Phase I trial of inhaled natural interleukin 2 for treatment of pulmonary malignancy: toxicity, pharmacokinetics, and biological effects

Safety, local and systemic immunomodulation, and tumor response to treatment with aerosolized natural interleukin 2 (nIL-2) applied five times a day were studied in a Phase I trial in 16 patients with pulmonary malignancies refractory to conventional therapy. The toxicity of inhaled nIL-2 was different from that observed after systemic administration. Reversible airway irritation causing a nonproductive cough represented the dose-limiting toxicity. Mild to moderate reduction of the vital capacity and forced expiratory volume (FEV1) with minor effects on relative FEV1, peak expiratory flow, airway resistance, and PaO2 was experienced by individual patients. In 14 patients suffering from pulmonary metastases due to renal cell cancer, one durable complete response, one partial response, and one mixed response were observed. Inhalation of nIL-2 aerosol resulted in a dose-dependent expansion of pulmonary immunocompetent cells in bronchoalveolar lavage fluid. Posttreatment bronchoalveolar lavage showed an activated lymphocyte phenotype with increased HLA-DR expression. The only systemic biological effect detectable in peripheral blood was a marked increase of soluble interleukin 2 receptor serum levels. We conclude that treatment with aerosolized nIL-2 is an effective means for site-specific immunomodulation and deserves further investigation for the treatment of malignant and inflammatory lung disease.     

Multipulse operation of a high average power, good beam qualityzig-zag dye laser

A laser pumped zig-zag dye laser operating at 568 nm with a pulse length ~2 μs has been sealed to high power using a MOPA configuration. Pulse energies in excess of 7 J with beam quality <2 XDL have been achieved under repetitively pulsed, 10 Hz operation. RMS jitter was measured as 0.12 of a 1 XDL spot. The device has operated with over 70 W output for runs up to 5 s. Substantially longer run times and output powers are possible. This device represents an advance in dye laser capabilities. Improvement in pointing accuracy of better than an order of magnitude have been demonstrated. In addition, an improvement in beam quality by about an order of magnitude has been achieved compared to other dye lasers operating in this power range     

Accurate determination of magnetic field gradients from four pointvector measurements. I. Use of natural constraints on vector dataobtained from a single spinning spacecraft

Cluster introduces a new generation of spacecraft that will measure the spatial gradients of the magnetic field in the Earth's magnetosphere. As gradients require knowledge of differences, small errors resulting from an inadequate knowledge of the orientations, zero levels and the scale factors of the magnetometer sensors affect the calculation of field gradients disproportionately and must be removed with high accuracy. We show that twelve calibration parameters are required for each of the spacecraft (for a total of 48 for the four spacecraft) to correctly infer the measured magnetic fields at each of the spacecraft. By application of a Fourier transform technique, some of the parameters can be recovered. We show that errors in eight of the twelve calibration parameters generate coherent monochromatic signals at the first and the second harmonics of the spin frequency in the despun data. We relate the real and the imaginary parts of the monochromatic signals to the eight calibration parameters. We then present a least squares scheme that improves the eight calibration parameters by iteration until the power of the coherent signal superimposed above the broad-band background is minimized     

The Effect of Organic Ligands on the Rate of Loss of Phenylmercuric Nitrate into Rubber Closures and Plastic Containers

The effect of the presence of various organic compounds containing a variety of functional groups on the rate of loss of phenylmericuric (PM) nitrate into plastic containers and rubber closures has been investigated. The presence of organic compounds profoundly influenced the loss of the phenylmercuric nitrate, that loss being dependent upon their chemical structure and concentration. This effect explains the unpredictability of the loss of PM nitrate into polymer matrices from pharmaceutical products.     

Cutoff frequencies and noise power law model of spectral density:adaptation of the multivariance method for irregularly spaced timingdata using the lowest-mode estimator approach

The concept of structure functions, which is an extension of the variance approach, is useful to determine the variance (the structure function) which is optimized for a type of noise and for an order of drift. The multivariance method was developed to use different variances over the same signal. It is then possible to select a set of variances in which each variance is optimized to the determination of one parameter (of one noise level, drift, or cutoff frequency). Recently, we adapted this method to irregularly spaced timing data. In this connection, we replaced the structure functions by another method of spectral density estimation: the lowest-mode estimator, introduced by J.E. Deeter and P.E. Boynton (1982, 1984) for the analysis of pulsar timing data. Different lowest-mode estimators can be constructed according to two priorities: the order of drifts that must be removed and the type of noise for which the sensitivity must be maximum. Thus, a multivariance system is developed using a set of different estimators. The details of this method are described, and the results for different signals are discussed in this paper