Systemic effects of locally injected platelet rich plasma in a rat model: an analysis on muscle and bloodstream.

Abundant evidence suggests that growth factors, contained in platelets alpha granules, may play a key role in the early stages of the muscle healing process with particular regard to the inflammatory phase. Although the contents of the platelet-rich plasma preparations have been extensively studied, the biological mechanisms involved as well as the systemic effects and the related potential doping implications of this approach are still largely unknown. The aim of the present study was to investigate whether local platelet-rich plasma administration may modify the levels of specific cytokines and growth factors both in treated muscle and bloodstream in rats. An additional aim was to investigate more deeply whether the local platelet-rich plasma administration may exert systemic effects by analyzing contralateral lesioned but untreated muscles. The results showed that platelet-rich plasma treatment induced a modification of certain cytokines and growth factor levels in muscle but not in the bloodstream, suggesting that local platelet-rich plasma treatment influenced directly or, more plausibly, indirectly the synthesis or recruitment of cytokines and growth factors at the site of injury. Moreover, the observed modifications of cytokine and growth factor levels in contralateral injured but not treated muscles, strongly suggested a systemic effect of locally injected platelet-rich plasma.

Effect of whole body vibration frequency on neuromuscular activity in ACL-deficient and healthy males.

Whole-body vibration (WBV) has been shown to enhance muscle activity via reflex pathways, thus having the potential to contrast muscle weakness in individuals with rupture of the anterior cruciate ligament (ACL). The present study aimed to compare the magnitude of neuromuscular activation during WBV over a frequency spectrum from 20 to 45 Hz between ACL-deficient and healthy individuals. Fifteen males aged 28±4 with ACL rupture and 15 age-matched healthy males were recruited. Root mean square (RMS) of the surface electromyogram from the vastus lateralis in both limbs was computed during WBV in a static half-squat position at 20, 25, 30, 35, 40 and 45 Hz, and normalized to the RMS while maintaining the half-squat position without vibration. The RMS of the vastus lateralis in the ACL-deficient limb was significantly greater than in the contralateral limb at 25, 30, 35 and 40 Hz (P<0.05) and in both limbs of the healthy participants (dominant limb at 25, 30, 35, 40 and 45 Hz, P<0.05; non dominant limb at 20, 25, 30, 35, 40 and 45 Hz, P<0.05). The greater neuromuscular activity in the injured limb compared to the uninjured limb of the ACL-deficient patients and to both limbs of the healthy participants during WBV might be due to either augmented excitatory or reduced inhibitory neural inflow to motoneurons of the vastus lateralis through the reflex pathways activated by vibratory stimuli. The study provides optimal WBV frequencies which might be used as reference values for ACL-deficient patients.

[Adult patients treated for focal epilepsy with antiepileptic drugs (AEDs) in combination in France: description according to the 2009 ILAE definition of AED resistance (ESPERA study)]. / Patients adultes traités par une association d'antiépileptiques pour une épilepsie focale en France: description et mode de prise en charge selon les nouveaux critères de définition de la pharmacorésistance (étude ESPERA).

AIMS: To describe the adult population treated with antiepileptic drugs (AEDs) in combination for focal epilepsy according to the definition of AED resistance proposed by the International League Against Epilepsy (ILAE) in 2009 and to evaluate its implementation in current practice. METHODS: ESPERA was a multicenter, observational, cross-sectional study with a clinical data collection covering the past 12 months conducted by neurologists. Classifications according to AED responsiveness established by investigators for each enrolled patient were revised by two experts. RESULTS: Seventy-one neurologists enrolled 405 patients. Their mean age was 42.7 years (sex-ratioM/F 0.98). According to the investigators, 60% of epilepsies were drug-resistant, 37% drug-responsive and 3% had an undefined drug-responsiveness. After revision of experts, 71% of epilepsies were classified as drug resistant, 22% as responsive and 7% as undefined. Among the participating neurologists, 76% have made at least one error in classifying their patients according to the 2009 ILAE definition of AED resistance. Because of epilepsy, 24% of patients (age≤65) were inactive and 42% could not drive (respectively 29 and 49% of patients with AED resistant epilepsy). Half of patients had at least one other chronic condition. Number of prescribed drugs in combination and health care resource utilisation were significantly higher in patients with drug-resistant epilepsies than in patients with drug responsive epilepsies. CONCLUSION: ESPERA study shows that the use of new definition of drug-resistance in everyday practice seems difficult without any additional training and that the social and professional disability is frequent in adults with focal epilepsies treated with polytherapy.

Management of relapsed or refractory multiple myeloma in French hospitals and estimation of associated direct costs: a multi-centre retrospective cohort study.

WHAT IS KNOWN AND BACKGROUND: For relapsed or refractory multiple myeloma (RRMM), a series of novel agents (thalidomide, bortezomib and lenalidomide) has emerged during the latest decade, but their use in routine clinical practice is not well documented as well as the cost of RRMM. OBJECTIVE: Our aim is to review the therapeutic management of such patients in France and to estimate the associated costs. METHODS: A retrospective cohort study, based on chart reviews, was conducted in French Haematology Departments over the period 2004-2007 and the associated direct costs estimated. RESULTS: One hundred and two patients with a relapse after first-line therapy were selected from five centres. The average follow-up from diagnosis or the date of first relapse to death or to the latest news was respectively 56.25 and 23.53 months. Novel agents were used in 73% of all cases, and in all cases of first relapse. Thalidomide and bortezomib were respectively the most frequently used second-line (57%) and third-line treatments (44%). The average number of lines of treatment received per patient as from first relapse was 2.75 (min 1; max 8) and the mean direct cost per month was estimated at 3130 € after the first relapse. This cost was represented in greater part by the cost of chemotherapy drugs (66%). WHAT IS NEW AND CONCLUSION: The use of novel agents such as thalidomide, bortezomib and lenalidomide for RRMM is highly prevalent in France from the first relapse. The associated medical cost is substantial mainly due to the cost of the new agents.

Endothelial (dys)function: the target of physical exercise for prevention and treatment of cardiovascular disease.

AIM: Endothelial dysfunction has been recognized as the early event and the common feature of chronic disorders associated with increased risk for atherosclerotic heart diseases. While the beneficial effects of aerobic, moderate-intensity exercise on endothelial function are very well assessed, an intriguing doubt exists about the effects of long-term high-intensity physical activity. The aim of the present study was to compare recent findings of our group concerning homocysteine levels in athletes to available data in literature in order to clarify the meaning of such apparent metabolic paradox. METHODS: The studied population included 185 athletes: 180 healthy age and sex matched subjects served as control group. The assessed variables included homocysteine, folate, vitamin B12, total and HDL cholesterol, LDH, CPK and IL-6. Results were compared to available data in literature. RESULTS: The prevalence of hyperhomocysteinemia (>15 µmol/L) in athletes and controls was 55% and 15%, respectively. In the studied population, no correlation was found between homocysteine and all the other investigated variables. CONCLUSION: The present results suggest that intensive physical training could induce a pathological increase of homocysteine levels. With this regard, it has been suggested that the observed increases of cardio-vascular risk factors in athletes could represent an adaptative feature marker of muscle demand but would not actually lead to endothelial damage. This remains, however, a speculative hypothesis and further analysis are needed in order to clarify the clinical significance of those observations in order to better preserve the athletes immediate and future health.

Morbidity and mortality associated with influenza exposure in long-term care facilities for dependent elderly people.

The purpose of this paper is to describe the impact of exposure to influenza on hospitalizations and deaths in the elderly residents of long-term care facilities (LTCFs). An observational, longitudinal, prospective, multicenter, cohort study collected influenza and influenza-like cases, diseases, hospitalizations, and deaths of dependent elderly residents of French LTCFs during the 2004-2005 seasonal influenza epidemic. A total of 8,041 residents of 98 participating LTCFs were included. The mean age was 85 +/- 9 years; 93% were vaccinated against influenza and 64% of the residents were exposed to influenza during the epidemic. Exposure to influenza increased both the all-cause risk of hospitalization (9.2% of the residents exposed vs. 7.4% of the residents not exposed) (relative risk, RR [95% confidence interval, CI] = 1.24 [1.05; 1.47]) and the all-cause risk of death (5.8% vs. 4.3%) (RR [95% CI] = 1.36 [1.10; 1.70]). Exposure to influenza increased the risks of death and hospitalization. Additional measures should be taken to avoid influenza exposure and apply recommendations more thoroughly in the particularly susceptible population of elderly LTCF residents.

N-terminal proB-type natriuretic peptide and homocysteine concentrations in athletes.

AIM: Several studies suggest that intense exercise may increase the athlete's thrombotic tendency. Available data on those metabolic alteration are still conflicting and their clinical significance is still worth of interest. The aim of the present study was to investigate if widely used markers of cardiac damage such as NT-proBNP levels are affected by homocysteine concentrations during sustained sport activities. METHODS: Seventy-eight competitive, non-professional athletes were enrolled in the study; 70 healthy age matched subjects, recruited from blood donors, served as controls. Besides the general clinical determinations, the assessed variables included homocysteine, folate, vitamin B12, total and HDL cholesterol, LDH, CPK, NT-proBNP and IL-6. RESULTS: The percentages of athletes with normal and elevated homocysteine levels resulted 46% and 54%, respectively. Mean NT-proBNP levels were significantly higher in athletes than in controls (1176.66 + or - 442.15 pg/mL versus 450.34 + or - 180.39 pg/mL). No correlation was found between homocysteine and NT-proBNP values. CONCLUSIONS: The previously described "sport related" homocysteine is not related to other markers of cardiovascular stress such as NT-proBNP. Available data suggest that both hyperhomocysteinemia and high NT-proBNP levels in healthy young athletes could be interpreted as markers of metabolic and morphologic adaptation to training rather than a risk factor for cardio-vascular diseases.

Bone mineral density and sport: effect of physical activity.

Osteoporosis is a multifactorial progressive skeletal disorder characterized by compromised bone mass which predisposes to increased fracture risk. Fractures are often associated with increased morbidity, mortality, loss of function, deformity and functional limitations. The major public health impact of osteoporosis calls for organized strategies for both primary and secondary prevention. Even if pharmacological therapeutic interventions provide substantial reduction in fracture risk, prevention of osteoporosis should begin early in life. Primary prevention during growth and adolescence aims to obtain a high peak bone mass, adequate calcium intake, exercise and early diagnosis and treatment of potential skeletal deformities. Secondary prevention, during middle age, aims to identify the subjects with low bone mass and more than one risk factor for an osteoporotic fracture, in order to plan multifactorial interventions with a special emphasis on nutritional aspects and individualized sport therapy.

Sport-related hyperhomocysteinaemia: a putative marker of muscular demand to be noted for cardiovascular risk.

OBJECTIVE: Regular physical activity is associated with a reduction of cardiovascular morbidity and mortality; however, evidence of unfortunate cardiovascular events accompanying elite sport involvement continues to accumulate. To date, no information is available on possible peculiarities of the cardiovascular risk profile in athletes. DESIGN: The aim of this study was to evaluate plasma homocysteine levels in a group of athletes and to search for relationship with vitamin status and other metabolic variables in order to confirm the existence of a "sport-related hyperhomocysteinaemia" and to explain its clinical significance. The study population was composed of 82 athletes (59 male and 23 female) practising different sports and 70 healthy age-matched subjects (40 male and 30 female) as a control group. Besides the general clinical and analytical determinations, the assessed variables included homocysteine, folate, vitamin B12, total and high-density lipoprotein (HDL) cholesterol, lactate dehydrogenase (LDH), creatine kinase (CPK) and interleukin-6 (IL-6). RESULTS: The prevalence of hyperhomocysteinaemia (>15 micromol/l) in athletes and controls was 47% and 15%, respectively. No correlation was found between homocysteine and any of the other investigated variables, in particular plasma folate, blood pressure, LDH, CPK, total and HDL cholesterol and IL-6. CONCLUSION: The results of this study confirm the existence of a sport-related hyperhomocysteinaemia which appears linked neither to the same variables found in the general population, nor to specific training-related variables. We suggest that it would represent an adaptation to training but the possibility of a secondary vascular damage cannot be excluded.