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Several Trials (several + trials)
Selected AbstractsTreatment with leuprolide acetate decreases the threshold of the ventilatory response to carbon dioxide in healthy malesTHE JOURNAL OF PHYSIOLOGY, Issue 2 2004Jason H. Mateika This investigation was designed to determine if suppression of testosterone alters the ventilatory response to carbon dioxide in the presence of high and low levels of oxygen. Eleven healthy male subjects completed a series of rebreathing trials during wakefulness, before and after treatment with a long-acting gonadotropin-releasing hormone agonist. Five subjects also completed studies during non-rapid eye movement (NREM) sleep. During wakefulness, subjects initially hyperventilated to reduce the partial pressure of carbon dioxide (PET,CO2) below 25 Torr. Subjects then rebreathed from a bag containing a normocapnic (42 Torr), low (50 Torr) or high oxygen (140 Torr) gas mixture. During each trial PET,CO2 increased while oxygen was maintained at a constant level. The threshold of the ventilatory response to carbon dioxide was considered to be the point at which minute ventilation began to rise in a linear fashion as PET,CO2 increased. The slope of the ventilatory response above the threshold was used as a measure of sensitivity to carbon dioxide. During NREM sleep, hypocapnia was induced via nasal mechanical ventilation. Several trials were completed until the cessation of mechanical ventilation resulted in a central apnoea which demarcated the threshold of the ventilatory response to carbon dioxide. In response to treatment with leuprolide acetate, the threshold measured in wakefulness decreased during carbon dioxide rebreathing in the presence of low (41.05 ± 0.77 versus 39.40 ± 0.83 Torr; P= 0.01) and high (46.32 ± 0.56 versus 44.78 ± 0.83 Torr; P= 0.01) oxygen levels. An increase in sensitivity (4.82 ± 0.61 versus 7.17 ± 1.20 l min,1 Torr,1; P= 0.02) was also observed during rebreathing in the presence of high but not low oxygen levels. The increase in sensitivity was accompanied by an increase in carbon dioxide production. The findings observed during NREM sleep were similar to those observed during wakefulness, since the PET,CO2 that demarcated the threshold was decreased after leuprolide treatment (42.1 ± 0.6 versus 39.6 ± 0.6 Torr; P= 0.002). Additionally, the decrease in PET,CO2 required to induce an apnoea was greater after treatment with leuprolide (2.56 ± 0.25 versus 4.06 ± 0.29 Torr; P= 0.004). We conclude that suppression of testosterone decreases the threshold of the ventilatory response to carbon dioxide during both wakefulness and sleep. [source] Mycophenolate Blood Level Monitoring: Recent ProgressAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2009T. Van Gelder The concentration,effect relationship for mycophenolic acid (MPA), and the high variability in MPA concentrations in patients on standard dose mycophenolate mofetil (MMF) therapy, for some centers has provided enough evidence to implement therapeutic drug monitoring (TDM) for MMF in daily practice. Two randomized trials Adaption de Posologie du MMF en Greffe Renale (APOMYGRE) and fixed-dose versus concentration controlled (FDCC) investigated the added benefit of TDM for MMF in renal transplant recipients. The APOMYGRE study showed a significant reduction in the incidence of acute rejection in concentration-controlled patients, while the FDCC study had a negative outcome, despite a similar study design. Although it was expected that these prospective trials would give the final answer to the question of whether or not TDM for MMF would be of benefit, it seems that the studies have not had much impact on patient management. Several trials have shown the importance of early adequate exposure to MPA in the first week after transplantation. As it will be hard to improve MPA exposure with TDM, this early, ongoing study now investigates the use of an increased starting dose. The increased starting dose will avoid underexposure to MPA in higher proportions of patients shortly after transplantation but may result in more toxicity in patients with MPA exposures exceeding the upper threshold of the therapeutic window. [source] A method to determine protein digestibility of microdiets for larval and early juvenile fishAQUACULTURE NUTRITION, Issue 6 2009J.M. HANSEN Abstract A method to evaluate protein quality using in vivo methods was developed for larval fish. FluoSpheres® fluorescent microspheres (10 ,m) were incorporated into two test diets, our standard zein microdiet (ZMD) and a microdiet with identical ingredients except for the replacement of high quality fish meal with the same product cooked for 24 h at 80 °C (ZMD-CF). Several trials were performed to design a reliable method to test digestibility using FluoSpheres® as a marker. The developed in vivo technique was tested on 35 days posthatch (dph) larval Atlantic cod (Gadus morhua L.) and two tropical fish species in the early juvenile stage. The method took into account loss of total protein to the faecal pellet and water column. Apparent digestibility of protein in larval cod fed ZMD was significantly higher than that of larvae fed ZMD-CF (P < 0.05). A growth study to validate differences between the two diets showed significant differences in growth and survival of larvae fed ZMD versus ZMD-CF (P < 0.05). Further validation of our results was indicated through the use of a pH-stat method using enzymes extracted from 35 dph larval cod guts. This novel technique will be advantageous for researchers to evaluate feed ingredients for larval marine fish and is adaptable to many different areas of larval fish nutrition. [source] Diminished cytokine signalling against bacterial components in mononuclear leucocytes from ulcerative colitis patients after leukocytapheresisCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2005K. Mitsuyama Summary Infiltration by circulating inflammatory cells is a prominent local inflammatory feature of ulcerative colitis (UC). Several trials have suggested that leukocytapheresis by filtration can benefit patients with active UC. We investigated how this therapy might modulate the inflammatory response. Patients with active UC who were beginning repeated filtration leukocytapheresis were studied. Mononuclear cell preparations were obtained from blood before and after the first treatment, and expression of cytokine signalling components and the cell-proliferative response were analysed in vitro. Leukocytapheresis reduced lipopolysaccharide-induced production of proinflammatory cytokines (interleukin-1, -6, -8 and tumour necrosis factor-,, P < 0·05 for all) and activation of intracellular signalling components (nuclear factor-,B, mitogen-activated protein kinases, and signal transducer and activator of transcription-3), as well as surface expression of toll-like receptor-4 (P < 0·05) in mononuclear cells. The therapy also reduced the cell-proliferative response by mononuclear cells stimulated with sonicated bacterial preparations from autologous intestine (P < 0·05). These results indicate that activated mononuclear cells in the peripheral blood of patients with active UC are removed by leukocytapheresis and replaced by cells with a lower activation status. This replacement may partly explain the therapeutic benefit. [source] The ARMYDA trials (Atorvastatin for Reduction of MYocardial Damage during Angioplasty) at Campus Bio-Medico University: rationale, results and future horizonsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2007Germano Di Sciascio Abstract Myocardial protection by atorvastation pretreatment was found in several trials applied to percutaneous coronary intervention by the ARMYDA study group. This article reviews those studies and explores future avenues. [source] Persistent Deficits in Heart Rate Response Habituation Following Neonatal Binge Ethanol ExposureALCOHOLISM, Issue 9 2009Katherine C. Morasch Background:, We have previously shown that the rate of habituation of the heart rate orienting response to a novel odor in rats is negatively affected by neonatal ethanol exposure. Thus far, however, only young rats (16 days of age) have been tested. Given the persistence of attention and memory problems evident in humans exposed to ethanol in utero, the purpose of this experiment was to examine the longer-term consequences of ethanol exposure on response habituation. Methods:, Ethanol (5.25 g/kg/d) was administered intragastrically to male and female Sprague-Dawley rats on postnatal days (PD) 4 to 9, and controls were given sham intubations. Animals were tested for heart rate orienting and response habituation to a novel olfactory stimulus (amyl acetate) on PD 16, 23, or 30. Results:, Animals tested on PD 16 or 23 showed normal heart rate deceleration to the novel odor, a measure of the orienting response. However, ethanol-treated subjects showed impaired response habituation compared with sham controls. While controls exhibited complete habituation within 4 to 5 trials, ethanol-treated animals continued to respond throughout the testing session, with little decrement in heart rate response magnitude across 10 stimulus presentations. A different pattern of responding was observed in animals tested during adolescence (PD 30). Control animals failed to show the typical heart rate decrease indicative of orienting, and instead showed a tendency toward tachycardia. In contrast, ethanol-treated animals tested on PD 30 showed orienting bradycardia that persisted for several trials. Conclusions:, These data suggest that there are relatively long-term consequences of neonatal ethanol exposure on nonassociative memory. This impairment in habituation may be relevant to the distractibility and poor focused attention that is pervasive among humans diagnosed with fetal alcohol spectrum disorders. [source] European Federation of Neurological Societies/Peripheral Nerve Society Guideline, on management of multifocal motor neuropathy.JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2006Report of a joint task force of the European Federation of Neurological Societies, the Peripheral Nerve Society Abstract Background: Several diagnostic criteria for multifocal motor neuropathy (MMN) have been proposed in recent years, and a beneficial effect of intravenous immunoglobulin (IVIg) and various other immunomodulatory drugs has been suggested in several trials and uncontrolled studies. Objectives: The aim of this guideline was to prepare consensus guidelines on the definition, investigation, and treatment of MMN. Methods: Disease experts and a representative of patients considered references retrieved from MEDLINE and the Cochrane Library in July 2004 and prepared statements that were agreed in an iterative fashion. Recommendations: The Task Force agreed on good practice points to define clinical and electrophysiological diagnostic criteria for MMN and investigations to be considered. The principal recommendations and good practice points were as follows: (1) IVIg (2 g/kg given over 2,5 days) should be considered as the first line of treatment (level A recommendation) when disability is sufficiently severe to warrant treatment; (2) corticosteroids are not recommended (good practice point); (3) if initial treatment with IVIg is effective, repeated IVIg treatment should be considered (level C recommendation). The frequency of IVIg maintenance therapy should be guided by the individual response (good practice point). Typical treatment regimens are 1 g/kg every 2,4 weeks or 2 g/kg every 4,8 weeks (good practice point); (4) if IVIg is not (or not sufficiently) effective, then immunosuppressive treatment may be considered. Cyclophosphamide, cyclosporine, azathioprine, interferon-,1a, or rituximab are possible agents (good practice point); and (5) toxicity makes cyclophosphamide a less desirable option (good practice point). [source] Efficacy of alosetron in irritable bowel syndrome: a meta-analysis of randomized controlled trialsNEUROGASTROENTEROLOGY & MOTILITY, Issue 1 2003F. Cremonini Abstract The 5HT3 receptor antagonist alosetron has been tested in several trials on irritable bowel syndrome (IBS) patients. The aim of the present meta-analysis was to determine its effect on adequate relief of pain or global improvement of symptoms in IBS patients. Six large, multicentre, randomized, placebo-controlled trials fulfilled pre-set criteria for high quality and were included in the meta-analysis; 1762 patients were randomized to alosetron treatment and 1356 to placebo. Seventy-five per cent of the patients experienced diarrhoea-predominant IBS and 93% were females. The pooled odds ratio for adequate relief of pain or global symptoms improvement was 1.81 [95% confidence interval (CI) 1.57,2.10). The average number of patients needed to treat with alosetron for one patient to achieve improvement over placebo treatment was seven (95% CI 5.74,9.43). The present analysis shows that alosetron 1 mg b.i.d. positively impacts global symptoms, and pain and discomfort in non-constipated IBS female patients. One in four patients treated with alosetron may develop constipation. The efficacy of alosetron is unclear in male patients. [source] Probiotics for the treatment of women with bacterial vaginosisCLINICAL MICROBIOLOGY AND INFECTION, Issue 7 2007M. E. Falagas Abstract This review considers whether probiotics are effective agents for the treatment and/or prevention of bacterial vaginosis (BV). There seems to be an association between the absence of, or low concentrations of, vaginal lactobacilli and the development of BV. Many studies have suggested that the presence of H2O2 -producing vaginal lactobacilli may protect against BV, although some studies do not support this hypothesis. In-vitro studies have suggested that certain specific strains of lactobacilli are able to inhibit the adherence of Gardnerella vaginalis to the vaginal epithelium and/or produce H2O2, lactic acid and/or bacteriocins, which inhibit the growth of bacteria causing BV. Clinical trials showed that intra-vaginal administration of Lactobacillus acidophilus for 6,12 days, or oral administration of L. acidophilus or Lactobacillus rhamnosus GR-1 and Lactobacillus fermentum RC-14 for 2 months, resulted in the cure of BV (defined as a 0,1 positive score according to Amsel's criteria), and/or reduced the recurrences of BV, and/or caused an increase in vaginal lactobacilli and restoration of a normal vaginal microbiota, significantly more frequently than did a placebo, acetic acid or no treatment. However, several trials have found no significant difference in the cure rate of BV and in the number of vaginal lactobacilli after intra-vaginal instillation of lactobacilli when compared with the effect of a placebo or oestrogen. Thus, although the available results concerning the effectiveness of the administration of lactobacilli for the treatment of BV are mostly positive, it cannot yet be concluded definitively that probiotics are useful for this purpose. [source] Pharmacokinetics and tolerability of intravenous busulfan in hematopoietic stem cell transplantationCLINICAL TRANSPLANTATION, Issue 3 2007Yo-Han Cho Abstract:, Intravenous (IV) busulfan has been developed to overcome variable absorption of oral busulfan and tested in several trials. We tested its pharmacological properties and tolerability in 16 Korean stem cell transplantation (SCT) patients. IV busulfan was administered at 0.8 mg/kg every six h for a total of 16 doses (days ,7 to ,4), which was followed by cyclophosphamide administration at 60 mg/kg every 24 h for two d (days ,3 and ,2). The median AUCinf values (at the first dose) and AUCss (at the steady state) were 1060.4 ,M·min (range: 511.1,1812.7) and 1092.5 ,M·min (range: 539.7,1560.8) respectively. All patients had an AUCinf of <1500 ,M·min at the first dose, and 13 of the 16 (81.3%) maintained AUCss levels between 800 and 1500 ,M·min. Thirteen of 16 patients showed successful engraftments but four patients (25%) developed hepatic VOD (two of which were fatal), three of whom had advanced disease at the time of SCT. Overall, pharmacokinetics of IV busulfan in our SCT patients appeared comparable with those observed in other study. However, hepatic VOD was a major morbidity in patients with advanced disease. [source] | ||||||||||