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Male Volunteers (male + volunteer)
Kinds of Male Volunteers Selected AbstractsMacroscopic Characteristics of Screwdriver TraumaJOURNAL OF FORENSIC SCIENCES, Issue 6 2007Alexandra M. Croft M.Sc. Abstract:, The main objective of the study was to determine the type of macroscopic trauma created by a flat-tipped and a cross-tipped screwdriver. The second objective was to determine if the trauma inflicted by the two screwdrivers could be macroscopically differentiated. Three tests were conducted, each by a male volunteer. Each test consisted of 12 samples of fleshed pig ribs; six were stabbed with a flat-tipped screwdriver and the remaining six with a cross-tipped screwdriver (Phillips®). Each sample received 15 stab wounds during the process. The stabbings were conducted at perpendicular and oblique angles, with fabric variables being utilized. Results illustrate two main categories of macroscopic skeletal trauma, fractures, and puncture wounds. By studying the macroscopic appearance in tandem with differing trauma frequencies, these two screwdriver types can be differentiated. [source] The urinary excretion of ,-hydroxybutyric acid in manJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2001P. V. Kavanagh ,-Hydroxybutyric acid (GHB) has been widely associated with drug-facilitated sexual assault (DFSA). However, its excretion profile in man has not been well characterized. To assess the detectability of GHB for forensic cases and to correlate urinary levels with dose, we have examined the excretion profiles of 1- and 2-g doses of GHB (sodium salt) in a healthy male volunteer. The urinary levels were measured by a novel, simple and highly reproducible method. The drug was found to be excreted in small amounts in the free form (0.86 and 1.16% for 1- and 2-g doses, respectively) rapidly in urine (, 10 h). The urinary levels were found to be in the low mg L,1 range (up to 29.1 mg L,1). The work presented demonstrates that it is of the utmost importance to collect the samples as soon as possible following the alleged assault. [source] Hepatectomy of living donors with a left-sided gallbladder and multiple combined anomalies for adult-to-adult living donor liver transplantationLIVER TRANSPLANTATION, Issue 1 2004Shin Hwang The left-sided gallbladder is very rare, but it is often accompanied by multiple anomalies of the liver, by which living donor hepatectomy cannot be feasible or becomes difficult. We have experienced 3 donors with a left-sided gallbladder out of 642 living donors. The first case was a male donor showing bifurcating portal anomaly with intrahepatic right portal vein confluence and extremely low bifurcation of the bile ducts. The right lobe was retrieved and implanted to his father. The second case was a male donor revealing trifurcating portal anomaly with separate right posterior portal branch and replacing right posterior hepatic artery. The right posterior segment graft was retrieved and implanted to his uncle. The third case was a male volunteer in whom the anterior portion of the medial segment was fed by an aberrant branch of the right anterior segment glisson. The small left lobe was retrieved and implanted simultaneously with another living donor's left lobe graft in the form of a dual living donor liver transplantation. There was no donor morbidity or recipient complication. Although there is a high possibility of diverse liver anomalies in living donors with a left-sided gallbladder, complete preoperative evaluation and mapping of the multiple anatomical variations may make certain types of living donor hepatectomy feasible. (Liver Transpl 2004;10:141,146.) [source] Forearm and leg amino acid metabolism in the basal state and during combined insulin and amino acid stimulation after a 3-day fastACTA PHYSIOLOGICA, Issue 3 2009J. Gjedsted Abstract Aim:, Fasting is characterized by a progressive loss of protein, but data on protein kinetics are unclear and few have studied the effects of re-feeding. The present study was designed to test the hypothesis that a combined infusion of insulin and amino acids after fasting would induce compensatory increases in protein synthesis and reductions in protein breakdown at the whole body level and in muscle. Methods:, We included 10 healthy male volunteers and studied them twice: (1) in the post-absorptive state and (2) after 72 h of fasting. Amino acid kinetics was measured using labelled phenylalanine and tyrosine, whole body energy expenditure was assessed and urea nitrogen synthesis rates were calculated. Results:, After fasting we observed an increase in arterial blood concentration of branched chain amino acids and a decrease in gluconeogenic amino acids (P < 0.05). Isotopically determined whole body, forearm and leg phenylalanine fluxes were unaltered apart from a 30% decrease in phenylalanine-to-tyrosine conversion (2.0 vs. 1.4 ,mol kg,1 h,1, P < 0.01). During infusion of insulin and amino acids, amino acid concentrations increased. Conclusion:, Our data indicate that after a 72-h fast basal and insulin/amino acid-stimulated regional phenylalanine fluxes in leg and forearm muscle are unaltered. During fasting concentrations of gluconeogenic amino acids decrease and hepatic and/or renal phenylalanine-to-tyrosine conversion decreases. Thus, as opposed to glucose and lipid metabolism, fasting does not induce insulin resistance as regards amino acid metabolism. [source] Adenosine infusion attenuates soluble RAGE in endotoxin-induced inflammation in human volunteersACTA PHYSIOLOGICA, Issue 1 2009A. Soop Abstract Aim:, To evaluate possible anti-inflammatory effects of pre-treatment with adenosine in a human experimental inflammatory model. Methods:, The study design was double-blind, crossover, placebo-controlled and randomized. In the Intensive Care Unit of a university hospital, 16 healthy male volunteers were treated for 5.5 h with infusions of adenosine 40 ,g kg,1 min,1 or placebo. Thirty minutes after the start of adenosine or placebo, 2 ng kg,1E-Coli endotoxin was administered. Heart rate, body temperature, blood pressure, plasma cytokines (TNF-,, IL-6 and IL-10), soluble RAGE and resistin, exhaled nitric oxide and nitrite/nitrate in urine were determined. Results:, Endotoxin elicited the expected clinical signs of an inflammatory reaction (tachycardia, fever) and led to prominent release of the cytokines studied (P < 0.001). Resistin in plasma increased after endotoxin (P < 0.001). After placebo treatment, soluble RAGE (sRAGE) in plasma increased 5 h after the endotoxin challenge (P < 0.001) but not after adenosine. After placebo, orally exhaled NO increased with a peak at 4 h (P < 0.001), although there was no statistically significant difference between the two treatments. Nitrite/nitrate in urine (n = 11) did not differ between adenosine and placebo treatments. Conclusion:, In conclusion, adenosine infusion starting before endotoxin challenge in humans attenuated sRAGE significantly but otherwise had no clear anti-inflammatory effect. Adenosine as a potential anti-inflammatory treatment in humans needs further study, including use of higher doses. The mechanism underlying the effect of adenosines on sRAGE remains unknown. [source] Effects of short-term cinnamon ingestion on in vivo glucose toleranceDIABETES OBESITY & METABOLISM, Issue 6 2007T. P. J. Solomon Aims:, Various spices display insulin-potentiating activity in vitro, and in particular, cinnamon spice and its phenolic extracts have been shown to exhibit these capabilities. In vivo study shows that cinnamon may have beneficial effects on glucose homeostasis; therefore the aim of this study was to further investigate this phenomenon in humans. Methods:, Seven lean healthy male volunteers, aged 26 ± 1 years, body mass index 24.5 ± 0.3 kg/m2 (mean ± s.e.m.), underwent three oral glucose tolerance tests (OGTT) supplemented with either a 5 g placebo (OGTTcontrol), 5 g of cinnamon (OGTTcin), or 5 g of cinnamon taken 12 h before (OGTTcin12hpre) in a randomized-crossover design. Results:, Cinnamon ingestion reduced total plasma glucose responses (AUC) to oral glucose ingestion [,13% and ,10% for OGTTcin (p < 0.05) and OGTTcin12hpre (p < 0.05), respectively], as well as improving insulin sensitivity as assessed by insulin sensitivity index measures based on Matsuda's model in both OGTTcin (p < 0.05) and OGTTcin12hpre (p < 0.05) trials compared with OGTTcontrol. Conclusions:, These data illustrate that cinnamon spice supplementation may be important to in vivo glycaemic control and insulin sensitivity in humans, and not only are its effects immediate, they also appear to be sustained for 12 h. [source] Effect of Sildenafil Citrate (Viagra) on Coronary Flow in Normal SubjectsECHOCARDIOGRAPHY, Issue 1 2008Fuminobu Ishikura M.D. Background: The purpose of this study was to evaluate the effect of sildenafil citrate (Viagra) on coronary function in normal subjects. Methods: The study assessed mean blood pressure, left anterior descending coronary artery (LAD) flow, and echocardiographic variables before and 30 and 60 minutes after taking 50 mg of sildenafil citrate. The mean velocity of LAD flow was assessed with Doppler flow imaging. The study subjects were 6 healthy male volunteers (mean age 37 years). Results: The mean velocity of LAD flow increased 60 minutes after taking sildenafil citrate, but there were no other changes. Two volunteers felt mild flashing and one had mild headache during the study. Conclusion: Sildenafil citrate caused vasodilatation in a normal coronary artery without systemic pressure drops. These results suggest that the agent itself did not have negative effects on the heart in normal subjects. [source] A Comparative Pharmacokinetic Study in Healthy Volunteers of the Effect of Carbamazepine and Oxcarbazepine on Cyp3a4EPILEPSIA, Issue 3 2007Astrid-Helene Andreasen Summary:,Purpose: Carbamazepine (CBZ) and oxcarbazepine (OXCZ) are well-known inducers of drug metabolism via CYP3A4. Indirect interaction studies and clinical experience suggest that CBZ has a stronger potential in this regard than OXCZ. However this has never been subject to a direct comparative study. We performed a study in healthy volunteers to investigate the relative inductive effect of CBZ and OXCZ on CYP3A4 activity using the metabolism of quinidine as a biomarker reaction. Methods: Ten healthy, male volunteers participated in an open, randomized crossover study consisting of two periods separated by a 4-week wash-out period. The subjects received 1200 mg oral OXCZ daily for 17 days and 800 mg oral CBZ for 17 days. A single 200 mg oral dose of quinidine was administered at baseline and following administration of CBZ and OXCZ. Outcome parameters were the formation clearance of 3-hydroxyquinidine dose and the ratio of the AUCs of 3-hydroxyquinidine to quinidine. Results: Formation clearance of 3-hydroxyquinidine was increased by means of 89% (CI: 36,164; p = 0.0022) and 181% (CI: 120,260, p < 0.0001) after treatment with OXCZ and CBZ, respectively, compared to baseline. The relative inductive effect of CBZ was 46% higher than for OXCZ. AUC ratio increased by means of 161% (CI: 139,187, p < 0.0001) (OXCZ) and 222% (CI: 192,257, p < 0.0001) (CBZ). Quinidine Cmax decreased by means of 29% (CI: 16,40, p = 0.0018) (OXCZ) and 33% (CI: 18,45, p = 0.0020) (CBZ). T½ decreased by means of 12% (CI: 6,17, p < 0.0014) (OXCZ) and 32% (CI: 25,38, p < 0.0001) (CBZ). tmax was not changed in either period. Conclusion: We confirm a clinically significant inductive effect of both OXCZ and CBZ. The inductive effect of CBZ was about 46% higher than that of OXCZ, a difference that may be of clinical relevance. [source] Parabolic flight primes cytotoxic capabilities of polymorphonuclear leucocytes in humansEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 8 2009I. Kaufmann Abstract Background, Previously performed in vitro studies suggested that gravitational stress may alter functions of immune cells. This study investigated the in vivo effects of parabolic flight manoeuvres as a short-term model of micro- and hypergravity on the cytotoxic and microbicidal polymorphonuclear leucocyte (PMN) functions as the key element of innate immunity. Material and methods, Twenty-one healthy male volunteers underwent 30 subsequent parabolic flight manoeuvres. Each manoeuvre produced 22-s periods of nearly weightlessness close to «0g», with each parabola starting with a pull-up and ending with a pull-out (hypergravity) at 1·8 g for about 20 s each. Blood samples were drawn 24 h prior to take off (T0), after 25,30 parabolas (T1), and 24 h (T2) and 48 h (T3) after flight for determination of (i) leucocyte number and subpopulations, (ii) PMNs' capabilities to produce hydrogen peroxide (H2O2) and to adhere and phagocytose particles and (iii) plasma cytokines known to prime PMN functions [interleukin-8 (IL-8), tumour necrosis factor-, (TNF-,), granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF)]. Results, Parabolic flight induced an increase in leucocyte number with a significant elevation of the PMN fraction. The spontaneous H2O2 production by PMNs did not change; however, the capability of PMNs to produce H2O2 in response to soluble stimuli [N -formyl-methionyl-leucyl-phenylalanine (fMLP), fMLP and TNF-,, calcium ionophore (A23187), phorbol myristate acetate (PMA)] was increased. Adhesive and phagocytic properties of PMNs were not altered. Regarding priming cytokines, IL-8 and G-CSF were significantly elevated. Conclusions, Our data indicate that parabolic flight induces priming of the cytotoxic capabilities of PMNs without affecting microbicidal functions. [source] Delayed genomic and acute nongenomic action of glucocorticosteroids in seasonal allergic rhinitisEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2004H.-C. Tillmann Abstract Background, Glucocorticosteroids are effective in the treatment of allergic rhinitis, a disease characterized by a variety of symptoms, e.g. rhinorrhea and itching. The time course of symptomatic relief for allergic rhinitis by steroids has not been examined in detail to date, although the onset of steroid action is one of the main discriminations between genomic and nongenomic actions of steroids. We therefore investigated the time course of subjective and objective measures of nasal affection after steroid administration in patients with allergic rhinitis following specific allergen challenge. Methods, Six female and 18 male volunteers (median age 26 years) with a history of allergic rhinitis but currently free of symptoms were included in this randomized, placebo-controlled, double-blind, three-period crossover study. A single dose of either betamethasone (60 mg), methylprednisolone (400 mg) or placebo was given intravenously, 5 min after intranasal allergen provocation. After 10, 20, 60, 150 and 240 min, nasal itching and nasal obstruction were assessed using a standardized visual analogue scale. In addition, nasal airflow was measured by anterior rhinomanometry. Results, Nasal itching was markedly reduced following either of the two steroids within 10 min after administration of study drug. Itching was depressed by 38% following betamethasone (P < 0·05) and by 18% following methylprednisolone (P = 0·07) compared with placebo. Nasal airflow and nasal obstruction were not significantly altered by steroids during the first 2 h of the study. However, after 150 min, nasal airflow was 21% rsp. 19% higher after methylprednisolone and betamethasone (P < 0·05) compared with placebo. After 240 min, nasal airflow was increased by 20% following betamethasone (P < 0·05) and by 19% following methylprednisolone. Nasal obstruction was also beneficially affected by both steroids 150 and 240 min after administration compared with placebo (P < 0·05 for both time points following betamethasone). Conclusion, This study for the first time shows rapid in vivo effects of external glucocorticosteroids in humans. Itching, a pathophysiologically complex sensation, is favourably influenced by steroids within 10 min, therefore presumably via nongenomic mechanisms. Though no detailed mechanisms can be derived from this study, steroid interaction with receptors in the central nervous system may play an important role in mediating this effect. [source] Cortical control of thermoregulatory sympathetic activationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2010M. Fechir Abstract Thermoregulation enables adaptation to different ambient temperatures. A complex network of central autonomic centres may be involved. In contrast to the brainstem, the role of the cortex has not been clearly evaluated. This study was therefore designed to address cerebral function during a whole thermoregulatory cycle (cold, neutral and warm stimulation) using 18-fluordeoxyglucose-PET (FDG-PET). Sympathetic activation parameters were co-registered. Ten healthy male volunteers were examined three times on three different days in a water-perfused whole-body suit. After a baseline period (32°C), temperature was either decreased to 7°C (cold), increased to 50°C (warm) or kept constant (32°C, neutral), thereafter the PET examination was performed. Cerebral glucose metabolism was increased in infrapontine brainstem and cerebellar hemispheres during cooling and warming, each compared with neutral temperature. Simultaneously, FDG uptake decreased in the bilateral anterior/mid-cingulate cortex during warming, and in the right insula during cooling and warming. Conjunction analyses revealed that right insular deactivation and brainstem activation appeared both during cold and warm stimulation. Metabolic connectivity analyses revealed positive correlations between the cortical activations, and negative correlations between these cortical areas and brainstem/cerebellar regions. Heart rate changes negatively correlated with glucose metabolism in the anterior cingulate cortex and in the middle frontal gyrus/dorsolateral prefrontal cortex, and changes of sweating with glucose metabolism in the posterior cingulate cortex. In summary, these results suggest that the cerebral cortex exerts an inhibitory control on autonomic centres located in the brainstem or cerebellum. These findings may represent reasonable explanations for sympathetic hyperactivity, which occurs, for example, after hemispheric stroke. [source] Cardiovascular Response to Graded Lower Body Negative Pressure in Young and Elderly ManEXPERIMENTAL PHYSIOLOGY, Issue 3 2001R. van Hoeyweghen Lower body negative pressure (LBNP) reduces central venous pressure (CVP) and cardiac output. The elderly are reported to have a limited capacity to increase cardiac output by increasing heart rate (HR), are especially dependent on end diastolic volume to maintain stroke volume and therefore should be especially vulnerable to LBNP. The present study compared the effects of LBNP in the young and old. Stroke volume was assessed non-invasively as stroke distance (SD) by aortovelography. Two groups of healthy male volunteers were studied: eight young (29.7 ± 2.0 years, mean ± S.E.M.) and nine old (70.1 ± 0.9 years). LBNP was applied progressively at 17.5, 35 and 50 mmHg in 20 min steps, with measurements taken during each steady state. There were similar, significant, falls in CVP in both groups. SD fell significantly in both groups from respective control values of 24.8 ± 1.6 and 16.6 ± 0.9 cm to 12.5 ± 1.3 and 8.9 ± 0.4 cm at a LBNP of 50 mmHg. Although SD in the elderly was significantly lower than in the young, the LBNP-induced changes were not different between groups. Both groups produced similar significant increases in vascular resistance, HR, plasma vasopressin (AVP) and noradrenaline. Mean arterial blood pressure (MBP) and plasma adrenaline did not change significantly. Therefore healthy old men respond to LBNP in a similar manner to the young, although MBP and SD are regulated around different baselines in the two groups. [source] Angiotensin-Converting Enzyme Genotype Affects the Response of Human Skeletal Muscle to Functional OverloadEXPERIMENTAL PHYSIOLOGY, Issue 5 2000Jonathan Folland The response to strength training varies widely between individuals and is considerably influenced by genetic variables, which until now, have remained unidentified. The deletion (D), rather than the insertion (I), variant of the human angiotensin-converting enzyme (ACE) genotype is an important factor in the hypertrophic response of cardiac muscle to exercise and could also be involved in skeletal muscle hypertrophy , an important factor in the response to functional overload. Subjects were 33 healthy male volunteers with no experience of strength training. We examined the effect of ACE genotype upon changes in strength of quadriceps muscles in response to 9 weeks of specific strength training (isometric or dynamic). There was a significant interaction between ACE genotype and isometric training with greater strength gains shown by subjects with the D allele (mean ± S.E.M.: II, 9.0 ± 1.7%; ID, 17.6 ± 2.2%; DD, 14.9 ± 1.3%, ANOVA, P 0.05). A consistent genotype and training interaction (ID DD II) was observed across all of the strength measures, and both types of training. ACE genotype is the first genetic factor to be identified in the response of skeletal muscle to strength training. The association of the ACE I/D polymorphism with the responses of cardiac and skeletal muscle to functional overload indicates that they may share a common mechanism. These findings suggest a novel mechanism, involving the renin-angiotensin system, in the response of skeletal muscle to functional overload and may have implications for the management of conditions such as muscle wasting disorders, prolonged bed rest, ageing and rehabilitation, where muscle weakness may limit function. [source] Lie detection by functional magnetic resonance imagingHUMAN BRAIN MAPPING, Issue 3 2002Tatia M.C. Lee Abstract The accurate detection of deception or lying is a challenge to experts in many scientific disciplines. To investigate if specific cerebral activation characterized feigned memory impairment, six healthy male volunteers underwent functional magnetic resonance imaging with a block-design paradigm while they performed forced-choice memory tasks involving both simulated malingering and under normal control conditions. Malingering that demonstrated the existence and involvement of a prefrontal-parietal-sub-cortical circuit with feigned memory impairment produced distinct patterns of neural activation. Because astute liars feign memory impairment successfully in testing once they understand the design of the measure being employed, our study represents an extremely significant preliminary step towards the development of valid and sensitive methods for the detection of deception. Hum. Brain Mapping 15:157,164, 2002. © 2002 Wiley-Liss, Inc. [source] Effects of DRD2 and CYP2D6 genotypes on delta EEG power response to aripiprazole in healthy male volunteers: a preliminary studyHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2006Euitae Kim Abstract The aim of the present study was to evaluate the effects of polymorphisms in dopamine D2 receptor (DRD2) and cytochrome P450 (CYP) 2D6 genes on delta EEG power response to aripiprazole in healthy male volunteers. Seventeen volunteers were recruited according to the DRD2 Taq1A genotype, and separated into the following groups: homozygous wild-type (A2/A2, n,=,7), heterozygous (A2/A1, n,=,5) and homozygous variant-type (A1/A1, n,=,5) groups. After enrollment in this study, they were genotyped for CYP2D6. The volunteers received single 10,mg oral doses of aripiprazole, in accordance with an open-label parallel group study design. Plasma levels of aripiprazole and its metabolite were determined and EEGs were obtained simultaneously. The pharmacodynamic parameter was absolute delta power in the Cz channel. The changes of delta power were not different according to DRD2 Taq1A genotypes. As to the CYP2D6 allele, the subjects had the following CYP2D6 genotypes: *10/*10 (n,=,4), *1/*10 (n,=,5), *1/*5 (n,=,2), *1/*1 (n,=,3), *2/*41 (n,=,1), *2/*2 (n,=,1), *2N/*10 (n,=,1). Subjects exhibiting the *1/*5 and *1/*10 genotypes showed a trend toward high area under the plasma aripiprazole concentration-time curve (AUC), which was linearly related to area under the EEG response-time curve (AUEC). Our results demonstrate a need for further evaluation of the CYP2D6 genotypic effect on the pharmacodynamics of aripiprazole. Copyright © 2006 John Wiley & Sons, Ltd. [source] Seasonal variations in [3H]citalopram platelet binding between healthy controls and violent offenders in FinlandHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 7 2005James Callaway Abstract Monthly binding densities (Bmax) of [3H]citalopram to the platelet serotonin transporter (SERT) was measured longitudinally over 1 year in a control group of 18 healthy Finnish male volunteers. Single platelet samples were also analysed from 33 men who were incarcerated for violent crimes during the same calendar year. A statistically significant seasonal variation in SERT Bmax was observed in both data sets, and bi-monthly floating averages for SERT Bmax were calculated and then fit to an annual sinusoidal curve for both groups. The Bmax for platelet [3H]citalopram binding showed a statistically significant (p,=,0.001) seasonal variance between a winter (January,February) maximum of 1590 fmol/mg protein and a summer (July,August) minimum of 1216 fmol/mg protein for the control group, with an R2 of 70% for the annual sinusoidal curve fit. A statistically significant (p,=,0.007) seasonal variance was also observed between a winter (January,February) maximum of 1980 fmol/mg protein and an autumnal (August,September) minimum of 1234 fmol/mg protein for the violent offenders, again with an R2 of 70% for the annual sinusoidal curve fit. This observation lends additional support to the idea that violent human behavior and impulsivity may be directly linked to values of SERT Bmax, which can be affected by various psychoactive drugs and also varies with the natural change of seasons. Copyright © 2005 John Wiley & Sons, Ltd. [source] Effects of restricted thoracic movement on the regional distribution of ventilationACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2010S. PULLETZ Background: Restricted thoracic movement is often encountered in patients, necessitating mechanical ventilation during surgery or intensive care treatment. High intraabdominal pressure, obesity or thorax rigidity and deformity reduce the chest distensibility and deteriorate the lung function. They render the selection of proper ventilator settings difficult and complicate the weaning process. Electrical impedance tomography (EIT) is currently being proposed as a bedside imaging method for monitoring regional lung ventilation. The objective of our study was to establish whether the effects of decreased chest compliance on regional lung ventilation can be determined by EIT. Methods: Ten healthy male volunteers were studied in our pilot study under three conditions: (1) unrestricted breathing and (2) restricted breathing by abdominal and (3) lower rib cage strapping. The subjects were followed during spontaneous tidal breathing in five postures (sitting, supine, prone, left and right side). EIT and spirometry data were acquired in each condition. Results: The distribution of ventilation in subjects with unrestricted breathing corresponded with the physiologically expected values. In the left and right lateral postures, abdominal and thoracic cage restrictions reduced the ventilation in the dependent lung areas; the non-dependent areas were unaffected. In the prone position, the ventilation of the dependent and non-dependent areas was reduced. The effects of strapping were least pronounced in the supine posture. Conclusions: We conclude that EIT is able to measure changes in the regional distribution of ventilation induced by restricted chest movement and has the potential for optimising artificial ventilation in patients with limited chest compliance of different origins. [source] ORIGINAL ARTICLE: Pro-hepcidin and iron metabolism parameters in multi-time blood donorsINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 5 2010J. BOINSKA Summary A high number of blood donations may cause iron depletion. The pathophysiology behind this process may involve hepcidin, a recently discovered peptide that acts by inhibiting iron absorption and promoting iron retention in reticuloendothelial macrophages. The aim of this study was to determine serum pro-hepcidin levels and iron metabolism parameters in multi-time blood donors. The study group consisted of 132 multi-time male blood donors and 25 healthy male volunteers (nondonors). Complete blood cell count and iron status including serum iron, ferritin, soluble transferrin receptor (sTfR), total iron binding capacity (TIBC), unsaturated iron binding capacity (UIBC), erythropoietin and pro-hepcidin (ELISA) were assessed. In blood donors, ferritin level drops markedly in relation to donation frequency (P < 0.001). In contrast, TIBC and UIBC levels increase progressively corresponding to annual donation frequency. Pro-hepcidin concentration increases significantly with the number of donations per year (P = 0.0290). In blood donors having donated blood with the highest frequency per year, pro-hepcidin levels were positively correlated with haemoglobin (R = 0.31, P < 0.05) and negatively with sTfR (R = ,0.31, P < 0.05). Pro-hepcidin levels increase in relation to blood donation frequency per year. Longitudinal studies focusing on changes in serum hepcidin levels are required to address the question whether hepcidin may contribute to iron metabolism disturbances in multi-times blood donors. [source] Measurement-specific bioavailable testosterone using concanavalin A precipitation: Comparison of calculated and assayed bioavailable testosteroneINTERNATIONAL JOURNAL OF UROLOGY, Issue 11 2009Kenrou Yamamoto Objective: To assess the value of calculated bioavailable testosterone (cBT) and assayed BT (aBT) for the diagnosis of late-onset hypogonadism (LOH) in middle-aged and elderly subjects. Methods: In order to assay serum BT, sex hormone-binding globulin was precipitated with concanavalin-A and then testosterone was measured using liquid chromatography-tandem mass spectrometry. To validate the non-sex-hormone-binding-globulin-bound testosterone, gel filtration chromatography and concanavalin-A sepharose were used. Following this validation, the usefulness between aBT and cBT was evaluated in clinical samples. Results: Eighty-eight healthy male volunteers (mean age 65.6 years, range: 50,86) were recruited for this study. A significant correlation was found between cBT and aBT (R2 = 0.53, P < 0.01). Mean value ratio (cBT/aBT) was 2.48. Both cBT (R2 = 0.122) and aBT (R2 = 0.251) decreased with age. Variations in aBT were less marked than those for cBT, suggesting that aBT can be used to determine age-related reduced testosterone levels. Conclusion: aBT levels are more reliable than cBT levels for the diagnosis of LOH in middle-aged and elderly subjects. [source] Urinary macromolecules and renal tubular cell protection from oxalate injury: Comparison of normal subjects and recurrent stone formersINTERNATIONAL JOURNAL OF UROLOGY, Issue 3 2006MASAO TSUJIHATA Aim:, To determine whether urinary macromolecules (UMM), which are the high molecular weight substances in urine, can provide protection against the oxalate-associated injury to the renal tubular cells. Methods:, UMM were extracted from 24-h urine of 12 healthy adult male volunteers and 13 recurrent-stone-former male patients. Urine parameters in relation to urolithiasis were measured, including the level of glycosaminoglycans (GAG) in the UMM. Madin-Darby canine kidney (MDCK) cells were used to evaluate the protective activity of UMM from oxalate-induced cytotoxicity by LDH release measurement and methyl-thiazolyl tertrazolium (MTT) assay. Results:, Considering urinary parameters, citrate was significantly higher in urine from normal subjects than stone-former subjects; the other parameters show no differences between the groups. Total UMM and the level of GAG in the UMM were also significantly higher in the normal subject group. Compared with normal subject and stone-former subject UMM, after cells were treated with the UMM and then exposed to oxalate solution, LDH release was significantly higher in stone-former group. In the MTT assay, we found that more viable cells were observed after treatment with UMM compared to control in both groups. Moreover, UMM from the normal subjects showed higher protective activity against oxalate-related cytotoxicity than UMM from the stone-former subjects. Conclusion:, UMM protected renal epithelial cells from oxalate-related injury. This protective activity was found to be higher in normal subject UMM than stone-former UMM. Among other factors, a higher concentration of GAG and citrate in normal subject UMM might affect some parts in this finding. [source] Impact of citrate therapy on the circadian rhythm of urinary magnesium ammonium phosphate saturation in normal individualsINTERNATIONAL JOURNAL OF UROLOGY, Issue 8 2000Yoshihide Ogawa Abstract Background: Alkaline citrate has been used widely in the prevention of stone formation. However, the risk of struvite stone during the alkalinizing therapy has not been adequately studied in terms of magnesium ammonium phosphate saturation. Methods: The circadian rhythm of the urinary saturation of magnesium ammonium phosphate was estimated by using the differential Gibbs' free energy values of magnesium ammonium phosphate before and during 5 days of treatment with sodium,potassium citrate (1 g t.i.d., 1 g q.i.d. or 3 g t.i.d.) in five healthy male volunteers. Results: The magnesium ammonium phosphate saturation varied during the day, peaking far below the solubility product between 08.00 and 10.30 h and between 13.00 and 18.00 h. The mean peak levels were increased by each treatment regimen in comparison with the control day. The mean increase on day 1 was significant between 10.30 and 23.00 h with the 3 g t.i.d. regimen, but the mean saturation still remained below the solubility product throughout the day. Conclusions: The urinary magnesium ammonium phosphate saturation appeared hard to exceed the solubility product with a high dose of alkaline citrate. [source] The intrinsic shape of the human lumbar spine in the supine, standing and sitting postures: characterization using an active shape modelJOURNAL OF ANATOMY, Issue 2 2009Judith R. Meakin Abstract The shape of the lumbar spine in the sagittal plane varies between individuals and as a result of postural changes but it is not known how the shape in different postures is related. Sagittal images of the lumbar spines of 24 male volunteers were acquired using a positional magnetic resonance scanner. The subjects were imaged lying supine, standing and sitting. An active shape model was used to characterize shape in terms of independent modes of variation. Two modes were identified that described the total (mode 1) and distribution (mode 2) of the curvature. The spinal shape was found to be intercorrelated between the three postures for both modes, suggesting that the lumbar spine has an element of shape that is partially maintained despite postural alterations. Mode 1 values indicated that the spine was straightest when standing and curviest when sitting. Mode 2 values indicated that the distribution in the curvature was most even when sitting and least even when lying supine. Systematic differences in the behaviour of the spine, when changing posture, were found that suggest that the shape of the spine may affect its biomechanics. [source] IL-2 gene C/T polymorphism is associated with prostate cancerJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 6 2006Hsi-Chin Wu Abstract Cytokines are reported to be associated with the formation of prostate cancer. Our aim was to investigate whether C/T polymorphisms of the interleukin-2 (IL-2) gene and IL-2 receptor beta (IL-2RB) gene are associated with prostate cancer. We compared the frequency of the polymorphisms of the IL-2 gene and the IL-2RB gene between 96 patients with prostate cancer and 105 healthy male volunteers from the same area (age >60 years). They were followed for at least 5 years. There was a significant difference in distribution of the genotype of the IL-2 gene polymorphism between the prostate cancer group and the control group (P = 0.017). The distribution of the TT homozygote of the IL-2 gene was significantly higher in the cancer group (32.3%) than in the control group (16.2%). However, no significant statistical difference was found between the polymorphism of the IL-2 gene and prostate cancer in survival analysis during a 5-year follow up period (log rank test; P = 0.19). There was no significant difference in the distribution of the genotype of the IL-2RB gene polymorphism between controls and cancer patients (P = 0.388). This study suggests that the IL-2 gene may be associated with susceptibility to prostate cancer in the Taiwan population. J. Clin. Lab. Anal. 20:245,249, 2006. © 2006 Wiley-Liss, Inc. [source] Smoking behaviour modulates pharmacokinetics of orally administered clopidogrelJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 4 2008A.-M. Yousef PhD Summary Background and objectives:, Clopidogrel is an important antiplatelet drug that is effective in preventing thrombotic events, especially for patients undergoing percutaneous coronary intervention. The therapeutic usefulness of clopidogrel has been limited by documented inter-individual heterogeneity in platelet inhibition, which may be attributable to known clopidogrel pharmacokinetic variability. The objective of this study was to assess the influence of smoking cigarettes and abnormal body weight on the pharmacokinetics of clopidogrel. Methods:, Seventy-six healthy adult male volunteers were selected randomly. Each subject received a single 75 mg oral dose of clopidogrel after overnight fast. Clopidogrel carboxylate plasma levels were measured and non-compartmental analysis was used to determine peak plasma concentration (Cmax), time to peak plasma concentration (Tmax), elimination half-life (t1/2e), and area under the curve (AUC0,,). Results:, One-third of volunteers were smokers (n = 27) and one-half had abnormal body weight (n = 39). Smokers had lower AUC0,, (smokers: 6·24 ± 2·32 ,g/h/mL vs. non-smokers: 8·93 ± 3·80 ,g/h/mL, P < 0·001) and shorter half-life (smokers: 5·46 ± 2·99 vs. non-smokers: 8·43 ± 4·26, P = 0·001). Smoking behaviour had no influence on Cmax (P = 0·3) and Tmax (P = 0·7). There was no statistically significant difference in Cmax, AUC0,,, Tmax and t1/2e between volunteers with abnormal body weight and normal body weight. However the difference in body weight of the two groups was relatively narrow (mean ± SE; 26·93 ± 0·16 vs. 23·11 ± 0·27). In general, the pharmacokinetic parameters were characterized by considerable inter-individual differences (Cmax = 3·09 ± 0·99 ,g/mL, CV = 32%), (Tmax =0·76 ± 0·24 h, CV = 31·6%), (AUC0,, = 7·98 ± 3·58 ,g/h/mL, CV = 44·8%), and (t1/2e = 7·38 ± 4·10 h, CV = 55·6%). Conclusion:, Smoking is a significant factor affecting the pharmacokinetics of clopidogrel, following administration of a single 75 mg dose in healthy young volunteers. The study supports smoking-cessation recommendations. Further studies are required to evaluate the influence of smoking and body weight on the pharmacokinetics of the active metabolite of clopidogrel and on the clinical effects of any differences observed. [source] Reduced oral itraconazole bioavailability by antacid suspensionJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2005M. Lohitnavy Summary Aims:, To investigate the effects of antacid suspension on oral absorption of itraconazole. Methods:, A randomized, open-labelled, two-period, crossover study with a 1-week washout period was conducted in 12 healthy Thai male volunteers. The participants were allocated in either treatment A or B in the first period. In treatment A, the volunteers were orally administered with 200 mg of itraconazole alone. In treatment B, the volunteers were administered orally with 200 mg of itraconazole co-administered with antacid suspension. Serial serum samples were collected over the period of 24 h and subsequently analysed by using a validated high-pressure liquid chromatographic method with ultraviolet detection. Pharmacokinetic parameters were determined by non-compartmental analysis. Results:, Time to reach maximal concentration (Tmax), maximal concentration (Cmax) and area under the curve (AUC0--,) were markedly decreased in antacid-treated group. Tmax for treatment A was 3·0 ± 0·4 and 5·1 ± 2·7 h for treatment B. Cmax and AUC0--, of treatments A and B were 146·3 ± 70·5 vs. 43·6 ± 16·9 (ng/mL) and 1928·5 ± 1114·6 vs. 654·8 ± 452·2 (ng·h/mL) respectively. 90% Confidence interval (90% CI) of Cmax and AUC0--, were 24·1,42·1 and 16·2,65·9 respectively. Conclusions:, Rate and extent of itraconazole oral absorption were markedly decreased by concurrent use of antacid suspension. Hence, co-administration of itraconazole and antacid suspension should be avoided. [source] Ketoconazole increases plasma concentrations of antimalarial mefloquine in healthy human volunteersJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2005W. Ridtitid MD FCFPT Summary Background:, Antimalarial mefloquine has a structure related to quinine. The major metabolite of quinine is 3-hydroxyquinine formed by cytochrome P450 3A4 (CYP3A4). Ketoconazole, a potent inhibitor of CYP3A4, is known to markedly increase plasma concentrations of various co-administered drugs including quinine. Objective:, To assess the effect of ketoconazole on plasma concentrations of mefloquine in healthy Thai male volunteers. Methods:, In an open, randomized two-phase crossover study separated by a 1-month period, eight healthy Thai male volunteers received a single oral dose of 500 mg mefloquine alone or co-administration with 400 mg/day ketoconazole orally for 10 days. Serial blood samples were collected at specific time points for a 56-day period. Plasma mefloquine and mefloquine carboxylic metabolite concentrations during 56 days were measured by a modified and validated high-performance liquid chromatographic method with UV detection. Results:, Co-administration with ketoconazole markedly increased the mean values of mefloquine AUC0,t, t1/2, and Cmax when compared with mefloquine alone by 79% (P < 0·001), 39% (P < 0·05) and 64% (P < 0·001) respectively. The AUC0,t,, and Cmax of mefloquine carboxylic acid metabolite were decreased by 28% (P < 0·05) and 31% (P < 0·05), respectively when compared with mefloquine alone. Conclusions:, Co-administration with ketoconazole increased plasma mefloquine concentrations in healthy human volunteers. One of possible mechanisms of the increase in plasma mefloquine concentrations may be the result of the inhibition of CYP3A4 by ketoconazole. In case of mefloquine is co-administered with ketoconazole, drug,drug interactions should be recognized and the dose of mefloquine should be adjusted to maximize the therapeutic efficacy and to reduce the cost of therapy. [source] Doppler sonography of the penile cavernosal artery: Comparison of intraurethral instillation and intracorporeal injection of prostaglandin E1JOURNAL OF CLINICAL ULTRASOUND, Issue 5 2001Jong Min Kim MD Abstract Purpose We compared the Doppler sonographic findings in the penile cavernosal artery (arteria profunda penis) after intraurethral instillation and intracorporeal injection of prostaglandin E1 (PGE1) to evaluate the hemodynamic changes during drug-induced erection. Methods Twenty healthy male volunteers were enrolled in the study. Ten subjects (intraurethral group) were examined with Doppler sonography of the penile cavernosal artery after intraurethral administration of 1 mg of PGE1. The remaining 10 subjects (intracorporeal group) underwent Doppler sonography of the cavernosal artery after intracorporeal injection of 5 ,g of PGE1. The peak systolic velocity, minimal diastolic velocity, and resistance index were determined at 5-minute intervals for 30 minutes following administration of PGE1 in both groups. The results were compared between the 2 groups. Results The peak systolic velocity in the intraurethral group increased progressively from a mean of 31.1 cm/second at 5 minutes to 65.6 cm/second at 30 minutes after intraurethral administration of PGE1. In the intracorporeal group, the mean peak systolic velocity ranged from 44.1 to 83.2 cm/second, reached a maximum at 10 minutes, and then decreased continuously through 30 minutes after intracorporeal injection of PGE1. The mean peak systolic velocities were significantly higher in the intracorporeal group at 10 and 15 minutes (p , 0.05); the mean minimal diastolic velocities were significantly lower in the intracorporeal group at 15, 20, and 25 minutes (p , 0.05); and the mean resistance indices were significantly higher in the intracorporeal group at all time points except 5 minutes (p , 0.05). Conclusions The intracorporeal injection of PGE1 produced a greater vasoactive response in the cavernosal artery than did intraurethral instillation. © 2001 John Wiley & Sons, Inc. J Clin Ultrasound 29:273,278, 2001. [source] Clinical trial: Inhibitory effect of revaprazan on gastric acid secretion in healthy male subjectsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2010Hyung-Keun Kim Abstract Background and Aim:, Revaprazan is a novel acid pump antagonist. The aim of this study was to investigate the inhibitory effect of revaprazan on gastric acid secretion in healthy male subjects. Methods:, In a double-blind, three-way cross-over study, 30 healthy male volunteers were randomized to 100, 150 or 200 mg of oral revaprazan daily for 7 days. Serum gastrin concentration was measured, and 24-h intragastric pH was recorded at baseline and on days 1 and 7 of each administration period. Serial blood samples were processed for pharmacokinetics. Results:, Median intragastric pH over 24 h and mean percentage time that pH was > 4 increased in a dose-dependent manner and were significantly higher on days 1 and 7 compared with baseline in all groups (P < 0.05). The antisecretory effect of revaprazan was rapid and nearly maximal on day 1 in all groups. Serum gastrin levels were rapidly normalized by 100 and 150 mg/day of revaprazan on days 1 and 7, but were significantly higher in the 200 mg/day revaprazan group. The pharmacokinetic effect was rapidly absorbed and eliminated on days 1 and 7 in all groups. Conclusions:, Revaprazan rapidly and effectively inhibits gastric acid secretion in healthy male subjects. Therefore, revaprazan can be used as an effective drug for acid-related disease. [source] Muscle mitochondrial activity increases rapidly after an endotoxin challenge in human volunteersACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2009K. FREDRIKSSON Background: Mitochondrial derangements in muscle of patients suffering from sepsis have been established in several studies and have been related to muscle dysfunction and organ failure. It is not possible to study the early phase of sepsis in patients; therefore, we used a human endotoxaemia model to study the effect of early sepsis on muscle mitochondria. Methods: Seven healthy male volunteers received a standardised endotoxin challenge. Muscle biopsies were obtained immediately before the challenge, and at 2 and 4 h following the endotoxin challenge. The muscle biopsies were analysed for maximal activities of citrate synthase and complexes I and IV of the respiratory chain. In addition, total and mitochondrial superoxide dismutase (SOD) activities were analysed. The concentrations of ATP, creatine phosphate and lactate were analysed to assess the cellular energy status. Total and phosphorylated AMP-activated protein kinase (AMPK-P), a key regulator in intracellular energy metabolism, was measured. Results: Activities of citrate synthase and complex I were significantly increased 2 h after the endotoxin challenge. SOD activities were unaffected by the endotoxin challenge. No changes in ATP, creatine phosphate or lactate were observed. Neither total nor AMPK-P changed. Conclusions: An endotoxin challenge given to healthy volunteers rapidly increases mitochondrial enzyme activity in skeletal muscle. The results of this human model indicate that possibly early during sepsis, mitochondrial activity might be increased in contrast to what has been shown in the later phases of sepsis. It is possible that this early activation leads to exhaustion of the mitochondria and a decreased function later during sepsis. [source] Recombinant factor VIIa and fibrinogen display additive effect during in vitro haemodilution with crystalloidsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2009C. FENGER-ERIKSEN Background: Major blood loss requires fluid resuscitation for maintaining hemodynamic stability. Excessive volume infusions predispose to dilutional coagulopathy through loss, consumption and dilution of cells and proteins involved in haemostasis. Further treatment with fibrinogen concentrate and/or recombinant activated factor VII (rFVIIa) may be initiated, although the haemostatic effects in a situation with haemodilution are not fully detailed. The present study evaluates haemostatic effect of fibrinogen and rFVIIa and their combination in an in vitro model of haemodiluted whole blood with two commonly used crystalloids. Methods: Eight healthy, male volunteers were enrolled. Outcome variables were clot initiation, propagation and strength assessed by thrombelastographic parameters: clotting time, clot formation time, maximum velocity, time until maximum velocity, maximum clot firmness evaluated at dilution levels of 0% (control), 10%, 30% and 50% with isotonic saline and Ringer's lactate in a model of tissue factor-activated whole blood. Fibrinogen and rFVIIa were additional final reaction concentrations, reflecting commonly used clinically therapeutic dosages. Results: Dose-dependent coagulopathy developed following haemodilution with isotonic saline and Ringer's lactate, characterised by a prolonged clot initiation, reduced clot propagation and reduced clot strength. Fibrinogen improved clot strength and propagation phase while rFVIIa shortened clot initiation, both with a positive dose dependency. Conclusions: The combination of fibrinogen and rFVIIa displays an additive effect and improves overall in vitro whole blood clot formation in a model of in vitro crystalloid-induced haemodilution. [source] | ||||||||||||||||||||||||||||||||||||||||