Mechanism of suppression of cell-mediated immunity by measles virus

The mechanisms underlying the profound suppression of cell-mediated immunity (CMI) accompanying measles are unclear. Interleukin-12 (IL-12), derived principally from monocytes and macrophages, is critical for the generation of CMI. Measles virus (MV) infection of primary human monocytes specifically down-regulated IL-12 production. Cross-linking of CD46, a complement regulatory protein that is the cellular receptor for MV, with antibody or with the complement activation product C3b similarly inhibited monocyte IL-12 production, providing a plausible mechanism for MV-induced immunosuppression. CD46 provides a regulatory link between the complement system and cellular immune responses.     

Encircling overlapping multipulse shock waveforms for transthoracic defibrillation

OBJECTIVES: This study was performed to determine the efficacy of new encircling overlapping multipulse, multipathway waveforms for transthoracic defibrillation. BACKGROUND: Alternative waveforms for transthoracic defibrillation may improve shock success. METHODS: First, we determined the shock success achieved by three different waveforms at varying energies (18-150 J) in 21 mongrel dogs after short-duration ventricular fibrillation. The waveforms tested included the traditional damped sinusoidal waveform, a single pathway biphasic waveform, and a new encircling overlapping multipulse waveform delivered from six electrode pads oriented circumferentially. Second, in 11 swine we compared the efficacy of encircling overlapping multipulse shocks given from six electrode pads and three capacitors versus encircling overlapping shocks given from a device utilizing three electrodes and one capacitor. RESULTS: In the first experiment, the encircling overlapping waveform performed significantly better than biphasic and damped sinusoidal waveforms at lower energies. The shock success rate of the overlapping waveform (six pads) ranged from 67+/-4% (at 18-49 J energy) to 99+/-3% at > or = 150 J; at comparable energies biphasic waveform shock success ranged from 26+/-5% (p < 0.01 vs. encircling overlapping waveforms) to 99+/-5% (p = NS). Damped sinusoidal waveform shock success ranged from 4+/-1% (p < 0.01 vs. encircling overlapping waveform) to 73+/-9% (p = NS). In the second experiment the three electrode pads, one capacitor encircling waveform achieved shock success rates comparable with the six-pad, three-capacitor waveform; at 18-49 J, success rates were 45+/-15% versus 57+/-12%, respectively (p = NS). At 100 J, success rates for both were 100%. CONCLUSIONS: We conclude that encircling overlapping multipulse multipathway waveforms facilitate transthoracic defibrillation at low energies. These waveforms can be generated from a device that requires only three electrodes and one capacitor.     

Impact of chronic cough on quality of life

STUDY DESIGN: The biomechanical influence of in situ setting hydroxyapatite cement was examined for use in pedicle screw revision surgery. Pull-out testing of control and pedicle screws augmented with hydroxyapatite cement was performed in human cadaver vertebrae. OBJECTIVES: To determine the immediate effect of using hydroxyapatite cement to augment revision pedicle screws after failure of the primary pedicle screw fixation. SUMMARY OF BACKGROUND DATA: The potential problems associated with using polymethylmethacrylate to augment revision pedicular instrumentation have prompted the search for other solutions. The introduction of resorbable hydroxyapatite pastes may have provided new biocompatible solutions for pedicle screw revision. METHODS: Ten human cadaver vertebrae were instrumented with 6.0-mm pedicle screws in each pedicle. The screws were loaded to failure in axial tension (pull-out). The failed pedicles then were instrumented with 7.0-mm pedicle screws, either augmented with hydroxyapatite cement or nonaugmented, which also were loaded to failure. Finally, the nonaugmented 7.0-mm screw hole was reinstrumented with a hydroxyapatite cement-augmented, 7.0-mm pedicle screw and loaded to failure. RESULTS: The pull-out strength of the 7.0-mm, hydroxyapatite cement-augmented screws was 325% (P = 2.9 x 10(-5)) of that of the 6.0-mm control screws, whereas the strength of the 7.0-mm nonaugmented screws was only 73% (P = 2.0 x 10(-2)) of that of the 6.0-mm control screws. The 7.0-mm screws augmented with hydroxyapatite cement also were able to salvage 7.0-mm pull-out sites to 384% (P = 6.9E-5) of the pull-out strength of the 7.0-mm nonaugmented screws. CONCLUSIONS: Hydroxyapatite cement may be a mechanically viable alternative to polymethyl methacrylate for augmenting revision pedicular instrumentation and should be considered for future experimental, animal, and clinical testing.     

Identification of potent inhibitors of Plasmodium falciparum plasmepsin II from an encoded statine combinatorial library

An encoded 13,020-member combinatorial library was synthesized containing a statine core. Evaluation of this library with plasmepsin II, an aspartyl protease required for hemoglobin metabolism in the malaria parasite, led to the identification of potent and selective inhibitors as well as novel structure-activity relationships.     

Fetal heart rate patterns preceding death in utero

Four cases of intrauterine fetal demise in term infants are presented. From these cases and other published reports, a sequence of fetal heart rate changes preceding intrapartum death is presented. Late or variable decelerations, if unrelieved or uncorrected, lead to baseline heart rate changes of tachycardia and loss of variability reflecting loss of fetal reserve and fetal distress. This is followed by an unstable heart rate, a sinusoidal pattern, or a rapidly changing fetal heart rate. The final event is a profound bradycardia just prior to fetal demise.     

Effects of hypertension on the static mechanical properties and chemical composition of the rat aorta

The contributions of the relative radius, relative wall thickness, incremental strain, incremental elastic modulus, and medial scleroprotein content to the static elastic properties of the rat aortic wall have been examined in three groups of rats. Controls, rats made hypertensive at four weeks of age, and rats whose blood pressure was lowered after 6 weeks hypertension, were studied. The results show evidence of adaptive changes in the aorta of hypertensive animals, and that irreversible alterations in the mechanical properties of the wall may be induced by a brief period of hypertension. A direct relationship between aortic medial scleroprotein content and the elastic properties of the wall is demonstrated.     

Beta-mercaptolactate cysteine disulphiduria in a mentally retarded Scottish male

Antenatal diagnosis of hereditary disease is highly dependent on sufficient theoretical knowledge and on a number of practical methods of studying the foetus such as obtaining, cultivating and assaying amniotic fluid cells. Knowledge of the primary defect in any monogenic disorder cannon be used in prenatal diagnosis unless the metabolic error is expressed in vitro. Modern cytogenetics can diagnose in utero a large majority of karyotyping abnormalities although the karyotype-phenotype correlation is not an absolute one. This task must be assigned to special laboratories where technical pitfalls are reliably avoided. In both metabolic and chromosomal hereditary disease, the pathologist can confirm and extend the phenotypic findings and improve knowledge on foetal features and physiopathology. Pathology is the more important, the less means of in utero diagnosis are available as in the non-chromosomal syndromes of localized or multiple malformations. Here it helps eliminating a present major drawback of prenatal diagnosis: the lack of a strict diagnosis in the previous patient in a family at risk.