Use of argatroban during multi-organ procurement: pharmacokinetics and sequelae in recipient of transplanted liver.

This report illustrates potential concerns regarding the administration of Argatroban (AGN), a small molecule, direct thrombin inhibitor, within the setting of multi-organ procurement (MOP). Herein, we outline the case of a large AGN bolus to the donor during MOP, and the passive transfer of a coagulopathy to the recipient of the transplanted liver. From this, we conclude that caution should be exercised when AGN is used in the setting of MOP.

Multimaterial actinic spatial control 3D and 4D printing.

Production of objects with varied mechanical properties is challenging for current manufacturing methods. Additive manufacturing could make these multimaterial objects possible, but methods able to achieve multimaterial control along all three axes of printing are limited. Here we report a multi-wavelength method of vat photopolymerization that provides chemoselective wavelength-control over material composition utilizing multimaterial actinic spatial control (MASC) during additive manufacturing. The multicomponent photoresins include acrylate- and epoxide-based monomers with corresponding radical and cationic initiators. Under long wavelength (visible) irradiation, preferential curing of acrylate components is observed. Under short wavelength (UV) irradiation, a combination of acrylate and epoxide components are incorporated. This enables production of multimaterial parts containing stiff epoxide networks contrasted against soft hydrogels and organogels. Variation in MASC formulation drastically changes the mechanical properties of printed samples. Samples printed using different MASC formulations have spatially-controlled chemical heterogeneity, mechanical anisotropy, and spatially-controlled swelling that facilitates 4D printing.

Prolonged-Release vs Immediate-Release Tacrolimus Capsules in Black vs White Kidney Transplant Patients: A Post Hoc Analysis of Phase III Data.

BACKGROUND: Black kidney transplant patients experience inferior outcomes compared with other ethnicities. Because scrutiny is required when immunosuppressant drugs are used in such at-risk populations, we report the first large-scale clinical efficacy data assessing prolonged-release tacrolimus (PR-T) in black de novo kidney transplant patients. METHODS AND MATERIALS: We used logistic regression and proportionate hazards to compare a composite outcome measure (biopsy-proven acute rejection, graft loss, mortality, and loss to follow-up) in black and white patients in treatment groups longer than 24 weeks, from 3 large Phase III randomized controlled trials. Secondary endpoints included tacrolimus trough concentration, dose, and estimated glomerular filtration rate. RESULTS: The study included 2162 patients whose treatments belonged to two categories (immediate-release tacrolimus: 77 black patients, 721 white patients; and PR-T: 87 black patients, 1277 white patients). Despite demographic factors generally predictive of worse outcomes, efficacy failure among black patients who received PR-T was non-inferior to that among white patients who received either therapy. Compared with immediate-release tacrolimus, black patients who received PR-T achieved stable tacrolimus concentrations 2.5 times faster (21 vs 56 days, P = .04), and more achieved stable target concentrations (76.7% vs 69.3%). Treatment-emergent adverse events were consistent with those reported separately in pivotal trials. CONCLUSIONS: Overall, black patients who received PR-T achieved non-inferior outcomes compared to white patients, despite higher pretransplant risk among black patients. Moreover, PR-T improved the time to achieve, and the likelihood of reaching, stable therapeutic concentrations among black patients, suggesting that PR-T could improve the consistency of tacrolimus exposure in this patient population.

Sequence analysis of the ribosomal RNA operon of the Lyme disease spirochete, Borrelia burgdorferi.

An 11,955-bp region of the Borrelia burgdorferi chromosome containing all the genes encoding ribosomal RNA (rRNA) has been sequenced. The region contains a single gene encoding 16S rRNA and two genes encoding the 23S and 5S rRNAs. The sizes of the 16S, 23S and 5S rRNAs encoded by these genes are 1537, 2926 and 112 nucleotides, respectively. In addition, the genes encoding tRNA(Ala) and tRNA(Ile) are located in the intergenic spacer between the 16S and 23S rDNAs. The tDNAs do not encode the common CCA 3' end which presumably must be added posttranscriptionally. All the genes are present in the same orientation, except for that encoding tRNA(Ile), which is transcribed from the opposite strand. The latter implies that the rDNAs are not transcribed as a single unit. The location of putative promoters and termination signals in the sequence suggest that the 16S rRNA and tRNA(Ala) are transcribed as a single unit, tRNA(Ile) is produced as an individual transcript and the 23S and 5S rDNAs are co-transcribed. Several of the features of this rDNA organization are unique, not having been described previously in any other eubacteria.

Peptide-mediated cellular delivery.

Peptide-mediated molecular therapeutic delivery systems have recently emerged as an alternative means to effectively substitute or augment present gene therapy technologies, e.g., TAT, VP22, engineered peptides. These systems show great promise for the elimination of the main bottleneck to safe, efficient, targeted gene therapy delivery and are able to efficiently introduce DNA, antisense peptide nucleic acids, oligonucleotides, small molecules and proteins into cells both in vitro and in vivo. They are versatile and easily designed to incorporate a number of specific attributes required for efficient cargo delivery. A fundamentally new property of these moieties will allow the therapeutic intervention in the biochemistry of the target cell without the need to alter its genome.

Molecular cloning and sequencing of infC, the gene encoding translation initiation factor IF3, from four enterobacterial species.

Translation initiation factor IF3 plays a crucial role in initiation of protein synthesis in bacteria. In order to elucidate the IF3 structural elements required for these functions, the evolutionary conservation of IF3 and its gene, infC, was investigated. Homologous infC sequences from Salmonella typhimurium, Klebsiella pneumoniae, Serratia marcescens and Proteus vulgaris were amplified by the polymerase chain reaction and sequenced. Analysis of these sequences, as well as that from Bacillus stearothermophilus, revealed several regions (e.g. residues 62-73 and 173-177) of absolute sequence conservation, suggesting an important role for these regions in IF3 function.

Analysis of 2-difluoromethyl-DL-ornithine in human plasma, cerebrospinal fluid and urine by cation-exchange high-performance liquid chromatography.

An analytical method has been developed based on cation-exchange liquid chromatography for the measurement of 2-difluoromethyl-DT-ornithine (DFMO) in human plasma, cerebrospinal fluid (CSF) and urine. Fluorescence detection at excitation/emission wavelengths of 340/440 nm is followed by postcolumn derivatization with o-phthalaldehyde-2,mercaptoethanol. All calibration ranges yielded linear relationships with correlation coefficients better than 0.999. In each case the limit of quantitation was equal to the lowest value of the standard curve. The variability of the assay, expressed as relative standard deviations, was less than 7.1%, 15.3% and 7.1% for plasma, CSF and urine, respectively. The accuracy of the assay (expressed as relative errors) ranged between 4.3% and 2.0% for plasma analysis, between -0.1% and 14.0% for CSF analysis and between -8.0% and 2.0% for urine analysis. Plasma, CSF and urinary DFMO concentrations were measured in samples obtained from patients undergoing treatment for trypanosomiasis. The method was found to be applicable for the measurement of DFMO levels in human body fluids for the determination of pharmacokinetic parameters in clinical studies.

Unexpected geographic variation in rates of hospitalization for patients who have fracture of the hip. Medicare enrollees in the United States.

With the use of data from hospitals for fiscal year 1985, we calculated the rates of hospitalization for fracture of the hip, by state of residence, for all enrollees in Medicare who were sixty-five years old or older; we adjusted for age and race. The rate of fracture of the hip was highest in the South and lowest in the Northeast, especially in women. The cause of this difference is not known.

HIV-related malignancies.

Since the recognition of Kaposi's sarcoma as a manifestation of the acquired immunodeficiency syndrome, subsequent malignancies such as non-Hodgkin's B-cell lymphoma and primary central nervous system lymphoma have been found to be associated with individuals infected with the human immunodeficiency virus (HIV). The epidemiology, clinical manifestations, and current concepts of pathogenesis are reviewed in this article. In addition, the relation between HIV and other malignancies, including Hodgkin's lymphoma, T-cell lymphomas, and anorectal carcinoma, is discussed. In general, HIV-related malignancies are more aggressive, respond poorly to treatment, and are associated with an extremely high rate of mortality.

Psychophysiological and psychometric studies after manipulating the GABA system by vigabatrin, a GABA-transaminase inhibitor.

This study is concerned with the alterations in central and peripheral psychophysiological measures and psychometric variables after experimental manipulation of the most important inhibitory transmitter system of the CNS, the gamma-aminobutyric acid (GABA) system. Vigabatrin (GVG), a new enzyme-activated, irreversible inhibitor of GABA transaminase, which increases cerebrospinal fluid concentrations of GABA and other substrates of GABA transaminase, was given in single oral doses of 1 g, 2 g and 3 g to 10 normal healthy volunteers. In this double-blind, placebo-controlled crossover study, 3 mg lorazepam was given as reference compound. Blood sampling for vigabatrin kinetics, EEG recordings and evaluation of pulse, blood pressure and side effects were carried out at the hours 0, 1, 2, 4, 6, 8 and 24, and psychometric tests at the same times (except the first hour). Pharmacokinetic analyses demonstrated good absorption of GVG with peak plasma concentrations found within the first two hours, dose-dependent areas under the plasma concentration-time curves and about 65% recovery in the 24-h urine. Computer-assisted spectral analysis of the EEG suggested that GVG produces only small changes in the normal CNS, characterized by an augmentation of total power, absolute and relative power of the beta activity and acceleration of the centroid of the total activity. There was also a trend towards an increase of alpha activity and of the absolute and relative power of the dominant frequency, decrease in the alpha centroid and increase of the centroid of the combined delta and theta activity. Lorazepam 3 mg, in contrast, produced highly significant changes characterized by a decrease of total power, alpha activity, absolute and relative power of the dominant frequency and centroid of the combined delta and theta activity, while beta activity as well as the centroid of the alpha, beta and total activity increased. In the resting condition an additional augmentation of slow activity suggested hypnotic properties of 3 mg lorazepam. The latter changes are typical for anxiolytic sedatives and were also reflected at the behavioral level where psychometric data demonstrated a deterioration in the noo- and thymopsychic parameters and sedative effects in psychophysiological variables. GVG, on the other hand, produced only subtle changes characterized by an improvement of noo- and thymopsychic variables and vegetative activation.

Assessing civil competence in the elderly.

This study was designed to establish reliability of the Community Competence Scale-Revised (CCS-R) and provide evidence for its validity in making discriminations relevant to civil competence in the elderly. The CCS-R is an individually administered structured interview of 17 subscales. Criterion groups were formed by drawing a sample of research participants from a retirement complex with various levels of care and with nurses having extensive knowledge of the residents' level of functioning. The study demonstrated high reliability and found converging evidence for the effectiveness of the CCS-R in making discrimination about competence in the elderly. The study had added to the growing evidence that it is possible to standardize the assessment of civil competence, thereby making the adjudication process a more accurate one.

Micropollutants in urban stormwater: occurrence, concentrations, and atmospheric contributions for a wide range of contaminants in three French catchments.

This study aimed at: (a) providing information on the occurrence and concentration ranges in urban stormwater for a wide array of pollutants (n = 77); (b) assessing whether despite the differences between various catchments (land use, climatic conditions, etc.), the trends in terms of contamination level are similar; and (c) analyzing the contribution of total atmospheric fallout (TAF) with respect to sources endogenous to this contamination. The studied contaminants include conventional stormwater contaminants (polycyclic aromatic hydrocarbons (PAHs), Zn, Cu, Pb, etc.), in addition to poorly or undocumented pollutants such as nonylphenol and octylphenol ethoxylates (NPnEO and OPnEO), bisphenol A (BPA), polybrominated diphenyl ethers (PBDEs), a wide variety of pesticides, and various metals of relevance (As, Ti, Sr, V). Sampling and analysis were performed using homogeneous methods on three urban catchments with different land use patterns located in three distinct French towns. For many of these pollutants, the results do not allow highlighting a significant difference in stormwater quality at the scale of the three urban catchments considered. Significant differences were, however, observed for several metals (As, Cr, Cu, Ni, Sr and Zn), PAHs, and PBDEs, though this assessment would need to be confirmed by further experiments. The pollutant distributions between dissolved and particulate phases were found to be similar across the three experimental sites, thus suggesting no site dependence. Lastly, the contributions of TAF to stormwater contamination for micropollutants were quite low. This finding held true not only for PAHs, as previously demonstrated in the literature, but also for a broader range of molecules such as BPA, NPnEO, OPnEO, and PBDEs, whose high local production is correlated with the leaching of urban surfaces, buildings, and vehicles.

Encoding of a spectrally-complex communication sound in the bullfrog's auditory nerve.

1. A population study of eighth nerve responses in the bullfrog, Rana catesbeiana, was undertaken to analyze how the eighth nerve codes the complex spectral and temporal structure of the species-specific advertisement call over a biologically-realistic range of intensities. Synthetic advertisement calls were generated by Fourier synthesis and presented to individual eighth nerve fibers of anesthetized bullfrogs. Fiber responses were analyzed by calculating rate responses based on post-stimulus-time (PST) histograms and temporal responses based on Fourier transforms of period histograms. 2. At stimulus intensities of 70 and 80 dB SPL, normalized rate responses provide a fairly good representation of the complex spectral structure of the stimulus, particularly in the low- and mid-frequency range. At higher intensities, rate responses saturate, and very little of the spectral structure of the complex stimulus can be seen in the profile of rate responses of the population. 3. Both AP and BP fibers phase-lock strongly to the fundamental (100 Hz) of the complex stimulus. These effects are relatively resistant to changes in stimulus intensity. Only a small number of fibers synchronize to the low-frequency spectral energy in the stimulus. The underlying spectral complexity of the stimulus is not accurately reflected in the timing of fiber firing, presumably because firing is 'captured' by the fundamental frequency. 4. Plots of average localized synchronized rate (ALSR), which combine both spectral and temporal information, show a similar, low-pass shape at all stimulus intensities. ALSR plots do not generally provide an accurate representation of the structure of the advertisement call. 5. The data suggest that anuran peripheral auditory fibers may be particularly sensitive to the amplitude envelope of sounds.

Molluscum contagiosum in patients with human immunodeficiency virus infection. A review of twenty-seven patients.

BACKGROUND: Molluscum contagiosum (MC) is a common and at times severely disfiguring cutaneous viral infection in patients with human immunodeficiency virus (HIV) infection. OBJECTIVE: The purpose of this study was to describe the clinical course of MC in patients with HIV infection and to examine the relation between presentation of MC and the stage of HIV infection, as measured by T-cell subsets. METHODS: This is a retrospective case study of 27 patients with MC and HIV infection who had T-cell subset determination within 60 days of diagnosis of MC. RESULTS: The overall mean CD4+ count, CD4+ percentage, and CD4+/CD8+ ratio were 85.7/mm3, 5.9%, and 0.10, respectively. An inverse relation between CD4+ count and the number of MC lesions was observed (p = 0.0023). Fourteen patients (52%) had facial and neck lesions alone, and seven (26%) had lesions in areas associated with sexual transmission. Pneumocystis carinii pneumonia had occurred in 8 patients (31%) and Kaposi's sarcoma in 15 patients (56%). CONCLUSION: MC can occur as a late manifestation of HIV infection and is a cutaneous correlate of cellular immune deficiency.

Auditory nerve representation of a complex communication sound in background noise.

A population study of auditory nerve responses in the bullfrog, Rana catesbeiana, analyzed the relative contributions of spectral and temporal coding in representing a complex, species-specific communication signal at different stimulus intensities and in the presence of background noise. At stimulus levels of 70 and 80 dB SPL, levels which approximate that received during communication in the natural environment, average rate profiles plotted over fiber characteristic frequency do not reflect the detailed spectral fine structure of the synthetic call. Rate profiles do not change significantly in the presence of background noise. In ambient (no noise) and low noise conditions, both amphibian papilla and basilar papilla fibers phase lock strongly to the waveform periodicity (fundamental frequency) of the synthetic advertisement call. The higher harmonic spectral fine structure of the synthetic call is not accurately reflected in the timing of fiber firing, because firing is "captured" by the fundamental frequency. Only a small number of fibers synchronize preferentially to any harmonic in the call other than the first, and none synchronize to any higher than the third, even when fiber characteristic frequency is close to one of these higher harmonics. Background noise affects fiber temporal responses in two ways: It can reduce synchronization to the fundamental frequency, until fiber responses are masked; or it can shift synchronization from the fundamental to the second or third harmonic of the call. This second effect results in a preservation of temporal coding at high noise levels. These data suggest that bullfrog eighth nerve fibers extract the waveform periodicity of multiple-harmonic stimuli primarily by a temporal code.