What is the real benefit of adjuvant chemotherapy in the Adjuvant Navelbine International Trialist Association trial?
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
C Moro
Publications and source records attributed to C Moro.
Dynamic strength training improves insulin sensitivity without altering plasma levels and gene expression of adipokines in subcutaneous adipose tissue in obese men.
CONTEXT: Obesity is characterized by a low-grade inflammatory state, which could play a role in insulin resistance. Dynamic strength training improves insulin sensitivity. OBJECTIVE: The objective of this study was to investigate, in obese subjects, whether the insulin sensitizing effect of dynamic strength training is associated with changes in plasma levels and gene expression of adipokines potentially involved in the development of insulin resistance. DESIGN: Twelve obese male subjects were investigated before and at the end of 3 months of dynamic strength training. Insulin sensitivity was evaluated using euglycemic-hyperinsulinemic clamp. Blood samples and needle biopsy samples of sc abdominal adipose tissue were obtained. The plasma levels and adipose tissue mRNA levels of adiponectin, leptin, IL-1beta, IL-6, and TNF-alpha were determined. RESULTS: The training induced an increase in the whole-body glucose disposal rate by 24% (P = 0.04). The body weight was not altered during the training. Plasma levels of leptin decreased during the training (16.6 +/- 6.3 vs. 13.1 +/- 5.7 ng/ml) by 21% (P < 0.02), whereas no change in plasma levels of other adipokines and C-reactive protein was observed. Gene expression of the investigated adipokines was not changed in sc adipose tissue during the training. CONCLUSIONS: In obese subjects, the dynamic strength training resulted in an improvement of whole-body insulin sensitivity. The increase in insulin sensitivity was not associated with training-induced modifications of plasma levels or adipose tissue gene expression of adipokines supposedly involved in the development of insulin resistance.
Adiponectin↗
Buprenorphine-induced acute respiratory depression during ifosfamide-based chemotherapy.
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Acute Disease↗
The RIONI study rationale and design: validation of the first stored electrograms transmitted via home monitoring in patients with implantable defibrillators.
Appropriate and inappropriate therapies of implantable cardioverter defibrillators (ICDs) have a major impact on morbidity and quality of life in ICD recipients. The recently introduced home monitoring of ICD devices is a promising new technique which remotely offers information about the status of the system. Stored intracardiac electrograms (IEGMs), which are essential for correct classification of appropriate and inappropriate ICD discharges, have until now not been available with ICD home monitoring on a day-by-day basis because of limitations of transferable data. We demonstrate the first compressed IEGMs daily transferable via home monitoring (IEGM-online). Validation of these electrograms will be performed in the Reliability of IEGM-Online Interpretation (RIONI) study. A total of 210 episodes of stored IEGMs will be collected by at least 12 European centres. The primary endpoint of this study is to investigate whether the IEGM-online based evaluation of the appropriateness of the ICDs therapeutic decision following episode detection is equivalent to the evaluation based on the complete ICD episode Holter extracted from the IEGM stored. The evaluation is independently done by an expert board of three experienced ICD investigators. The equivalence of the two methods is accepted if the evaluations yield a different conclusion for <10% of all evaluated IEGMs. The conclusion of the study is expected at the beginning of 2007. If RIONI successfully validates IEGMs transmitted via home monitoring, a strong basis for the use of this promising technique will be established.
Death, Sudden, Cardiac↗
Dynamic strength training improves insulin sensitivity and functional balance between adrenergic alpha 2A and beta pathways in subcutaneous adipose tissue of obese subjects.
AIMS/HYPOTHESIS: The aim of this study was to investigate whether dynamic strength training modifies the control of lipolysis, with particular attention paid to the involvement of the antilipolytic adrenergic alpha 2A receptor (ADRA2A) pathway. METHODS: Twelve obese men (age: 47.4+/-2.8 years; BMI: 32.7+/-0.9) were investigated during a 210-min euglycaemic-hyperinsulinaemic clamp conducted before and after 3 months of dynamic strength training. Before and during the third hour of the clamp, the lipolytic effect of a perfusion of isoproterenol or adrenaline (epinephrine) alone or associated with the ADRA2A antagonist phentolamine was evaluated using the microdialysis method of measuring extracellular glycerol concentration (EGC) in subcutaneous abdominal adipose tissue (SCAAT). In addition, biopsies of SCAAT were carried out before and after training to determine mRNA levels RESULTS: The training increased insulin sensitivity in adipose tissue. The decrease of EGC was more pronounced during the clamp conducted after the training period than during the clamp done in pre-training conditions. Before and after the training, catecholamines induced an increase in EGC, the increase being lower during the clamp on each occasion. The isoproterenol-induced increase in EGC was higher after the training. Adrenaline-induced lipolysis was potentiated by phentolamine after but not before the training. There were no training-induced changes in mRNA levels of key genes of the lipolytic pathway in SCAAT. CONCLUSIONS/INTERPRETATION: In obese subjects, dynamic strength training improves whole-body and adipose tissue insulin responsiveness. It increases responsiveness to the adrenergic beta receptor stimulation of lipolysis and to the antilipolytic action of catecholamines mediated by ADRA2As.
3',5'-Cyclic-AMP Phosphodiesterases↗
Effect of endurance training on adrenergic control of lipolysis in adipose tissue of obese women.
The effect of a 12-wk training program on sc abdominal adipose tissue (SCAAT) was studied in 11 obese women. Before and after the training, biopsies of SCAAT were performed for mRNA levels determination. Using the microdialysis method, involvement of alpha(2)- and beta-adrenergic receptor (ARs) in the control of lipolysis in SCAAT was studied using local perfusion of epinephrine alone or supplemented with phentolamine, an alpha(2)-AR antagonist. In addition, the variation in dialysate glycerol concentrations during exercise (50% peak oxygen consumption at 40 min) in a probe perfused with Ringer's solution was compared with that obtained in a probe perfused with Ringer's solution plus phentolamine. Training did not promote changes in the expression of key genes of the lipolytic pathway. The epinephrine-induced rise in the dialysate glycerol concentration was identical before and after training and was similarly potentiated by phentolamine. During exercise, the potentiating effect of phentolamine on the glycerol response was apparent before, but not after, training. The exercise-induced increase in plasma norepinephrine was lower after training (P = 0.04). In conclusion, training did not modify either the expression of genes involved in the control of lipolysis or alpha(2)- and beta-ARs in situ sensitivity to epinephrine in SCAAT. Training reduced the antilipolytic action of catecholamines mediated by alpha(2)-ARs during exercise, probably due to a reduction of exercise-induced catecholamine increase.
Abdomen↗
Aerobic training improves exercise-induced lipolysis in SCAT and lipid utilization in overweight men.
The aim of this study was to investigate whether endurance training improves lipid mobilization and oxidation in overweight subjects. Eleven young men (25.6 +/- 1.4 yr and body mass index 27.7 +/- 0.2) performed a 4-mo training program consisting of practicing aerobic exercise 5 days/wk. Before and after the training period, lipid oxidation was explored during a 60-min exercise at 50% of peak O2 consumption by use of indirect calorimetry. Lipid mobilization and antilipolytic alpha2-adrenoceptor effect were also studied using the microdialysis method in abdominal subcutaneous adipose tissue (SCAT). After training, plasma nonesterified fatty acid (NEFA) levels, at rest and during exercise, were significantly lower than before (P < 0.001). Lipolysis in SCAT was significantly higher after than before training. An antilipolytic alpha2-adrenoceptor effect in SCAT was underlined during exercise before training and disappeared after. The respiratory exchange ratio was lower after training, i.e., the percentage of lipid oxidation was higher only at rest. The amount of lipid oxidized was higher after training, at rest, and during exercise. Although exercise power was higher after training, the relative intensity was equivalent, as suggested by a similar increase in plasma catecholamine concentrations before and after training. In conclusion, 4-mo training in overweight men improved lipid mobilization through a decrease of antilipolytic alpha2-adrenoceptor effect in SCAT and lipid oxidation during moderate exercise. Training induced a decrease of blood NEFA, predicting better prevention of obesity.
Abdomen↗
[Radiofrequency ablation of recurrent monomorphic ventricular tachycardia in a patient with severe systemic scleroderma].
A case of progressive systemic scleroderma in a 33 year-old woman who was referred to our Arrhythmia Unit due to daily palpitations and dizziness is presented. The 24-hour Holter recording showed monomorphic ventricular tachycardia which lasted several minutes. Hemodynamic study showed dilated right chambers and right ventricular dysfunction, without pulmonary hypertension. Left ventricular angiography and coronary arteries were normal. During programmed electrical stimulation, two different ventricular tachycardia were induced and ablated with radiofrequency on the right ventricle. The patient remains free of recurrence of tachycardia after (10 months of follow up). Patients with progressive systemic scleroderma may present several different cardiac arrhythmias. Involvement of the right ventricle is particularly frequent as is the origin of ventricular tachycardia in this ventricle. Radiofrequency catheter ablation is safe and effective in the management of these patients.
Adult↗
[Macroscopic and microscopic study of the right coronary artery after radiofrequency catheter ablation of cavotricuspid isthmus in an experimental model].
INTRODUCTION AND OBJECTIVES: The right coronary artery (RCA) is found in the AV groove, just below the ablation target of atrial flutter, the cavotricuspid isthmus (ICT). After radiofrequency (RF) ablation with standard catheters, there have been no reports of complications, but it may not be successful in 10% of the cases. However, the use of irrigated tip catheters, which create deeper lesions, might potentially damage the coronary tree. METHODS: We analyzed the effects of ICT RF ablation on the coronary tree, with macroscopic and microscopic anatomopathological study. Ablation on ICT was performed using an irrigated tip catheter in 16 pigs and was randomly compared with a standard ablation catheter. There were no clinical problems, modifications of ST or new arrhythmias during the ablation. The heart was extracted at 1 week. RESULTS: The macroscopic study demonstrated that the right coronary artery was preserved, along the ICT, surrounded by the epicardial fat. The microscopic study showed an inflammatory reaction in the epicardial fat that reached the adventitia of the coronary artery, but never produced necrosis in 14 cases. The muscular wall of the artery had signs of focal inflammation without endothelium involvement in 2 cases. However, we found a subepicardial vein completely damaged by the radiofrequency. CONCLUSIONS: Although the right coronary artery is located just below the isthmus, no necrosis was observed in any case. However, there was an inflammatory reaction that focally reached the muscular wall. The veins may be damaged in RF ablation, perhaps due to the different blood flow of each vessel.
Animals↗
[Evaluation of the anatomopathological characteristics and the safety of radiofrequency lesions at the atrial level with two different systems of irrigated tip catheters on an experimental level].
INTRODUCTION AND OBJECTIVES: We performed this study to evaluate the security and efficacy in the lesions produced on the atrial wall by different irrigated catheters in an experimental model. We evaluated the anatomopathologic characteristics of the lesions produced by two different systems of irrigated tip catheters, with opened or closed circuit. METHODS: This study was performed in 16 pigs applying 60 sec radiofrequency pulses with three different energy levels (15, 25 y 50 Watts). Two different systems of radiofrequency ablation irrigated catheters were used, opened and closed. We used 4 pigs in which we performed ablation with a standard catheter as a control group. Under fluoroscopic guidance, catheters were placed on the high and low right atrial lateral wall, where lesions were produced. After 7 days, animals were sacrificed for anatomopathological study. RESULTS: A total of 27 lesions were performed with irrigated catheters (11 closed circuit and 16 opened) and 6 with standard catheters in the control group. We did not find significant differences in the lesion characteristics between the two different systems of irrigated tip catheter used, nevertheless lesions performed with the closed system were slightly greater. Th lesions produced with irrigated catheters were always superior in the control group. Transmurality in the free atrial wall is frequent with both systems. We did not see any perforation in the atrial wall. CONCLUSIONS: We did not find significant differences in the size of the lesions produced with the two systems of irrigated catheters used. These data from an experimental model can provide useful information for atrial tachycardia radiofrequency ablation procedures in humans.
Animals↗
Lack of efficacy of atenolol for the prevention of neurally mediated syncope in a highly symptomatic population: a prospective, double-blind, randomized and placebo-controlled study.
OBJECTIVES: This study was designed to evaluate the efficacy of atenolol for the long-term management of patients with vasovagal syncope. The primary hypothesis was that atenolol is not superior to placebo for the treatment of vasovagal syncope. BACKGROUND: There is no definitive well-controlled analysis of the efficacy of beta-adrenergic blocking agents in patients with recurrent vasovagal syncope. METHODS: This is a prospective, randomized, double-blind, placebo-controlled study. Fifty patients with recurrent vasovagal syncope were included (at least two episodes in the last year). A baseline tilt test was performed. Twenty patients (40%) had a positive tilt test. Intravenous atenolol prevented a second positive tilt in five patients. The patients were randomized to receive either atenolol or a placebo (26 patients atenolol 50 mg/day, 24 patients placebo). The follow-up procedure lasted one year. The primary end point of the study was the time to first recurrence of syncope. RESULTS: In the intention-to-treat analysis, the group treated with atenolol had a similar number of patients with recurrent syncopal episodes as the placebo group. The Kaplan-Meier actuarial estimates of time to first syncopal recurrence showed that the probability of remaining free of syncope drops similarly in both groups and that there was no statistical difference between both curves (patients treated with atenolol vs. the placebo) with a log-rank test p value of 0.4517. CONCLUSIONS: The recurrence of neurocardiogenic syncope in highly symptomatic patients treated with atenolol is similar to that of patients treated with placebo.
Adolescent↗
The effect of thiamine supplementation on tumour proliferation. A metabolic control analysis study.
Thiamine deficiency frequently occurs in patients with advanced cancer and therefore thiamine supplementation is used as nutritional support. Thiamine (vitamin B1) is metabolized to thiamine pyrophosphate, the cofactor of transketolase, which is involved in ribose synthesis, necessary for cell replication. Thus, it is important to determine whether the benefits of thiamine supplementation outweigh the risks of tumor proliferation. Using oxythiamine (an irreversible inhibitor of transketolase) and metabolic control analysis (MCA) methods, we measured an in vivo tumour growth control coefficient of 0.9 for the thiamine-transketolase complex in mice with Ehrlich's ascites tumour. Thus, transketolase enzyme and thiamine clearly determine cell proliferation in the Ehrlich's ascites tumour model. This high control coefficient allows us to predict that in advanced tumours, which are commonly thiamine deficient, supplementation of thiamine could significantly increase tumour growth through transketolase activation. The effect of thiamine supplementation on tumour proliferation was demonstrated by in vivo experiments in mice with the ascites tumour. Thiamine supplementation in doses between 12.5 and 250 times the recommended dietary allowance (RDA) for mice were administered starting on day four of tumour inoculation. We observed a high stimulatory effect on tumour growth of 164% compared to controls at a thiamine dose of 25 times the RDA. This growth stimulatory effect was predicted on the basis of correction of the pre-existing level of thiamine deficiency (42%), as assayed by the cofactor/enzyme ratio. Interestingly, at very high overdoses of thiamine, approximately 2500 times the RDA, thiamine supplementation had the opposite effect and caused 10% inhibition of tumour growth. This effect was heightened, resulting in a 36% decrease, when thiamine supplementation was administered from the 7th day prior to tumour inoculation. Our results show that thiamine supplementation sufficient to correct existing thiamine deficiency stimulates tumour proliferation as predicted by MCA. The tumour inhibitory effect at high doses of thiamine is unexplained and merits further study.
Animals↗
Randomized comparison of efficacy of cooled tip catheter ablation of atrial flutter: anatomic versus electrophysiological complete isthmus block.
There is a subset of patients with failed ablation of the cavotricuspid isthmus (CTI) using standard catheters and with 10% of the patients having recurrences. The purpose of this study was to compare the cooled and standard ablation with regard to acute successful electrophysiological achievement of bidirectional isthmus block and the subacute anatomic characteristics of the lesions. This randomized, experimental study compares the effects of ablation on the isthmus using a cooled catheter with those of a standard ablation catheter in 16 pigs. In 12 animals, CTI block was achieved after ablation (8/8 cooled and 4/8 standard). In two animals, it was not possible to achieve complete isthmus block and two had persistent slow conduction (all four using the standard catheter). After 1 week, the animals were slaughtered. The size of the lesion was greater with the irrigated tip catheters. Transmural lesions were found in 14 animals. A complete line of anatomic isthmus block was not documented after thefirst line in six animals, four with the standard and two with the cooled catheter. A conduction block was never present across gaps > or = 5 mm. In conclusion cooled catheters achieved a complete line of electrophysiological and anatomical block in a significantly higher percentage than the standard catheters.
Animals↗
Progress report on the palliative therapy of 100 patients with neoplastic effusions by intracavitary low-dose interleukin-2.
OBJECTIVE: Several cytokines, particularly IL-2 and interferons, are thought to be effective in the palliative therapy of neoplastic effusions. We report on the activity and toxicity of intracavitary administration of low-dose IL-2 in a case series of 100 cancer patients with neoplastic effusions. METHODS: One hundred patients with advanced solid tumors and neoplastic effusions underwent IL-2 intracavitary injection as first-line treatment. The most common sites of fluid accumulation were pleura (n = 68), peritoneum (n = 21) and pericardium (n = 11). Breast cancer, lung cancer and mesothelioma were the most frequent neoplasms in our series. One cycle consisted of intracavitary IL-2 at 6,000,000 IU on days 1 and 7. RESULTS: According to Paladine's criteria, an objective clinical response was achieved in 72% (complete response in 27% and partial response in 45%), with a median duration of 5 months (range: 1-11 months). The peritoneum was the least responsive site for neoplastic effusion reduction. IL-2 intracavitary injection was well tolerated in all patients; the only toxicity observed was fever >38 degrees C in 6% of the patients. CONCLUSION: This study shows that intracavitary injection of IL-2 represents a feasible, well-tolerated and effective therapy of neoplastic fluid accumulation. Further studies are needed in order to compare the effectiveness of intracavitary IL-2 with other standard treatments.
Adult↗
[Recurrent ventricular fibrillation during a febrile illness in a patient with the Brugada syndrome].
Different situations have been involved in the origin of ventricular arrhythmic events in patients with the Brugada syndrome such as bradycardia, alcohol consumption and mental stress. We present a 30 year old male with recurrent ventricular fibrillation due to a febrile illness with intense sweating. He had been previously studied at our Unit in 1995 because of an episode of resuscitated cardiac arrest due to ventricular fibrillation. The twelve-lead electrocardiogram showed the typical characteristics of a patient with the Brugada syndrome. Different invasive and non-invasive tests performed were normal. He received a defibrillator and had no recurrences during 4 years of follow up. In March,1999, after an upper respiratory tract infection he had high fever treated with paracetamol but at down he had sweating and chills, followed by 3 defibrillator shocks. Late interrogation showed 5 episodes of ventricular fibrillation, two of them non-sustained, and the rest adequately treated by the defibrillator. Activation and inactivation kinetics for early INa are twofold faster at higher temperature, and shift activation and steady-state inactivation. This may explain the role of the temperature as a trigger for ventricular arrhythmias in our patient.
Adult↗
A prospective multicenter study on the safety of a pacemaker with automatic energy control: influence of the electrical factor on chronic stimulation threshold. PEACE Investigators.
The effectiveness and safety of a pacemaker with automatic control of capture was evaluated in 162 patients followed at 27 Spanish centers. The aim of our prospective, multicenter, and randomized trial was to determine the relationship between the voltage output of the pulse generator and the stimulation threshold. We randomized 162 patients (107 men, mean age 75 +/- 12 years). We implanted a ventricular pacemaker model Regency SR+ or SC+ with Pacesetter's low polarization bipolar leads Membrane E 1450. The patients were randomized to receive Autocapture or not; group I (81 patients) Autocapture On, pulse output automatically adjusted and group II (81 patients) Autocapture Off, fixed output parameters (3.9 V, 0.37 ms). We performed a 6-month follow-up measuring stimulation threshold by means of the VARIO test and Autocapture test, evoked response signal, and R wave signal. The mean R wave was 15.77 +/- 3.5 mV at the end of the follow-up for group I, and 14.91 +/- 6.8 mV for group II (P = NS). The measured evoked response at the end of the follow-up was 9.25 mV in Group I and 8.48 mV in Group II (P = NS). The stimulation threshold was not different between groups. The current density created with the voltage and pulse width used in this study (< or = 3.9 V and 0.37 ms) at the tip of this electrode during the maturation process had no influence on the development of the chronic detection and stimulation thresholds.
Adult↗
[Anatomopathological and biochemical correlation of lesions produced by standard and irrigated 4 mm radiofrequency catheters].
INTRODUCTION AND OBJECTIVES: The influence on the size of radiofrequency lesions by cooling of the tip of the electrode remains unclear. Moreover, the possible effects of two different cooling systems, closed and open, have not been well differentiated. We designed this study to compare both systems of irrigated-tip catheters and the lesions produced with standard 4 mm catheters and also to evaluate the pathological and biochemical marker release correlation (cardiac troponin I) in an experimental model. METHODS: The study was performed in 20 pigs. Applying between 1-8 radiofrequency pulses, at a power of 15, 25 or 50 watts, for 15-60 seconds to each animal. After 7 days, the pigs were sacrificed for anatomopathological study. RESULTS: A total of 54 lesions were produced, 25 with standard catheters and 29 with irrigated catheters. The mean volume of the lesions produced with standard catheters was 146 +/- 110 microl and with irrigated-tip catheters 856 +/- 864 microl (p < 0.001). Peak values of cardiac troponin I were also higher for irrigated catheters (18 +/- 15 ng/ml) than for standard (6.5 +/- 3 ng/ml). The correlation between the size of the lesion and the levels of cardiac troponin I were 0.86 and 0.79 with the standard and irrigated-tip catheters, respectively. The incidence of cratering was higher with standard catheters (60%) than with irrigated (27%). CONCLUSIONS: The lesions produced with an irrigated catheter are greater than those observed with standard catheters. The mean peak value of postablation cardiac troponin demonstrate a good correlation with the real size of the necrosis.
Animals↗
[The diagnostic yield of cardiac troponin I versus the classic markers of a myocardial lesion in a clinical model of acute myocardial necrosis].
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Acute Disease↗