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Healthy Males (healthy + male)
Terms modified by Healthy Males Selected AbstractsRepeated high-frequency transcranial magnetic stimulation over the dorsolateral prefrontal cortex reduces cigarette craving and consumptionADDICTION, Issue 4 2009Revital Amiaz ABSTRACT Aims To evaluate the effect of repeated high-frequency transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC), combined with either smoking or neutral cues, on cigarette consumption, dependence and craving. Design Participants were divided randomly to real and sham stimulation groups. Each group was subdivided randomly into two subgroups presented with either smoking-related or neutral pictures just before the daily TMS intervention. Ten daily rTMS sessions were applied every week-day and then a maintenance phase was conducted in which rTMS sessions were less frequent. Setting Single-site, out-patient, randomized, double-blind, sham-controlled. Participants Forty-eight chronic smokers who smoked at least 20 cigarettes per day and were motivated to quit smoking. Healthy males and females were recruited from the general population using advertisements in newspapers and on internet websites. Intervention Ten daily rTMS sessions were administered using a standard figure-8 coil over the DLPFC. Stimulation included 20 trains/day at 100% of motor threshold. Each train consisted of 50 pulses at 10 Hz with an inter-train interval of 15 seconds. Measurements Cigarette consumption was evaluated objectively by measuring cotinine levels in urine samples and subjectively by participants' self-reports. Dependence and craving were evaluated by standard questionnaires. Findings Ten daily rTMS sessions over the DLPFC reduced cigarette consumption and nicotine dependence. Furthermore, treatment blocked the craving induced by daily presentation of smoking-related pictures. However, these effects tended to dissipate over time. Conclusions Multiple high-frequency rTMS of the DLPFC can attenuate nicotine craving. [source] PURGING THE GENOME WITH SEXUAL SELECTION: REDUCING MUTATION LOAD THROUGH SELECTION ON MALESEVOLUTION, Issue 3 2009Michael C. Whitlock Healthy males are likely to have higher mating success than unhealthy males because of differential expression of condition-dependent traits such as mate searching intensity, fighting ability, display vigor, and some types of exaggerated morphological characters. We therefore expect that most new mutations that are deleterious for overall fitness may also be deleterious for male mating success. From this perspective, sexual selection is not limited to influencing those genes directly involved in exaggerated morphological traits but rather affects most, if not all, genes in the genome. If true, sexual selection can be an important force acting to reduce the frequency of deleterious mutations and, as a result, mutation load. We review the literature and find various forms of indirect evidence that sexual selection helps to eliminate deleterious mutations. However, direct evidence is scant, and there are almost no data available to address a key issue: is selection in males stronger than selection in females? In addition, the total effect of sexual selection on mutation load is complicated by possible increases in mutation rate that may be attributable to sexual selection. Finally, sexual selection affects population fitness not only through mutation load but also through sexual conflict, making it difficult to empirically measure how sexual selection affects load. Several lines of enquiry are suggested to better fill large gaps in our understanding of sexual selection and its effect on genetic load. [source] Efficacy of four insect repellents against mosquito bites: a double-blind randomized placebo-controlled field study in SenegalFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2009Bernard Uzzan Abstract Insect-borne diseases represent a worldwide threat. In addition to fight against vectors (insecticides) and disease prevention (vaccination against yellow fever, chemoprophylaxis against malaria), insect repellents applied on the skin could help reduce the heavy burden related to these diseases. In a field study performed in Senegal, we compared the efficacy of one skin application between 3 and 4 p.m. of four spray repellents [icaridine 20%, para-menthane-diol (PMD) 20% and 50% and DEET 50%] against placebo, among 100 healthy male and female volunteers experienced with mosquito capture. Double-blind randomized cross-over placebo-controlled study (Latin-square design) during five consecutive nights (7 p.m. to midnight) in two villages was conducted. To avoid residual effect, right or left leg was alternately exposed during consecutive nights and the exposed leg was washed before next night. The statistical model was random and mixed effects anova. All four active repellents provided a significant and similar protection compared with placebo, lasting 8 h. However, there was a non-significant trend for a higher protection by DEET 50% than by PMD 20% (P = 0.07). Duration of protection was similar for all repellents. Their effects were similar among men and women, and against Anopheles or other species. No serious adverse drug reaction was noticed. Using a rigorous methodology and a large number of volunteers, our well-controlled study demonstrated an important and similar protective effect of all four repellents compared with placebo. Such field studies should be required before approval of any newly developed repellent. [source] Mirtazapine and paroxetine: a drug-drug interaction study in healthy subjectsHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2001F. J. L. Ruwe Abstract Paroxetine inhibits cytochrome P450 2D6, which is involved in the metabolism of mirtazapine. The possible drug-drug interaction between two pharmacologically distinct antidepressants, mirtazapine and paroxetine, has been investigated in a randomized, three-way crossover study in 24 healthy male and female subjects. After a titration phase of 3 days, each subject received single daily doses of 30,mg mirtazapine, 40,mg paroxetine or the combination for 6 days. Assessments included serial blood sampling for pharmacokinetics at steady state, cognitive testing using the test battery of CDR Ltd, a visual analogue mood rating scale (Bond and Lader) and the Leeds Sleep Evaluation Questionnaire. Paroxetine inhibits the metabolism of mirtazapine, as shown by increases of approximately 17% and 25% of the 24,h AUC's of mirtazapine and its demethyl metabolite, respectively. Mirtazapine did not alter the pharmacokinetics of paroxetine. The combined administration of mirtazapine and paroxetine probably does not alter cognitive functioning or result in major changes on the visual analogue mood rating scale and Sleep Evaluation Questionnaire, compared with the administration of either drug alone. The incidence of adverse events was lower during combined administration of mirtazapine and paroxetine than during administration of either drug alone. Fatigue, dizziness, headache, nausea, anxiety and somnolence were the most common adverse events during combined administration. These data suggest that the combination of mirtazapine and paroxetine is unlikely to lead to clinically relevant drug-drug interactions and can be used without dose adjustment of either drug. The combination may even be better tolerated than either drug alone. Copyright © 2001 John Wiley & Sons, Ltd. [source] IODINE-FORTIFIED RICE AND ITS ABSORPTIONJOURNAL OF FOOD BIOCHEMISTRY, Issue 2 2009VANNA TULYATHAN ABSTRACT Iodine deficiency remains a major health problem in many parts of Thailand with over 50% of the population lacking sufficient iodine in their diet. Since rice is the main staple for Thai people with rice consumed in one form or another in almost every meal, enrichment of rice with iodine offers an effective way to remedy this deficiency of iodine. The present paper investigates the enrichment of iodine in milled rice seeds using flour gel coating technique. Milled rice (Klong-laung 1 variety) was coated with iodine-enriched flour gel (rice : gel = 100:5 w/w) by mixing at 40 rpm and drying to less than 13% moisture. Washing or cooking of the iodine-enriched rice resulted in about 99% and 94% retention of original iodine, respectively. Sensory properties of the cooked rice were acceptable and almost comparable to non-iodine rice. When the iodine-fortified rice was fed to healthy male and female subjects, significant excretion of iodine in the urine was found. PRACTICAL APPLICATION A common form of rice consumed widely among Thai people (also popular in Laos and Cambodia) is a food known simply as "sticky rice." The reason for its popularity is the simple way it is prepared and, above all, its good taste. It is made from a short type of rice and when prepared, the resulting texture is quite sticky, thus its name. However, its nutritional value is quite low and is a good candidate for the introduction of iodine coating. It can be made by a quick steaming process and this simplicity in preparation makes it widely popular and can be a vehicle for the introduction of iodine to the local mass. [source] Thoracic myelitis as a possible cause of myocardial infarctionJOURNAL OF INTERNAL MEDICINE, Issue 6 2005K. T. LAPPEGÅRD Abstract. During the course of an inflammatory process in the thoracic part of the spinal cord, a previously healthy male suffered two myocardial infarctions in separate coronary territories. A coronary angiogram revealed only minor wall changes in one coronary artery. We hypothesize that the myocardial infarctions may have been caused by vasospastic reactions secondary to his spinal cord pathology, and present the case report and a review of the literature. [source] Modulation of salivation and heartburn in response to the site of acid infusion in the human oesophagusALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2010S. K. Dutta Summary Background, The pathogenesis of gastro-oesophageal reflux disease includes increased acid reflux, reduced salivation and impaired peristalsis. This may depend upon the height of acid wave and magnitude of oesophageal mucosal exposure. Interestingly, the effect of site of acid infusion upon salivary secretion and heartburn has not been examined in any detail. Aim, To examine whether acid infusion in the upper oesophagus may cause increased salivation and heartburn as compared with acid infusion in the lower oesophagus. Methods, Twelve healthy male subjects (mean age 30) received infusions of HCl, citric acid and acetic acid at 10 and 20 cm above the lower oesophageal sphincter (LES) for fixed time periods. Parotid saliva collected periodically and heartburn severity scored using standardized scale. Standard statistical methods (paired t -tests, analysis of variance) were used to determine the significance of results. Results, Acid infusion in the upper oesophagus increased parotid flow rate as compared with that in the lower oesophagus (P < 0.05). Likewise, there was a significantly increased heartburn score at 20 cm as well as 10 cm above LES (P < 0.05) as compared with that in the stomach. Conclusion, These data suggest a significant increase in salivation and heartburn in response to acid infusion in the upper vs. lower part of the oesophagus. [source] The pharmacodynamics and pharmacokinetics of S-tenatoprazole-Na 30 mg, 60 mg and 90 mg vs. esomeprazole 40 mg in healthy male subjectsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2010R. H. HUNT Aliment Pharmacol Ther,31, 648,657 Summary Background, Racemic tenatoprazole 40 mg/day provides more prolonged acid suppression than esomeprazole 40 mg/day. Aim, To compare pharmacodynamic and pharmacokinetic profiles of tenatoprazole and esomeprazole. Methods, A single-centre, double-blind, double-dummy, randomized, 4-way, cross-over study was conducted in 32 healthy male subjects. S-tenatoprazole-Na 30, 60 or 90 mg, or esomeprazole 40 mg was administered once daily for 5 days with 10-day washout intervals. The 24-h intragastric pH was recorded at baseline and on day 5 of each period. Results, On day 5, median pH (5.34 ± 0.45 and 5.19 ± 0.52 vs. 4.76 ± 0.82, respectively, P < 0.002) and percentage time with pH > 4 (80 ± 11 and 77 ± 12, vs. 63 ± 11 respectively, P < 0.0001) for 24-h were higher with S-tenatoprazole-Na 90 mg and 60 mg than esomeprazole. In nocturnal periods, S-tenatoprazole-Na 90 mg, 60 mg and 30 mg were superior to esomeprazole with regard to median pH (5.14 ± 0.64, 4.94 ± 0.65, 4.65 ± 0.86 and 3.69 ± 1.18 respectively, P < 0.0001) and percentage time with pH > 4 (77 ± 12, 73 ± 17, 64 ± 17 and 46 ± 17 respectively, P < 0.0001). Proportion of subjects with nocturnal acid breakthrough with S-tenatoprazole-Na 90 mg, 60 mg and 30 mg was significantly less than with esomeprazole (54.8, 43.3, 56.7 and 90.3 respectively, P < 0.04). The proportion of subjects with >16 hrs with pH >4 was significantly higher with S-tenatoprazole-Na 90 mg and 60 mg than with esomeprazole (87.1%, 83.3% and 41.9% respectively, P < 0.02). Conclusions, S-tenatoprazole-Na produced significantly greater and more prolonged dose-dependent 24-h and nocturnal acid suppression than esomeprazole. S-tenatoprazole-Na may provide greater clinical efficacy compared with current PPIs for patients with ineffective once-daily therapy. [source] 5-aminosalicylic acid release from a new controlled-release mesalazine formulation during gastrointestinal transit in healthy volunteersALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2006M. BRUNNER Summary Background Mesalazine (5-aminosalicylic acid, 5-ASA) containing formulations represent a cornerstone in the treatment of inflammatory bowel diseases. A novel formulation with an Eudragit L/S mixture coating has been developed to provide selective release of 5-ASA to the ileo-caecal region and the colon. Aim To determine the release of 5-ASA during the gastrointestinal transit. Methods A single oral dose of mesalazine EC 500 mg gastroresistant tablets (Asamax) was administered to eight healthy male volunteers. Gastrointestinal transit and tablet disintegration were monitored by scintigraphy. 5-ASA release was verified by assessing plasma pharmacokinetics. Results Initial tablet disintegration was observed 5.65 ± 0.86 h after dosing, corresponding to the detection of 5-ASA in plasma. This occurred in the ileo-caecal region in three subjects and the ascending colon in the remaining five. The relative percentage of 5-ASA absorption was more pronounced in the ascending colon (41 ± 27.4%) than the ileo-caecal region (6.6 ± 9.2%). Conclusion This mesalazine EC gastroresistant tablets release locally active 5-ASA specifically in the ileo-caecal region and the ascending colon. [source] The stable isotope ketoisocaproic acid breath test as a measure of hepatic decarboxylation capacity: a quantitative analysis in normal subjects after oral and intravenous administrationLIVER INTERNATIONAL, Issue 9 2009Heiner K. Berthold Abstract Background and aims: There is no generally accepted kinetic evaluation method for the stable isotope [13C]ketoisocaproic acid (KIC) breath test. Differences found in the results between women and men are contradictory. Methods: Oral and intravenous breath tests using 1 mg/kg stable isotope-labelled KIC were performed in healthy male and female volunteers. A power exponential function was fitted to the mass spectrometric data of breath 13CO2 enrichment, allowing mathematical analysis of time-to-peak-excretion, half-excretion time, percent label recovery and parameters describing the shape of the curve. Body composition was determined using bioelectrical impedance analysis. Results: After oral administration, total label recovery after 3 h was about 22% and was not different between men (n=7) and women (n=8). The time to maximal label excretion was 0.67 ± 0.12 h in men and 0.9 ± 0.32 h in women (P=0.028) and the excretion curve showed an initially slower rise in women compared with men. Adjusting for lean body mass or body water abrogated the sex differences. Total label recovery after intravenous administration was about 9%, suggesting that the substrate was rapidly catabolized in the muscle compartment after intravenous administration. Conclusions: The modified power exponential function described allows standardized estimates of the KIC breath test results. When corrected for body composition, there are no differences in breath test results between men and women. The comparison between oral and intravenous results provides robust evidence that the KIC breath test measures predominantly hepatic and not muscle decarboxylation and is thus a highly specific liver function test. [source] Development and validation of a gas chromatography/mass spectrometry metabonomic platform for the global profiling of urinary metabolitesRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 19 2008Kishore K. Pasikanti This paper presents a simple and reliable gas chromatography/mass spectrometry (GC/MS) method for the metabonomic analysis of human urine samples. The sample preparation involved the depletion of excess urea via treatment with urease and subsequent protein precipitation using ice-cold ethanol. An aliquot of the mixture was separated, dried, trimethylsilyl (TMS)-derivatized and 1.0,µL of the derivatized extract was injected into the GC/MS system via split injection (1:10). Approximately 150 putative metabolites belonging to different chemical classes were identified from the pooled human urine samples. All the identified metabolites were selected to evaluate precision and stability of the GC/MS assay. More than 95% of the metabolites demonstrated good reproducibility, with intra-day and inter-day precision values below 15%. Metabolic profiling of 53 healthy male and female urine samples in combination with pattern recognition techniques was performed to further validate the GC/MS metabolite profiling assay. Principal component analysis (PCA) followed by orthogonal partial least squares analysis (OPLS) revealed differences between urinary metabolite profiles of healthy male and female subjects. This validated GC/MS metabolic profiling method may be further applied to the metabonomic screening of urinary biomarkers in clinical studies. Copyright © 2008 John Wiley & Sons, Ltd. [source] Clenbuterol marketed as dietary supplementBIOMEDICAL CHROMATOGRAPHY, Issue 3 2008Maria K. Parr Abstract In several studies it has been demonstrated that products containing pharmaceutically active ingredients are marketed as dietary supplements. Most of these products contain anabolic steroids. Recently products for weight loss containing active drugs have also appeared on the market. In the present case a healthy male ordered the product ,Anabolic burner' via the Internet. The product was received from a German dispatcher and paid by bank transfer to a German bank account. After ingesting one tablet he reported tremor and delivered a urine sample. This urine was found to contain 2 ng/mL of clenbuterol utilizing LC-MS/MS analysis. Additionally the product itself was analyzed with GC-MS for clenbuterol, yielding a content of about 30 µg per tablet. The beta-2 agonist clenbuterol is only legally available on prescription and is classified as prohibited doping substance in sports. The present case for the first time confirms the presence of clenbuterol in a dietary supplement. It again demonstrates the common problem with products on the supplement market, where non-licensed pharmaceuticals and doping substances are easily available. The ingestion of these products containing additions of therapeutic drugs can lead to side effects and/or interactions with conventional medicines. Copyright © 2007 John Wiley & Sons, Ltd. [source] The effect of gender on the pharmacokinetics of verapamil and norverapamil in humanBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 7 2006S. Dadashzadeh Abstract The effects of gender on the pharmacokinetics of verapamil and its active metabolite, norverapamil, following single oral dose (80mg, Isoptin) to 12 healthy male (mean age: 25.75±2.42 years, mean body weight: 70.59±9.94kg) and 12 healthy female subjects (mean age: 24.08±2.84 years, mean body weight: 56.67±5.23kg) were investigated in the present study. Plasma concentrations of verapamil and norverapamil were analysed using a modified high-pressure liquid chromatography method. Pharmacokinetic parameters were calculated by non-compartmental analysis for each subject. For verapamil the half-life (t1/2) and mean residence time (MRT) were significantly shorter in women than men (p<0.01 and p<0.05, respectively). For other pharmacokinetic parameters of verapamil there were no significant differences between males and females. For norverapamil, t1/2, MRT and time to reach to the maximum plasma concentration (Tmax) showed statistically significant differences between the two genders. The AUC0,24 and AUC0,, ratios of norverapamil to verapamil were also calculated. The ratios were significantly higher in women compared with men. These observations indicate that the elimination rate of verapamil is faster in women than men which may be attributed to the higher activity of CYP3A4 or lower activity of P-glycoprotein in women compared with men. A contribution of both factors in the appearance of gender differences in verapamil pharmacokinetics is also possible. Copyright © 2006 John Wiley & Sons, Ltd. [source] Inflammatory choroidal neovascular membrane in presumed ocular Lyme borreliosisACTA OPHTHALMOLOGICA, Issue 3 2009Radgonde Amer Abstract. Introduction:, Lyme disease is a multisystemic disease with protean ocular manifestations. We describe the occurrence of inflammatory choroidal neovascular membrane (CNVM) in two patients suffering from presumed Lyme disease. Methods:, Descriptive review of the clinical records of two patients. Results:, Patient 1: 16-year-old healthy male presenting with a visual acuity of counting fingers [oculus dexter (OD)] and 6/6 [oculus sinister (OS)] 3 months after a tick bite. He had papillitis and an exudative subretinal macular lesion OD. Treatment was started with intravenous (IV) ceftriaxone; a week later, IV methylprednisolone was administered with a tapering dose of oral steroids thereafter. Three months later, VA had improved to 3/60 OD. Patient 2: 38-year-old healthy female presenting with reduced left-eye vision (6/24) 6 weeks after a tick bite. She also suffered from erythema migrans and arthralgias. She had left-eye papillitis, macular haemorrhages and vascular sheathing. Treatment was started with IV ceftriaxone. One month later, there was profound loss of vision with development of CNVM. Treatment was declined by the patient and eventually retinal fibrosis developed. Conclusion:, Inflammatory CNVM has not been described previously in the setting of ocular Lyme borreliosis. We herein describe the occurrence of inflammatory CNVM in two patients whose diagnosis with Lyme disease was clinically based , both were sero-negative. Visual outcome in the two patients was profoundly impaired because of the ensuing macular scar. [source] Visuospatial attention disturbance in Duchenne muscular dystrophyDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 2 2010MARIA CLARA DRUMMOND SOARES DE MOURA Aim, The cognitive deficits present in the Duchenne muscular dystrophy (DMD) are not yet well characterized. Attention, considered to be the brain mechanism responsible for the selection of sensory stimuli, could be disturbed in DMD, contributing, at least partially, to the observed global cognitive deficit. The aim of this study was to investigate attentional function in individuals with DMD. Method, Twenty-five males (mean age 12y; SD 2y 2mo) with DMD and 25 healthy males (mean age 12y; SD 2y) were tested in a visuospatial task (Posner computerized test). They were instructed to respond as quickly as possible to a lateralized visual target stimulus with the ipsilateral hand. Their attention was automatically orientated by a peripheral prime stimulus or, alternatively, voluntarily orientated by a central spatially informative cue. Results, The main result obtained was that the attentional effect (sum of the benefit and the cost of attention) did not differ between the two groups in the case of automatic attention (p=0.846) but was much larger for individuals with DMD than for comparison individuals in the case of voluntary attention (p<0.001). Interpretation, The large voluntary attentional effect exhibited by the participants with DMD seems similar to that of younger children, suggesting that the disease is associated with delayed maturation of voluntary attention mechanisms. [source] Sensitivity and reproducibility of indirect calorimetry in measurement of resting metabolic rateDRUG DEVELOPMENT RESEARCH, Issue 8 2008Cecilia Karlsson Abstract The aim of this study was to assess indirect calorimetry measurement of resting metabolic rate (RMR) with respect to sensitivity and reproducibility in a human study population suitable for early clinical studies to evaluate new anti-obesity candidate drugs. Twenty-four overweight, but otherwise healthy males were included in this randomized, single-blind, placebo-controlled, crossover study. Three different doses of epinephrine (0.005, 0.01, 0.03,µg · kg fat-free mass (FFM),1 · min,1) were used as active treatment. There were two identical study periods, separated by a 4-week washout. Increases in RMR were seen with all tested concentrations of epinephrine when compared with placebo. Changes in RMR of ,1.8% could be detected with 90% power in this crossover study design. The RMR values measured at the two study periods revealed a highly significant correlation (Spearman correlation 0.803, P=0.0007). To conclude, indirect calorimetry is a sensitive and robust means of measuring RMR. The method can be used to assess RMR in diverse clinical settings, even when considering modest differences. Drug Dev Res 69: 2008. © 2008 Wiley-Liss, Inc. [source] Decreased cortisol production in male type 1 diabetic patientsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2003M. N. Kerstens Abstract Background It is unclear whether cortisol production and the 11,HSD-mediated cortisol to cortisone interconversion are different between type 1 diabetic patients and healthy subjects. Materials and methods Fourteen male, nonobese, normotensive type 1 diabetic patients without severe complications (HbA1c < 8·5%) were studied twice during a daily sodium intake of 50 and 200 mmol, and were then compared with 14 individually matched healthy subjects. Cortisol production was assessed by the sum of urinary cortisol metabolite excretion. Urinary ratios of (tetrahydrocortisol + allo-tetrahydrocortisol)/tetrahydro-cortisone [(THF + allo-THF)/THE] and of free cortisol/free cortisone [UFF/UFE] were determined as parameters of 11,HSD activity. Results Sum of urinary cortisol metabolite excretion during low- and high-salt diet was 7·4 ± 2·5 vs. 7·7 ± 2·3 nmol min,1 m,2 (NS) in diabetic patients and 9·7 ± 2·1 vs. 11·2 ± 4·1 nmol min,1 m,2 (NS) in healthy subjects, respectively (P < 0·05 vs. healthy subjects at both diets). The allo-THF excretion and allo-THF/THF ratios were lower in the diabetic than in the healthy males during both diets (P < 0·05). Urinary (THF + alloTHF)/THE and UFF/UFE were similar in both groups and remained unchanged after salt loading. Conclusions The sum of urinary cortisol metabolite excretion as a measure of cortisol production is lower in nonobese, normotensive type 1 diabetic males with adequate glycaemic control and without severe complications, irrespective of sodium intake. We suggest that this is at least in part as result of diminished 5, reductase activity, resulting in a decreased cortisol metabolic clearance. In type 1 diabetic and in healthy males, the 11,HSD setpoint is not affected by physiological variations in sodium intake. [source] Effects of adrenaline and potassium on QTc interval and QT dispersion in manEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2003S. Lee Abstract Background Hypoglycaemia alters cardiac repolarization acutely, with increases in rate-corrected QT (QTc) interval and QT dispersion (QTd) on the electrocardiogram (ECG); such changes are related to the counterregulatory sympatho-adrenal response. Adrenaline produces both QTc lengthening and a fall in plasma potassium (K+) when infused into healthy volunteers. Hypokalaemia prolongs cardiac repolarization independently however, and therefore our aim was to determine whether adrenaline-induced repolarization changes are mediated directly or through lowered plasma K+. Materials and methods Ten healthy males were studied on two occasions. At both visits they received similar l- adrenaline infusions but on one occasion potassium was also administered; infusion rates were adjusted to maintain circulating K+ at baseline. The QTc interval, QTd, peripheral physiological responses and plasma adrenaline and potassium concentrations were measured during both visits. Results The QTc interval and QTd increased both with and without potassium clamping. Without K+ replacement, mean (SE) QTc lengthened from 378 (5) ms to a final maximum value of 433 (10) ms, and QTd increased from 36 (5) ms to 69 (8) ms (both P < 0·001). During K+ replacement, QTc duration at baseline and study end was 385 (7) ms and 423 (11) ms, respectively (P < 0·001), and QTd 38 was (4) ms and 63 (5) ms (P = 0·001). Conclusions These data suggest that disturbed cardiac repolarization as a result of increases in circulating adrenaline occurs independently of extracellular potassium. A direct effect of adrenaline upon the myocardium appears the most likely mechanism. [source] Aberrant increase in the immature platelet fraction in patients with myelodysplastic syndrome: a marker of karyotypic abnormalities associated with poor prognosisEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2009Naomi Sugimori Abstract Objectives:, Some patients with myelodysplastic syndrome (MDS) show a marked increase in the percentage of immature platelet fraction (IPF%) despite the absence of severe thrombocytopenia. To determine the significance of such an unbalanced increase in the IPF%, we investigated the IPF% and other laboratory findings of 51 patients recently diagnosed with MDS. Method:, Subjects consisted of 80 healthy males, 90 healthy females, and 51 patients with MDS and 20 patients with idiopathic thrombocytopenic purpura (ITP). The IPF and IPF% were determined using a Sysmex XE-2100 system loaded with IPF Master software (XE IPF Master, Sysmex). Platelet counts were measured simultaneously. Results:, IPF% and platelet counts of these patients ranged from 1.1% to 25.1% (median, 5.3%) and from 6 to 260 × 109/L (median, 71 × 109/L), respectively. Twelve patients showed platelet counts more than 50 × 109/L with 10% or more IPF%. All of the 12 patients had chromosome abnormalities including monosomy 7 and complex abnormalities involving 7 or 5q. In the other 39 patients who did not show the aberrant IPF% increase, chromosomal abnormalities were seen only in seven patients and none of them had chromosome 7 abnormalities. The IPF% of two patients increased to more than 10% in association with the appearance of monosomy 7. Conclusions:, These findings suggest that a high IPF% in MDS patient may be a marker for karyotypic abnormalities with a poor prognosis, including chromosome 7 abnormalities. [source] Cortical mechanisms of smooth pursuit eye movements with target blanking.EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2004An fMRI study Abstract Smooth pursuit eye movements are evoked by retinal image motion of visible moving objects and can also be driven by the internal representation of a target due to extraretinal mechanisms (e.g. efference copy). To delineate the corresponding neuronal correlates, functional magnetic resonance imaging at 1.5 T was applied during smooth pursuit at 10 °/s with continuous target presentation and target blanking for 1 s to 16 right-handed healthy males. Eye movements were assessed during scanning sessions by infra-red reflection oculography. Smooth pursuit performance was optimal when the target was visible but decreased to a residual velocity of about 30% of the velocity observed during continuous target presentation. Random effects analysis of the imaging data yielded an activation pattern for smooth pursuit in the absence of a visual target (in contrast to continuous target presentation) which included a number of cortical areas in which extraretinal information is available such as the frontal eye field, the superior parietal lobe, the anterior and the posterior intraparietal sulcus and the premotor cortex, and also the supplementary and the presupplementary eye field, the supramarginal gyrus, the dorsolateral prefrontal cortex, cerebellar areas and the basal ganglia. We suggest that cortical mechanisms such as prediction, visuo-spatial attention and transformation, multimodal visuomotor control and working memory are of special importance for maintaining smooth pursuit eye movements in the absence of a visible target. [source] No pharmacokinetic interaction between paliperidone extended-release tablets and trimethoprim in healthy subjects,HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 7 2009An Thyssen Abstract Objective The effect of trimethoprim, a potent organic cation transport inhibitor, on the pharmacokinetics (PK) of paliperidone extended-release tablets (paliperidone ER), an organic cation mainly eliminated via renal excretion, was assessed. Methods Open-label, two-period, randomized, crossover study in 30 healthy males. Single dose of paliperidone ER 6,mg was administered either alone on day 1 or day 5 during an 8-day treatment period of trimethoprim 200,mg twice daily. Serial blood and urine samples were collected for PK and plasma protein binding of paliperidone and its enantiomers. The 90% confidence interval (CI) of ratios with/without trimethoprim for PK parameters of paliperidone and its enantiomers calculated. Results Creatinine clearance decreased from 119 to 102,mL,min,1 with trimethoprim. Addition of trimethoprim increased unbound fraction of paliperidone by 16%, renal clearance by 13%, AUC, by 9%, and t½ by 19%. The 90% CIs for ratios with/without trimethoprim were within the 80,125% range for Cmax, AUClast, and renal clearance. For AUC,, 90% CI was 79.37,101.51, marginally below the lower bound of the acceptance range. Paliperidone did not affect steady-state plasma concentrations of trimethoprim. Conclusions No clinically important drug interactions are expected when paliperidone ER is administered with organic cation transport inhibitors. Copyright © 2009 John Wiley & Sons, Ltd. [source] Expression of Fas and Fas ligand in human testicular germ cell tumoursINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 2 2009E. Baldini Summary In the present study, we analysed the expression of Fas ligand (FasL) and its cognate receptor Fas in 14 seminomatous testicular germ cell tumours (TGCT) and six normal testicular tissues obtained following orchiectomy. Tissue samples have been processed to prepare either total RNA or protein extracts or fixed and embedded in paraffin for immunohistochemistry (IHC) experiments. Quantitative RT-PCR experiments demonstrated in TGCT a significant (p < 0.01) increase of the FasL mRNA expression of 21.1 ± 5.4 fold, with respect to normal tissues. On the contrary, in the same cancer tissues, the levels of Fas mRNA were significantly (p < 0.01) reduced to 0.27 ± 0.06 fold. These observations were confirmed in western blot experiments showing a significant increase of FasL and a concomitant decrease of Fas proteins in testicular cancer tissues, with respect to normal testis. Moreover, IHC experiments showed a strong FasL immuno-reactivity in six out of eight TGCT samples analysed, while Fas immuno-positivity was found in cancer cells of only two TGCT tissues. In addition, in all tumour samples, infiltrating lymphocytes were Fas positive. However, no correlation could be observed between Fas or FasL mRNA variations and clinical parameters such as patient's age, TNM stage or tumour size. We also compared the serum levels of soluble FasL (sFasL) of 15 patients affected by seminomatous TGCT, of four patients with non-seminomatous TGCT and six age-matched healthy males. No significant differences in sFasL serum level could be identified. In conclusion, our data demonstrated that the majority of seminomas are characterized by an increased expression of FasL and a concomitant reduction of Fas, with respect to human normal testis, and that sFasL serum level is not a tumour marker for patients affected by TGCT. [source] Ejaculatory dysfunction caused by the new ,1 -blocker silodosin: A preliminary study to analyze human ejaculation using color Doppler ultrasonographyINTERNATIONAL JOURNAL OF UROLOGY, Issue 10 2008Atsushi Nagai Objectives: In order to clinically investigate the mechanism of ejaculatory dysfunction attributable to the ,1 -blocker silodosin, a real-time observation of ejaculation by healthy males was performed. Methods: Following intake of silodosin, a newly developed selective ,1 -blocker for benign prostatic hypertrophy, ejaculation was dynamically observed using color Doppler ultrasound in three healthy males. Normal ejaculation was also investigated in the same manner. Results: With silodosin intake, no antegrade ejaculation was observed in cases 1 or 2. In case 1, seminal fluid slowly but continuously flowed out from the seminal vesicles into the bladder. In case 2, only a small amount of seminal fluid flowed into the bladder during the ejaculatory sensation. In case 3, ejection of a small amount of semen from the external urethral orifice was observed and inflow of a small amount of seminal fluid into the bladder was also captured. Without silodosin intake, all three subjects exhibited antegrade ejaculation. Conclusions: The mechanism of ejaculatory dysfunction is intricately related to retrograde ejaculation (retrograde inflow of seminal fluid), insufficient contraction of the seminal vesicles, and insufficient rhythmic contraction of the muscles of the pelvic floor. [source] Regulation of C-Terminal and Intact FGF-23 by Dietary Phosphate in Men and Women,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2006Sherri-Ann M Burnett MD Abstract FGF-23 is a novel regulator of phosphate metabolism. We studied the regulation of FGF-23 by dietary phosphate in 66 men and women using two assays. Dietary phosphate restriction decreased FGF-23 and loading increased FGF-23 significantly. An assay that measured intact FGF-23 showed the effects of dietary phosphate much more clearly than an assay that also measures presumed biologically inactive fragments. Dietary phosphate is a key regulator of circulating FGF-23; choice of assay is critical when studying FGF-23 physiology. Introduction: Fibroblast growth factor 23 (FGF-23) is a novel phosphaturic factor discovered through genetic studies of patients with renal phosphate wasting disorders. Ablation of the FGF-23 gene in mice reduces renal phosphate excretion and increases serum phosphate, suggesting that FGF-23 is critical for normal phosphate homeostasis. We examined the role of dietary phosphate in the regulation of FGF-23 in humans. Materials and Methods: Sixty-six healthy males and females were randomized to either phosphate-depleted or -loaded diets for 5 days, after a 4-day run-in diet. FGF-23 was measured using an "intact" assay that only detects intact FGF-23 peptide and with a "C-terminal" assay that measures both intact FGF-23 peptide and presumed biologically inactive carboxyl terminal fragments. The main outcome was the within group change in FGF-23 with either phosphate depletion or loading. Results: Using the intact FGF-23 assay, mean FGF-23 area under the curve (AUC) decreased by 9 ± 16% with phosphate depletion (p = 0.0041) and increased by 35 ± 29% with loading (p < 0.0001). Using the C-terminal FGF-23 assay, mean FGF-23 AUC decreased by 8 ± 12% with phosphate depletion (p = 0.0003) and increased by 13 ± 20% with loading (p = 0.0016). Increases in FGF-23 with phosphate loading were greater with the intact assay than with the C-terminal assay (p = 0.0003). Using the intact assay only, FGF-23 was significantly associated with serum phosphate (r = 0.39, p < 0.01), 24-h urinary phosphate (r = 0.47, p < 0.01), fractional excretion of phosphate (r = 0.29, p < 0.01), and 1,25-dihydroxyvitamin D (r = ,0.30, p < 0.01). The association between the assays was weak (r = 0.26, p < 0.01). Conclusions: Dietary phosphate is a key regulator of circulating FGF-23 levels in humans. Additionally, choice of assay is critical when performing physiologic investigations of FGF-23. [source] Is there a greater mandibular movement capacity towards the left?JOURNAL OF ORAL REHABILITATION, Issue 4 2005Verification of an observation from 192 summary, In 1921, the German dentist Hans Wertheim reported that more individuals were able to shift the mandible more towards the left than to the right. This study analyses the deviation from symmetrical mobility of the lower jaw in either direction. Using a millimetre ruler, maximum jaw opening (MJO), maximum left laterotrusion (MLL), and maximum right laterotrusion (MRL) were recorded in 141 healthy individuals and in 141 patients with temporomandibular disorders (TMDs). For both sexes, the mean maximum movements to the left and to the right were greater in the healthy group as compared with the TMD group. Healthy subjects as well as patients were able to move the mandible more to one side. Only a minority had identical values for MLL and MRL. The majority of healthy individuals and TMD patients could move more to the left (P < 0·001). In the healthy group, the mean ratio between MJO and MLL was 5·0, and 5·5 between MJO and MRL. In the TMD group, the corresponding values were 4·6 and 6.1. The mean absolute difference between MLL and MLR (in mm) was 1·24 [95% confidence interval (CI): 0·99; 1·49] among healthy females, and 2·09 (95% CI: 1·52; 2·66) among healthy males. In the TMD group, the corresponding values were 2·62 (95% CI: 2·21; 3·04) and 2·83 (95% CI: 1·67; 4·00), respectively. From the results of our study we conclude that moderate deviations from symmetric movements (mean: 1·2 mm for women, 2·1 mm for men) appear to be the norm even in healthy individuals. [source] Comparison of maximum bite force and dentate status between healthy and frail elderly personsJOURNAL OF ORAL REHABILITATION, Issue 6 2001H. Miura The purpose of the present study was to (1) determine the standard value of maximum bite force and to (2) compare the maximum bite force of the elderly between healthy and frail subjects. Subjects included 349 healthy elderly individuals (149 males, 200 females) and 24 frail elderly individuals (seven males, 17 females) ranging from 65 to 74 years of age. Maximum bite force was evaluated using a Dental Prescale systemÔ. The maximum bite force of the healthy subjects was significantly higher than that of the frail subjects in both males (P=0·020) and females (P=0·015). However, no significant difference was observed in the number of present teeth between the healthy and frail subjects. Median of maximum bite force in healthy males was 408,0 N, and that of the healthy females was 243,5 N. These results suggest that the frail elderly have latent bite force problems. [source] Genioglossus muscle activity during rhythmic open,close jaw movementsJOURNAL OF ORAL REHABILITATION, Issue 8 2000S. Hiyama The purpose of this study was to examine genioglossus muscle activity during rhythmic open,close jaw movements. The electromyographic activity of the genioglossus muscle was recorded with a bipolar fine-wire electrode in six healthy males. The electromyographic activities of the ipsilateral masseter and digastric muscles were simultaneously recorded with bipolar surface electrodes. The subjects were instructed to perform rhythmic open,close jaw movements in time with a metronome set at 23, 27, 33, 42 and 50 beats/min. In all of the subjects, rhythmic electromyographic activity of the genioglossus muscle was recorded in both the jaw-opening and jaw-closing phases. The activity of the genioglossus muscle was predominantly recorded in the jaw-opening phase in two subjects, and in the jaw-closing phase in two subjects. The burst duration of the electromyographic activity of the genioglossus muscle changed linearly in accordance with the cycle duration. However, the latency from the onset of the electromyographic activity of the masseter or digastric muscle to that of the genioglossus muscle was almost constant, independent of the cycle duration. Based on these findings, we conclude that the activity of the human genioglossus muscle is closely linked to that of masticatory muscles under the control of a closely related central pattern generator. [source] Robust circadian rhythm in heart rate and its variability: influence of exogenous melatonin and photoperiodJOURNAL OF SLEEP RESEARCH, Issue 2 2007GILLES VANDEWALLE Summary Heart rate (HR) and heart rate variability (HRV) undergo marked fluctuations over the 24-h day. Although controversial, this 24-h rhythm is thought to be driven by the sleep,wake/rest,activity cycle as well as by endogenous circadian rhythmicity. We quantified the endogenous circadian rhythm of HR and HRV and investigated whether this rhythm can be shifted by repeated melatonin administration while exposed to an altered photoperiod. Eight healthy males (age 24.4 ± 4.4 years) participated in a double-blind cross-over design study. In both conditions, volunteers were scheduled to 16 h,8 h rest : wake and dark : light cycles for nine consecutive days preceded and followed by 29-h constant routines (CR) for assessment of endogenous circadian rhythmicity. Melatonin (1.5 mg) or placebo was administered at the beginning of the extended sleep opportunities. For all polysomnographically verified wakefulness periods of the CR, we calculated the high- (HF) and low- (LF) frequency bands of the power spectrum of the R,R interval, the standard deviation of the normal-to-normal (NN) intervals (SDNN) and the square root of the mean-squared difference of successive NN intervals (rMSSD). HR and HRV variables revealed robust endogenous circadian rhythms with fitted maxima, respectively, in the afternoon (16:36 hours) and in the early morning (between 05:00 and 06:59 hours). Melatonin treatment phase-advanced HR, HF, SDNN and rMSSD, and these shifts were significantly greater than after placebo treatment. We conclude that endogenous circadian rhythmicity influences autonomic control of HR and that the timing of these endogenous rhythms can be altered by extended sleep/rest episodes and associated changes in photoperiod as well as by melatonin treatment. [source] Atorvastatin and omega-3 fatty acids protect against activation of the coagulation system in patients with combined hyperlipemiaJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2003A. Nordøy Summary., Activation of factor (F)VII by tissue factor may represent a critical event during plaque rupture in acute coronary syndromes. Patients with combined hyperlipemia are at high risk for developing coronary heart disease and their tendency to thrombosis may be accelerated during postprandial hyperlipemia. In the present double-blind, placebo-controlled parallel study, 42 patients with combined hyperlipemia and serum triglycerides between 2.0 and 15.0 mmol L,1 and serum cholesterol >5.3 mmol L,1 at the end of a 3-month dietary run-in period were treated with atorvastatin at 10 mg day,1 for at least 10 weeks. During the last 5 weeks the patients were randomized into two groups receiving 1.68 g day,1 omega-3 fatty acids (,-3 FA) or placebo (corn oil). The fasting levels of FVII antigen (FVII-Ag) and FVII coagulant activity (FVII:C) were high compared with healthy males. The fasting levels of activated FVII (FVIIa) and FVII-Ag correlated both to serum triglycerides and apolipoprotein A1 (apoA1). FVIIa and FVII:C increased during postprandial hyperlipemia. This increase of FVIIa correlated to the fasting triglyceride and apoA1 levels, but not to the degree of postprandial hypertriglyceridemia. The concentrations of fasting FVIIa in these patients were reduced in parallel with a reduction of fasting triglycerides by treatment with atorvastatin + placebo. This treatment also reduced the postprandial level of FVIIa. ,-3 FA in addition to atorvastatin further reduced FVIIa concentrations, fasting and postprandially, and also significantly reduced FVII:C and FVII-Ag during postprandial hyperlipemia. Prothrombin fragment 1 + 2 (F1 + 2) increased during postprandial hyperlipemia. This increase was significantly reduced after treatment with atorvastatin plus ,-3 FA. The increase of F1 + 2 measured as incremental area under the curve (iAUC) during postprandial hyperlipemia correlated to the fasting levels of FVIIa, FVII:C and FVII-Ag and also to the levels of these factors during postprandial lipemia. In conclusion, patients with combined hyperlipemia are at risk for activation of the coagulation system, particularly during postprandial lipemia. This activation may be significantly reduced by statins and ,-3 FA. [source] Correlation between electroencephalography and heart rate variability during sleepPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 1 2003MMLSC , Mina Ako MT Abstract It is known that autonomic nervous activities change in correspondence with sleep stages. However, the characteristics of continuous fluctuations in nocturnal autonomic nerve tone have not been clarified in detail. The study aimed to determine the possible correlation between the electroencephalogram (EEG) and autonomic nervous activities, and to clarify in detail the nocturnal fluctuations in autonomic nerve activities. Overnight EEGs and electrocardiograms of seven healthy males were obtained. These EEGs were analyzed by fast Fourier transformation algorithm to extract delta, sigma and beta power. Heart rate and heart rate variability (HRV) were calculated in consecutive 5-min epochs. The HRV indices of low frequency (LF), high frequency (HF) and LF/HF ratio were calculated from the spectral analysis of R-R intervals. The sleep stages were manually scored according to Rechtschaffen and Kales' criteria. Low frequency and LF/HF were significantly lower during non-rapid eye movement (NREM) than REM, and were lower in stages 3 and 4 than in stages 1 and 2. Furthermore, delta EEG showed inverse correlations with LF (r = , 0.44, P < 0.001) and LF/HF (r = , 0.41, P < 0.001). In contrast, HF differed neither between REM and NREM nor among NREM sleep stages. Detailed analysis revealed that correlation was evident from the first to third NREM, but not in the fourth and fifth NREM. Delta EEG power showed negative correlations with LF and LF/HF, suggesting that sympathetic nervous activities continuously fluctuate in accordance with sleep deepening and lightening. [source] | |||||||||||||||||||||||||||||||