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.     

The greenhouse effect; Impact upon and the role to be played by construction

The authors highlight several possible ways in which the construction industry could lower present emissions of the greenhouse gas, carbon dioxide. It is an excellent discussion document and is recommended reading.     

Influence of joint detail on the flexural/torsional interaction of thin-walled structures

For a structure formed from two thin-walled open members connected at 90°, torsion applied to one member can result in torsion as well as flexure in the second member, with the magnitude and direction of this torsion as well as flexure in the second member being determined by the type of joint used. Conventional structural analysis would normally assume the presence of only flexure in the second member. The results from a finite element study of structures formed from thin-walled channel sections connected by box, mitre and stiffened mitre joints is presented and an explanation for the behaviour of the different joint types is given. It is shown that for the box joint the warping deformation of the loaded member is the dominant factor in determining the magnitude and direction of the twisting of the second member, whilst this is determined for the stiffened mitre joint primarily by the St Venant rotation deformation of the loaded member. For the unstiffened joint it is shown that the warping and St Venant rotation deformation effects tend to cancel each other out.     

THE FRACTURE MECHANISM OF 475°C EMBRITTLEMENT IN A DUPLEX STAINLESS STEEL

The mechanism of “475°C embrittlement” of a duplex stainless steel was investigated using finite element modelling of the stress distribution at brittle fracture initiation. Brittle fracture initiated at a critical shear stress, which increased with ferrite hardness. The fracture stress was affected by the duplex microstructure. Fracture was nucleated by deformation twins, which were identified using electron back-scatter diffraction. The ductile-to-brittle fracture transition was sensitive to age-hardening and could be described simply by the effect of age-hardening and test temperature on the yield stress.     

Electrical characterization of very-narrow-gap bulk HgCdTe single crystals by variable magnetic field hall measurements

Variable-magnetic-field Hall measurements (0 to 1.5 T) are performed on very-narrow-gap bulk-grown Hg_1−xCd_xTe single crystals (0.165 ≤ x ≤ 0.2) at various temperatures (10 to 300K). The electron densities and mobilities are obtained within the one-carrier (electrons) approximation of the reduced-con-ductivity-tensor scheme. The present data together with the selected data set reported by other workers exhibit a pronounced peak when the electron mobility is plotted against the alloy composition x-value which has been predicted to be due to the effective-mass minimum at the bandgap-crossing (E_g ≈ 0). The observed position (x ≈ 0.165), height (≈4 x 10² m²Vs), and width (≈0.01 in x) of the mobility-peak can be explained by a simple simulation involving only ionized-impurity scattering. A lower bound of the effective mass is introduced as a fitting parameter to be consistent with the finiteness of the observed electron mobility and is found to be of the order of 10⁻⁴ of the mass of a free electron.     

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.