A single-day paradigm of self-regulated human cocaine administration.

UNLABELLED: Prior work by our group has shown the feasibility, safety, and validity of a multi-day, multi-dose paradigm of self-regulated cocaine administration in humans. The current work sought to consolidate these methods in a single-day design focused on reducing logistical complexity, decreasing research burden to human subjects, and increasing suitability for medication development designs. METHODS: Eleven experienced cocaine users participated in a 6-hour, single-day design, consisting of one safety/eligibility and three experimental cocaine periods (during which subjects were allowed to self-administer 8, 16, and 32 mg/70 kg cocaine doses under a fixed-ratio 1:5 minute timeout schedule). Changes in cocaine-induced cardiovascular response, self-administration behavior, and subjective effects were assessed. RESULTS: Procedures were well tolerated by participants, and no significant adverse events were noted. Significant (p < 0.05), changes in measures of cocaine self-administration (e.g., responses, infusions, interinfusion intervals, consumption, and plasma levels), cardiovascular response (HR), and subjective effects ("high") were observed. In contrast, cocaine-induced increases in other vital signs (e.g., SBP, DBP) and subjective effect measures (e.g., paranoia) did not differ between doses. CONCLUSIONS: These data support the safety, tolerability and validity of our single-day design. Depending on the application, such methods may afford advantages for assessing the self-regulation of cocaine administration behavior in humans (e.g., including medication development designs).

Reduction of physiological noise with independent component analysis improves the detection of nociceptive responses with fMRI of the human spinal cord.

The evaluation of spinal cord neuronal activity in humans with functional magnetic resonance imaging (fMRI) is technically challenging. Major difficulties arise from cardiac and respiratory movement artifacts that constitute significant sources of noise. In this paper we assessed the Correction of Structured noise using spatial Independent Component Analysis (CORSICA). FMRI data of the cervical spinal cord were acquired in 14 healthy subjects using gradient-echo EPI. Nociceptive electrical stimuli were applied to the thumb. Additional data with short TR (250 ms, to prevent aliasing) were acquired to generate a spatial map of physiological noise derived from Independent Component Analysis (ICA). Physiological noise was subsequently removed from the long-TR data after selecting independent components based on the generated noise map. Stimulus-evoked responses were analyzed using the general linear model, with and without CORSICA and with a regressor generated from the cerebrospinal fluid region. Results showed higher sensitivity to detect stimulus-related activation in the targeted dorsal segment of the cord after CORSICA. Furthermore, fewer voxels showed stimulus-related signal changes in the CSF and outside the spinal region, suggesting an increase in specificity. ICA can be used to effectively reduce physiological noise in spinal cord fMRI time series.

Pain perception: is there a role for primary somatosensory cortex?

Anatomical, physiological, and lesion data implicate multiple cortical regions in the complex experience of pain. These regions include primary and secondary somatosensory cortices, anterior cingulate cortex, insular cortex, and regions of the frontal cortex. Nevertheless, the role of different cortical areas in pain processing is controversial, particularly that of primary somatosensory cortex (S1). Human brain-imaging studies do not consistently reveal pain-related activation of S1, and older studies of cortical lesions and cortical stimulation in humans did not uncover a clear role of S1 in the pain experience. Whereas studies from a number of laboratories show that S1 is activated during the presentation of noxious stimuli as well as in association with some pathological pain states, others do not report such activation. Several factors may contribute to the different results among studies. First, we have evidence demonstrating that S1 activation is highly modulated by cognitive factors that alter pain perception, including attention and previous experience. Second, the precise somatotopic organization of S1 may lead to small focal activations, which are degraded by sulcal anatomical variability when averaging data across subjects. Third, the probable mixed excitatory and inhibitory effects of nociceptive input to S1 could be disparately represented in different experimental paradigms. Finally, statistical considerations are important in interpreting negative findings in S1. We conclude that, when these factors are taken into account, the bulk of the evidence now strongly supports a prominent and highly modulated role for S1 cortex in the sensory aspects of pain, including localization and discrimination of pain intensity.

Use of the transurethral prostatectomy clinical path to monitor health outcomes.

PURPOSE: We evaluated the effect on cost and medical care quality of use of the transurethral prostatectomy clinical path. MATERIALS AND METHODS: Results in 100 patients treated when the transurethral prostatectomy clinical path was used were compared to those of 100 treated by the same physicians before implementation of this path. RESULTS: After implementation of the transurethral prostatectomy clinical path the length of hospital stay was significantly decreased from 5.9 to 5.0 days (p < 0.01) and Foley catheterization time was significantly decreased from 3.13 to 2.84 days (p < 0.01). Antibiotics were routinely used from the day before surgery to the day of hospital discharge as required by patient conditions. Therefore, a shorter hospital stay will significantly decrease the use of antibiotics. After implementation of the clinical path the average admission charges were decreased significantly by 17% (p < 0.01). Although some results from use of this path will not significantly affect costs, they will reflect some quality improvement. The effect of clinical path implementation on length of hospital stay between patients treated by junior and senior attending physicians was not significant. However, there was a statistically significant difference (p < 0.01) between results obtained by junior and senior attending physicians regarding average admission charges. CONCLUSIONS: Implementation of the transurethral prostatectomy clinical path can improve health care outcome by decreasing length of stay and admission charges, and improving quality of medical care, particularly for patients treated by junior attending physicians.

Fiber full-polarization-state controller.

A fiber full-polarization-state controller made by applying variable axial strains to both ends of a section of properly central-twisted high linearly birefringent fiber is proposed and thoroughly studied. The equations for polarization control are extremely simple. Experimental results are in good agreement with theoretical predictions.

New metal-clad fiber polarizer.

UNLABELLED: High quality fiber polarizers are made easily by consecutively overcoatingsuitably polished fibers withMgF2and Al films. KEYWORDS: Fiberpolarizer.

Amino-acid sequence of the 20 000-molecular-weight light chain of chicken gizzard-muscle myosin.

The light chain fraction was separated from chicken gizzard muscle myosin. After S-carboxymethylation or performic acid oxidation, two light chain components (20 000-Mr and 17 000-Mr chains) were isolated by chromatography on a column of DEAF-cellulose in the presence of 4 M urea. Tryptic peptides of the S-carboxymethylated 20 000-Mr chain were isolated, and their sequences were determined. The alignment of these tryptic peptides in the chain was deduced from the amino acid compositions and from the partial sequences of peptic peptide of the oxidized protein. The established sequence consists of 171 amino acids and its calculated molecular weight is 19692. Comparing the sequence with those of L-2 chains from chicken and rabbit skeletal muscle myosins, 81 and 78 amino acid substitutions were recognized, respectively, including insertions and/or deletions.