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PubMed1999

Safety issues of plateletpheresis: comparison of the effects of two cell separators on the activation of coagulation, fibrinolysis, and neutrophils and on the formation of neutrophil-platelet aggregates.

BACKGROUND: Although many donors undergo repeated plateletpheresis, data on the consequences of plateletpheresis for the donor's health remain scarce. Thus, the effect of plateletpheresis on the activation of coagulation, fibrinolysis, and neutrophils was investigated. STUDY DESIGN AND METHODS: Part 1: Sixteen healthy men were randomly assigned to undergo plateletpheresis on a cell separator (AMICUS, Fenwal Baxter; or MCS 3p, Haemonetics). The effects of plateletpheresis on plasma levels of prothrombin fragment (F(1+2)), D-dimer, plasmin-plasmin inhibitor (PPI) complexes, and plasminogen activator inhibitor (PAI-1); on the activation of neutrophils (% L-selectin+); and on the frequency of platelet-neutrophil aggregates (% CD41+ neutrophils) were compared. Part 2: Ten healthy men received infusions of ACD-A and placebo without apheresis in a randomized, double-blind crossover study to control for the pharmacologic effects of citrate. RESULTS: Part 1: No change in F(1+2) occurred (p>0.05), which indicated that plateletpheresis did not enhance coagulation. Levels of D-dimer, PPI, and PAI-1 decreased over time on the AMICUS (p<0.001). Plateletpheresis did not activate neutrophils (p>0.05), but it decreased the percentage of CD41+ neutrophils (p<0.003). An approximately 80-percent drop in mononuclear cells was observed in the extracorporeal circulation of the AMICUS (p<0.001 vs. baseline and p = 0.005 vs. MCS 3p), and circulating lymphocyte and monocyte counts decreased concomitantly. Part 2: Infusion of ACD-A slightly decreased D-dimer levels (p<0.05), and both infusions decreased the circulating lymphocyte counts. CONCLUSION: Plateletpheresis can be regarded as safe with respect to the activation of coagulation or neutrophils. The consequences for the donor's health of the decrease in D-dimer, PPI, and PAI-1 may deserve further investigation.

Adult↗
PubMed2000

Skin irritation and dryness associated with two hand-hygiene regimens: soap-and-water hand washing versus hand antisepsis with an alcoholic hand gel.

OBJECTIVE: To compare the frequency of skin irritation and dryness associated with using an alcoholic-hand-gel regimen for hand antisepsis versus using soap and water for hand washing. DESIGN: Prospective randomized trial with crossover design. Irritation and dryness of nurses' hands were evaluated by self-assessment and by visual assessment by a study nurse. Epidermal water content of the dorsal surface of nurses' hands was estimated by measuring electrical capacitance of the skin. SETTING: Miriam Hospital, a 200-bed university-affiliated teaching hospital. PARTICIPANTS: Thirty-two nurses working on three hospital wards participated in the trial, which lasted 6 weeks. RESULTS: Self-assessment scores of skin irritation and dryness decreased slightly during the 2 weeks when nurses used the alcoholic-hand-gel regimen (mean baseline score, 2.72; mean final score, 2.0; P=.08) but increased substantially during the 2 weeks when nurses used soap and water (mean baseline score, 2.0; mean final score, 4.8; P<.0001). Visual assessment scores by the study nurse of skin irritation and dryness did not change significantly when the alcoholic-hand-gel regimen was used (mean baseline and final scores were both 0.55), but scores increased substantially when nurses used soap and water (baseline score, 0.59; mean final score, 1.21; P=.05). Epidermal water content of the dorsal surface of nurses' hands changed little when the alcoholic-hand-gel regimen was used (mean+/-standard deviation baseline electrical capacitance reading, 24.8+/-6.8; mean final reading, 25.7+/-7.3), but decreased significantly (skin became dryer) with soap-and-water hand washing (mean baseline, 25.9+/-7.5; mean final reading, 20.5+/-5.4; P=.0003). CONCLUSIONS: Hand antisepsis with an alcoholic-hand-gel regimen was well tolerated and did not result in skin irritation and dryness of nurses' hands. In contrast, skin irritation and dryness increased significantly when nurses washed their hands with the unmedicated soap product available in the hospital. Newer alcoholic hand gels that are tolerated better than soap may be more acceptable to staff and may lead to improved hand-hygiene practices.

Antisepsis↗
PubMed2004

Dynamics of human walking at steady speeds.

Biped locomotion is discussed through a Lagrangian formulation for velocity-dependent, body driving forces. An analysis of level walking in humans is given through the known experimental data on the ground-reaction force and the external work without recourse to inverted-pendulum modeling. At a certain speed, rectilinear motion of the center of mass with its backward rotation along a shortened hypocycloid is ensured by double-frequency nonlinear oscillations, whose energy cost is 1% of the external work. With increasing speed, a peculiarity and an instability of the trajectory indicate, respectively, a slow-to-normal gait crossover and the maximal fast walking speed. Key words: integrative biology, biped locomotion, human gaits, muscles.

Biomechanical Phenomena↗
PubMed2005

ac Stark shift and dephasing of a superconducting qubit strongly coupled to a cavity field.

We have performed spectroscopy of a superconducting charge qubit coupled nonresonantly to a single mode of an on-chip resonator. The strong coupling induces a large ac Stark shift in the energy levels of both the qubit and the resonator. The dispersive shift of the resonator frequency is used to nondestructively determine the qubit state. Photon shot noise in the measurement field induces qubit level fluctuations leading to dephasing which is characteristic for the measurement backaction. A crossover in line shape with measurement power is observed and theoretically explained. For weak measurement a long intrinsic dephasing time of T2>200 ns of the qubit is found.

Journal Article↗
PubMed1986

Very close linkage between D2S1 and ACP1 on chromosome 2p.

The genomic DNA-probe L2.30 was used to assign D2S1 to 2p23-pter by in situ hybridization. The RFLP revealed by BglII was then used for linkage studies in the Oslo-NHIK families segregating for the acid phosphatase ACP1 protein polymorphism. Evidence for very close linkage was found by a lod score of +17.17 at recombination fraction theta = 0.01. By this close linkage 92 informative meioses could be inferred from the families and with only a single crossover. The upper probability limit to the recombination fraction is 0.06 according to the HGM 8 criterion. No association between ACP1 alleles and D2S1 BglII alleles was found. The Norwegian gene frequencies for D2S1 were A1 (9.0 kb) = 0.65 and A2 (6.3 kb) = 0.35.

Acid Phosphatase↗
PubMed2002

Dilational rheology of monolayers of a miscible polymer blend: from good- to poor-solvent conditions.

The viscoelastic moduli (elasticity and dilational viscosity) of monolayers of PVAc + P4HS has been studied over a broad frequency range (0.1 mHz-200 kHz) using a combination of relaxation and capillary-waves techniques. The analysis of the surface pressure, the elasticity and the viscosity on the semidilute regime show that the air-water interface is a good solvent for the monolayers of PVAc-rich blends, and a poor (near-Theta) solvent for the monolayers of P4HS-rich blends. The solvent quality changes continuously over a broad concentration range. The results of viscoelastic moduli show that there is a broad relaxation process in the low-frequency range (omega < 1 Hz). While for PVAc-rich monolayers this relaxation process follows the reptation-like behavior described by Noskov, for P4HS-rich monolayers the model does not describe the amplitudes of the different relaxation modes. For PVAc-rich monolayers two processes are clearly distinguished at higher frequencies: one centered at around 500 Hz and another one at around 40 kHz. However, for P4HS-rich monolayers only one broad relaxation mode is found below 1 kHz. The crossover from one type of behavior to the other one takes place in a very narrow blend-composition range, and is not clearly related to the crossover from good- to poor-solvent condition.

Journal Article↗
PubMed2004

Unique invasions and resolutions: DNA repair proteins in meiotic recombination in Drosophila melanogaster.

To ensure the accurate disjunction of homologous chromosomes during meiosis, most eukaryotes rely on physical connections called chiasmata, which form at sites of crossing over. In the absence of crossing over, homologs may segregate randomly, resulting in high frequencies of aneuploid gametes. The process of meiotic recombination poses unique problems for the cell that must be overcome to ensure normal disjunction of homologous chromosomes. How is it ensured that crossovers occur between homologous chromosomes, rather than between sister chromatids? What determines the number and location of crossovers? The functions of DNA repair proteins hold some of the answers to these questions. In this review, we discuss DNA repair proteins that function in meiotic recombination in Drosophila melanogaster. We emphasize the processes of strand invasion and Holliday junction resolution in order to shed light on the questions raised above. Also, we compare the variety of ways several eukaryotes perform these processes and the different proteins they require.

Animals↗
PubMed1993

Restriction to a limited set of EEG-target variables may lead to misinterpretation of pharmaco-EEG results.

The number and types of target variables quantified from the spectrally analyzed EEG used in topographic pharmaco-EEG studies are still being discussed. Drug-induced changes of target variables obtained in the alpha frequency band--four absolute and four relative powers as well as three frequency measures--were utilized to assess the effects of xantinolnicotinate in demented patients using a parallel group design and the effects of buspirone in a double-blind, placebo-controlled crossover design. We conclude that for the proper evaluation of the different drug effects on the alpha activity, all these target variables should be considered. Descriptive p values of multiple comparisons within the framework of descriptive data analyses are important tools in interpreting drug effects.

Adolescent↗
PubMed1999

The contribution of the swallowed fraction of an inhaled dose of salmeterol to it systemic effects.

Salmeterol is approximately eight times as potent as salbutamol for systemic effects. This may be because the drug is eight times more potent on receptors or there may be differences in systemic bioavailability. The systemic effects of salbutamol are limited by its fairly high first-pass metabolism, but the oral bioavailability of salmeterol is unknown. The contribution of the swallowed fraction of an inhaled dose of salmeterol to its systemic effects were analysed in a randomized, double-blind, crossover study. Twelve healthy subjects were given inhaled salmeterol 400 microg, inhaled salmeterol 400 microg plus oral activated charcoal or inhaled placebo plus oral activated charcoal on three separate days. Cardiac frequency (fC), Q-T interval corrected for heart rate (QTc), plasma potassium and glucose concentrations were measured for 4 h following the inhaled drug. Salmeterol with and without oral charcoal produced significant changes for all measures compared to placebo. The magnitude of effect following salmeterol alone was significantly greater than that following salmeterol plus charcoal for fC and glucose (mean (95% confidence interval) differences 8 (2-13) beats x min(-1), 0.59 (0.04, 1.13) mmol x L(-1), respectively) and nonsignificantly greater for QTc interval and potassium concentration. The differences between salmeterol given with and without charcoal suggest that 28-36% of the systemic response to salmeterol administered from a metered-dose inhaler are due to drug absorbed from the gastrointestinal tract. Thus, most of the systemic effects are due to the inhaled fraction of the drug.

Administration, Inhalation↗
PubMed1978

Imipramine in absence and myoclonic-astatic seizures.

A double-blind crossover study with imipramine was conducted in 10 patients with absence and myoclonic-astatic seizures who had not responded to conventional medications. Imipramine produced a significant initial decrease in seizure frequency in 5 of the 10 patients, and in 2 patients the beneficial effect was maintained for more than 1 year. An open trial of imipramine in another 16 patients showed an initial reduction in seizure frequency in 10 patients (63 percent), and this decrease persisted for more than 1 year in 4 patients (25 percent). The effect of imipramine on the EEG did not always correlate with the clinical response. Serum content of imipramine in the patients who showed a long-term response was 40 to 120 ng per milliliter, on a total daily dose of 0.7 to 3.5 mg per kilogram. These results suggest that imipramine is a valuable addition to the treatment of seizures.

Adolescent↗
PubMed1985

Sustained effects of transdermal nitroglycerin in patients with angina pectoris.

The antianginal efficacy of a transdermal therapeutic delivery system for nitroglycerin (TNG) was compared with that of placebo in a double-blind crossover study. Twenty-five patients with stable angina pectoris were evaluated. The transdermal system delivered 5 mg of nitroglycerin over a 24-hour period and was applied once every 48 hours. Treadmill exercise testing (Bruce protocol) was done 48 hours after the patch was applied in the first phase of the crossover and at the conclusion of the second phase of the crossover, 48 hours after the final dose of the second treatment. Exercise performance was significantly improved (P less than 0.05, analysis of covariance) with TNG as compared with placebo, as were frequency of episodes of angina and nitroglycerin consumption (P less than 0.05, analysis of variance). The incidence of mild-to-moderate headache in patients was greater during treatment with TNG (20%) than during placebo treatment (6.7%). Four cases of mild transient dermatitis and occasional reports of dizziness, lightheadedness, and nausea were noted.

Administration, Topical↗
PubMed1998

Secondary photon scatter in imaging cassettes.

Secondary photon processes within a cassette image receptor have been identified in the literature for at least three decades. These secondary processes have varying effects on the contrast, resolution and noise of a resulting radiographic image. The magnitude of these effects can be quantified in terms of the percentage of scatter to total absorbed energy for each process recorded by the radiographic cassette, and also as a reduction in system MTF. Two of these processes, cassette face scatter and particularly film crossover, have been subject to considerable past study. The third, due to K-characteristic photon 'crossover', has only recently been quantified. The total magnitude of all secondary cassette effects for a radiographic image, could vary from a worst case where in excess of 40% of the total absorbed energy is due to secondary processes (for an aluminium cassette with Gd2O2S screen with high crossover film, exposed at high kVp) to a best case of less than 10% (for a carbon fibre cassette, tantilate screens with 'zero crossover' film) leading to corresponding contrast reductions of > 40% to < 10% respectively. The MTF components of all secondary effects have been determined and are shown to decrease rapidly with increasing spatial frequency. This results in the MTF of the total image receptor system being reduced for high spatial frequencies by the same percentage as the contrast reduction. Theory predicts that the affected image noise due to cassette secondary processes will be complex and vary with spatial frequency.

Biophysical Phenomena↗
PubMed1992

In vivo phosphorus NMR spectroscopy of skin using a crossover surface coil.

A modified crossover surface coil with minimal B1 field penetration was used for collection of skin phosphorus NMR spectra. Projection imaging experiments show that the coil-sensitive volume is uniform at the phosphorus frequency, but strikingly nonuniform at the proton frequency. Experiments with an in vitro phosphorus phantom, designed to simulate skin and underlying tissue, demonstrated that 45.1% (+/- 1.2%) of total signal was derived from Sprague-Dawley rat skin and 19.3% (+/- 1.4%) of total signal was derived from Fischer-344 rat skin. 31P MR spectra of rat skin in vivo permitted resolution of four phosphorus compounds: nucleoside triphosphates, phosphocreatine (PCr), inorganic phosphate (Pi), and phosphomonoester. Spectra collected after skin flap surgery in Fischer-344 rats showed a 50.1% (+/- 7.6%) reduction in the ratio of PCr/Pi within 30 min of surgery, compared to presurgical PCr/Pi levels (P less than 0.01). Skin phosphorus spectra are potentially useful for assessment of skin flap and skin graft viability.

Animals↗
PubMed1986

Encainide for ventricular arrhythmias: placebo-controlled and standard comparison trials.

Efficacy data obtained from the use of encainide in the treatment of patients with benign or potentially lethal ventricular arrhythmias are reviewed. These include an oral dose multicenter titration study involving 111 patients in whom encainide was given from 25 to 75 mg, 4 times/day, which was followed by a 3-center, reduced dose study in which 35 patients received a forced escalation of encainide from 10 to 30 mg, 4 times/day. Frequent Holter monitoring was used to judge efficacy. An 8-center, double-blind, parallel, placebo-controlled outpatient trial was conducted using encainide from 10 to 50 mg, 3 times/day, in 125 patients. This trial defined the lower end of the dose response curve for encainide to be 25 mg, 3 times/day. The data from all these trials show that when properly titrated, encainide is effective in decreasing ventricular premature complex frequency by at least 75% in about 80% of patients. A similar percentage will have abolition of ventricular tachycardia. When encainide was compared with quinidine in a 9-center placebo-controlled crossover study, encainide demonstrated more efficacy at 25 mg, 4 times/day, compared with quinidine at 200 mg, 4 times/day, in all arrhythmia parameters. Encainide was also better tolerated than quinidine and there was no statistically significant difference in the prevalence of asymptomatic proarrhythmia as detected by Holter monitoring between these 2 drugs. Long-term data in 220 patients over 36-month follow-up show continued encainide efficacy. Thus, encainide is a potent, effective class 1C antiarrhythmic agent and it has minimal negative inotropic effects and is well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Bepridil hydrochloride compared with placebo in patients with stable angina pectoris.

Bepridil is a calcium antagonist with a unique chemical composition and a long elimination half-life (42 hours). We evaluated the efficacy of bepridil 300 mg once/day in a crossover comparison with placebo in 45 patients with angina. Patients had an average of 7.6 anginal episodes/week during the placebo baseline phase of the trial. After 4 weeks of bepridil therapy, anginal frequency decreased to 2.9 episodes/week (p less than 0.05). Likewise, mean nitroglycerin consumption declined from 7.4 tablets/week during the placebo baseline phase to 4.0 tablets/week during bepridil therapy (p less than 0.05). Statistically significant increases over the previous period (placebo baseline or double-blind placebo) were seen in total exercise time, time to angina, and total work (p less than 0.05). During bepridil therapy, 13 of 45 patients (29%) no longer experienced angina as an exercise end point despite the increase in work and exercise time. Bepridil significantly prolonged both the QT and corrected QT (QTc) intervals; the mean increases were 10.0% and 5.6%, respectively. Side effects were reported with equal frequency in the placebo and bepridil arms of the trial, and no serious side effects were reported. In an intermediate fixed dose of 300 mg/day, bepridil relieved anginal symptoms with few side effects. Bepridil appears to be a safe and effective treatment for stable angina.

Analysis of Variance↗
PubMed2000

The use of ultrasonic standing waves to enhance optical particle sizing equipment

Fluid dynamics modelling augmented with routines to simulate acoustic forces on aerosol particles has been used to investigate the potential of combining ultrasonic standing wave fields with optical particle analysis equipment. Simulations of particle dynamics in airstreams incorporating acoustic forces predict that particles in the 1-10 microns diameter range may be effectively focused to the velocity nodes of the standing wave field. Particles move to the velocity nodes within tens of milliseconds for acoustic frequencies of 10-100 kHz and at an acoustic energy density of 100 Jm-3. Larger particles are predicted to move to the velocity antinodes within similar times; however, there is a crossover region at approximately 15-20 microns particle diameter where longer times are predicted due to the competing forces driving particles to the vibration node and antinode. With sufficient transverse flow velocities the models predict that disturbances due to acoustic streaming can be overcome and a useful degree of focusing achieved for the aerosol particles. Results from a model demonstrating sampling and acoustic focusing of 3-9 microns aerosol particles to a 200 microns wide analysis area are presented.

Journal Article↗
PubMed1980

Total suppression of ventricular arrhythmias by encainide. Pharmacokinetic and electrocardiographic characteristics.

We studied the antiarrhythmic effect of a range of oral doses of encainide in 11 patients with stable high-frequency ventricular arrhythmias. Total suppression of arrhythmia was documented in 10 patients at a wide range of doses and plasma concentrations, and the suppression was subsequently verified in a placebo-controlled crossover study. Drug elimination was rapid (the half-life was 1.9 to 3.8 hours), but the margin between efficacy and side effects was sufficiently wide for therapy every six to 12 hours to be feasible in all 10 patients, with continuing outpatient treatment at six to 12 months. Marked prolongation of PR (mean, 44 per cent) and QRS (mean, 47 per cent) durations coincided with abolition of arrhythmia, but no evidence that these effects were detrimental was observed in radionuclide ventriculograms, exercise testing, or prolonged monitoring. A single patient whose arrhythmia and electrocardiogram were unchanged during therapy eliminated the drug much more slowly than the others and was the only patient in whom no O-demethyl form could be detected in plasma, suggesting that this metabolite may be active. In this study, encainide was a highly effective, well-tolerated antiarrhythmic agent.

Adult↗
PubMed2006

Lupin kernel fibre foods improve bowel function and beneficially modify some putative faecal risk factors for colon cancer in men.

Consumption of some dietary fibres may benefit bowel health; however, the effect of Australian sweet lupin (Lupinus angustifolius) kernel fibre (LKFibre) is unknown. The present study examined the effect of a high-fibre diet containing LKFibre on bowel function and faecal putative risk factors for colon cancer compared to a control diet without LKFibre. Thirty-eight free-living, healthy men consumed an LKFibre and a control diet for 1 month each in a single-blind, randomized, crossover study. Depending on subject energy intake, the LKFibre diet was designed to provide 17-30 g/d fibre (in experimental foods) above that of the control diet. Bowel function self-perception, frequency of defecation, transit time, faecal output, pH and moisture, faecal levels of SCFA and ammonia, and faecal bacterial beta-glucuronidase activity were assessed. In comparison to the control diet, the LKFibre diet increased frequency of defecation by 0.13 events/d (P=0.047), increased faecal output by 21 % (P=0.020) and increased faecal moisture content by 1.6 % units (P=0.027), whilst decreasing transit time by 17 % (P=0.012) and decreasing faecal pH by 0.26 units (P<0.001). Faecal butyrate concentration was increased by 16 % (P=0.006), butyrate output was increased by 40 % (P=0.002) and beta-glucuronidase activity was lowered by 1.4 micromol/h per g wet faeces compared to the control diet (P<0.001). Addition of LKFibre to the diet incorporated into food products improved some markers of healthy bowel function and colon cancer risk in men.

Adult↗