Assessment of Intravascular Volume Status in Children with Nephrotic Edema Using Serum and Urinary Indices and Its Correlation with Inferior Vena Cava Collapsibility Index.

Identification of volume status in nephrotic syndrome (NS) is important but clinically challenging. Urinary and serum indices can be helpful in assessing the volume status and so can be inferior vena cava collapsibility index (IVCCI). This study was done to assess the serum and urinary indices in children with nephrotic edema and to correlate them with IVCCI for intravascular volume assessment. Fifty children with nephrotic edema and 47 children in remission were analyzed for blood and urine indices. Volume status was defined as overfilling or underfilling based on the biochemical indices and also by IVCCI. Eighty-four percent individuals among cases and 23% among controls had sodium retention (FENa < 0.5%). Among cases, 54% had primary sodium retention compared to 17% among controls (p = 0.0002). Hypovolemia was observed among 36% cases based on biochemical indices and in 20% cases as per IVCCI. Hypovolemia was significantly associated with low urinary sodium and low serum albumin.

Reliability and precision of single frequency bioelectrical impedance assessment of lower extremity swelling following total knee arthroplasty.

Total knee arthroplasty (TKA) is the most common elective orthopedic surgery performed in the United States. Following surgery patients experience significant lower extremity swelling that is related to poor satisfaction with surgery and is hypothesized to contribute to functional decline. However, in practice, precise and reliable methods for measuring lower extremity swelling do not exist. The purpose of this study was to provide reliability and precision parameters of an innovative approach, single frequency bioelectrical impedance assessment (SF-BIA), for measuring post-TKA lower extremity swelling. Swelling in 56 patients (64.3 ± 9.3 years; 29 males) was measured before and after TKA using SF-BIA and circumferential measures (CM). Reliability of the measures was calculated using Intraclass Correlation Coefficients (ICC). Precision of the measures was provided using standard error of the measurement and minimal detectable change (MDC90). Change values between time points for SF-BIA and CM are provided. SF-BIA was found to have greater reliability following surgery compared to CM (ICC = 0.99 vs 0.68). SF-BIA was found to have an MDC90 = 2% following surgery, indicating improved ability to detect minute fluctuations in swelling compared to CM (MDC90 = 6%) following surgery. These results indicate that SF-BIA improves the precision and reliability of swelling measurement compared to CM.

Elicitation of disease concepts in patients with diabetic foot ulcers: a qualitative study.

OBJECTIVE: To identify in-depth information directly from patients with diabetic foot ulcers (DFU) on DFU symptoms, impacts on functioning and effects on health-related quality of life (HRQoL). METHOD: Semi-structured, qualitative concept elicitation interviews were conducted with patients with DFUs (Wagner grade 1 or 2) until saturation was reached. Qualitative analysis (using MAXQDA, VERBI GmbH, Germany) of interview transcripts was conducted to identify concepts relevant to patients with DFUs, based on the frequency of mentions, and elucidate themes regarding impacts on HRQoL. RESULTS: Of the 18 participants, most were male (n=14; 78%) and 10 (56%) presented with a Wagner grade of 1. Frequently reported symptoms were pain/discomfort (n=15; 83%), weeping/discharge (n=10; 56%), bleeding (n=10; 56%) and swelling (n=8; 44%). Overall, patients reported more impacts than symptoms-wound care/treatment burden (n=14; 78%), limitations on exercise/physical activity (n=13; 72%), mobility limitations (n=12; 67%), and offloading (n=12; 67%) were the most frequently mentioned. Based on findings from the patient interviews, a draft conceptual model was developed outlining interrelationships between DFU symptoms, impacts, and HRQoL from the patient perspective. CONCLUSION: Qualitative interviews captured the breadth of disease-related concepts of direct importance to patients. The draft conceptual model developed from the analysis can help identify measures or instruments for use in assessing patient-reported symptoms or HRQoL in clinical practice and may have wider research applicability, including evaluation of treatment benefits in patients with DFUs.

The Concept of Chronic Edema-A Neglected Public Health Issue and an International Response: The LIMPRINT Study.

Lymphedema has always been a neglected global health care problem. A central requirement for the development of any chronic disease is the clear use of public health definitions that can be used internationally to define populations. The term "lymphedema" has historically been defined as either primary, resulting from failure of lymphatic development, or secondary, following damage to the lymphatics (e.g., cancer treatment, injury, or filariasis). Attempts to integrate causes of edema arising from damage to the venous system or the effects of gravity, immobility, and systemic disease have rarely been integrated. More recently, the prominent role of the lymphatics in tissue fluid homeostasis in all forms of chronic edema has been recognized. These advances led to the development of the term: "Chronic edema: a broad term used to describe edema, which has been present for more than three months." It can be considered an umbrella term that includes not only conventional "lymphedema" but also chronic swelling, which may have a more complex cause. This definition has been adapted in the international epidemiology study (LIMPRINT) that identified people throughout the health and social care systems in participating countries. Clearer definitions will allow for examination of this important public health problem that is likely to escalate given the projections of an aging population with multiple comorbidities. It will be possible to define both the hidden mortality and morbidity associated with complications, such as cellulitis and the impact on health-related quality of life. This evidence is urgently required to lobby for increased resource and effective health care in an increasingly competitive health care arena in which more established conditions have greater priority and funding.

LIMPRINT Study: The Turkish Experience.

Background: Lymphedema and chronic edema is a major health care problem in both developed and nondeveloped countries The Lymphoedema Impact and Prevelance - International (LIMPRINT) study is an international health service-based study to determine the prevalence and functional impact in adult populations of member countries of the International Lymphoedema Framework (ILF). Methods and Results: A total of 1051 patients from eight centers in Turkey were recruited using the LIMPRINT study protocol. Data were collected using the core and module tools that assess the demographic and clinical properties as well as disability and quality of life (QoL). Most of the Turkish patients were recruited from specialist lymphedema services and were found to be women, housewives, and having secondary lymphedema because of cancer treatment. The duration of lymphedema was commonly <5 years and most of them had International Society of Lymphology (ISL) grade 2 lymphedema. Cellulitis, infection, and wounds were uncommon. The majority of patients did not get any treatment or advice before. Most of the patients had impaired QoL and decreased functionality, but psychological support was neglected. Although most had social health security access to lymphedema centers, nevertheless access seemed difficult because of distance and cost. Conclusion: The study has shown the current status and characteristics of lymphedema patients, treatment conditions, the unmet need for the diagnosis and treatment, as well as burden of the disease in both patients and families in Turkey. National health policies are needed for the prevention, diagnosis, and treatment in Turkey that utilize this informative data.

Numerical modeling of fluid and oxygen exchanges through microcirculation for the assessment of microcirculation alterations caused by type 2 diabetes.

Type 2 diabetes mellitus (DM2) is frequently accompanied by microcirculation complications, including structural and functional alterations, which may have serious effects on substance exchanges between blood and interstitial tissue and the health of organs. In this paper, we aim to study the influence of microcirculation alterations in DM2 patients on fluid and oxygen exchanges through a model analysis. A fluid flow and oxygen transport model were developed by considering the interplay between blood in capillary network and interstitial tissue. The two regions were separately represented by 1D network model and 3D volume model, and the immersed boundary method (IBM) was adopted to solve fluid and mass transfer between these two regions. By using the model, the steady flow field and the distributions of oxygen in capillary network and surrounding tissue were firstly simulated. In the interstitial volume, fluid pressure and oxygen tension decreased with the increase of distance from the network; in the network, oxygen tension in blood plasma dropped from 100 mm Hg at the entrance to about 40 mm Hg at the exit. We further tested several structural and functional disorders related to diabetic pathological conditions. Simulated results show that the impaired connectivity of the network could result in poor robustness in maintaining blood flow and perfused surface; under high fluid permeability conditions of capillary walls, the pressure gradient was much larger around the capillary bed, and this alteration led to a saturation level of the interstitial pressure when lymphatic flow drainage can't work effectively; the variations in network connectivity and permeability of capillary wall also had unfavorable influence on oxygen distributions in interstitial tissue. In addition, when the oxygen releasing capacity of hemoglobin was confined by glycosylated hemoglobin (HbA1) in the case of diabetes, the plasma could not be complemented with adequate oxygen and thus the hypoxic tissue range will be extended. This study illustrates that when microcirculation disturbances, including the structure of capillary network, the wall osmosis property and the capacity of blood binding oxygen occur in DM2, some negative impacts are raised on microvascular hemodynamics and metabolism circumstance of interstitial tissue.

Modeling the impact of prostate edema on LDR brachytherapy: a Monte Carlo dosimetry study based on a 3D biphasic finite element biomechanical model.

Prostate volume changes due to edema occurrence during transperineal permanent brachytherapy should be taken under consideration to ensure optimal dose delivery. Available edema models, based on prostate volume observations, face several limitations. Therefore, patient-specific models need to be developed to accurately account for the impact of edema. In this study we present a biomechanical model developed to reproduce edema resolution patterns documented in the literature. Using the biphasic mixture theory and finite element analysis, the proposed model takes into consideration the mechanical properties of the pubic area tissues in the evolution of prostate edema. The model's computed deformations are incorporated in a Monte Carlo simulation to investigate their effect on post-operative dosimetry. The comparison of Day1 and Day30 dosimetry results demonstrates the capability of the proposed model for patient-specific dosimetry improvements, considering the edema dynamics. The proposed model shows excellent ability to reproduce previously described edema resolution patterns and was validated based on previous findings. According to our results, for a prostate volume increase of 10-20% the Day30 urethra D10 dose metric is higher by 4.2%-10.5% compared to the Day1 value. The introduction of the edema dynamics in Day30 dosimetry shows a significant global dose overestimation identified on the conventional static Day30 dosimetry. In conclusion, the proposed edema biomechanical model can improve the treatment planning of transperineal permanent brachytherapy accounting for post-implant dose alterations during the planning procedure.

Revealing the Concealed Nature of Long-QT Type 3 Syndrome.

BACKGROUND: Gain-of-function mutations in the voltage-gated sodium channel (Nav1.5) are associated with the long-QT-3 (LQT3) syndrome. Nav1.5 is densely expressed at the intercalated disk, and narrow intercellular separation can modulate cell-to-cell coupling via extracellular electric fields and depletion of local sodium ion nanodomains. Models predict that significantly decreasing intercellular cleft widths slows conduction because of reduced sodium current driving force, termed "self-attenuation." We tested the novel hypothesis that self-attenuation can "mask" the LQT3 phenotype by reducing the driving force and late sodium current that produces early afterdepolarizations (EADs). METHODS AND RESULTS: Acute interstitial edema was used to increase intercellular cleft width in isolated guinea pig heart experiments. In a drug-induced LQT3 model, acute interstitial edema exacerbated action potential duration prolongation and produced EADs, in particular, at slow pacing rates. In a computational cardiac tissue model incorporating extracellular electric field coupling, intercellular cleft sodium nanodomains, and LQT3-associated mutant channels, myocytes produced EADs for wide intercellular clefts, whereas for narrow clefts, EADs were suppressed. For both wide and narrow clefts, mutant channels were incompletely inactivated. However, for narrow clefts, late sodium current was reduced via self-attenuation, a protective negative feedback mechanism, masking EADs. CONCLUSIONS: We demonstrated a novel mechanism leading to the concealing and revealing of EADs in LQT3 models. Simulations predict that this mechanism may operate independent of the specific mutation, suggesting that future therapies could target intercellular cleft separation as a compliment or alternative to sodium channels.

A Robust System for Longitudinal Knee Joint Edema and Blood Flow Assessment Based on Vector Bioimpedance Measurements.

We present a robust vector bioimpedance measurement system for longitudinal knee joint health assessment, capable of acquiring high resolution static (slowly varying over the course of hours to days) and dynamic (rapidly varying on the order of milli-seconds) bioresistance and bioreactance signals. Occupying an area of 78×90 mm(2) and consuming 0.25 W when supplied with ±5 V, the front-end achieves a dynamic range of 345 Ω and noise floor of 0.018 mΩrms (resistive) and 0.055 mΩrms (reactive) within a bandwidth of 0.1-20 Hz. A microcontroller allows real-time calibration to minimize errors due to environmental variability (e.g., temperature) that can be experienced outside of lab environments, and enables data storage on a micro secure digital card. The acquired signals are then processed using customized physiology-driven algorithms to extract musculoskeletal (edema) and cardiovascular (local blood volume pulse) features from the knee joint. In a feasibility study, we found statistically significant differences between the injured and contralateral static knee impedance measures for two subjects with recent unilateral knee injury compared to seven controls. Specifically, the impedance was lower for the injured knees, supporting the physiological expectations for increased edema and damaged cell membranes. In a second feasibility study, we demonstrate the sensitivity of the dynamic impedance measures with a cold-pressor test, with a 20 mΩ decrease in the pulsatile resistance associated with increased downstream peripheral vascular resistance. The proposed system will serve as a foundation for future efforts aimed at quantifying joint health status continuously during normal daily life.

SmartSock: a wearable platform for context-aware assessment of ankle edema.

Ankle edema an important symptom for monitoring patients with chronic systematic diseases. It is an important indicator of onset or exacerbation of a variety of diseases that disturb cardiovascular, renal, or hepatic system such as heart, liver, and kidney failure, diabetes, etc. The current approaches toward edema assessment are conducted during clinical visits. In-clinic assessments, in addition to being burdensome and expensive, are sometimes not reliable and neglect important contextual factors such as patient's physical activity level and body posture. A novel wearable sensor, namely SmartSock, equipped with accelerometer and flexible stretch sensor embedded in clothing is presented. SmartSock is powered by advanced machine learning, signal processing, and correlation techniques to provide real-time, reliable, and context-rich information in remote settings. Our experiments on human subjects indicate high confidence in activity and posture recognition (with an accuracy of > 96%) as well as reliable edema quantification with intra-class correlation and Pearson correlation of 0.97.

Assessment of voice quality after carbon dioxide laser and microdebrider surgery for Reinke edema.

OBJECTIVES: Surgery of Reinke edema requires reduction of the degenerated superficial lamina propria and preservation of the vibratory epithelium. MATERIAL AND METHODS: Sixteen patients were included for microdebrider and 10 patients for carbon dioxide (CO2) laser surgery. Vocal analysis was performed before and at 1 and 3 months after surgery. Subjective rating of voice quality was completed by the grade, roughness, breathiness, asthenia, and strain scale. The objective assessment was conducted by Multi-Dimensional Voice Program software. RESULTS: We found consistent improvement in all parameters both in CO2 laser and microdebrider group. The normalization of all parameters were statistically better after microdebrider surgery. The most statistically significant improvements were accounted in reduction in grade of hoarseness, roughness, and asthenia and acoustic analysis. CONCLUSIONS: Microdebrider is a useful and safe tool for Reinke edema treatment. The oscillatory cutting knife and low suction protect lamina propria resulting in better vibratory function.

[Comparative assessment of endoscopic and open methods of autovenous conduit exposure for coronary artery bypass grafting operations].

AIM: comparative assessment of endoscopic and open exposure of the great saphenous vein during the operation of coronary artery bypass grafting. MATERIAL AND METHODS: a total of 228 patients with endured coronary artery bypass graft operation were randomized depending on the method of exposing the great saphenous vein (GSV) - an open method of vein exposure (OVE) - 115 patients and endoscopic vein exposure (EVE) - 113 patients. The evaluated parameters included healing of the postoperative wounds, postoperative oedema, pain intensity, and neuropathies in the early postoperative period. We performed lymphoscintigraphy of the lower limbs, as well as morphological examination of the venous wall by means of light and electron scanning microscopy. RESULTS: the duration of vein exposure was less in the EVE group than in the OVE group, amounting to 31.8 ± 6.2 min and 40.3 ± 15.8 min, respectively (p<0.01). Complications after GSV isolation were encountered considerably less often in the EVE group (11.5%) as compared to 44.4% in the OVE (p=0.001). According to the results of the multivariate analysis, diabetes mellitus was the only risk factor for postoperative complications in OVE. According the findings of lymphoscintigraphy the EVE group had no significant impairments of lymph outflow after the operation, whereas during OVE, accumulation of radiopaque material in the lymph nodes decreased twofold (p ≤ 0.001). Histological assessment of the sampled vein specimens showed no considerable lesions of the venous wall in the examined groups. CONCLUSION: the obtained findings confirm high efficacy of using EVE during operations of CABG, lower traumaticity of this method with a conduit of good quality, which was proven based on electron microscopy of the vein fragments.

Multidimensional assessment of vocal changes in benign vocal fold lesions after voice therapy.

OBJECTIVE: To evaluate through a multidimensional protocol voice changes after voice therapy in patients with benign vocal fold lesions. METHODS: 65 consecutive patients affected by benign vocal fold lesions were enrolled. Depending on videolaryngostroboscopy the patients were divided into 3 groups: 23 patients with Reinke's oedema, 22 patients with vocal fold cysts and 20 patients with gelatinous polyp. Each subject received 10 voice therapy sessions and was evaluated, before and after voice therapy, through a multidimensional protocol including videolaryngostroboscopy, perception, acoustics, aerodynamics and self-rating by the patient. Data were compared using Wilcoxon signed-rank test. Kruskal-Wallis test was used to analyse the mean variation difference between the three groups of patients. Mann-Whitney test was used for post hoc analysis. RESULTS: Only in 11 cases videolaryngostroboscopy revealed an improvement of the initial pathology. However a significant improvement was observed in perceptual, acoustic and self-assessment ratings in the 3 groups of patients. In particular the parameters of G, R and A of the GIRBAS scale, and the noise to harmonic ratio, Jitter and shimmer scores improved after rehabilitation. A significant improvement of all the parameters of Voice Handicap Index after rehabilitation treatment was found. No significant difference among the three groups of patients was visible, except for self-assessment ratings. CONCLUSION: Voice therapy may provide a significant improvement in perceptual, acoustic and self-assessed voice quality in patients with benign glottal lesions. Utilization of voice therapy may allow some patients to avoid surgical intervention.

Assessment of cardiac structure and function in patients without and with peripheral oedema during rosiglitazone treatment.

BACKGROUND: Thiazolidinediones cause peripheral oedema, the aetiology of which remains poorly understood. METHODS: In a sub-study of a 6-month trial comparing rosiglitazone (Rsg) versus placebo, we compared those with versus without oedema among the 74 subjects treated with Rsg with respect to peak oxygen consumption indexed to fat-free mass (VO(2peak-FFM) ), cardiac MRI and markers of plasma volume expansion. RESULTS: Almost half (49%) of the Rsg-treated patients developed oedema. Baseline VO(2peak-FFM) was not different between those with versus without oedema (25.8 versus 28.2 ml/kg/min; p = 0.22) and declined 5% in the oedema group (Δ -1.3 ml/min/kg; p = 0.005) with no change in those without oedema. Stroke volume increased in both groups (Δ 8.7 and 8.8 ml; p < 0.001 for each); end-diastolic volume increased only in those with oedema (+13.1 ml; p = 0.001). No other cardiac function changes were observed. In both groups, weight increased (3.6 and 2.2 kg) and haematocrit decreased (-3.2% and -2.1%; p < 0.001 for each). In those with oedema, albumin decreased (-0.2 g/dl) and brain natriuretic peptide increased (11.9 pg/ml; p < 0.03 for each). CONCLUSIONS: Oedema was associated with a small decline in VO(2peak FFM), no adverse effects on cardiac function, and changes in selected measures suggesting that volume expansion underpins Rsg oedema.

Noninvasive assessment of visco-elasticity in the presence of accumulated soft tissue fluid.

BACKGROUND: The diagnosis of compartment syndrome is made by clinical examination, but direct compartmental measurements are important and serve an adjunctive role in establishing the diagnosis. This study examines a noninvasive screening method for differentiating compartmental syndrome from edema without elevated internal pressure. MATERIALS AND METHODS: The study groups consisted of 16 normals, 22 subjects with edema, and 2 subjects with compartmental syndrome. Force-displacement curves on the posterior and anterior surface of the extremity at mid-calf of each extremity were recorded using a noninvasive mechanical tester. A cyclic force peaking at 120 N was applied over a skin area of 1.5 cm(2). In a uniform applied force environment, the peak force would be comparable to an applied pressure of 60 mm Hg. Mechanical parameters associated with tissue softness (SOFT), degree of hysteresis, and departure from linear elastic behavior were calculated. In seven subjects, direct intracompartment pressure readings were obtained by the Stryker method. RESULTS: Posterior SOFT was significantly larger than anterior SOFT, as expected, for all study groups, except those with compartmental syndrome. SOFT for subjects with compartment syndrome fell below the 99% confidence interval of all other groups in the affected compartment(s). Departure from linear elastic behavior values were also depressed in the posterior compartment for subjects with compartment syndrome as compared with the other groups. Degree of hysteresis was significantly increased for pitting edema. Extremities with nonpitting edema were not distinguishable from normal extremities for the levels of applied pressure used in this study. CONCLUSION: Noninvasively measured mechanical properties were significantly different between normal tissues and tissues with pitting and nonpitting edema. The mechanical properties of the extremity with compartmental syndrome were different than those with edema as well as normal extremities. A noninvasive mechanical tester is seen as a possible clinical tool to diagnose and monitor compartmental syndrome.

Assessment of nutritional status in adult patients with cystic fibrosis: whole-body bioimpedance vs body mass index, skinfolds, and leg-to-leg bioimpedance.

OBJECTIVE: To investigate whether body mass index (BMI) or body fat percentage estimated from BMI, skinfolds, or leg-to-leg bioimpedance are good indicators of nutritional status in adult patients with cystic fibrosis. Body fat percentage measured by whole-body bioimpedance was used as the reference method. DESIGN: Cross-sectional study using four methods to estimate body fat percentage. All patients filled out a food frequency and a physical activity questionnaire for assessment of their habitual food intake and energy requirements, respectively. SUBJECTS/SETTING: Thirty-five adult patients (23 men/12 women) with cystic fibrosis, age range 18 to 46 years, were measured during their yearly visit at the outpatient clinic of the Cystic Fibrosis Center in Utrecht, the Netherlands. STATISTICAL ANALYSIS: Mean+/-standard deviation was calculated for all measurements and 95% confidence intervals for differences between methods. Bland-Altman plots were used to assess differences between the measures of body composition and Pearson correlation coefficients were calculated to determine the relationships between them, and between the energy requirements and the energy intakes. RESULTS: For men the whole-body body fat percentage reference was 14.1%+/-3.0, body fat percentage estimated from BMI was 15.8%+/-4.3, body fat percentage estimated from skinfolds was 8.6%+/-4.8, and body fat percentage estimated from leg-to-leg bioimpedance was 13.1%+/-4.9. For women the whole-body body fat percentage reference was 24.0%+/-5.9, body fat percentage estimated from BMI was 25.1%+/-4.0, body fat percentage estimated from skinfolds was 17.0%+/-4.8, and body fat percentage estimated from leg-to-leg bioimpedance was 25.0%+/-6.9. Body fat percentage estimated from BMI and body fat percentage estimated from skinfolds were significantly different from the reference value for body fat percentage (P <.05). The correlation coefficients between the reference body fat percentage and body fat percentage estimated from BMI, from skinfolds, and from leg-to-leg bioimpedance were all more than 0.72. In all but one patient, nutritional status was correctly assessed by BMI: those with a BMI less than 18.5 had body fat percentage less than 10% (men) or less than 20% (women). The mean energy intake of the men was 141% of the Recommended Dietary Allowance as proposed in European and Dutch guidelines. The mean energy intake of the women was 94% of the Recommended Dietary Allowance. CONCLUSIONS: A simple calculation of BMI is adequate to diagnose nutritional status in adult patients with cystic fibrosis. Bioimpedance measurements are only needed when nutritional therapy specifically focuses on lean body mass.

Assessment of spinal cord pathology following trauma using early changes in the spinal cord evoked potentials: a pharmacological and morphological study in the rat.

The possibility that spinal cord pathology following trauma can be assessed with early changes in the spinal cord evoked potentials (SCEPs) was examined in a rat model. Spinal cord injury (SCI) was produced in Equithesin-anesthetized (3 ml/kg, i.p.) rats through a longitudinal incision into the right dorsal horn at the T10-11 segments. The SCEPs were recorded with epidural electrodes placed over the T9 (rostral) segment of the cord. The SCEPs consisted of a small positive amplitude and a broad and high negative amplitude (NA). SCI resulted in an instant depression of the rostral NA that lasted for 1 h. However, the latency of NA continued to increase over time. At 5 h, spinal cord blood flow declined by 30% in the T9 segment, whereas the spinal cord water content and the permeability of the blood-spinal cord barrier (BSCB) were markedly increased. Damage to the nerve cells, glial cells, and myelin was quite common in the spinal cord, as seen by light and electron microscopy. Pretreatment with p-chlorophenylalanine, indomethacin, ibuprofen, and nimodipine attenuated the SCEP changes immediately after trauma and resulted in a marked reduction in edema formation, BSCB permeability, and blood flow changes at 5 h. However, pretreatment with cyproheptadine, dexamethasone, phentolamine, and propranolol failed to attenuate the SCEP changes after SCI and did not reduce the cord pathology. These observations suggest that early changes in SCEP reflect secondary injury-induced alterations in the cord microenvironment. Obviously, these changes are crucial in determining the ultimate magnitude and severity of cord pathology.

Chronic venous insufficiency: worldwide results of the RELIEF study. Reflux assEssment and quaLity of lIfe improvEment with micronized Flavonoids.

Chronic venous insufficiency (CVI) results in considerable morbidity and may seriously affect patients' quality of life. The RELIEF (Reflux assEssment and quaLity of life improvEment with micronized Flavonoids) Study was a prospective controlled study designed to assess differences in the severity and in the evolution of symptoms and signs of CVI according to presence or not of venous reflux. Patients were thus separated into 2 comparative groups: those presenting venous reflux and those without venous reflux. The design of the study was multicentric and international, carried out in 23 countries over 2 years, in which 5,052 symptomatic patients assigned to classes C0 to C4 (on the basis of CEAP clinical classification) were enrolled. Patients were treated with micronized purified flavonoid fraction (MPFF), consisting of 450 mg of micronized diosmin and 50 mg of flavonoids expressed in hesperidin over 6 months. In order to document changes in the quality of life of these patients during MPFF treatment, a new validated Quality of Life Questionnaire specific to CVI (CIVIQ) was used. The study also set out to gather epidemiologic data including the prevalence of venous reflux in symptomatic patients. The RELIEF study provided important information about the epidemiology and clinical manifestations of CVI. Of particular interest was the observation that venous reflux was found to be absent in 57% of patients diagnosed as suffering from CVI belonging to CEAP classes C0 to C4. A positive relationship between symptoms of CVI (pain, leg heaviness, sensation of swelling, and cramps) and presence of venous reflux was found in the RELIEF study: symptoms were more frequent and more severe at presentation in patients with venous reflux. Moreover, during MPFF treatment, all symptoms showed a greater decrease in the group without venous reflux compared with the other group. This difference in the evolution of symptoms between the 2 groups was significant for pain, sensation of swelling, and cramps. Regarding leg heaviness and signs such as edema (assessed by leg circumference), patients improved equally independently of the presence or not of venous reflux. The significant and progressive improvement in the signs of CVI was reflected in significant changes in the clinical class of the CEAP classification, ie, from more severe to less severe stages. Continuous clinical improvement was found throughout the study and after treatment with MPFF for 6 months, the clinical scores of all symptoms and signs had significantly decreased (p=0.0001 versus DO) in both groups. This improvement was also associated with a significant and continuous progression in the quality of life scores of all patients. Age of patients, average time since diagnosis, and presence of venous reflux increased with the severity of the disease. The relationship shown in this study between these parameters and clinical CEAP classification reflects the progressive nature of CVI. Despite obvious symptoms of CVI, a very low percentage (21.8%) of the "intention-to-treat" (ITT) population had previously been treated. This was the case whether venous reflux was present or not.

RELIEF study: first consolidated European data. Reflux assEssment and quaLity of lIfe improvement with micronized Flavonoids.

The RELIEF study (Reflux assEssment and quality of life improvement with micronized Flavonoids in chronic venous insufficiency [CVI]) is a prospective, controlled, multicenter, international study performed in patients with or without venous reflux. This study was conducted between March 1997 and December 1998 in 23 countries worldwide with the participation of more than 10,000 patients suffering from CVI. The European countries, the subject of this report, were represented by the Czech and Slovak Republics, Hungary, Poland, Russia, and Spain. The principal aims of the study were: 1. To validate the first quality-of-life scale specific to chronic venous insufficiency (CMVIQ) in different languages and to assess the evolution of quality of life in patients suffering from CVI, with or without venous reflux, treated with micronized purified flavonoid fraction (MPFF*) (1,000 mg/day). 2. To collect international epidemiologic data on venous reflux assessed with pocket Doppler and photoplethysmography. 3. To assess the evolution of symptoms and signs with a specific emphasis on edema through validated Leg-O-Meter measurement (heaviness, pain, cramps, sensation of swelling, edema) in patients suffering from CVI and treated with MPFF, 1,000 mg/day, during 6 months. The first country-by-country statistical analysis and the European consolidated analysis are now available. The CIVIQ questionnaires adapted to each participating country have been validated with highly significant validity and reproducibility (p<0.0001). All dimensions have demonstrated a highly significant and evolving improvement during the study. The results show several interesting findings concerning the epidemiologic data and, of these, two were particularly interesting: - More than 50% of patients suffering from CVI (class 0 to 4 of the CEAP classification) were reflux-free, which means that they were suffering from functional CVI. Patient distribution between the different classes of the CEAP classification changed in a statistically significant manner after 6 months' treatment with MPFF; the number of patients in the more severe classes decreased to the benefit of the less severe classes. Symptoms such as pain, leg heaviness, sensation of swelling, and cramps were significantly improved (p=0.0001). This was associated with a significant decrease in edema, when present, measured by leg circumferences with the Leg-O-Meter (p=0.0001). In conclusion, the European results of the RELIEF study showed the perfect validity and reproducibility of CIVIQ questionnaire adaptations, and the positive progression of quality-of-life scores on MPFF treatment. This progression was paralleled by clinical improvement of patients reflected not only by assessment of CVI symptoms and signs but also by evolution of the CEAP classification.

Assessment of peripheral sympathetic nervous function for diagnosing early post-traumatic complex regional pain syndrome type I.

Clinical diagnosis of complex regional pain syndrome type I (CRPS I) in post-traumatic patients is often delayed since the clinical appearance of this disease resembles normal post-traumatic states to a certain extent (pain, edema, loss of function). The purpose of this study was to assess the incidence of specific clinical features in CRPS I patients and normal post-traumatic patients and to evaluate the diagnostic value of a bedside test that measures the sympathetic nervous function. Fifty patients with post-traumatic CRPS I of the upper limb and 50 patients 8 weeks after distal radius fracture with an undisturbed course of disease were subjected to a detailed clinical examination. Pain was assessed using the VAS (visual analog scale), skin temperature measured with an infrared camera and grip-strength with a pneumatic manometer. In CRPS I patients, motor disturbances defined as an impaired active range of motion of the hand, were most frequent (96%, fracture patients: 40%), followed by edema (88%, fracture patients: 80%) and spontaneous pain (VAS 4.0 +/- 2.3, fracture patients: VAS 1.3 +/- 0.6). Systematic temperature differences (>1 degree C) between the affected and unaffected limbs were seen in only 42% of CRPS I patients and in 34% of the fracture patients. Further sensory, sudomotor or trophic changes of the hands were rare. As expected, there were significant differences in the quantity of edema, motor disturbances and sensory disturbances between CRPS I patients and normal fracture patients. However, normal fracture patients still suffered from several of the evaluated symptoms 8 weeks after trauma, which makes an early clinical diagnosis of the complication more difficult. Using a newly developed bedside test, the peripheral sympathetic nervous function was assessed in both groups of patients and in 50 age-matched healthy controls. The decrease in skin blood flow following sympathetic provocation maneuvers, detected by laser Doppler flowmetry, was quantified as sympathetic reactivity. In the affected hands of CRPS I patients, as well as in the contralateral hands, the sympathetic reactivity was obliterated or diminished in contrast to the age-matched controls and normal fracture patients. A multivariate analysis did not reveal any correlation between sympathetic function and the severity of any clinical symptom. Sympathetic reactivity seems to be an independent variable in CRPS I and the test presented may facilitate the difficult clinical diagnosis of this disease.