Biomedical subjects
L D Marks
Publications and source records attributed to L D Marks.
Developments in the dynamical theory of high energy electron reflection.
High energy electron reflection (HEER) is an important technique in surface science and uses the information carried by high energy electrons reflected from surfaces to study surface structures and surface electronic states. With the development of reflection high energy electron diffraction (RHEED), high energy electron microscopy (REM), and high energy electron energy loss spectroscopy (EEL) in surface science, the usefulness of HEER has been widely recognized and demonstrated. However, a stationary dynamical solution for an arbitrary surface for HEER has not been obtained yet. In this paper, some developments in understanding the dynamical theory of HEER, particularly in recent years, are reviewed: 1. The introduction of the concept of current flow for a semi-infinite crystal model has removed the confusion around the wave points in the "band gap." 2. The consistency between the Bloch wave and multislice in the Bragg case has verified the validity of the argument of current flow and led to the emergence of the BMCR method (Bloch wave + Multislice Combined for Reflection). 3. The failure of the Bloch Wave-Only solution (the BWO solution) on Au (110) surfaces in the Bragg case revealed by the BMCR method implies that previous BWO calculations in the Bragg case might be at fault. 4. The 2-D dependence of the electron wave fields and Picard iteration-like character of multislice calculation in the Bragg case has led to the emergence of an Edge Patching method in Multislice-mode-Only (the EPMO method). The new method yields an infinitely convergent stationary dynamical solution for an arbitrary surface.
Phase II trial of esorubicin (4'deoxydoxorubicin, DxDx) in patients with small cell lung cancer.
Esorubicin (4'-deoxydoxorubicin or DxDx) is an analog of doxorubicin with preclinical antitumor activity and no significant cardiotoxicity in model systems. Eleven patients with small cell lung cancer who had previously received chemotherapy were given esorubicin (25 mg/m2 intravenously) every 3 weeks. No major objective responses were observed (95% confidence limits: 0-25%). Nine of the 11 patients had grade 2 or greater toxicity, with 55% of the patients experiencing grade 3 or greater toxicity [myelosuppression (4/11), anemia (2/11) or elevated liver enzymes (3/11)]. Nausea, vomiting, alopecia and intravenous site phlebitis were also seen. Three of the 11 patients received 3 or more course of esorubicin without evidence of significant cardiotoxicity. At this dose and schedule, no significant antitumor response were seen in this population of patients. Esorubicin, with this low response rate and significant toxicity, appears to be of limited utility in this disease.
Phase II trial of amonafide in patients with stage III and IV non-small-cell lung cancer.
Amonafide (benzisoquinolinedione, nafidimide, NSC 308847) is an anticancer agent that functions as a DNA intercalator. Sixteen patients with stage III or IV non-small-cell lung cancer who had not previously received chemotherapy were given amonafide at an initial dose of 300 mg/m2 i.v. daily for 5 days every 21 days. No major objective responses were observed among the 14 patients adequately treated (95% confidence limits 0-20%). Local reactions at the injection site or phlebitis were seen in 14 of the 16 patients. Leukopenia (44%), nausea or vomiting (38%), and thrombocytopenia and rash (each 25%) were also noted. With the low response rate and the toxicity observed, amonafide at this dosage and schedule has limited use in the treatment of non-small-cell lung cancer.
Phase II trial of trimetrexate in patients with stage III and IV non-small-cell lung cancer.
Trimetrexate is a nonclassical antifolate with greater preclinical antitumor activity than methotrexate. Fourteen patients with stage III or IV non-small-cell lung cancer who had not previously received chemotherapy were given trimetrexate (12 mg/m2 intravenously daily for 5 days) every 3 weeks. No major objective responses were observed (95% confidence limits: 0-20%). Ten of the 14 patients had grade 2 or greater toxicity, with 50% experiencing grade 2 or greater leukopenia and/or thrombocytopenia. Nausea, vomiting, rash, mucositis, diarrhea, and serum glutamic-oxaloacetic transaminase (SGOT) elevations were also seen. At the dosage and schedule of trimetrexate used, no responses occurred in this population of patients with non-small-cell lung cancer. With the low response rate and the observed degree of myelosuppression, trimetrexate appears to have limited utility in this disease.
Phase I trial and clinical pharmacological evaluation of 10-ethyl-10-deazaaminopterin in adult patients with advanced cancer.
10-Ethyl-10-deazaaminopterin (10-EDAM) is an analogue of methotrexate with improved preclinical anticancer activity, more selective entry, and greater conversion to polyglutamate forms in neoplastic cells. In this Phase I trial, we have treated 62 adults with advanced solid tumors, giving 10-EDAM i.v. on either a weekly x 3 schedule (35 patients) or a weekly schedule (27 patients). The dosage levels ranged from 5 to 120 mg/m2. The toxicity observed with 10-EDAM was qualitatively similar to that of methotrexate. Oral mucositis was the dose-limiting toxicity; diarrhea, skin rash, leukopenia, thrombocytopenia, and mild elevations of serum glutamic-oxaloacetic transaminase, prothrombin, and partial thromboplastin times were also observed, but were not dose limiting. A weekly dosage of 80 mg/m2 with escalation or attenuation in accordance with patient tolerance, or 100 mg/m2 weekly for 3 weeks, followed by a 2-week "rest period" are recommended for Phase II assessment. 10-EDAM produced partial remissions in three patients with non-small cell lung cancer and one patient with breast cancer lasting 6, 40+, 26+, and 15 months, respectively. Pharmacokinetic studies carried out at the 5, 30, and 100 mg/m2 dosage levels demonstrated the drug to have a triphasic disappearance from plasma. Elimination was independent of dose over the range tested, with mean plasma half-lives of: alpha = 12.9 min, beta = 1.5 h, and gamma = 11.9 h. Cumulative urinary excretion of the drug ranged from 13 to 55% of the administered dose (mean = 33%); 88% of the urinary drug appeared within the first 4 h following drug administration. The pharmacokinetic behavior of the first and second weekly dosages were consistent within a given patient. The metabolites 7-hydroxy-10-EDAM, and 10-ethyl-10-deaza-2,4-diamino-pteroic acid were demonstrated in the plasma and urine of treated patients. In studies of tissue homogenates from two patients with skin metastases, more extensive retention of the drug and of its polyglutamates was observed in the breast cancer metastases than in the metastases from a kidney cancer or in normal skin.
High-resolution electron microscopy of high-temperature superconductors.
We review recent results obtained at Northwestern using high-resolution electron microscopy to study high-temperature superconductors. While in general these materials form large, very perfect single crystal grains which display very few imperfections, there is also evidence of slip defects, amorphous regions, and order-disorder transformations. We also report that the gadolinium-based superconductors and in one case yttrium-based superconductors show evidence for some copper solid solubility in the form of copper-rich planar defects. The structure of a metastable trigonal polytype is also reported, as are the effects of electron beam and water vapor damage to the materials.
Phase II study of 10-ethyl-10-deaza-aminopterin in patients with stage III and IV non-small-cell lung cancer.
10-ethyl-10-deaza-aminopterin (10-EDAM) is an analog of methotrexate that differs from its compound by modification of the N10 position and demonstrates greater preclinical antitumor activity and less toxicity. In this phase II trial, 20 patients with stage III or IV non-small-cell lung cancer (NSCLC) were administered 10-EDAM at a dose of 80 mg/m2 once weekly for 5 weeks. No patient had previously received chemotherapy. Nineteen of the 20 patients were adequately treated for response assessment. Six of 19 patients (32%) experienced a major objective response (exact 95% confidence limits, 15% to 55%). The median duration of response has not been reached and will exceed 13 months. Mucositis was the most common toxicity observed. Leukopenia was seen in only 10%, and 15% had platelet nadirs less than 100,000/microL. At the dosage and schedule used, 10-EDAM is an active agent in patients with NSCLC who are previously untreated with chemotherapy with a predicted response rate greater than or equal to 15% (P = .05). Because of its level of antitumor activity and the fact that 10-EDAM causes minimal myelosuppression, it is a suitable agent for further study in combination with other chemotherapeutic agents in this disease.
Phase II trial of oral piritrexim (BW301U) in patients with stage III non-small cell lung cancer.
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Phase II trial of esorubicin in patients with advanced non-small cell lung cancer.
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