Health management program: factors influencing completion of therapy with high-dose interferon alfa-2b for high-risk melanoma.

The goal of the 1-year observational, multicentre, open-label study reported here was to identify factors influencing adherence to high-dose interferon alfa-2b adjuvant therapy in patients at high risk of recurrence following surgical excision of malignant melanoma. The study was carried out in 23 tertiary-care centres across Canada.The 225 patients enrolled in the study all had malignant melanoma that was surgically excised and that required adjuvant treatment with interferon alfa-2b. Of these patients, 64% were men. Mean age was 51.7 years. All patients received interferon alfa-2b treatment during a 4-week induction phase (20 MU/m(2) intravenously 5 days per week) followed by a 48-week maintenance phase (10 MU/m(2) subcutaneously 3 days per week).Oncology nurses reviewed side-effect management with the patients before the induction and maintenance phases. Patients were provided with daily diaries, comprehensive educational materials, and ongoing nursing support. Data on side effects and discontinuations were obtained from patient interviews and diaries. THE MAIN OUTCOME MEASUREMENTS WERE RELATED TO TREATMENT DISCONTINUATION: rate, timing, reason, and prevention. Of the 225 patients, 75 (33.3%) discontinued interferon during the induction phase, and 58 (25.8%) discontinued during the maintenance phase. The main reasons for discontinuation were adverse events (58%) and disease progression (26%). Patients with a daily fluid intake greater than 1.5 L were more likely to complete therapy than were those with an intake less than 1.5 L (64% vs. 36%, p < 0.0001).Of 225 patients enrolled in the interferon alfa-2b health management program, 41% completed the 1-year treatment course. Higher fluid intake (>1.5 L daily) was associated with increased adherence to therapy.

Field-dependent diamagnetic transition in magnetic superconductor Sm1.85Ce0.15CuO4-y.

The magnetic penetration depth of single crystal Sm(1.85)Ce(0.15)CuO(4-y) was measured down to 0.4 K in dc fields up to 7 kOe. For insulating Sm2CuO4, Sm3+ spins order at the Ne el temperature, T(N)=6 K, independent of the applied field. Superconducting Sm(1.85)Ce(0.15)CuO(4-y) (T(c) approximately 23 K) shows a sharp increase in diamagnetic screening below T(*)(H) which varied from 4.0 K (H=0) to 0.5 K (H=7 kOe) for a field along the c axis. If the field was aligned parallel to the conducting planes, T(*) remained unchanged. The unusual field dependence of T(*) indicates a spin-freezing transition that dramatically increases the superfluid density.

Genetic relatedness of antibiotic-resistant pneumococci isolated during case clusters.

Multilocus sequence typing of Streptococcus pneumoniae associated with two case clusters of disease is reported here for the first time. Isolates from the first cluster were serotype 19F, resistant to penicillin and erythromycin, and were characterized as ST 320. Isolates from the second cluster were serogroup 4, resistant to ciprofloxacin, and were characterized as ST 206. Therefore, the isolates from these clusters were antibiotic-resistant, of serotypes infrequently isolated, and of uncommon sequence types.

Nodal order parameter in electron-doped Pr(2-x)CexCuO(4-delta) superconducting films.

The London penetration depth, lambda(ab)(T), is reported for thin films of the electron-doped superconductor Pr(2-x)Ce(x)CuO(4-delta) with varying Ce concentration, x=0.13, 0.15, and 0.17. Measurements down to 0.35 K were carried out using a tunnel-diode oscillator with excitation fields applied both perpendicular and parallel to the conducting planes. Films at all three doping levels exhibited power law behavior indicative of d-wave pairing with impurity scattering. These results are fully consistent with previous measurements on single crystals.

Evidence for two superconducting gaps in MgB2.

We have measured the Raman spectra of polycrystalline MgB2 from 25 to 1200 cm(-1). A superconductivity-induced redistribution in the electronic Raman continuum was observed. Two pair-breaking peaks appear in the spectra, suggesting the presence of two superconducting gaps. The measured spectra were analyzed using a quasi-two-dimensional model in which two s-wave superconducting gaps open on two sheets of Fermi surface. For the gap values we have obtained Delta(1) = 22 cm(-1) ( 2.7 meV) and Delta(2) = 50 cm(-1) ( 6.2 meV). Our results suggest that a conventional phonon-mediated pairing mechanism occurs in the planar boron sigma bands and is responsible for the superconductivity of MgB2.

Thrombolytic therapy: impact on coronary care in a district general hospital.

The introduction of routine thrombolytic therapy in the Cardiac Care Unit (CCU) of a District General Hospital has resulted in an increased demand for admission particularly in the 70+ age group. Complications and side effects of such treatment have been similar to those reported in several large multicentre trials. The percentage of patients with myocardial infarction receiving thrombolysis has increased to 60% with the commonest reason for withholding of such treatment being the lack of ECG changes. Mortality rates have fallen and there has been an increased referral rate for urgent angiography. To maximise benefit CCU's should encourage early direct admission and ensure that, if not present on site, facilities for angiography can easily be arranged.

Construction, expression, and biologic activity of murine/human chimeric antibodies with specificity for the human alpha/beta T cell receptor.

Murine/human chimeric antibodies with specificity for the human TCR-alpha/beta have been produced by genetic engineering. The L and H chain V region exons encoding the murine mAb BMA 031 were isolated and inserted into mammalian expression vectors containing the human kappa and gamma 1 or gamma 4 C region exons. The chimeric genes were transfected into murine Sp2/O hybridoma cells by electroporation and transfectomas secreting chimeric antibody were isolated. Secretion levels ranged from 1 to 7 pg/cell/24 h. The chimeric antibodies bound specifically to T cells and competed effectively with the parental murine mAb for binding to these sites. The ability to promote antibody-dependent cell-mediated cytolysis was significantly enhanced in the chimeric antibodies as compared with murine BMA 031. C-dependent cytolysis, however, was not detectable with any of the antibodies. Chimeric BMA 031 is a clinically relevant, genetically engineered antibody with potential uses in transplantation, graft-vs-host disease, autoimmune diseases and other T cell-related disorders.

Construction, expression and characterization of a murine/human chimeric antibody with specificity for hepatitis B surface antigen.

A murine/human chimeric antibody with specificity for Hepatitis B surface antigen has been produced by genetic engineering. The light and heavy chain variable region exons encoding the murine monoclonal antibody 2H1 were isolated and inserted into mammalian expression vectors containing the human kappa and gamma 1 constant region exons. The chimeric genes were transfected into murine Sp2/0 hybridoma cells by electroporation and transfectomas secreting chimeric antibody were isolated. Secretion levels ranged from 1-7 pg/cell/24 hr. The chimeric antibody bound specifically to Hepatitis B surface antigen and competed effectively with the parental murine monoclonal antibody for binding to these sites. Chimeric 2H1 is the first clinically relevant, genetically engineered anti-viral antibody and may represent an improved agent for the prevention of hepatitis B virus transmission.

Parallel supercomputing today and the cedar approach.

More and more scientists and engineers are becoming interested in using supercomputers. Earlier barriers to using these machines are disappearing as software for their use improves. Meanwhile, new parallel supercomputer architectures are emerging that may provide rapid growth in performance. These systems may use a large number of processors with an intricate memory system that is both parallel and hierarchical; they will require even more advanced software. Compilers that restructure user programs to exploit the machine organization seem to be essential. A wide range of algorithms and applications is being developed in an effort to provide high parallel processing performance in many fields. The Cedar supercomputer, presently operating with eight processors in parallel, uses advanced system and applications software developed at the University of Illinois during the past 12 years. This software should allow the number of processors in Cedar to be doubled annually, providing rapid performance advances in the next decade.

Evaluation of serum gentamicin assay procedures for a clinical microbiology laboratory.

Four methods for the measurement of serum gentamicin concentration were evaluated with respect to cost-effectiveness, accuracy, and precision. Gentamicin concentration was determined in 112 clinical samples by the Staphlococcus epidermidis agar diffusion bioassay procedure in routine service in our laboratory at the time this study was initiated. Appropriate portions of these clinical samples were frozen and later thawed for remeasurement of gentamicin by bioassay or for measurement of gentamicin in one of three other systems. These included the Enzymatic Radiochemical Assay, the Diagnostic Products Corporation Radioimmunoassay and the New England Nuclear Corporation Radioimmunoassay. In addition, gentamicin dissolved in horse serum at 2, 4, 6, 8, 10, and 12 micrograms/ml was aliquoted, frozen, and later thawed for assay in each of the above systems. The data were analyzed for evidence of constant and proportional bias as well as for accuracy and precision.

Microbiology subsystem of a total, dedicated laboratory computer system.

The computer system used by the Microbiology Service of the Clinical Pathology Department, Clinical Center, National Institutes of Health is discussed. This microbiology subsystem is a part of a dedicated on-line laboratory computer system used by the entire department. The laboratory computer is connected on-line to a hospital computer which provides patient admission, transfer, and discharge data. Mark sense worksheets and cathode ray tube terminals are used for result entry and correction. Cumulative patient reports are printed. Results for both active and completed accessions can be easily retrieved on cathode ray terminals in the laboratory. All laboratory data are archived on magnetic tape from which a research data base and microfiched laboratory records are generated. The manner in which the system is integrated in the routine operation of the microbiology laboratory is emphasized. In addition, some of the costs, benefits, liabilities, and pitfalls associated with the introduction of the computer in the laboratory are reviewed. Finally, we have presented our concept of some of the future enhancements to our present system and some of the directions in which any future microbiology system might develop.