Intranasal oxytocin has sympathoexcitatory effects on vascular tone in healthy males.

Oxytocin appears to be involved in the neuroendocrine regulation of sympathetic blood pressure (BP) homeostasis. In animals, intracerebral administration of oxytocin induces BP-relevant sympathetic activation. In humans, central nervous effects of oxytocin on BP regulation remain unclear. Intranasal administration supposedly delivers oligopeptides such as oxytocin directly to the brain. We investigated the effects of intranasal oxytocin on sympathetic vascular baroreflex function in humans using microneurographic techniques. In a balanced, double-blind crossover design, oxytocin or placebo was administered intranasally to 12 lean, healthy males (age 25 ± 4 yr). Muscle sympathetic nerve activity (MSNA) was assessed microneurographically before (presubstance), 30-45 min (postsubstance I), and 105-120 min (postsubstance II) after oxytocin administration. Baroreflex was challenged via graded infusions of vasoactive drugs, and correlation of BP with MSNA and heart rate (HR) defined baroreflex function. Experiments were conducted in the afternoon after a 5-h fasting period. After oxytocin, resting MSNA (burst rate and total activity) showed significant net increases from pre to postsubstance II compared with placebo [Δincrease = +4.3 ± 1.2 (oxytocin) vs. +2.2 ± 1.4 bursts/min (placebo), ANOVA; P < 0.05; total activity = 184 ± 11.5% (oxytocin) vs. 121 ± 14.3% (placebo), ANOVA; P = 0.01). This was combined with a small but significant net increase in resting diastolic BP, whereas systolic and mean arterial BP or HR as well as baroreflex sensitivity at vasoactive drug challenge were not altered. Intranasally administered oxytocin induced vasoconstrictory sympathoactivation in healthy male humans. The concomitant increase of diastolic BP was most likely attributable to increased vascular tone. This suggests oxytocin-mediated upward resetting of the vascular baroreflex set point at centers superordinate to the mere baroreflex-feedback loop.

Acute and chronic effects on central hemodynamics and arterial stiffness in professional rowers.

Controversial data exist on acute and chronic effects of competitive sports on central hemodynamics and arterial stiffness. We investigated chronic as well as acute training effects in professional rowers. The trial was planned as a non-randomized, controlled pilot-study comparing athletes and controls. 13 German national team rowers (24.1 ± 1.5 years) and 12 controls (23.8 ± 0.8 years) participated. Aortic, brachial hemodynamics and arterial stiffness were measured (Arteriograph, TensioMed(®), Hungary) before and after a standardized exercise test. Chronic heart rate (49 [Formula: see text] 2 bpm versus 70 [Formula: see text] 2 bpm, p < 0.05) as well as brachial diastolic pressure (65 [Formula: see text] 2 mmHg versus 74 [Formula: see text] 2 mmHg, p < 0.05) was significantly lower in rowers. Physical power (305 [Formula: see text] 63 versus 158 [Formula: see text] 60 W, p < 0.001) was better. Chronic aortic pulse pressure (41.6 [Formula: see text] 6.0 versus 35.2 [Formula: see text] 3.8 mmHg; p < 0.01) and AIx (9.1 [Formula: see text] 5.4 versus 7.0 [Formula: see text] 10.2; p < 0.01) were significantly higher in athletes. After the all-out test (acute effects) pulse wave velocity (rowers: 6.6 [Formula: see text] 1.2 m s(-1) versus 7.8 [Formula: see text] 1.6 m s(-1), p < 0.001; control group 6.0 [Formula: see text] 0.4 m s(-1) versus 8.0 [Formula: see text] 1.4 m s(-1), p = 0.005) and heart rate (rowers: 49 [Formula: see text] 2 bpm versus 91 [Formula: see text] 3 bpm, p < 0.001; control group 70 [Formula: see text] 2 bpm versus 92 [Formula: see text] 4 bpm, p < 0.001) increased significantly in both groups. The controls' aortic AIx (7.0 [Formula: see text] 10.2 versus 2.0 [Formula: see text] 6.0; p < 0.01) decreased significantly after exercise. Professional rowers showed higher chronic aortic pulse pressure and arterial stiffness. Given the risk associated with elevated aortic pulse pressure and AIx for development of cardiovascular diseases, longterm observations of professional rowers are needed with respect to arterial stiffness and prognosis. Furthermore the acute effects need additional research.

Production of high intensity 48Ca for the 88-Inch Cyclotron and other updates.

Recently the Versatile ECR for NUclear Science (VENUS) ion source was engaged in a 60-day long campaign to deliver high intensity (48)Ca(11+) beam to the 88-Inch Cyclotron. As the first long term use of VENUS for multi-week heavy-element research, new methods were developed to maximize oven to target efficiency. First, the tuning parameters of VENUS for injection into the cyclotron proved to be very different than those used to tune VENUS for maximum beam output of the desired charge state immediately following its bending magnet. Second, helium with no oxygen support gas was used to maximize the efficiency. The performance of VENUS and its low temperature oven used to produce the stable requested 75 eµA of (48)Ca(11+) beam current was impressive. The consumption of (48)Ca in VENUS using the low temperature oven was checked roughly weekly, and was found to be on average 0.27 mg/h with an ionization efficiency into the 11+ charge state of 5.0%. No degradation in performance was noted over time. In addition, with the successful operation of VENUS the 88-Inch cyclotron was able to extract a record 2 pµA of (48)Ca(11+), with a VENUS output beam current of 219 eµA. The paper describes the characteristics of the VENUS tune used for maximum transport efficiency into the cyclotron as well as ongoing efforts to improve the transport efficiency from VENUS into the cyclotron. In addition, we briefly present details regarding the recent successful repair of the cryostat vacuum system.

Recent progress on the superconducting ion source VENUS.

The 28 GHz Ion Source VENUS (versatile ECR for nuclear science) is back in operation after the superconducting sextupole leads were repaired and a fourth cryocooler was added. VENUS serves as an R&D device to explore the limits of electron cyclotron resonance source performance at 28 GHz with its 10 kW gryotron and optimum magnetic fields and as an ion source to increase the capabilities of the 88-Inch Cyclotron both for nuclear physics research and applications. The development and testing of ovens and sputtering techniques cover a wide range of applications. Recent experiments on bismuth demonstrated stable operation at 300 eµA of Bi(31+), which is in the intensity range of interest for high performance heavy-ion drivers such as FRIB (Facility for Rare Isotope Beams). In addition, the space radiation effects testing program at the cyclotron relies on the production of a cocktail beam with many species produced simultaneously in the ion source and this can be done with a combination of gases, sputter probes, and an oven. These capabilities are being developed with VENUS by adding a low temperature oven, sputter probes, as well as studying the RF coupling into the source.

Adaptive control of laser modal properties.

An adaptive optical system for precise control of a laser beam's mode structure has been developed. The system uses a dynamic lens based on controlled optical path deformation in a dichroic optical element that is heated with an auxiliary laser. Our method is essentially aberration free, has high dynamic range, and can be implemented with high average power laser beams where other adaptive optics methods fail. A quantitative model agrees well with our experimental data and demonstrates the potential of our method as a mode-matching and beam-shaping element for future large-scale gravitational wave detectors.

Confinement of a large number of antiprotons and production of an ultraslow antiproton beam.

We have used a radio frequency quadrupole decelerator to decelerate antiprotons emerging from the CERN Antiproton Decelerator from MeV- to keV-scale energy, and collected five decelerated pulses in a multiring trap. Some 5 x 10(6) antiprotons were stacked in this way. Cooling of the trapped antiprotons by a simultaneously trapped electron plasma was studied nondestructively via shifts in plasma mode frequencies. We have also demonstrated the first step in extracting a 10-500 eV antiproton beam from the trap.

Radial compression of protons and H3+ ions in a multiring trap for the production of ultralow energy antiproton beams.

Radial compression of a proton cloud was performed in a multiring trap which was designed to trap and cool a large number of antiprotons for the production of low-energy ( 10-1000 eV ) antiproton beams. The resonance frequency for the radial compression was almost constant from 3 x 10(5) to 3 x 10(6) protons. The collision process of the trapped protons was also investigated to estimate the energy of the protons inside the trap. This technique will be applied to the ASACUSA experiment at the antiproton decelerator, CERN, to extract ultraslow antiprotons with good emittance.

Electron cooling of high-energy protons in a multiring trap with a tank circuit monitoring the electron-plasma oscillations.

Electron cooling of energetic protons in a multiring trap was investigated experimentally with a tank circuit monitoring electron-plasma oscillations in the trap. The energy of protons was determined by time-of-flight measurements. It is found that a simple model can explain the qualitative behavior of both electron and proton energy when the initial energy of protons is less than 2 keV. Monitoring the electron-plasma temperature with a tank circuit can be an effective tool when energetic particles are electron cooled in a multiring trap.

Theta bursts, closed head injury, and partial seizure-like symptoms: a retrospective study.

The purpose of this retrospective, chart-review study was to provide additional information on the clinical correlates ofparoxysmal theta activity on EEG and to further examine the previously proposed relation (Varney, Hines, Bailey, & Roberts, 1992) between episodic symptoms in the context of prior closed-head injury and theta bursts. Allparticipants were veterans receiving their health care at a single, tertiary-care, Veterans Affairs medical center. Compared with patients with normal EEGs (comparison group, n = 30) and nonparoxysmal theta-delta slowing (comparison group, n = 30), consecutive patients with theta bursts (n = 38) were found to have significantly more episodic (ie., partial seizure-like) symptoms documented in their medical records. History of closed-head trauma was also associated with increased reporting of episodic symptoms across all three clinical groups. These findings suggest that, in the presence of theta bursts on EEG, clinicians may wish to interview systematicallyfor episodic, partial seizure-like phenomena, especially when paroxysmal theta activity occurs in the context of prior closed head injury.

The kinetics of mycophenolic acid and its glucuronide metabolite in adult kidney transplant recipients.

BACKGROUND: Mycophenolic acid kinetics have been reported to vary after renal transplantation, and mycophenolic acid area under the concentration-time curve (AUC) is the best predictor of suppression of graft rejection. METHODS: To determine whether mycophenolic acid kinetics vary after renal transplantation and to examine the potential role of enterohepatic recirculation, we investigated the kinetics of mycophenolic acid and mycophenolic acid glucuronide on days 2, 5, and 28 after transplantation in 10 kidney transplant recipients (male/female ratio, 1.5; mean age, 41.7 +/- 5.0 years) given 1 g mycophenolate mofetil twice a day. To facilitate therapeutic drug monitoring, we examined a limited sampling strategy for estimating 12-hour mycophenolic acid [AUC(0-12)]. RESULTS: The mean +/- SE AUC(0-12) for mycophenolic acid on day 28 was 38.5 +/- 1.6 mg x h/L, with a secondary peak 4 to 8 hours after dosing that was attributable to enterohepatic recirculation. Marked variability was shown in the kinetic profile of mycophenolic acid among patients across the three sampling days. Mycophenolic acid AUC(0-12) was positively predicted by both serum creatinine (P = .01) and serum albumin (P = .03) but not by time after transplantation, body weight, or trough concentration. Limited sampling (at 0, 1, 3, and 6 hours) accounted for 84.1% of the variability in the mycophenolic acid AUC(0-12) data and predicted the AUC(0-12) closely (r2 = 0.954) when evaluated in 10 different kidney transplant recipients. CONCLUSIONS: Mycophenolic acid AUC(0-12) is predicted by serum albumin and creatinine after kidney transplantation, and the AUC(0-12) may be determined during the early posttransplant period while the patient remains hospitalized with use of a limited sampling strategy to facilitate therapeutic drug monitoring.

Design fluency among normals and patients with closed head injury.

A Design Fluency task was administered to 86 patients who had suffered closed head injury (CHI) with loss of consciousness and 87 normal control subjects. Subjects were asked to draw as many novel designs as they could in 5 minutes without scribbling, drawing a nameable object, or repeating a design that had been drawn previously. The mean performance of the CHI group was significantly poorer than that of the control group, with 47% of head injured performing defectively (below the 5th percentile of controls There was no significant relationship between Design Fluency and prorated IQ, psychomotor speed, or Word Fluency. The findings demonstrate that a standardized version of the "free condition" of Design Fluency is likely to be useful in the evaluation of patients with closed head injury.

A developmental study of the Tinker Toy test: normative and clinical observations.

Tinker Toy test performance is presented for a normative group of 5- to 12-year-old children. Contrary to reported findings for some executive function tasks, developmental trends in Tinker Toy Test performance were not found. Results from a large group (N=55) of children who had sustained traumatic brain injury demonstrated that Tinker Toy Test performance was sensitive to the effects of traumatic brain injury and significantly associated with separate clinical ratings of functional or executive impairment. Present findings support the utility of the Tinker Toy Test as one component of the pediatric neuropsychological evaluation following traumatic brain injury.

The Dichotic Word Listening Test: preliminary observations in American and Canadian samples.

The present article describes observations of 670 American and Canadian child and adult control subjects on the recently developed Dichotic Word Listening Test (DWLT). The task was also administered to a sample of American children with traumatic brain injuries (n=21) of varying severity and a sample of American adults with mild traumatic injuries (n=36). The conceptual focus in this line of research was on using normative observations to identify clinically defective channels of auditory processing among patients. The principal findings were as follow: 1) the DWLT was sensitive to the effects of cerebral dysfunction following traumatic brain injury; 2) differences among normal samples with different demographic backgrounds were frequently observed, arguing for the development of local norms; 3) a shorter form of the DWLT task (DWLT30) can be used for screening purposes with relatively little reduction in sensitivity to cerebral dysfunction; 4) there appeared to be considerable improvement of DWLT performance between the ages of five and seven, due largely to higher scores from the left auditory channel; and 5) there were indications that use of French (rather than English) as one's native language before age six can negatively influence performance in adulthood on an English version of the DWLT. In general, the present findings suggest that the DWLT is likely to have relatively broad applicability for neuropsychological assessment across the life-span.

Neuropsychologic dysfunction in women following leuprolide acetate induction of hypoestrogenism.

OBJECTIVE: The study investigated the neuropsychological status of women with induced hypoestrogenism. DESIGN: An ABA design was employed in which neuropsychological measures were repeated prior to, during, and after induction of hypoestrogenism with leuprolide acetate. SETTING: The study took place in a medical school affiliated in vitro fertilization clinic. INTERVENTIONS: Leuprolide acetate was administered to all subjects as part of in vitro fertilization. METHODS: Eighteen women receiving in vitro fertilization treatment underwent neuropsychological testing before, during, and after treatment with leuprolide acetate and gonadotrophins. The neuropsychological test battery was selected on the basis of previous patients' symptomatic complaints during periods of hypoestrogenism with leuprolide acetate. RESULTS: Depending upon the tests administered, some individuals showed significant cognitive deficits during therapy particularly in the areas of memory, fine motor coordination, and two-point discrimination. Two of the 18 subjects showed very substantial neuropsychological sequelae including memory gaps and disturbances in a variety of neuropsychological test performances. However, in terms of group statistics, only two-point discrimination and delayed recall memory test performance proved significant. Not all measures were sensitive for the group, as many tests displayed a balance between individuals who showed practice effects and those who showed detrimental effects. CONCLUSIONS: For a substantial portion of individuals, hypoestrogenism can result in statistically significant or clinically noteworthy problems with memory, dexterity, and two-point discrimination.

Changes in laboratory variables induced by isotretinoin treatment of acne.

During a trial of isotretinoin (0.5 mg/kg body weight/day for 3 months) in 90 patients with severe acne, the leucocyte (WBC) count, and particularly the number of neutrophils, decreased significantly. In patients with a good response the mean WBC count fell by 24% and the neutrophils by 33%, whereas in those with a poor response these variables decreased by 8% and 14%, respectively. The serum ALAT, ASAT, cholesterol and triglyceride levels increased significantly. Patients with a poor response (n = 35) received a higher dosage (0.75 mg/kg) for an additional 3 months, and during this period there was a further decrease in the WBC and neutrophil counts and an increase in the triglyceride level. In the other patients, who initially responded well, the dosage was decreased to 0.1 or 0 mg/kg during the second 3-month period, which resulted in reversion of the laboratory variables to the pre-treatment levels. The observed changes were clearly both dose-dependent and reversible.

[Development of volatile compounds from radicals arising during intermediate steps of the lipoxygenase-reaction (author's transl)]. / Untersuchungen über die Entstehung flüchtiger Verbindungen aus radikalischen Reaktionszwischenstufen bei der Lipoxygenase-Reaktion.

The development of volatile compounds arising from radicals during intermediate reaction steps of the lipoxygenase-linoleic-acid-reaction (from soy) was investigated in model experiments with defined conditions. The results indicate as follows: Among the volatile compounds formed, hexanal has a special position. Its development is closely connected to the enzymatic formation of the 13-linoleic-acid-hydroperoxide because it is formed from the 13-linoleic-acid-peroxy-radical, which is a direct precursor of the 13-linoleic-acid-hydroperoxide. The other volatile products are apparently formed in the same way as by autoxidation. Their development is favoured by lack of oxygen, when the primarily formed linoleic-acid-radicals cannot react rapidly with the oxygen-radicals to form hydroperoxides. A small part of the volatile compounds is formed by autoxidation which always accompanies the enzymatic reaction.

[Investigations on the development of volatile substances during lipoxygenase-linolic-acid-reaction (author's transl)]. / Untersuchungen über Entstehungswege flüchtiger Substanzen bei der Lipoxygenase-Linolsäure-Reaktion

During incubation of soja-lipoxygenase with linolic acid, volatile compounds are formed the development of which can be seen in two possible ways:from preformed linolic-acid-hydroperoxides splitproducts arise or volatile substances of different chemical nature are built depending on the reaction conditions like temperature, O2-pressue, partner-concentration etc. By trials with hydroperoxyde-decomposing enzymes (peroxidase) and by means of radio-active labelled linolic-acid-hydroperoxides the pathways mentioned above were investigated. The results indicate that the volatile compounds are built from by-products; n-hexanal was formed from these by-products as well as from decomposed hydroperoxide. The previously proposed reaction-scheme has this been ascertained by experimental means.

[Analysis of volatile aldehydes by radio-gaschromatography (author's transl)]. / Radiogaschromatographische Analyse flüchtiger Aldehyde, die bei der mit Soja- und Hafer-Lipoxygenase katalysierten Linolsäure-Oxidation entstehen

Soya- and oats-lipoxygenase (E.C. 1.13.1.13.) are incubated by 14C-marked linoleic acid. The volatile aldehydes arising thereby are isolated. The activity of the components separated by gaschromatography is written down by a printing indicator and the impulses/min are registered and printed out by a ratemeter. Thus the aldehydes which are produced by the enzymatic oxydation with lipoxygenase from the molecule of the linoleic acid can be determined. The composition of the mixture of aldehyde is calculated in mol-% from the measured impulses per peak. A possible origin of pathway is indicated for the main reaction products hexanal (soya-lipoxygenase) and non-trans-2-enal (oats-lipoxygenase).