Longitudinal gradient coil optimization in the presence of transient eddy currents.

The switching of magnetic field gradient coils in magnetic resonance imaging (MRI) inevitably induces transient eddy currents in conducting system components, such as the cryostat vessel. These secondary currents degrade the spatial and temporal performance of the gradient coils, and compensation methods are commonly employed to correct for these distortions. This theoretical study shows that by incorporating the eddy currents into the coil optimization process, it is possible to modify a gradient coil design so that the fields created by the coil and the eddy currents combine together to generate a spatially homogeneous gradient that follows the input pulse. Shielded and unshielded longitudinal gradient coils are used to exemplify this novel approach. To assist in the evaluation of transient eddy currents induced within a realistic cryostat vessel, a low-frequency finite-difference time-domain (FDTD) method using the total-field scattered-field (TFSF) scheme was performed. The simulations demonstrate the effectiveness of the proposed method for optimizing longitudinal gradient fields while taking into account the spatial and temporal behavior of the eddy currents.     

Outcomes at 3 years of a prospective pilot study of Campath-1H and sirolimus immunosuppression for renal transplantation

Campath-1H (alemtuzumab) induction was used for renal transplantation in combination with sirolimus as immunosuppression. We previously reported a high (28%) rate of early rejection with this regimen, and now report 3-year outcomes. Twenty-nine patients were recipients of either deceased donor or non-HLA (Human Leukocyte Antigen) identical living donor primary renal allografts. Clinical parameters including infection, malignancy, kidney function, and kidney histology were followed prospectively for 3 years. Three-year cumulative graft and patient survival were 96% and 100%, respectively. Twenty patients were maintained on steroid-free immunosuppressive regimens, and 15 patients were maintained on monotherapy for immunosuppression (12 on sirolimus). No serious infectious complications were observed and two patients developed basal cell skin cancer. The 3-year results of our initial pilot study demonstrate good graft (96%) and patient (100%) outcomes. Campath-1H induction has yielded a high proportion of patients maintained on immunosuppressive monotherapy (57%) without serious infectious- and no malignancy-related complications. The reported regimen yielded novel insights into both Campath-1H and sirolimus therapy in renal transplantation. Because of the higher incidence of early rejection, we recommend a modified strategy of immunosuppression including a brief course of a calcineurin inhibitor.     

Relationships Between Arousal-Related Moods and Episodic Tension-Type Headache: A Biopsychological Study

An exploratory study was conducted examining arousal-related moods and episodic tension-type headache. Twelve subjects meeting International Headache Society criteria for episodic tension-type headache and 12 headache-free controls recorded headache activity and mood eight times daily for 14 consecutive days. Moods were measured using the Activation-Deactivation Adjective Check List, a self-report list that subjectively represents general arousal along two dimensions of Tension and Energy. Headache subjects had higher Tension levels than controls even in the absence of pain, and greater variation in this dimension as well. Within the headache group, Tension during pain-free periods was significantly lower than when experiencing headache, and was correlated with headache activity. The results were taken to support Thayer's (1989) biopsychological model of mood and arousal, and are discussed in terms of the model's heuristic value for general arousal and headache research.     

Effects of acute administration of d-amphetamine and haloperidol on procedural learning in man

The effects of an indirect dopamine-agonist, d-amphetamine, and a non-selective dopamine receptor antagonist, haloperidol, were investigated in normal male volunteers using a between-subjects double-blind design in a procedural learning task, thought mainly to involve unconscious/automatic learning. The results showed: (1) d-amphetamine facilitated response speed, whereas haloperidol inhibited it, in comparison to placebo; (2) the linear increase in procedural learning corresponded with pharmacological manipulation of degree of dopaminergic activity, i.e. subjects given haloperidol showed the least, and subjects given d-amphetamine the greatest, procedural learning. The implications of these findings are discussed in relation to investigation of abnormalities of procedural learning processes in schizophrenia. Received: 28 June 1996/Final version: 2 October 1996     

Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans.

Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may give rise to many herb-drug interactions. Serial plasma concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo. Twenty healthy volunteers were randomly assigned to receive a standardized goldenseal (3210 mg daily) or kava kava (1227 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin, 0.5 mg) was administered p.o. before and at the end of each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), C(max,) CL/F, and elimination half-life were used to assess the effects of goldenseal, kava kava, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p < 0.01) in AUC((0-3)), AUC((0-24)), CL/F, t(1/2), and C(max), whereas clarithromycin increased these parameters significantly (p < 0.01). With the exception of goldenseal's effect on C(max) (14% increase), no statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava. When compared with rifampin and clarithromycin, supplementation with these specific formulations of goldenseal or kava kava did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo.