Ultra high-resolution NMR: sustained induction decays of long-lived coherences.

Long-lived coherences (LLCs) in homonuclear pairs of chemically inequivalent spins can be excited and sustained during protracted radio frequency irradiation periods that alternate with brief windows for signal observation. Fourier transformation of the sustained induction decays recorded in a single scan yields NMR spectra with line-widths in the range 10 < Δν < 100 mHz, even in moderately inhomogeneous magnetic fields. The resulting doublets, which are reminiscent of J-spectra, allow one to determine the sum of scalar and residual dipolar interactions in partly oriented media. The signal intensity can be boosted by several orders of magnitude by "dissolution" dynamic nuclear polarization (DNP).

Hyperpolarizing gases via dynamic nuclear polarization and sublimation.

A high throughput method was designed to produce hyperpolarized gases by combining low-temperature dynamic nuclear polarization with a sublimation procedure. It is illustrated by applications to 129Xe nuclear magnetic resonance in xenon gas, leading to a signal enhancement of 3 to 4 orders of magnitude compared to the room-temperature thermal equilibrium signal at 7.05 T.

Long-lived states to sustain hyperpolarized magnetization.

Major breakthroughs have recently been reported that can help overcome two inherent drawbacks of NMR: the lack of sensitivity and the limited memory of longitudinal magnetization. Dynamic nuclear polarization (DNP) couples nuclear spins to the large reservoir of electrons, thus making it possible to detect dilute endogenous substances in magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI). We have designed a method to preserve enhanced ("hyperpolarized") magnetization by conversion into long-lived states (LLS). It is shown that these enhanced long-lived states can be generated for proton spins, which afford sensitive detection. Even in complex molecules such as peptides, long-lived proton states can be sustained effectively over time intervals on the order of tens of seconds, thus allowing hyperpolarized substrates to reach target areas and affording access to slow metabolic pathways. The natural abundance carbon-13 polarization has been enhanced ex situ by almost four orders of magnitude in the dipeptide Ala-Gly. The sample was transferred by the dissolution process to a high-resolution magnet where the carbon-13 polarization was converted into a long-lived state associated with a pair of protons. In Ala-Gly, the lifetime T(LLS) associated with the two nonequivalent H(alpha) glycine protons, sustained by suitable radio-frequency irradiation, was found to be seven times longer than their spin-lattice relaxation time constant (T(LLS)/T(1) = 7). At desired intervals, small fractions of the populations of long-lived states were converted into observable magnetization. This opens the way to observing slow chemical reactions and slow transport phenomena such as diffusion by enhanced magnetic resonance.

Quantitative radiography of magnetic fields using neutron spin phase imaging.

We report on a novel neutron radiography technique that uses the Ramsey principle, a method similar to neutron spin echo. For the first time quantitative imaging measurements of magnetic objects and fields could be performed. The strength of the spin-dependent magnetic interaction is detected by a change in the Larmor precession frequency of the neutron spins. Hence, one obtains in addition to the normal attenuation radiography image a so-called neutron spin phase image, which provides a two-dimensional projection of the magnetic field integrated over the neutron flight path.

A 140 GHz prepolarizer for dissolution dynamic nuclear polarization.

Apart from their very classical use to build polarized targets for particle physics, the methods of dynamic nuclear polarization (DNP) have more recently found application for sensitivity enhancement in high-resolution NMR, both in the solid and in the liquid state. It is often thought that the possible signal enhancement in such applications deteriorates when the DNP is performed at higher fields. We show that for a dissolution-DNP method that uses conventional (2,2,6,6-tetramethylpiperidine 1-oxyl) radicals as the paramagnetic agent, this is not the case for fields up to 5 T.

Producing over 100 ml of highly concentrated hyperpolarized solution by means of dissolution DNP.

New low-temperature inserts compatible with an existing hyperpolarizer were developed to dynamically polarize nuclei in large samples. The performance of the system was tested on 8 ml glassy frozen solutions containing 13C-labeled molecules and doped with nitroxyl free radicals. The obtained 13C low-temperature polarization was comparable to the one measured on 20 times smaller sample volume with only 3-4 times higher microwave power. By using a dissolution insert that fits to the new design, it was possible to obtain about 120 ml of room-temperature hyperpolarized solution. The polarization as well as the molecule concentration was comparable to the values obtained in standard size hyperpolarized samples. Such large samples are interesting for future studies on larger animals and possibly for potential clinical applications.

Cold neutron energy dependent production of ultracold neutrons in solid deuterium.

A measurement of the production of ultracold neutrons from velocity-selected cold neutrons on gaseous and solid deuterium targets is reported. The expected energy dependence for two-particle collisions with well defined neutron and Maxwell-Boltzmann distributed molecular velocities is found for the gas target. The solid target data agree in shape with the phonon density-of-states curve and provide strong evidence for the phonon model including multiphonon excitations.

Measured total cross sections of slow neutrons scattered by solid deuterium and implications for ultracold neutron sources.

The total scattering cross sections for slow neutrons with energies in the range 100 neV to 3 meV for solid ortho-2H2 at 18 and 5 K, frozen from the liquid, have been measured. The 18 K cross sections are found to be in excellent agreement with theoretical expectations and for ultracold neutrons dominated by thermal up scattering. At 5 K the total scattering cross sections are found to be dominated by the crystal defects originating in temperature induced stress but not deteriorated by temperature cycles between 5 and 10 K.

Measured total cross sections of slow neutrons scattered by gaseous and liquid 2H(2).

The total scattering cross sections for slow neutrons with energies E in the range 300 neV to 3 meV for gaseous and liquid ortho-2H2 have been measured. The cross sections for 2H2 gas are found to be in excellent agreement with both the Hamermesh and Schwinger and the Young and Koppel models. For liquid 2H(2), we confirm the existing experimental data in the cold neutron range and the discrepancy with the gas models. We find a clear 1 / square root[E'] dependence at low energies for both states. A simple explanation for the liquid 2H2 cross section is offered.

Investigation of Solid D 2 for UCN Sources.

Solid deuterium (sD2) will be used for the production of ultra-cold neutrons (UCN) in a new generation of UCN sources. Scattering cross sections of UCN in sD2 determine the source yield but until now have not been investigated. We report first results from transmission and scattering experiments with cold, very cold and ultra-cold neutrons on sD2 along with light transmission and Raman scattering studies showing the influence of the sD2 crystal properties.

Reporting sexual function disorders caused by antipsychotic drugs: is there a role for the community pharmacy?

Sexual function disorders are frequent adverse effects of antipsychotic use. These effects can lead to non-compliance to medication, which dramatically worsen the outcome of the psychotic disease. Detecting sexual dysfunction by the carers may be difficult, since feelings of embarrassment may occur in both care-taker as in patient. In order to prevent underreporting, strategies to recognise sexual dysfunction should be developed, based upon collaboration between care providers of the psychotic patient. Community pharmacies in many countries can detect non-compliance to medication in prescription data and report this to psychiatric services of the patient. Exchanging information by cross-sectoral networks may optimise the disease management of the psychotic patient.

[Reversible tooth discoloration during oral use of antibiotics]. / Reversibele tandverkleuring tijdens oraal gebruik van antibiotica.

From January 1991 until June 1995. 25 cases were reported to the Netherlands Pharmacovigilance Foundation LAREB of yellow to brown tooth discoloration following the oral use of medication; 21 cases (84%) involved antibiotics, of which 14 were amoxicillin. 17/21 patients were children, with ages ranging from 1 to 10 years. All children used liquid formulations (suspension or solutabs). Discoloration was reversible in all cases, but had a protracted course in some. Presumably a pigment precipitated on (and not in) the teeth, but the nature of the pigment was uncertain.

[Potentiation of digoxin by itraconazole]. / Potentiëring van digoxine door itraconazol.

The case is reported of a 71-year-old woman with clinical signs of digoxin intoxication, presumably developing as a result of the simultaneous use of digoxin for cardiac abnormalities and itraconazole for infection with Candida albicans. Five similar experiences have previously been reported in the literature. Itraconazole may induce a decreased elimination of digoxin, but the mechanism of interaction is still unknown. Comedication and renal function may perhaps contribute to the degree of interaction. When itraconazole is needed in a patient also using digoxin the blood level of the latter drug should be monitored; the daily dose of digoxin may have to be decreased to only one-quarter of the original. Nausea and anorexia may be mistaken for side effects of itraconazole and be overlooked as early signs of digoxin intoxication.

[Tendinitis of the Achilles tendon caused by pefloxacin and other fluoroquinolone derivatives]. / Achillespeestendinitis door pefloxacine en andere fluorochinolon-derivaten.

Four cases were reported to the Netherlands Pharmacovigilance Foundation LAREB of Achilles tendinitis, as a suspected adverse reaction to pefloxacin; the patients were two men of 64 years old, one of 33 and one of 76 years old. More than twenty cases of tendinitis have previously been described in the literature in association with pefloxacin and various other fluoroquinolone derivatives; tendon rupture was a frequent complication. In the data base of the WHO Collaborating Centre for International Drug Monitoring tendon disorders are a very rare reaction, with the exception of fluoroquinolone derivatives. More information is needed with regard to the frequency of tendinopathy during the use of pefloxacin and the other drugs in this group. Achilles tendon rupture is an serious condition, often requiring surgical treatment. Patients using a fluoroquinolone derivative should be informed of the risk of developing tendinitis and tendon rupture.