Single- and multiple-dose pharmacokinetic studies of tramadol immediate-release tablets in children and adolescents.

In these combined analyzes from 3 open-label, phase-1 studies, the pharmacokinetic profile of tramadol and its metabolite (M1) following administration of tramadol immediate-release (IR) tablets in children and adolescents, 7-16 years old (studies 1 and 2: n = 38; study 3: n = 21) with painful conditions following single oral dose of tramadol IR (25-100 mg) (studies 1 and 2) or multiple oral doses of tramadol IR tablets every 6 hours for 3 days (study 3) were compared with that of healthy adults following similar treatment. Area under the curve of tramadol and its metabolite M1 in children and adolescents was lower compared with adults (Dose-normalized [DN] AUC, h ng/mL: tramadol: 1316.87 [children]; 1418.02 [adolescents];1838.29 [adults]; M1: 342.56 [children]; 475.4 [adolescents]; 636.13 [adults]) while the Cmax remained similar (DN Cmax , ng/mL: tramadol: 203.75 [children]; 165.35 [adolescents]; 226.92 [adults]; M1: 34.93 [children]; 38.42 [adolescents]; 52.14 [adults]). The DN AUC was further lower in children and adolescents with a lower body weight (<50 kg). The weight normalized oral clearance of tramadol was higher in children and adolescents compared with adults (CL/F, mL/min/kg: 12.66 [children]; 11.75 [adolescents]; 9.06 [adults]). No new safety findings emerged. Tramadol was generally safe and well-tolerated by children and adolescents with painful conditions.

Impact of shale gas development on regional water quality.

Unconventional natural gas resources offer an opportunity to access a relatively clean fossil fuel that could potentially lead to energy independence for some countries. Horizontal drilling and hydraulic fracturing make the extraction of tightly bound natural gas from shale formations economically feasible. These technologies are not free from environmental risks, however, especially those related to regional water quality, such as gas migration, contaminant transport through induced and natural fractures, wastewater discharge, and accidental spills. We review the current understanding of environmental issues associated with unconventional gas extraction. Improved understanding of the fate and transport of contaminants of concern and increased long-term monitoring and data dissemination will help manage these water-quality risks today and in the future.

Cognitive aspects of freezing of gait in Parkinson's disease: a challenge for rehabilitation.

Freezing of gait (FOG) is a very disabling symptom affecting up to half of the patients with Parkinson's disease (PD). Evidence is accumulating that FOG is caused by a complex interplay between motor, cognitive and affective factors, rather than being a pure motor phenomenon. In the current paper, we review the evidence on the specific role of cognitive factors in FOG. Results from behavioral studies show that patients with FOG experience impairments in executive functioning and response selection which predict that motor learning may be compromised. Brain imaging studies strengthen the neural basis of a potential association between FOG and cognitive impairment, but do not clarify whether it is a primary or secondary determinant of FOG. A FOG-related reduction of cognitive resources implies that adaptation of rehabilitation interventions is indicated for patients with FOG to promote the consolidation of learning.

[How to improve the management of heart failure by the general practitioner?]. / Comment améliorer la prise en charge de l'insuffisance cardiaque par le médecin généraliste?

Current treatment of heart failure remains suboptimally implemented, leading to less favorable outcome. Readmission due to decompensation, remains frequent, in about 20% of patients at one month and 50% at six months. Precipitating factors of deterioration are known, including inappropriate drug interactions, and the early detection can be facilitated by simple clinical features (weight, heart rate, dyspnea) that can be confirmed by biomarkers (BNP, Nt-ProBNP). Medical treatment relies upon the proper use of drugs that have been demonstrated efficacious in the randomized clinical trials, and have been proposed in the international clinical guidelines. The basic principle of their titration consists on a gradual increase of the dosage, up to the target dosages, or maximal clinically tolerated dosages. Particular attention shall be paid to renal function and kaliemia, besides clinical parameters; close monitoring is mandatory along the treatment.

Left atrial impression due to lymphadenopathy in an HIV seropositive patient infected with tuberculosis.

We describe a unique case of a 37-year-old patient who was diagnosed with human immunodeficiency virus/tuberculosis co-infection due to a cardiac involvement that consisted in atrial fibrillation as a consequence of a compression of the left atrium by a giant necrotic lymphadenopathy and a pericardial effusion.

Turning and unilateral cueing in Parkinson's disease patients with and without freezing of gait.

BACKGROUND: Freezing of gait (FOG) is one of the most disabling symptoms in Parkinson's disease (PD), and cueing has been reported to improve FOG during straight-line walking. Studies on how cueing affects FOG during turning are lacking. Given the asymmetrical nature of turning and the asymmetrical disease expression, we aimed to gain a new perspective on how unilateral cueing may alleviate FOG. OBJECTIVE: To explore disease dominance and turning side as contributing factors to turning problems and FOG and to investigate the effect of unilateral cueing. METHODS: In the first study, 13 PD patients with FOG (freezers) and 13 without FOG (nonfreezers) turned toward their disease-dominant and nondominant side (off medication). During the second study, 16 freezers and 14 nonfreezers turned with and without a unilateral auditory cue at -10% of preferred cadence. Total number of steps, turn duration, cadence, and FOG episodes were measured using VICON. RESULTS: Cadence, but not FOG frequency, was higher when turning toward the disease-dominant side. FOG started more frequently (64.9%) on the inner side of the turning cycle. Unilateral cueing seemed to prevent FOG in most patients, irrespective of the side at which the cue was offered. A carryover effect was found for cadence during turning, but the effect on FOG disappeared when the cue was removed. CONCLUSIONS: The occurrence of FOG is not influenced by turning toward the disease-dominant or nondominant side, which is confirmed by the fact that it does not make a difference at which side unilateral cueing is applied. Cueing reduces FOG during turning, but these effects disappear dramatically after cue removal. This raises further questions as to the influence of training on cue dependency and on the feasibility of either continuous application of cues or using cognitive strategies as an alternative.

Conflict and freezing of gait in Parkinson's disease: support for a response control deficit.

We investigated response activation and suppression processes in Parkinson's disease patients with freezing of gait (FOG). Fourteen freezers, 14 nonfreezers, and 14 matched healthy controls performed the attention network task (ANT) and the Stroop task. The former task has more stimulus-response overlap and is expected to elicit stronger irrelevant response activation, requiring more inhibition. Congruency effects were used as a general measure of conflict resolution. Supplementary reaction time (RT) distribution analyses were utilized to calculate conditional accuracy functions (CAFs) and delta plots to measure response activation and suppression processes. In agreement with previous research, freezers showed a general conflict resolution deficit compared with nonfreezers and healthy controls. Moreover, CAFs pointed to a strong initial incorrect response activation in FOG. As expected, conflict resolution impairment was only apparent in the ANT, and not in the Stroop task. These results suggest an imbalance between automatic and controlled processes in FOG, leading to a breakdown in both motor and cognitive response control.

Rupture of papillary muscle during dobutamine stress echocardiography.

A 72-year-old man presented with an acute myocardial infarction, he did not receive any reperfusion therapy because he presented as a non-ST elevation myocardial infarction (MI). A dobutamine stress echocardiography was done five days after. A partial rupture of the posterior papillary muscle occurred during the stress test. The patient developed cardiogenic shock; he improved after medical management, and mitral repair was done a few days after.

[Impact of the mode of arrival in the emergency department for patients with a STEMI and the clinical outcomes in terms of ejection fraction and survival]. / Impact du mode d'arrivée aux urgences chez les patients avec un syndrome coronarien aigu avec elevation du segment ST (SCAST+) sur le devenir clinique en termes de FEVG et de survie.

Emergency Medical Services (EMSs) play a key role in the recognition and treatment of ST-segment elevation myocardial infarction (STEMI). This study evaluates patient outcome according to his mode of arrival in the care unit dealing with acute coronary syndromes. METHODS: Retrospective analysis of STEMI infarctions registered by the Belgian Interdisciplinary Working Group on Acute Cardiology (BIWAC) at Saint-Pierre University Hospital, Brussels (C.H.U. Saint-Pierre), between 01/01/2005 and 31/12/2006. Comparison of two groups according to their arrival in the care system: group 1: brought in following an emergency call by mobile medical team (SMUR) or normal ambulance ; group 2: arrived at the hospital by their own means and classic admission to Emergency Service. STUDIED PARAMETERS: descriptive patient characteristics, localisation of the infarction and survival to the end of hospitalization, to six months and to one year. RESULTS: Among 136 patients, 56.6 % arrived by EMS and 43.4 % by their own means. Patients who arrived by EMS were older (p = 0.008) and had a higher Killip score (p < 0.05). Pain-to-Angiography and Door-to-Angiography intervals were shorter in patients who arrived by EMS (222 vs 416 mins, p < 0.0001 and 62.6 vs 147 mins, p < 0.0001, respectively). There were no differences in the left ventricular ejection fraction (LVEF) and survival. However, for patients suffering an IVA attack, survival to six months and one year was better in the EMS group (88.9% vs 78.3%, p < 0.05 and 80.5 % vs 69.6 %, p = 0.05). In conclusion, dealing with STEMI infarctions is quicker by EMS admission. The infarctions admitted by this way are more serious. Wherever STEMI infarctions were localised, no improvement of LV function and survival was observed according to the mode of arrival, contrary to the subgroup with an IVA attack where survival is better at six months and one year by EMS admission.

[The first our quintet or the channel of care for the most usual urgent pathologies]. / Le quintette de la première heure ou les filières de soins des pathologies urgentes les plus fréquentes.

The European Community has named five emergencies as being priorities. These five emergencies are: the cardiorespiratory arrest, the myocardial infarction, the severe polytrauma, the cerebral vascular accident and the severe acute dyspnoea. In this article three of them are discussed. Seen with the eyes of a generalist the severe polytrauma requires simple gestures, such as an early call for help by the SMUR, axialisation of head, trunk and members, compression of overtly sources of bleeding and opening the airway to facilitate breathing. The acute myocardial infarction continues to pose problems of diagnosis. The pathognomonic presentations are the STEMI and the N-STEMI infarction. In these cases it is a priority to call for the help of a SMUR unit. In the case of a STEMI infarction it is an absolute priority to admit the patient quickly to hospital and to directly move on to the coronarography ward for a primary angioplasty procedure. Within the first three hours of the infarction, if primary angioplasty is not a possibility within the first 90 minutes, thrombolysis is absolutely indicated. In the case of N-STEMI infarction a quick admission to a coronary care unit is urgent but the treatment is mainly medical. The cerebral vascular incident occurs more frequently than the myocardial infarction, but, culturally, not enough importance is attached to this pathology. Within the first three hours the aim is to get the patient to an emergency department (by means of the SMUR), to evaluate the coagulation values of the patient and to perform a head scan (without the injection of contrast) of good quality. If the patient is not too severely incapacitated (NIH score between 4 and 25), if the head scan does not show a hemorrhagic lesion and if there is no contraindication for thrombolysis, Actilyse should be administered. The time it takes to do all of these acts can not exceed the above mentioned three hours.

[Acute myocarditis: from chest pain to cardiogenic shock]. / Les myocardites aiguës: de la douleur thoracique au choc cardiogénique--a propos de trois cas.

We report the observations of three patients with myocarditis. The first one with chest pain, the second one with a pseudo-infarct presentation and the third one with a cardiogenic shock. We discuss the different anatomo-clinical presentations of myocarditis, the diagnosis, the indications of endomyocardial biopsies and the prognosis of this pathology.

[Fenfluramines and cardiac valvular lesions]. / Fenfluramines et lésions valvulaires cardiaques.

We report cardiac valvulopathy occurring after prolonged intake of anorectic drugs containing fenfluramine (Fen) and/or dexfenfluramine (D-Fen) in 14 patients whose evolution was followed by Doppler echocardiography. A relation between these drugs and valvular regurgitation was first suspected after 4 cases reported in 1991-1992 and confirmed after 3 more patients in 1993-94-95, who were taken D-Fen or Fen alone. All were women, aged 42 to 73 years. Patient 1 to 7 had been taking Fen and/or D-Fen for 14 to 52 months. Patients 8 to 14 had been taking a mixture of Fen and/or D-Fen, diethylpropion and chinese-herbs for 3 to 69 months. These last 7 patients developed renal failure requiring hemodialysis or peritoneal dialysis in 5 and subsequent renal transplantation in 4. All presented with cardiac murmur(s) and some with dyspnea or palpitations. An initial echocardiography was performed at the time of diagnosis, and was repeated annually for a follow-up period extending to 8 years. We conclude that a relation between Fen and/or D-Fen and the outbreak of valvular heart disease is identified in our patients, confirming previous findings. The nephrotoxicity observed in 7 patients is due to the "chinese-herbs". When Fen and/or D-Fen are stopped and proper therapy initiated, the cardiac symptoms may stabilize or even subside, though slowly. Hemodynamic unstability and/or infection appear to be an aggravating factor. These patient's follow up must be prolonged for several years and is readily achieved with echocardiography. Systematic screening of all patients having taken Fen and/or D-Fen must be performed, as renal and urinary screening for all patients having taken chinese-herbs. Endocardial prophylaxis must always be prescribed.

[The thromboembolic risk of atrial fibrillation]. / Le risque thrombo-embolique de la fibrillation auriculaire.

The assessment of the thrombo-embolic risk is currently well defined in case of atrial fibrillation, in the general population as well as in several subgroups. Predictive factors of thrombo-embolism have been identified, they are clinical and echocardiographic criteria. They allow to stratify the individual risk of each patient and to establish the therapeutic attitude best suited to its thrombo-embolic and haemorrhagic risk profile. Recent clinical trials have demonstrated that oral anticoagulation with coumarinics, adjusted at an INR between 2 and 3, provided a greater protection for patients at higher risk, compared to aspirin, with an acceptable low rate of haemorrhagic complications. When atrial fibrillation is of recent onset, the therapeutic attitude will take into account the time delay between onset of the arrhythmia and the medical consultation, 48 h representing the maximal delay allowed to perform cardioversion without prolonged anticoagulation.

Cardiac and autonomic evaluation in a pediatric population with human immunodeficiency virus.

BACKGROUND: Cardiac involvement in children with human immunodeficiency virus (HIV) infection is a well-known entity and occurs clinically more often in patients with advanced acquired immunodeficiency syndrome (AIDS). Autonomic dysfunction is less known, especially in children. HYPOTHESIS: The aim of this study was to asses the prevalence of cardiovascular abnormalities in a pediatric population with HIV. We also aimed to evaluate whether autonomic involvement occurs in the same population and is dependent on echocardiographic abnormalities. METHODS: The occurrence of echocardiographic abnormalities was evaluated in 22 children with HIV infection, and five noninvasive tests were performed to evaluate the presence of autonomic dysfunction. RESULTS: We found cardiac lesions in four children (18%), consisting of pericardial effusion in three children, wall motion abnormalities in three children, and acute aortic endocarditis in one child. All cardiac abnormalities were found at Stage C by Center for Disease Control (CDC) revised classification. We also found left ventricular filling pattern abnormalities consisting of E-wave maximal velocity decrease and prolonged deceleration time compatible with diastolic dysfunction. One of the five autonomic tests (Valsalva maneuver) was significantly altered, even in patients without abnormal echocardiography, suggesting mild autonomic dysfunction. CONCLUSION: The study demonstrated a high prevalence of cardiac lesions in children with HIV infection and indicated the presence of autonomic dysfunction even when there are no echocardiographically detected abnormalities.

[Role of beta-blockers in the treatment of cardiac insufficiency]. / Place des beta-bloquants dans le traitement de l'insuffisance cardiaque.

Despite Beta-blockade therapy has been considered as an absolute contraindication in the treatment of heart failure, it has been shown that they could have a beneficial effect, provided that they were introduced at very low dose, and very progressively in addition of the traditional treatment. The advances in the understanding of the neuro-hormonal mechanisms of heart failure have modified the therapeutic strategy: the deleterious effect of the activation of the sympathetic nervous system on the myocardium has served as the rationale for randomized clinical trials comparing beta-blockade to placebo: the current data are promising, suggesting a beneficial effect on survival as well as on quality of life. However, these results have to be confirmed by larger trials, currently underway, before to consider that beta-blockade should definitely be incorporated in the treatment of heart failure.

Quantification of mitral regurgitation by the automated cardiac output method: an in vitro and in vivo study.

BACKGROUND: Recently, the automated cardiac output method (ACM) was introduced for the calculation of blood flow at the left ventricular outflow tract (LVOT). This study was performed to examine the possibility of using ACM for flow calculation at the level of the mitral valve and for the quantification of mitral regurgitation (MR) in vitro and in vivo. METHODS AND RESULTS: In a computer-controlled in vitro model of the human heart, aortic and mitral normal bioprosthetic valves were inserted. ACM and electromagnetic probe flow measurements correlated well at the LVOT and at the mitral level (r2 = 0.79 and 0.77, respectively). For stroke volumes ranging from 30 to 100 ml/beat, there was no statistically significant bias between ACM and electromagnetic flow probe (-1.5 and 1.3 ml for LVOT and mitral level, respectively). Limits of agreement were [-14; +11] ml and [-18; +16] ml, respectively. We evaluated 68 patients in our in vivo study. They were divided into three groups according to the results of "standard" echocardiographic Doppler methods for the semiquantification of MR: echocardiographic color Doppler cartography, intensity of the continuous wave Doppler spectra, and in some patients, pulmonary venous flow, conventional Doppler, and proximal isovelocity surface area quantitative data. Group 1 consisted of 35 patients without MR or a physiologic one; the 17 patients in group 2 had a mild MR (1-2/4) and in group 3, 16 patients with MR 3-4/4 were included. Regurgitant volume (RV) was calculated as the difference between ACM mitral flow and ACM aortic flow, and regurgitant fraction (RF) was defined as the ratio between RV and ACM mitral flow. When mitral flow was measured only from the four-chamber view, we found in group 1, RV = -0.57 (0.67) L/min and RF = -16% (19%); in group 2, RV = -0.31 (1.06) L/min and RF = -8% (19%); and in group 3, RV = 1.53 (0.94) L/min and RF = 23% (13%). RV and RF were statistically higher in group 3 compared with group 2 or group 1 (p < 0.0005), but no significant difference was found between groups 1 and 2. When mitral flow was measured by the mean value of ACM four-chamber and two-chamber views, this resulted in group 1, RV = -0.26 (0.63) L/min and RF = -8% (15%); in group 2, RV = 0.01 (1.04) L/min and RF = -2% (18%); and in group 3, RV = 2.07 (1.21) L/min and RF = 34% (19%). RV and RF were again significantly higher in group 3 (p < 0.0001). There was no significant difference between group 1 and group 2, but in group 1 RF was no longer statistically different from 0%. CONCLUSIONS: (1) In our in vitro setting, ACM is reliable both at the LVOT and at the mitral valve. (2) In the in vivo situation, some overlapping does exist between the three groups of MR. However, ACM is a very easy, rapid, and objective method to differentiate hemodynamic nonsignificant (<3/4) from significant (> or =3/4) MR. Together with other well-known methods for the quantification of MR, it should facilitate the gradation of MR in the clinical setting. The absence of significant differences between group 1 and group 2 proves that the accuracy of ACM measurements at the mitral valve needs to be ameliorated before ACM can be used as a gold standard for the noninvasive measurement of RV and RF.

Aortic valve aneurysm after acute endocarditis.

Endocarditis at the aortic level is usually characterized by the presence of a vegetation or an abscess on echocardiography. This paper reports on what is believed by the authors to be the first case of endocarditis presenting as an aneurysmal deformation of one aortic cusp without a vegetation.