Enhanced transdermal delivery of sex hormones in swine with a novel topical aerosol

This study investigated the enhanced transdermal delivery of testosterone (Tes) and estradiol (E2) in swine in vivo with novel metered-dose topical aerosols containing the penetration enhancer padimate O (PadO) and predicted the dose deliverable in humans from the calculated drug flux across the skin. Weanling swine were catheterized and castrated under general anaesthesia and used as a conscious hypogonadal model. Tes and E2 (with and without PadO) were applied once, and venous blood samples were taken over 24 h. Tes and E2 plasma levels were determined by radioimmunoassay. After daily topical dosing of Tes for 6 days, the plasma Tes levels were determined and the transdermal flux was calculated by correcting the pseudo steady-state plasma concentration versus time profile with the clearance of an iv dose within the same swine. After a single application of the E2 aerosol over 30 cm2, or the Tes aerosol over 180 cm2, the mean AUC0-24 h when PadO was included in the spray was 14.1- and 2.0-fold greater than control, respectively (p < 0.03). After the sixth application of the Tes spray with PadO, the mean flux (+/-SE, n = 4) across swine skin in vivo was 2.12 +/- 0.35 microg/cm2.h, which gave a predicted flux in humans of 0.95 microg/cm2.h. From these data the expected plasma levels of Tes in hypogonadal men would compare well with the normal diurnal Tes profile in healthy men. These novel topical aerosols are capable of enhanced transdermal delivery of sex hormones in vivo, and they have the potential to deliver clinically relevant doses to humans.     

Analysis of nickel refinery dusts

After characterization of bulk samples by inductively coupled plasma emission spectroscopic (ICP-ES) quantitative analysis and X-ray powder diffraction studies, single particle techniques using quantitative image analysis, scanning electron microscopy--energy dispersive analysis by X-ray, and finally laser beam ionization mass spectrometry analysis (LIMA) for surface analysis have been applied to historical nickel refinery dust samples from the nickel refining plant at Clydach in Wales. There were two historical samples of processed material from 1920 and 1929. These samples had a remarkably small particle size range, mean 3 microns and range, 0.75-24 microns. The most significant difference in elemental composition was the presence of 10% arsenic in the 1920 sample compared with 1% in the 1929 sample. The X-ray spectra revealed the presence of NiO in both. However, surprisingly, CuO was identified only in the 1929 sample. Of particular interest was the presence of a component, in the 1920 sample only, identified as the mineral orcelite, a copper-iron-nickel-arsenide-sulphide mineral, predominantly, Ni5-XAs2. Using the LIMA technique, it was found that in both samples, arsenic and arsenic derivative peaks are prominent, indicating the surface availability of arsenic compounds.     

Meningitis after combined spinal-extradural anaesthesia in obstetrics

We report two cases of meningitis which developed after combined spinal-extradural procedures for obstetric analgesia. The first case was thought to be caused by aseptic or chemical meningitis and the second was a case of bacterial meningitis in a patient who also received an extradural blood patch. It is important that meningitis is considered as a differential diagnosis in patients who present with headache after spinal anaesthesia and that antibiotic therapy is selected to cover unusual organisms.     

Differential regulation of vitamin D receptors in clonal populations of a chronic myelogenous leukemia cell line

BACKGROUND: Both crystalloid and blood cardioplegia result in cardiac dysfunction associated with myocardial edema. This edema is partially due to the lack of myocardial contraction during cardioplegia, which stops myocardial lymph flow. As an alternative, acceptable surgical conditions have been created in patients undergoing coronary artery bypass operations with esmolol-induced minimal myocardial contraction. We hypothesized that minimal myocardial contraction during circulatory support using either standard cardiopulmonary bypass (CPB) or a biventricular assist device would prevent myocardial edema by maintaining cardiac lymphatic function and thus prevent cardiac dysfunction. METHODS: We placed 6 dogs on CPB and 6 dogs on a biventricular assist device and serially measured myocardial lymph flow rate and myocardial water content in both groups and preload recruitable stroke work only in the CPB dogs. In all dogs we minimized heart rate with esmolol for 1 hour during total circulatory support. RESULTS: Although myocardial lymph flow remained at baseline level during CPB and increased during biventricular assistance, myocardial water accumulation still occurred during circulatory support. However, as edema resolved rapidly after separation from circulatory support, myocardial water content was only slightly increased after CPB and biventricular assistance, and preload recruitable stroke work was normal. CONCLUSIONS: Our data suggest that minimal myocardial contraction during both CPB and biventricular assistance supports myocardial lymphatic function, resulting in minimal myocardial edema formation associated with normal left ventricular performance after circulatory support. The concept of minimal myocardial contraction may be a useful alternative for myocardial protection, especially in high-risk patients with compromised left ventricular function.     

Effects of sleep on wake-induced c-fos expression

We investigated the effects of sleep on wake-induced c-fos expression in the cerebral cortex of rats and c-fos-lacZ transgenic mice. In the cortex of rats, the levels of c-Fos, detected both by immunocytochemistry and Western blot, remained high during 6 or 12 hr of enforced wakefulness but declined rapidly (within 1 hr) with increasing time of recovery sleep. Similarly, in the transgenic mice in which lacZ expression is driven from the c-fos promoter, beta-galactosidase activity was high after enforced wakefulness and declined with increasing amounts of sleep. These results suggest that the decrease in c-Fos protein in cortical neurons during sleep may be attributable to cessation of c-fos expression, activation of a process that degrades the wake-induced c-Fos, or both.     

ESD laboratory simulations and signature analysis of a CMOS programmable logic product

It is well established in the semiconductor I/C industry that the proportion of customer field returns attributed to damage resulting from electrical over-stress (EOS) and electro-static discharge (ESD) can amount to 40% to 50% (Cook C, Daniel S. Characteristics and failure analysis of advanced CMOS submicron ESD protection structures. EOS/ESD symposium proceedings ?14, Dallas, TX, 1992. p. 147; Denson WK, Green TJ. A review of EOS/ESD field failures in military equipment. EOS/ESO symposium proceedings-10, 1988. p. 7. Straub RJ. Automotive Electronics IC Reliability. CICC Proceedings, 1990; Euzent BL, Maloney TJ, Donner II R. Reducing field failure rate within proven EOS/ESO design. EOS/ESO Symposium Proceedings ?13, Los Vegas, NV, 1991. p. 59). ESD events are the subset of EOS events caused by high voltages that are associated with electrostatic charge. Although additional hard and soft failures can occur in the factory, these are normally screened by effective test programs. It is therefore necessary to determine the probable cause of failure before cost effective corrective action can be initiated.Distinguishing between EOS and ESD failures and differentiating the subtle differences between damage due to the several distinct ESD models continues to challenge failure analysis capabilities as dimensions shrink and critical defect sizes are reduced. Many of the damage sites are not visible with optical microscopy. De-processing together with very high magnification examination using the scanning electron microscope (SEM) is most often necessary. However, the use of test model simulators to replicate the ESD events can most often replicate a failure signature, i.e. a unique die location and morphology associated with the specific model (Morgan IH. ESO Failure Analysis Signatures. Proceedings of the 3rd ESO Forum, Grain, Germany, 1993. p. 275).This paper summarizes the evaluation performed on a standard programmable logic complimentary metal-oxide silican (CMOS) product to ascertain the ESD immunity. The study entailed ESD simulation using a variety of ESD models, conducting detailed physical failure analysis and then comparing the results with documented analyses performed on customer field returns and factory failures. As a result of the differences in current stress magnitude and over-stress time domain, the location, type and severity of damage at the failure site is known to show considerable variation (Morgan IH. A Handbook of ESO models. AMD Internal Publication, 1992 (available from AMD literature department upon request)). The purpose of the study was to develop a catalogue of failure signatures, and to determine to what extent this catalogue could be used to relate a signature to electrical failure for a particular die and pin function.     

Active RF filter for high voltage transmission lines

A new technique is described for a general active radio frequency (RF) filter trap that can be used to suppress noise or interference on high-voltage (HV) transmission line carrier signals. The techinque exploits the Miller effect of an RF amplifier in conjunction with a special sensing circuit and is potentially far more economical to implement than conventional techniques that use passive HV filter components     

Nonnecessary conditions or useful procedures in desensitization: A reply to Wilkins.

Discusses W. Wilkins's (see record 1972-06967-001) claim that the 3 procedures defining M. Wolpe's systematic desensitization-muscle relaxation, a graded hierarchy of fear-relevant scenes, and imagination of these scenes concommitant to muscle relaxation-are unnecessary. It is proposed that these claims follow from a somewhat prejudiced review of largely analog studies and may be misleading to the practicing behavior therapist. It is suggested that (a) explanations of the success of densitization in terms of cognitive and social variables have no more support or utility than Wolpe's original theoretical formulations and (b) it is premature to discard the defining procedures of desensitization as unnecessary when they are quite useful and perhaps necessary for success in treating highly fearful patients. (17 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Flammability of polystyrene layered silicate (clay) nanocomposites: Carbonaceous char formation

Polymer layered‐silicate (clay) nanocomposites have not only the unique advantage of reduced flammability, but also improved mechanical properties. This is a key advantage over many flame retardants, which reduce flammability but also reduce the mechanical properties of the polymer. In our efforts to further understand the mechanism of flame retardancy with polymer‐clay nanocomposites, we investigated the effect of the clay, the loading level and polymer melt viscosity on the flammability of polystyrene‐clay nanocomposites. The nanoscale dispersion of the clay in the polymer was analysed by wide‐angle X‐ray diffraction (XRD) and transmission electron microscopy (TEM). Cone calorimetry and gasification studies were used to evaluate the flammability of these nanocomposites. There were major reductions in peak heat release rates (HRRs), and increased carbonaceous char formation, for these nanocomposites. It was determined that while the viscosity of the PS nanocomposite played a role in lowering the peak HRR, the clay loading level had the largest effect on peak HRR. Finally, it was found that clay catalysed carbonaceous char formation, and the reinforcement of the char by the clay was responsible for the lowered flammability of these nanocomposites. Published in 2002 by John Wiley & Sons, Ltd.     

The role of radiation damage on the current-voltage characteristics of p-n junctions

The effects of radiation damage on the current-voltage characteristics of silicon p-n diodes are studied. Radiation damage is introduced by the implantation of carbon ions into the depletion region of the device. The physical properties of the damage centres are examined by means of thermally stimulated current (T. S. C.) measurements, and by the measurement of the temperature dependence of the reverse leakage. The results at low implantation doses are explained by means of a single level Shockley-Read-Hall model, while at higher doses charge compensation effects are introduced. Capacitance-voltage measurements are used as a means of verifying these conclusions, and further useful data is obtained from the results of low temperature annealing experiments.