Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 148
Filter
1.
J Diabetes Res ; 2018: 5601351, 2018.
Article in English | MEDLINE | ID: mdl-29693021

ABSTRACT

AIM: The prevalence of cardiovascular autonomic neuropathy (CAN) in diabetes mellitus is well documented. However, the rate and predictors of both the development and progression of CAN have been less studied. Hereby, we assessed the rate and the major risk factors for CAN initiation and progression in a cohort of type 1 diabetic patients followed over a three-year period. METHODS: 175 type 1 diabetic patients (mean age: 50 ± 11 years; female/male: 76/99) with positive bedside screening for CAN were included and underwent 2 standardized autonomic testings using 4 standardized tests (deep breathing, Valsalva maneuver, 30/15 ratio, and changes in blood pressure during standing), separated by 3 ± 1 years. CAN staging was achieved according to the Toronto Consensus Panel on Diabetic Autonomic Neuropathy into 4 categories: absent, possible, confirmed, or severe CAN. RESULTS: Out of the 175 patients included, 31.4% were free of CAN, 34.2% had possible CAN, 24.6% had confirmed CAN, and 9.7% exhibited severe CAN at the first assessment. Among the 103 patients with nonsevere CAN at inclusion, forty-one (39.8%) had an increase of at least one category when reassessed and 62 (60.2%) remained stable. A bivariate analysis indicated that only BMI and exposure to selective serotonin reuptake inhibitors (SSRIs) were significantly different in both groups. A multivariate analysis indicated that lower BMI (OR: 0.15, CI 95%: 0.05-0.48, p = 0.003) and SSRI exposure (OR: 4.18, CI 95%: 1.03-16.97, p = 0.04) were the sole predictors of CAN deterioration. In the 55 patients negative for CAN at the first laboratory assessment, 12 became positive at the second assessment. CONCLUSION: No clear predictive factor for CAN onset was identified. However, once present, CAN progression was related to low BMI and SSRI exposure.


Subject(s)
Autonomic Nervous System Diseases/etiology , Autonomic Nervous System/physiopathology , Cardiovascular Diseases/etiology , Cardiovascular System/innervation , Diabetes Mellitus, Type 1/complications , Diabetic Neuropathies/etiology , Adult , Autonomic Nervous System Diseases/diagnosis , Autonomic Nervous System Diseases/physiopathology , Body Mass Index , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/physiopathology , Chi-Square Distribution , Diabetes Mellitus, Type 1/diagnosis , Diabetic Neuropathies/diagnosis , Diabetic Neuropathies/physiopathology , Disease Progression , Female , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Neurologic Examination , Odds Ratio , Risk Factors , Selective Serotonin Reuptake Inhibitors/adverse effects , Time Factors
2.
Brain Struct Funct ; 223(1): 255-265, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28779306

ABSTRACT

Atomic force microscopy (AFM) is emerging as an innovative tool to phenotype the brain. This study demonstrates the utility of AFM to determine nanomechanical and nanostructural features of the murine dorsolateral frontal cortex from weaning to adulthood. We found an increase in tissue stiffness of the primary somatosensory cortex with age, along with an increased cortical mechanical heterogeneity. To characterize the features potentially responsible for this heterogeneity, we applied AFM scan mode to directly image the topography of thin sections of the primary somatosensory cortical layers II/III, IV and V/VI. Topographical mapping of the cortical layers at successive ages showed progressive smoothing of the surface. Topographical images were also compared with histochemically derived morphological information, which demonstrated the deposition of perineuronal nets, important extracellular components and markers of maturity. Our work demonstrates that high-resolution AFM images can be used to determine the nanostructural properties of cortical maturation, well beyond embryonic and postnatal development. Furthermore, it may offer a new method for brain phenotyping and screening to uncover topographical changes in early stages of neurodegenerative diseases.


Subject(s)
Brain Mapping , Frontal Lobe/growth & development , Frontal Lobe/ultrastructure , Microscopy, Atomic Force , Age Factors , Analysis of Variance , Animals , Animals, Newborn , Biomechanical Phenomena , Biotin , Male , Mice , Mice, Inbred C57BL , Plant Lectins/metabolism , Receptors, N-Acetylglucosamine/metabolism
3.
J Physiol Biochem ; 72(3): 567-82, 2016 Sep.
Article in English | MEDLINE | ID: mdl-26792656

ABSTRACT

Resveratrol is beneficial in obese and diabetic rodents. However, its low bioavailability raises questions about its therapeutic relevance for treating or preventing obesity complications. In this context, many related natural polyphenols are being tested for their putative antidiabetic and anti-obesity effects. This prompted us to study the influence of piceatannol, a polyhydroxylated stilbene, on the prevention of obesity complications in Zucker obese rats. A 6-week supplementation was followed by the determination of various markers in plasma, liver, adipose tissue and heart, together with a large-scale analysis of gut microbiota composition. When given in doses of 15 or 45 mg/kg body weight/day, piceatannol did not reduce either hyperphagia or fat accumulation. It did not modify the profusion of the most abundant phyla in gut, though slight changes were observed in the abundance of several Lactobacillus, Clostridium, and Bacteroides species belonging to Firmicutes and Bacteroidetes. This was accompanied by a tendency to reduce plasma lipopolysaccharides by 30 %, and by a decrease of circulating non-esterified fatty acids, LDL-cholesterol, and lactate. While piceatannol tended to improve lipid handling, it did not mitigate hyperinsulinemia and cardiac hypertrophy. However, it increased cardiac expression of ephrin-B1, a membrane protein that contributes to maintaining cardiomyocyte architecture. Lastly, ascorbyl radical plasma levels and hydrogen peroxide release by adipose tissue were similar in control and treated groups. Thus, piceatannol did not exhibit strong slimming capacities but did limit several obesity complications.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antioxidants/therapeutic use , Dietary Supplements , Dysbiosis/prevention & control , Heart Diseases/prevention & control , Obesity/diet therapy , Stilbenes/therapeutic use , 3T3-L1 Cells , Adipose Tissue, White/immunology , Adipose Tissue, White/metabolism , Adiposity , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Antioxidants/administration & dosage , Antioxidants/metabolism , Biomarkers/blood , Biomarkers/metabolism , Dysbiosis/etiology , Heart Diseases/etiology , Hydrogen Peroxide/metabolism , Hyperlipidemias/etiology , Hyperlipidemias/prevention & control , Liver/immunology , Liver/metabolism , Male , Mice , Myocardium/immunology , Myocardium/metabolism , Myocardium/pathology , Obesity/metabolism , Obesity/microbiology , Obesity/physiopathology , Random Allocation , Rats, Zucker , Stilbenes/administration & dosage , Stilbenes/metabolism
4.
J Clin Pharm Ther ; 38(5): 341-9, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23594161

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: Positive inotropic agents are frequently used in acute decompensated heart failure (ADHF) due to left ventricular systolic dysfunction. These agents are known to improve cardiac performance and peripheral perfusion in the short-term treatment. However, several preclinical and clinical studies emphasized detrimental effects of these drugs on myocardial oxygen demand and on sympathetic tone entailing arrhythmogenesis. Levosimendan is an inotropic agent with an original mechanism of action. This review focuses on major data available for levosimendan. METHODS: A literature search was conducted in the PubMed database by including studies published in English using combinations of the following key words, levosimendan, inotropic drugs and acute heart failure. Furthermore, bibliographies of selected references were also evaluated for relevant articles. The collection for this review was limited to the most recently available human and animal data. RESULTS AND DISCUSSION: Levosimendan's vasodilatory and cardioprotective effects are mediated by calcium sensitization of contractile proteins and opening of adenosine triphosphate (ATP)-dependent K+ channels in vascular smooth muscle cells and on mitochondrial ATP-sensitive potassium [mito.K(ATP)] channels. This inotropic agent has mild PDE inhibitory action. Unlike other inotropic agents, levosimendan improves cardiac performance without activating the sympathetic nervous system. Moreover, there are evidences that levosimendan has additional anti-inflammatory and anti-apoptotic properties that prevent cardiac toxicity and contributes to positive hemodynamic response of the drug. Four randomized trials evaluated the effects of levosimendan on mortality in patients with acute decompensated chronic heart failure; nevertheless, a clear benefit has not been demonstrated so far. Although levosimendan is indicated for the treatment of ADHF (class of recommendation IIa, level of evidence B), it is has not been approved in all countries. WHAT IS NEW AND CONCLUSION: This review summarizes the characteristics and the current knowledge of the literature on levosimendan and its active metabolite OR-1896.


Subject(s)
Cardiotonic Agents/pharmacology , Hydrazones/pharmacology , Pyridazines/pharmacology , Vasodilator Agents/pharmacology , Animals , Cardiotonic Agents/therapeutic use , Humans , Hydrazones/therapeutic use , Pyridazines/therapeutic use , Randomized Controlled Trials as Topic , Simendan , Vasodilator Agents/therapeutic use
5.
Ann Fr Anesth Reanim ; 30(11): 814-8, 2011 Nov.
Article in French | MEDLINE | ID: mdl-21981846

ABSTRACT

OBJECTIVE: To improve the quality of proton pump inhibitors (PPI) prescription in an orthopaedic department. STUDY DESIGN: Prospective professional practice evaluation study. PATIENTS AND METHODS: A specific protocol concerning the best practice for using PPI in the perioperative period was established by anaesthesiologists and validated by all prescribers, according to recent recommendations published by French Afssaps. PPI prescription pertinence, mainly using the oral route, was based upon the presence of clearly identified risk factors. PPI mensual consumption and severe gastric complications were analyzed and compared with those obtained from the previous year. Ten months after the beginning of the protocol, the pertinence of PPI prescription was analyzed in 20 randomly selected medical records. Data are expressed in defined daily dose (DDD). RESULTS: After one year, a 35.5% decrease in oral PPI consumption was noted (901 ± 211 before vs 581 ± 235 DDD, after, P<0.05). A similar trend to a decrease in intravenous PPI consumption was observed (40 ± 23 vs 22 ± 26, P=0.06). During the same period, the overall incidence of severe gastric complication remained stable. The PPI prescription was pertinent in 85% of selected medical records. CONCLUSION: This study confirmed the interest of professional practice evaluation protocols to improve PPI prescription. A strong implication of all medical staff members is mandatory to maintain such benefits over time.


Subject(s)
Drug Prescriptions/statistics & numerical data , Proton Pump Inhibitors/therapeutic use , Anesthesiology/trends , Drug Utilization , France , Gastrointestinal Diseases/prevention & control , Humans , Practice Guidelines as Topic , Professional Practice , Prospective Studies , Proton Pump Inhibitors/administration & dosage , Proton Pump Inhibitors/adverse effects
6.
Rev Neurol (Paris) ; 166(10): 779-84, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20817229

ABSTRACT

The aim of this short review is to illustrate, using orthostatic hypotension as an example, the clinical problems related to autonomic features in Parkinson's disease. Orthostatic hypotension is frequently encountered in Parkinson's disease and its diagnosis remains manometric (a fall of at least 20 and/or 10 mmHg in standing blood pressure). It is often associated with supine hypertension to be taken into account before prescribing. To distinguish between the role of disease and of drugs (not only antiparkinsonian drugs), a simple clinical test of autonomic nervous system activity (deep breathing test and standing test with measurement of 30/15 ratio) can be used. When diagnosis with multisystem atrophy is discussed, cardiac [¹²³I]-metaiodobenzylguanidine (MIBG) scintigraphy is of value showing in Parkinson's disease a decreased uptake of the radiopharmaceutical indicating postganglionic sympathetic denervation. Concerning treatment, nonpharmacological methods have to be systematically used since no drug has been specifically evaluated for the treatment of orthostatic hypotension of Parkinson's disease.


Subject(s)
Parkinson Disease/complications , Shy-Drager Syndrome/etiology , Antiparkinson Agents/therapeutic use , Diagnosis, Differential , Humans , Multiple System Atrophy/drug therapy , Multiple System Atrophy/etiology , Shy-Drager Syndrome/drug therapy
7.
Clin Auton Res ; 20(3): 205-7, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20063034

ABSTRACT

We describe the effects of chronic droxidopa in a patient with Dopamine beta-hydroxylase deficiency diagnosed at the age of 73. Investigations were performed to assess sympathetic activity (MIBG scintigraphy, catecholamines) and cardiovascular droxidopa safety.


Subject(s)
Autonomic Nervous System Diseases/drug therapy , Autonomic Nervous System Diseases/enzymology , Dopamine beta-Hydroxylase/deficiency , Droxidopa/therapeutic use , 3-Iodobenzylguanidine , Aged , Autonomic Nervous System Diseases/diagnosis , Autonomic Nervous System Diseases/diagnostic imaging , Catecholamines/blood , Humans , Hypotension, Orthostatic/complications , Male , Radionuclide Imaging , Radiopharmaceuticals
8.
J Mol Cell Cardiol ; 42(3): 526-39, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17222424

ABSTRACT

Obesity is a risk factor for heart failure through a set of hemodynamic and hormonal adaptations, but its contribution at the molecular level is not clearly known. Therefore, we investigated the kinetic cardiac transcriptome and metabolome in the Spontaneous Hypertensive Heart Failure (SHHF) rat. The SHHF rat is devoid of leptin signaling when homozygous for a mutation of the leptin receptor (ObR) gene. The ObR-/- SHHF rat is obese at 4 months of age and prone to heart failure after 14 months whereas its lean counterpart ObR-/+ is prone to heart failure after 16 months. We used a set of rat pangenomic high-density macroarrays to monitor left ventricle cardiac transcriptome regulation in 4- and 10-month-old, lean and obese animals. Comparative analysis of left ventricle of 4- and 10-month-old lean rat revealed 222 differentially expressed genes while 4- and 10-month-old obese rats showed 293 differentially expressed genes. (1)H NMR analysis of the metabolome of left ventricular extracts displayed a global decrease of metabolites, except for taurine, and lipid concentration. This may be attributed to gene expression regulation and likely increased extracellular mass. The glutamine to glutamate ratio was significantly lower in the obese group. The relative unsaturation of lipids increased in the obese heart; in particular, omega-3 lipid concentration was higher in the 10-month-old obese heart. Overall, several specific kinetic molecular patterns act as a prelude to heart failure in the leptin signaling deficient SHHF obese rat.


Subject(s)
Glutamates/metabolism , Glutamine/metabolism , Heart Failure/metabolism , Intracellular Membranes/metabolism , Lipid Metabolism , Obesity/metabolism , Transcription, Genetic/genetics , Adaptation, Biological , Aging/physiology , Animals , Gene Expression Profiling , Heart Failure/genetics , Magnetic Resonance Spectroscopy , Male , Multigene Family , Obesity/genetics , Oligonucleotide Array Sequence Analysis , Phenotype , Rats
9.
Eur J Neurol ; 13(3): 209-14, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16618334

ABSTRACT

Recent case reports of 'sleep attacks' (SA) in patients with Parkinson's disease (PD) generated concerns about drug-induced daytime somnolence in this population. However, there are nearly no comparative data on sleep and vigilance problems between PD patients and normal controls. We performed a cross-sectional survey in PD patients and age-matched controls using a structured questionnaire on PD history, treatments, co-morbidity, activities of daily living, habits, exercise, sleep pattern, driving, pre-existing nocturnal problems, daytime somnolence, episodes of SA and the circumstances in which such episodes occurred. Daytime somnolence was also measured with the Epworth Sleepiness Scale (ESS) and sleep quality with the Pittsburgh Sleep Quality Index (PSQI). 176 PD patients and 174 controls were included. The same proportion of PD patients (27%) and controls (32%) reported episodes of SA, but these were more frequent in PD patients and occurred more frequently during situations requiring attention (10.8% vs. 1.7%, p<10(-3)). More PD patients had abnormal daytime somnolence (ESS) and poor sleeping quality (PSQI). The most consistent factor associated with SA was the duration of levodopa therapy and the predictive value of an abnormal ESS score was rather poor (40.7%). Abnormal daytime somnolence and poor sleep quality at night are more frequent in PD patients than in normals. However, SA are reported in both groups, although less frequently in the normals during activities that requires attention.


Subject(s)
Antiparkinson Agents/adverse effects , Disorders of Excessive Somnolence/chemically induced , Parkinson Disease/complications , Sleep Wake Disorders/complications , Activities of Daily Living , Aged , Case-Control Studies , Chi-Square Distribution , Cross-Sectional Studies , Exercise , Female , Humans , Male , Middle Aged , Parkinson Disease/drug therapy , Parkinson Disease/epidemiology , Predictive Value of Tests , Severity of Illness Index , Sleep Disorders, Circadian Rhythm , Sleep Wake Disorders/epidemiology , Surveys and Questionnaires
10.
Rev Neurol (Paris) ; 161(10): 949-56, 2005 Oct.
Article in French | MEDLINE | ID: mdl-16365624

ABSTRACT

INTRODUCTION: A national survey has been conducted with 349 general practitioners in order to analyze the management of concerned episodic headache in general practice. METHOD: This survey enabled collection of data from 2537 headache patients. The main data concered IHS diagnosis, severity of headache using the MIGSEV scale, management, practices and the impact on daily living (QVM and HIT-6 scales). RESULTS: Out of the 2537 included patients, 52 percent were migraine sufferers according to IHS criteria (code 1.1/1.2), 34 percent presented with migrainous disorders (code 1.7), and 14 percent were non-migraine headache patients. The distribution of management practices showed that 71 percent of them were given non-specific treatments, 46 percent of them specific treatments and 27 percent of them prophylactic treatments. Analysis of the impact of headache using the QVM or the HIT-6 demonstrated a relationship between diagnosis, migraine severity and disability. Analysis of the correlation between the severity of the last migraine attack as evaluated by the patient and that estimated by the doctor showed that the practitioner tended to underestimate the patient's pain. These results highlight the importance of communication between practitioners and migraine sufferers. CONCLUSION: Training of general practitioners in the use of simple tools such as the HIT-6 scale, should be helpful for a better evaluation of the impact of headache on daily living, and hence should lead to more optimal therapeutic management of headache patients.


Subject(s)
Migraine Disorders/therapy , Adult , Cross-Sectional Studies , Family Practice , Female , France , Humans , Male , Middle Aged , Migraine Disorders/epidemiology , Practice Patterns, Physicians' , Surveys and Questionnaires
11.
Int J Obes (Lond) ; 29(2): 176-82, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15505636

ABSTRACT

OBJECTIVE: To determine whether decreased cardiac parasympathetic activity observed in obesity is due to insulin-induced alterations in cardiac M(2)-muscarinic receptors and/or adenylyl cyclase activity. DESIGN AND METHODS: After incubation with increasing concentrations of insulin, adult rat atrial cardiomyocytes were assayed for M(2)-muscarinic receptor binding density and affinity, and for M(2)R mRNA expression using RT-PCR analysis. Forskolin-stimulated adenylyl cyclase activity and its inhibition by carbachol were also assayed, as was endothelial nitric oxide synthase mRNA expression. The effects of insulin on M(2)-muscarinic receptor density and mRNA expression levels were analyzed using the insulin signaling inhibitors rapamycin, wortmanin and PD 098059. RESULTS: Insulin induces a concentration- and time-dependent decrease in expression of the M(2)R mRNA, and in [(3)H]N-methylscopolamine binding by the receptor. These effects on the M(2)R mRNA levels and on [(3)H]N-methylscopolamine binding were prevented by PD 98059, but not by wortmanin or rapamycin. Basal and forskolin-induced cAMP production did not differ, but the inhibition of forskolin-simulated enzyme activity by carbachol was blunted by insulin. No change in the mRNA levels for endothelial nitric oxide synthase was observed. CONCLUSION: In rat atrial cardiomyocytes, insulin markedly alters both the M(2)-muscarinic receptor density, and its mRNA expression through transcriptional regulation and adenylyl cyclase activity. These data suggest that the obesity-associated decrease in cardiac parasympathetic tone may be related to hyperinsulinemia, which could directly contribute to cardiovascular morbidity in obese patients.


Subject(s)
Down-Regulation/drug effects , Insulin/pharmacology , Myocytes, Cardiac/drug effects , Obesity/metabolism , Receptor, Muscarinic M2/biosynthesis , Adenylyl Cyclases/metabolism , Animals , Cardiovascular Diseases/etiology , Cardiovascular Diseases/metabolism , Cells, Cultured , Dose-Response Relationship, Drug , Male , Myocytes, Cardiac/metabolism , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type III , Obesity/complications , Parasympathetic Nervous System/drug effects , RNA, Messenger/genetics , Rats , Rats, Wistar , Receptor, Muscarinic M2/drug effects , Receptor, Muscarinic M2/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods , Signal Transduction/drug effects
13.
J Neurol Neurosurg Psychiatry ; 75(5): 689-95, 2004 May.
Article in English | MEDLINE | ID: mdl-15090561

ABSTRACT

OBJECTIVE: To compare the efficacy and safety of clozapine in drug induced psychosis in Parkinson's disease (PD). METHODS: A four week, randomised, double blind, parallel comparison of clozapine and placebo, followed by a 12 week clozapine open period, plus a one month period after drug discontinuation, in 60 patients with PD. The primary efficacy outcome was the "clinical global impression scale" (CGI); the positive subscore of the "positive and negative syndrome scale" (PANSS) was used as the secondary efficacy parameter and the "unified Parkinson's disease rating scale" (UPDRS) and the "mini mental test examination" (MMSE) as safety outcomes. RESULTS: The mean (SD) dosage of clozapine was 35.8 (12.5-50) mg at the end of the double blind period. The mean (SD) scores on the CGI improved by 1.8 (1.5) for the clozapine group compared with 0.6 (1.1) for the placebo group (p = 0.001). The mean (SD) positive subscore of PANSS improved by 5.6 (3.9) for the clozapine group (0.8 (2.8) for the placebo group; p < 0.0001). At the end of the open period, 25 patients had completely recovered from delusions and hallucinations, and 19 experienced a relapse within one month after the clozapine washout period. The UPDRS motor and MMSE mean scores did not change significantly in either group. Somnolence was more frequent with clozapine than with placebo. CONCLUSIONS: Clozapine at a mean dose lower than 50 mg/day improves drug induced psychosis in PD without significant worsening of motor function, and the effect wears off once the treatment stops.


Subject(s)
Clozapine/therapeutic use , GABA Antagonists/adverse effects , Levodopa/adverse effects , Parkinson Disease/drug therapy , Psychoses, Substance-Induced/diagnosis , Psychoses, Substance-Induced/etiology , Aged , Clozapine/administration & dosage , Dose-Response Relationship, Drug , Double-Blind Method , Feasibility Studies , Female , Follow-Up Studies , GABA Antagonists/administration & dosage , Humans , Male , Prospective Studies
14.
Br J Dermatol ; 149(5): 1041-5, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14632812

ABSTRACT

BACKGROUND: Intradermal injections of type A botulinum toxin have been reported to reduce excessive sweating in patients with primary palmar hyperhidrosis. Two preparations are commercially available in Europe: Botox (Allergan; 100 U per vial) and Dysport (Beaufour Ipsen Biotech; 500 U per vial), which are not bioequivalent. A few studies have tried to find an appropriate conversion factor between the two preparations in dystonic patients but results remain controversial. OBJECTIVES: To compare the efficacy of Botox and Dysport in palmar hyperhidrosis using a conversion factor of 1 : 4. METHODS: In a double-blind, randomized study, eight patients with severe primary palmar hyperhidrosis received in the same session intradermal injections of Dysport in one palm and Botox in the other, after regional median and ulnar nerve blocks. Quantification of sweat production was performed by Minor's iodine starch test at baseline, 1, 3 and 6 months after the treatment. Subjective assessment of sweat production was performed using a visual analogue scale. RESULTS: The mean +/- SD number of injection sites (28 +/- 1), mean volume of reconstituted solution injected (2.8 mL) and mean sweating area at baseline (BSA) were similar in each palm group. The mean +/- SD dose injected was 69.3 +/- 3.1 U for the Botox-treated palms and 283.7 +/- 11.3 U for the Dysport-treated palms (1 : 4). At 1 month, Minor's test revealed significant decreases in mean sweating area for each preparation (Dysport palms: -78.6% vs. BSA, P = 0.0002; Botox palms: -56.6% vs. BSA, P = 0.003). The percentage of decrease was more pronounced in Dysport palms compared with Botox palms but the difference did not reach statistical significance. At 3 months, the decrease in sweating area remained significant for Dysport palms (-69.4% vs. BSA, P = 0.008) but not for Botox palms (-48.8% vs. BSA). Self-evaluation showed a similar amount of improvement in both palm groups at 1 and 3 months (77% and 75% for Dysport; 68% and 72% for Botox). Local side-effects were more frequent in Dysport palms (weakness of thumb-index pinch in four cases, lasting 8-30 days) than in Botox palms (weakness of thumb-index pinch in two cases, lasting 15-21 days). The mean duration of positive effect was similar: 17 weeks in Dysport (range 8-32) and 18 weeks in Botox palms (range 8-32). CONCLUSIONS: Using a conversion factor of 1 : 4, the efficacy of Botox and Dysport injections was similar. However, there was a trend towards a larger improvement after Dysport treatment but with a higher incidence of adverse effects.


Subject(s)
Botulinum Toxins, Type A/therapeutic use , Hand Dermatoses/therapy , Hyperhidrosis/therapy , Neuromuscular Agents/therapeutic use , Adult , Botulinum Toxins, Type A/adverse effects , Double-Blind Method , Female , Humans , Injections, Intradermal , Iodine , Male , Neuromuscular Agents/adverse effects , Patient Satisfaction , Therapeutic Equivalency , Treatment Outcome
15.
Arch Mal Coeur Vaiss ; 95(7-8): 651-5, 2002.
Article in French | MEDLINE | ID: mdl-12365074

ABSTRACT

UNLABELLED: High fat diet (HFD) in dogs is associated with obesity and hypertension (HTN) but also with a significant and early decrease in heart rate variability (HRV). Decreased HRV has been shown to be a good predictor of sudden cardiac death due mainly to arrhythmic event. The aim of this work was to investigate the changes in ventricular repolarization through 24 hours EKG recordings in dogs with hypertension and rendered obese by 20 weeks of HFD. This was achieved through 24 hour EKG recording analysis of QT parameters. The aims of this work was i) feasibility of this method in dogs and ii) identification of potential arrhythmic risk factors that could explain overmortality during obesity. METHOD: Six dogs received a high fat diet (HFD) ad libitum during 20 weeks. A 24 hour EKG recording was realized just before and after 20 weeks of HFD. The following parameters studying QT interval were collected: QT interval lasting from the beginning of the Q wave to the apex (QTa) and to the end of the T wave (QTe), QT intervals plotted against RR intervals and two regression lines were calculated characterized by their slope and intersection with the Y axis, QT dispersion (longest minus shortest QT interval for each RR value) as well as the difference of QT interval between night and day at a fixed RR value considered as a marker of the sympathovagal balance. Our results show that HFD significantly increased body weight, blood pressure, heart rate, left ventricular mass and insulinemia. QT dispersion was increased in a non-significant manner both during day (+35%) and night (16%) for QTa and only during day for QTe (+27%). This increased dispersion of QT was not associated to any increase of QT interval. There was no effect of HFD on QT dynamicity parameter nor on the night-day difference at any RR interval from 300 to 1,300 ms. CONCLUSION: HFD tend increase QT dispersion without any effect on QT interval. These results are compatible with a heterogeneous repolarization probably related to abnormal autonomic nervous system tone. This study could partly explain occurrence of lethal arrhythmias during obesity which might lead to overmortality of obese patients. These results are different for QTa and QTe, but these two parameters are characterizing different type of ventricular cells. This study confirms the feasibility of this method in an experimental model, but results need to be validated in larger groups and in human.


Subject(s)
Heart Rate/physiology , Hypertension/etiology , Hypertension/physiopathology , Obesity/complications , Ventricular Function , Animals , Dietary Fats , Disease Models, Animal , Dogs , Electrocardiography/veterinary , Hypertension/veterinary , Male , Obesity/veterinary
16.
Arch Mal Coeur Vaiss ; 95(7-8): 695-9, 2002.
Article in French | MEDLINE | ID: mdl-12365082

ABSTRACT

High fat diet (HFD) induces both arterial hypertension and tachycardia in dogs. Changes in heart rate occur early and are in part due to a decrease in the parasympathetic drive to the heart secondary to down-regulation of atrial muscarinic M2 receptors (Pelat et al. Hypertension 1999; 340: 1066-72). These data suggest that HFD is able to modify genic expression at atrial level. Thus, the aim of this work was to perform a systematic study of the genic expression profile in dogs made obese and hypertensive by 9 weeks of HFD. Blood pressure and heart rate were measured by telemetry implanted 15 days before starting regimen in 6 HFD and in 6 control dogs. HFD was the normal canine diet administered to controls but mixed with 300 g of beef fat. At the end of the experience, animals were sacrified and right atria were collected. Gene regulation was assessed in pooled tissue samples from both groups using suppressive substractive hybridization and microarray analysis. Genes with induction or repression rates of at least 20% when compared to controls were sequenced. As previously reported HFD induced a significant increase in body weight, blood pressure and heart rate when compared to controls. The results of SSH experiments led to the identification of 32 genes which are differentially regulated in atria from HFD dogs. Most are genes encoding proteins which have been previously shown to be regulated during various cardiopathies (MMP9, Na/K-ATPase 3...). These changes indicate the existence of early remodeling processes of atrial myocardium secondary to HFD. Other group of genes encodes proteins with no role identified in heart up today (lec-3, ERK-3, TRIP1, nucleophosmin...) or which function remains totally unknown. This work confirms that HFD is associated with early changes in gene expression in atrium. These changes are unlikely to be related to ventricular hypertrophy which is observed only during long-term HFD. Further studies are necessary to demonstrate the role of these modifications in the pathophysiological mechanisms leading to the increase in heart rate in this model of obesity-related arterial hypertension.


Subject(s)
Dietary Fats , Gene Expression Regulation , Genetic Predisposition to Disease , Hypertension/genetics , Obesity/complications , Animals , Atrial Function , Blood Pressure/genetics , Blood Pressure/physiology , Dogs , Gene Expression Profiling , Heart Rate/genetics , Heart Rate/physiology , Hypertension/physiopathology , Hypertension/veterinary , Male , Obesity/genetics , Obesity/veterinary
17.
Encephale ; 28(3 Pt 1): 241-7, 2002.
Article in French | MEDLINE | ID: mdl-12091785

ABSTRACT

Subjects with posttraumatic stress disorder exhibit abnormalities in many psychobiological systems. Studies of the effects of stress on learning and memory processes suggest that fear conditioning, behavioural sensitisation, and a failure of extinction may be important in the persistence and reexperiencing of traumatic memories and stress sensitivity. All these symptoms are supported by specific biological mechanisms including NMDA receptors, noradrenergic system, etc. Recent findings show that amino acid transmitters, glutamate and GABA, are intimately involved in the process of factual memory registration, and suggest that amine neurotransmitters, norepinephrine and serotonin, are involved in encoding emotional memory. In addition, research suggests that 5-HT neurones have directs effects on both adrenergic and HPA function. Such findings provide important information that should guide current pharmacological practice and the development of innovative biological therapeutics.


Subject(s)
Neurotransmitter Agents/physiology , Stress Disorders, Post-Traumatic/physiopathology , Synaptic Transmission/physiology , Adaptation, Psychological/physiology , Arousal/physiology , Humans , Mental Recall/physiology , Neurosecretory Systems/physiopathology , Stress Disorders, Post-Traumatic/diagnosis , Stress Disorders, Post-Traumatic/psychology
18.
Clin Auton Res ; 11(4): 235-42, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11710796

ABSTRACT

This study was designed to determine the efficacy and tolerability of increasing doses of L-threo-dihydroxyphenylserine (L-threo-DOPS) in treating symptomatic orthostatic hypotension associated with multiple system atrophy (MSA) and pure autonomic failure (PAF). Following a one-week run-in, patients (26 MSA; 6 PAF) with symptomatic orthostatic hypotension received increasing doses of L-threo-DOPS (100, 200 and 300 mg, twice daily) in an open, dose-ranging study. Incremental dose adjustment (after weeks two and four of outpatient treatment) was based on clinical need until blood pressure (BP), and symptoms improved. Final dosage was maintained for six weeks. With L-threo-DOPS, systolic BP decrease was reduced during orthostatic challenge (-22+/-28 mm Hg reduction from a baseline decrease of 54.3+/-27.7 mm Hg, p = 0.0001, n = 32; supine systolic BP at final visit was 118.9+/-28.2 mm Hg). By the end of the study, 25 patients (78%) improved, and in 14 patients (44%) orthostatic hypotension was no longer observed. Decreased orthostatic systolic BP decrease occurred in 22% (7/32), 24% (6/25) and 61% (11/18) of patients treated with 100, 200, and 300 mg L-threo-DOPS twice daily, respectively. An improvement occurred in symptoms associated with orthostatic hypotension, such as light-headedness, dizziness (p = 0.0125), and blurred vision (p = 0.0290). L-threo-DOPS was well tolerated, with the 2 serious adverse events reported being a possible complication of the disease under study, and with no reports of supine hypertension. In conclusion, L-threo-DOPS (100, 200, and 300 mg, twice daily) was well tolerated. The dosage of 300 mg twice daily L-threo-DOPS seemed to offer the most effective control of symptomatic orthostatic hypotension in MSA and PAF.


Subject(s)
Antiparkinson Agents/therapeutic use , Autonomic Nervous System Diseases/drug therapy , Droxidopa/therapeutic use , Hypotension, Orthostatic/drug therapy , Multiple System Atrophy/drug therapy , Adolescent , Adult , Aged , Antiparkinson Agents/administration & dosage , Antiparkinson Agents/adverse effects , Autonomic Nervous System Diseases/complications , Autonomic Nervous System Diseases/physiopathology , Blood Pressure/drug effects , Dose-Response Relationship, Drug , Droxidopa/administration & dosage , Droxidopa/adverse effects , Female , Humans , Hypotension, Orthostatic/etiology , Hypotension, Orthostatic/physiopathology , Male , Middle Aged , Multiple System Atrophy/complications , Multiple System Atrophy/physiopathology , Norepinephrine/blood
19.
Arch Mal Coeur Vaiss ; 94(8): 790-4, 2001 Aug.
Article in French | MEDLINE | ID: mdl-11575205

ABSTRACT

BACKGROUND: Previous studies of heart rate variability (HRV) in systemic hypertension have yielded conflicting results. We sought to assess the alterations of HRV in hypertensive patients with or without left ventricular hypertrophy (LVH). METHODS: 195 hypertensive patients in sinus rhythm, mean age 53 +/- 11 years, without diabetes mellitus, nor symptomatic coronary disease or systolic dysfunction, were prospectively enrolled. Echocardiographic examination allowed their subdivision in 3 groups: normal geometry (112), concentric remodeling (43) and LVH (40). Time and frequency domain measures of HRV were obtained from 24 h Holter ECG recordings in all patients as in 40 control subjects. RESULTS: In comparison with control subjects, the 3 hypertensive groups presented a significant decrease of SDNN and total frequency power both indexes of global HRV; a significant decrease of pNN50 and high frequency power, indexes of HRV reflecting parasympathetic tone, and a significant decrease of SDANN and low frequency power, indexes reflecting sympathetic modulation of HRV. Comparisons among the three hypertensive groups showed that patients with LVH had significantly (p < 0.05) lower low frequency power (5.5 +/- 1.0 Ln m2) than patients with left ventricular normal geometry (5.9 +/- 0.8 Ln m2) or concentric remodeling (5.9 +/- 0.9 Ln m2). CONCLUSION: Assessment of HRV in hypertensive patients shows a constant decrease of parasympathetic indexes and a more markedly reduction of sympathetic parameters in presence of LVH.


Subject(s)
Heart Rate/physiology , Hypertension/complications , Hypertrophy, Left Ventricular/etiology , Aged , Female , Humans , Hypertrophy, Left Ventricular/pathology , Male , Middle Aged , Parasympathetic Nervous System/physiology
20.
J Card Fail ; 7(3): 241-8, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11561225

ABSTRACT

BACKGROUND: Management of heart failure includes beta-blockade (betaB) therapy and cardiac rehabilitation. The aim of this study was to compare the exercise training response of patients with congestive heart failure (CHF) receiving betaB therapy with that of patients not receiving treatment. METHODS AND RESULTS: Thirty-four consecutive patients with CHF were included in a 4-week training program at their ventilatory threshold (VT); 6 patients received betaB treatment and 18 did not. The patients underwent a cardiopulmonary exercise test before and after training. Oxygen uptake (VO(2)) at peak exercise and at VT increased in both groups (P < or =.0001) without any significant differences between the groups. The same results were found after adjustment to ejection fraction and VO(2) at the start of the training program. There was no difference in VT improvement, measured as a percentage of utilization of maximal oxygen uptake, between the groups. After training, heart rate and ventilation decreased (P < or =.0001) at submaximal levels in both groups without significant differences between the groups. CONCLUSIONS: betaB therapy does not impair functional improvement induced by a rehabilitation program in patients with CHF. betaB therapy does not interfere with exercise training prescription if patient exercise evaluations are made at the time of therapeutic intake.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Exercise Therapy , Heart Failure/drug therapy , Heart Failure/rehabilitation , Case-Control Studies , Exercise Test , Heart Rate , Humans , Middle Aged , Oxygen Consumption , Prospective Studies , Pulmonary Ventilation , Time Factors
SELECTION OF CITATIONS
SEARCH DETAIL
...