole leg was significantly decreased from the normal value of 3.41 +/- 0.45 to 1.95 +/- 0.40 for ASO (P less than 0.001) and 1.82 +/- 0.47 for TAO (P less than 0.001). A defect or decreased activity on the stress scintigraph was well correlated with the angiographic findings.

Adult↗

Treatment of vasculitic leg ulcers in connective tissue disease with iloprost.

Leg ulcers are a recognised manifestation of cutaneous vasculitis in connective tissue diseases (CTDs) including rheumatoid arthritis (RA). Iloprost a stable prostacyclin analogue has been successfully used to treat Raynaud's phenomenon and digital ulcers associated with CTD's. Our aim was to assess iloprost in the treatment of vasculitic leg ulcers in CTD. In this paper we describe eight cases of vasculitic leg ulceration in association with RA and CTD, treated with intravenous iloprost. The iloprost was administered for 6-8 hours daily and continued for 21-28 days. Immunosuppressive therapy was required in three patients with severe necrotising vasculitis (RAnv). Complete ulcer healing was achieved in four patients within 6 weeks of commencing therapy while rapid improvement occurred in the other four patients. This suggests that iloprost may be useful as an adjunct to therapy for vasculitic leg ulcers. A double-blind placebo controlled study of iloprost therapy for RA leg ulcers is under way.

Aged↗

[Ultrasound determination of leg length].

A diagnostic method is presented for measuring the leg length and the difference in leg lengths with ultrasound. A special device for holding and moving the ultrasound transducer was constructed. The measuring points on the hip, knee, and upper ankle can be visualized with a 5- or 7.5-MHz linear scanner. The measuring device gives the distance of the points in centimeters so that the difference corresponds to the real length of the leg, femur, and tibia. Tests conducted on corpses and clinical examples show that ultrasound in combination with our special device is an ideal method for determining the exact length of the leg. Ultrasound measurement of the leg length offers a reliable, noninvasive, and easily performed method. Because ultrasound is not limited by radiation hazards, our technique can be used for clinical screening.

Adolescent↗

Anticipatory postural adjustments while sitting: the effects of different leg supports.

The aim of this study was twofold, to analyze the effects of changes in body position and changes in the location of body supports on anticipatory postural adjustments (APAs). Eight healthy subjects were studied while sitting and standing. Subjects exerted upward or downward vertical force against an object attached to a rigid frame and released the object with a fast bilateral shoulder abduction movement. While sitting, four support conditions were studied: with and without feet support, and with anterior or posterior lower-leg supports. The electromyographic activity of leg and trunk muscles was recorded and quantified for APA activity. APAs in sitting with feet support were attenuated in the leg muscles (tibialis anterior, soleus, rectus femoris, and biceps femoris) but not in trunk muscles (erector spinae, rectus abdominis) when compared with standing. In the sitting task, series with and without feet support showed no difference in APAs. Anterior or posterior supports to the lower legs while sitting were associated with enhanced anticipatory activity in biceps femoris and rectus femoris muscles, respectively. However, trunk muscles showed similar anticipatory patterns across all the support conditions. We conclude that the central nervous system uses flexible, adaptive control strategies to adjust APAs to particular mechanical conditions induced by modification of a leg support.

Adult↗

Discrepancies in CPAK classification between CT and long-leg radiography: a systematic review and meta-analysis.

OBJECTIVE: To determine whether substantial differences in coronal plane alignment of the knee phenotype distribution, as well as systematic angular measurement discrepancies, exist between CT and long-leg radiography. MATERIALS AND METHODS: From February 2021 to April 2025, we searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for studies comparing CT- and long-leg radiography-derived coronal plane alignment classifications of the knee in patients with osteoarthritis. The primary outcome was distribution of coronal plane alignment phenotypes. Secondary outcomes included differences in medial proximal tibial angle, lateral distal femoral angle, arithmetic hip-knee-ankle angle, and joint line obliquity. RESULTS: Four studies (1,134 knees) were included. Compared with long-leg radiography-derived classification, CT-derived classification increased type I phenotypes (risk difference: 0.10; 95% confidence interval: 0.01-0.20; P&#x2009;=&#x2009;0.040) and decreased type III (risk difference: -0.04; 95% confidence interval: -0.07 to -0.01; P&#x2009;=&#x2009;0.020) and type V phenotypes (risk difference: -0.04; 95% confidence interval: -0.07 to -0.01; P&#x2009;=&#x2009;0.004). CT yielded significantly lower medial proximal tibial angle (weighted mean difference:&#x2009;-&#x2009;1.18&#xb0;; P&#x2009;<&#x2009;0.001), arithmetic hip-knee-ankle angle (weighted mean difference:&#x2009;-&#x2009;0.95&#xb0;; P&#x2009;<&#x2009;0.001), and joint line obliquity (weighted mean difference:&#x2009;-&#x2009;1.40&#xb0;; P&#x2009;<&#x2009;0.001) than long-leg radiography. Heterogeneity was high for type I phenotype (I2&#x2009;=&#x2009;81%), lateral distal femoral angle (I2&#x2009;=&#x2009;70%), and joint line obliquity (I2&#x2009;=&#x2009;69%). CONCLUSION: Discrepancies between CT-based software-generated and long-leg radiography-derived measurements substantially affect coronal plane alignment classification and angular parameters. Surgeons should consider these modality-specific variations and employ compensatory verification strategies to ensure optimal alignment.

Humans↗

Oxygen uptake and heart rate kinetics during heavy exercise: a comparison between arm cranking and leg cycling.

This study examined the oxygen uptake (VO(2)) and heart rate (HR) kinetics during arm cranking and leg cycling at work rates above the anaerobic threshold (AT). Ten untrained male subjects [21.6 (1.3) years] completed two 7 min 15 s constant-load arm cranking and two leg cycling tests at a power output halfway between the mode-specific AT and peak VO(2). The time constants for phase II VO(2) (tau) and HR (tau) kinetics were determined by fitting a monoexponential curve from the end of phase I until 3 min of exercise. VO(2) tau and HR tau values were significantly (P < 0.001) slower in arm cranking [VO(2) tau = 66.4 (3.0) s; HR tau = 74.7 (4.4) s] than in leg cycling [VO(2) tau = 42.0 (1.9) s; HR tau = 55.6 (3.5) s]. The VO(2) slow component (VO(2SC)) accounted for a significantly (P < 0.001) greater percentage of the total exercise response during arm cranking [23.8 (1.6)%] than during leg cycling [14.2 (1.5)%]. The greater relative VO(2SC) and the slower VO(2) tau with arm exercise are consistent with a greater recruitment of metabolically inefficient type II muscle fibres during arm cranking than during leg cycling.

Adult↗

Cardiorespiratory and subjective responses to prolonged arm and leg exercise in healthy young and older men.

Ten young (aged 23-30 years) and nine older (aged 54-59 years) healthy men with a similar size of limb muscle mass performed arm crank and leg cycle exercise for 30 min at relative exercise intensities of 50% and 75% of maximal oxygen uptake for the corresponding muscle group. In the tests, heart rate, blood pressure, gas exchange variables, rating of perceived exertion and blood lactate concentration were measured. The limb muscle mass was determined by anthropometric measurements. At the 75% target exercise level, four of the older men and two of the young men could not complete the arm-cranking test, and one of the older men and two of the young men could not complete the leg-cycle test. During arm-cranking the absolute exercise intensity was similar for the young and older men because of similar maximal values during arm-cranking. But during leg-cycling the absolute exercise intensity was higher for the young men than for the older men due to the difference in corresponding maximal values. During arm-cranking there were no significant differences in the physiological responses between the age groups except that a higher ventilatory response was noted among the older compared to the young men. During leg-cycling the heart rate values were higher among the young compared to the older men. But, when the heart rate values were expressed as a percentage of maximal heart rate in the corresponding maximal tests, no significant differences between the age groups were found. The results indicated that 30-min of arm or leg exercise at the same relative submaximal exercise intensity produces a similar degree of physiological strain in healthy older compared to young men. During armcranking, the young and the older men exercised at the same external intensity, indicating a similar ability to perform prolonged excercise using smaller muscle groups expressed both in absolute and relative terms.

Adult↗

The effect of leg flexion angle on the mechanomyographic responses to isometric muscle actions.

The purpose of this investigation was to examine the effect of leg flexion angle on the relationship between mechanomyographic (MMG) amplitude and isometric torque production. Adult males (n = 9) performed isometric muscle actions of the leg extensors at 25, 50, 75, and 100 percent maximal voluntary contraction (%MVC) on a calibrated CYBEX 6000 dynamometer at 25, 50, and 75 degrees below full extension. A piezoelectric MMG recording device was placed over the mid-portion of the rectus femoris. At 25 degrees of leg flexion, the MMG amplitude increased to 100%MVC. At 50 and 75 degrees of leg flexion, however, MMG amplitude increased to 75%MVC, and then did not change significantly (P > 0.05) between 75 and 100%MVC. These findings indicate that the MMG amplitude-isometric torque relationship is joint angle specific and may be the result of leg flexion angle differences in: (1) muscle stiffness, or (2) motor unit activation strategies.

Adult↗