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T L Evans

Publications and source records attributed to T L Evans.

At least 19 recordsLinked to original sources
PubMed2001

Lung cancer.

Is any one combination therapy for metastatic non-small cell lung cancer (NSCLC) superior to other regimens for metastatic NSCLC? The answer is "probably no." More than 4,000 patients with advanced NSCLC participated in randomized trials presented at the 37th Annual Meeting of the American Society of Clinical Oncology. TAX326 was the only study in which the investigational arm (cisplatin/docetaxel) showed a statistically significant difference in survival compared with the reference standard (cisplatin/vinorelbine). We did learn, however, that what we administer may make some difference: cisplatin might be superior to carboplatin, and patients treated with nonplatinum chemotherapy regimens have a trend toward poorer survival than those who receive platinum doublets. Although there is still no clear best regimen for advanced NSCLC, we may now know how much chemotherapy to give: a randomized study presented found that four cycles produces as much survival benefit as treating until progression. The most significant abstracts presented at this year's lung cancer session involved the use of novel agents with unique mechanisms of action. The median survival in the large, randomized trials of chemotherapy in advanced NSCLC remains a bleak 9 months. ISIS 3521, an antisense oligonucleotide that targets protein kinase C, was found to produce a near doubling of survival when combined with carboplatin and paclitaxel. OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, was shown to have impressive single agent activity in the second-line treatment of lung cancer. The future of lung cancer therapy will involve combining these novel agents with active chemotherapy regimens in an effort to improve outcome. While we appear to have reached a plateau in what we can accomplish with various combinations of cytotoxic chemotherapy in metastatic NSCLC, in locally-advanced disease new chemotherapy combinations can achieve remarkable results when combined with radiation therapy. The Southwest Oncology Group presented unprecedented phase II data on the use of cisplatin and etoposide with concurrent radiation therapy followed by consolidation docetaxel in patients with stage IIIB NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Tick-raccoon associations and the potential for Lyme disease spirochete transmission in the coastal plain of North Carolina.

Raccoons (Procyon lotor) were live-trapped and examined for ticks from July 1990 to July 1993 in the coastal plain of North Carolina on Marine Corps Base, Camp Lejeune, North Carolina (USA). Five species of ixodid ticks were found on 351 (78%) of 449 raccoons. Amblyomma americanum was the most abundant tick found on raccoons. Dermacentor variabilis, Ixodes texanus, and Ixodes scapularis were frequently collected, while Ixodes cookei were rarely collected from raccoons. Tick burdens were not affected by the age, sex, or trap location of captured raccoons. Ticks parasitizing raccoons had varying seasonal patterns of abundance. Amblyomma americanum were generally collected from raccoons year around, but infestation intensities were greatest in summer from June to September. Dermacentor variabilis adults were most abundant in mid-summer while peak numbers of larvae were collected in the fall. Infestation intensities of Ixodes texanus larvae were greatest in fall and winter months while nymphs were most abundant in winter and spring. No males were collected from raccoons, but females were most frequently collected in the spring and declined in abundance in the summer with no specimens collected in the fall or winter. Numbers of 1. scapularis adults appeared to reach peak numbers in the fall while larvae and nymphs were most abundant on raccoons in winter. Spirochetes, Borrelia burgdorferi, were identified in a small percentage (0.2%) of host-seeking A. americanum nymphs and adults, and I. scapularis adults by immunofluorescent antibody assays. Similarly, a small percentage (1.9%) of host-associated A. americanum, D. variabilis, I. texanus and I. cookei contained B. burgdorferi. Borrelia burgdorferi spirochetes were cultured from the blood of 23 (26%) of 87 raccoons.

Animals↗
PubMed1993

Relative utilization of reptiles and rodents as hosts by immature Ixodes scapularis (Acari: Ixodidae) in the coastal plain of North Carolina, USA.

The interaction of immature black-legged ticks, Ixodes scapularis, with reptiles and rodents was investigated in various woodland habitats in the coastal plain of North Carolina. Reptiles were sampled from April 1 to September 30, 1991. No ticks were found on 95 specimens representing 16 species of snakes. Ticks were found on 54 (36.7%) of 147 lizards. I. scapularis was the only tick recovered from lizards. Some lizards were collected in drift fence traps each month of the study except August. Capture rates averaged one lizard per 16 trap-days. Larvae and nymphs of I. scapularis were removed from the southeastern five-lined skink (Eumeces inexpectatus), the ground skink (Scincella lateralis), the broad-headed skink (E. laticeps) and the eastern glass lizard (Ophisaurus ventralis), but ticks were not found on three other lizard species. Tick infestation rates and loads for parasitized species are presented. Ticks were almost exclusively attached at the base or in the axils of forelimbs of skinks and in the lateral grooves of eastern glass lizards. Rodents were live-trapped at sites where lizards were sampled and at other sites from 1 July, 1990 to 30 January, 1992. Capture rates averaged one rodent per 47 trap-nights. Ticks were found on 23 (17.8%) of 129 animals inspected. Five species of rodents were examined but only four species were found to be tick-infested. In contrast to lizards, few I. scapularis were collected. Rodents, principally the white-footed mouse (Peromyscus leucopus) and cotton mouse (P. gossypinus) were most frequently infested with immature American dog ticks, Dermacentor variabilis, during winter and early spring months. Burdens of D. variabilis on these rodents averaged 0.3 ticks per rodent. Effects of the diversion of ticks from feeding on Peromyscus mice on the transmission of the Lyme disease spirochete are discussed.

Animals↗
PubMed1988

Defective T-cell colony formation and IL-2 receptor expression at all stages of HIV infection.

The T-cell colony assay is a highly sensitive measure of immunological dysfunction. The present study evaluated this in vitro response in asymptomatic HIV-infected homosexuals, those with chronic adenopathy as their only clinical manifestation and patients with either ARC or AIDS. The mean colony count in antibody-positive asymptomatic individuals was significantly reduced when compared to either heterosexual controls or antibody-negative homosexuals. Furthermore, there were no differences in the responses of these antibody-positive individuals and those with chronic lymphadenopathy as their only clinical manifestation. By contrast, patients with AIDS or ARC showed a profound defect; this suggests that the colony assay can detect a functional gradient across the spectrum of HIV infections. Colony growth was correlated with the absolute number of T-helper cells and the ability of PHA-stimulated lymphocytes to express IL-2 receptors; no correlation was found with the number of suppressor/cytotoxic cells or in vitro production of IL-2. Recent HIV seroconverters had normal colony counts but impaired ability to express IL-2 receptors. These data suggest a sequential loss of T-cell function as a result of HIV infection; the earliest manifestations are impaired expression of IL-2 receptors and reduced proliferative responses, as measured in the colony assay.

AIDS-Related Complex↗
PubMed1988

Large-scale production of murine monoclonal antibodies using hollow fiber bioreactors.

We have produced large quantities of murine monoclonal antibodies for in vivo human clinical trials using hollow fiber bioreactors (HFBRs). Thirty-three different hybridoma cell lines have been evaluated in various HFBR systems. Monoclonal antibody (Ab) productivity is highly dependent on the intrinsic secretory rate of each cell line. Other factors that affect Ab production include capillary membrane molecular weight cutoff, and HFBR design. Studies comparing HFBRs to static and suspension culture systems revealed similar Ab productivity. An advantage of the HFBR is that the Ab is concentrated in the extracapillary space, simplifying downstream processing.

Animals↗
PubMed1986

High-dose megestrol acetate therapy of ovarian carcinoma: a phase II study by the Northern California Oncology Group.

The activity of high-dose megestrol acetate was studied in 47 patients with epithelial ovarian cancers after failure of initial chemotherapy. The dose of megestrol acetate was 800 mg/d orally (PO) for 4 weeks and then 400 mg/d until tumor progression. Patients generally had far-advanced disease. Prior therapy included cisplatin, doxorubicin, and cyclophosphamide (PAC) or other cisplatin-containing regimens in 37, other combinations in eight, and single agents in only two patients. Seventeen patients (36%) developed intestinal obstructions within the first 2 months on study. Tumor histology was serous in 37, endometrioid in six, and clear-cell in two. Two thirds of the tumors were histologic grade 3, and the others were grade 2. Complete remission was obtained in one patient, with time to progression of 4 months. There were three partial remissions, with times to progression of 4, 5, and 18 months. The overall response rate (complete and partial) was 8%. Three additional patients had minor remissions (3, 5, and 8 months), and five had stable disease, for 3, 4, 5, 6, and 9 months. There was no correlation of response with grade, histologic type, or site of disease, but responding patients had a longer survival from diagnosis to protocol entry and from protocol failure to death than did nonresponding patients. The major side effect of megestrol acetate was increased appetite, which caused one patient to withdraw from the study, and resulted in a 10- to 20-kg weight gain in five patients. Plasma levels of megestrol acetate averaged 600 ng/mL in the first month of therapy and decreased to approximately 400 ng/mL at 8 and 12 weeks, after the drug dosage had been reduced. Serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were markedly lower during megestrol therapy compared with pretreatment values. Megestrol acetate at 1 microgram/mL in vitro inhibited soft agar colony formation from one of 17 specimens of ovarian carcinomas. We conclude that megestrol acetate in high doses has modest, but definite, palliative effects in some patients with advanced ovarian carcinoma in whom chemotherapy has failed. A controlled trial of megestrol plus combination chemotherapy as first-line treatment of advanced ovarian carcinoma should be considered.

Adult↗
PubMed1985

Defective in vitro T cell colony formation in the acquired immunodeficiency syndrome.

Depressed T cell immunity is a universal characteristic of the acquired immunodeficiency syndrome (AIDS). In the present study, 25 patients with AIDS and opportunistic infections, 22 individuals with AIDS-related complex (ARC, or chronic lymphadenopathy syndrome), and 20 healthy homosexuals were evaluated by means of the T cell colony assay. Forty-seven healthy heterosexual controls showed an average of 3964 +/- 319 colonies/7.5 X 10(5) cells, with a range of 880 to 9340. The mean in the 20 healthy homosexuals (3173 +/- 483) did not differ significantly from the controls; in this group, only three patients had values less than 1000 colonies/plate. By contrast, all AIDS patients and 14 ARC patients had colony counts less than 1000. The mean value for the AIDS patients was only 24 +/- 15 (p less than 0.0005 compared with either controls or healthy homosexuals); values in the ARC group were intermediate (1180 +/- 360). The addition of interleukin 2 to the plates promoted correction of the proliferative abnormality in ARC patients. This interleukin increased colony scores in the AIDS group, but the mean value was still significantly less than controls. Comparison indicated that the colony assay is a more sensitive indicator for detecting proliferative abnormalities than responses to PHA, Con A, or pokeweed mitogen in suspension cultures.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Thrombotic thrombocytopenic purpura: clinical course and response to therapy in eight patients.

The clinical manifestations, pathologic findings, and responses to therapy were reviewed in eight patients with thrombotic thrombocytopenia purpura (TTP). Only one exhibited all five cardinal manifestations; five showed a triad of anemia, thrombocytopenia, and neurologic abnormalities. Microangiopathic red cell changes on peripheral blood smear and severe thrombocytopenia were present in all. The serum LDH levels were initially elevated in all eight; this enzyme determination was extremely useful for following the course of the disease and its response to therapy. Pathologic evidence of TTP was most consistently found in lymph nodes, spleen, and bone marrow biopsies. All patients were treated with a combination of therapeutic modalities including plasma exchange with replacement by fresh frozen plasma. Using this approach, 7/8 entered a complete remission; however, disappearance of all clinical manifestations was not seen in two patients prior to splenectomy.

Adult↗
PubMed1984

Failure of erythromycin in treatment of Legionella micdadei pneumonia.

A 59-year-old immunocompromised woman had nosocomial Legionella micdadei infection that failed to respond to two weeks of erythromycin in high intravenous doses and oral rifampin. Treatment with intravenous trimethoprim-sulfamethoxazole and oral rifampin, which previously has not been used in this infection, resulted in cure.

Drug Combinations↗
PubMed1984

T lymphocyte colony assay in hemophiliacs.

Unexplained lymphadenopathy, with or without accompanying symptoms, known as the "lymphadenopathy syndrome," has been recognized in groups at risk for acquired immune deficiency syndrome (AIDS), namely, homosexuals and hemophiliacs. To date, however, no test has been defined that discriminates between asymptomatic individuals and those with adenopathy in these high-risk groups. The T colony assay, which measures T lymphocyte growth in soft agar and which allows selective T cell proliferation with minimal cell-cell contact, was evaluated in asymptomatic hemophiliacs. Significantly lower mean colony counts were found in eight hemophiliacs with adenopathy (HA), 763 +/- 348 (+/- SEM), than in 16 healthy hemophiliacs (HH) 3,044 +/- 661 (P less than .005), or than in 24 heterosexual control subjects, 3,964 +/- 395 (P less than .005). The in vitro addition of exogenous interleukin-2 (IL-2) restored normal colony growth in the HA population. These results indicate that the T colony assay can detect abnormal cell-mediated immunity among hemophiliacs and specifically discriminates between asymptomatic hemophiliacs (HH) and those with adenopathy (HA). In addition, IL-2 may be of potential benefit in improving T cell defects in AIDS or the "lymphadenopathy syndrome"; however, this remains to be proven.

Cell Division↗
PubMed1983

Clinical responses of dogs to experimentally induced Dipetalonema reconditum infection.

Six male and 6 female Beagles, 6 to 7 months old, were allotted to 2 groups: group I--inoculated subcutaneously with 30 Dipetalonema reconditum infective larvae/dog, and group II--noninoculated controls. Group comparisons were made in regard to hematologic values, Knott test results, body weights, blood urea nitrogen, total serum protein, serum albumin and alanine aminotransferase and creatine kinase activities. Routine urinalysis data were compared at 1 week before and at 28 weeks after the inoculations. Mean total leukocyte counts were significantly (P less than 0.05) greater in group I dogs than in group II dogs at postinoculation weeks (PIW) 4, 5, and 7 to 12, and mean eosinophil counts were significantly greater in group I dogs at PIW 3 to 11, 13 to 15, 20, and 23 to 24. Microfilariae were detected as early as the 10th week and sporadically thereafter. Only 1 D reconditum adult worm was recovered from all of the inoculated dogs. Five other dogs (group III) with chronic, patient experimentally induced dipetalonemiasis, were evaluated with the same tests at PIW 70 to 89. Eosinophilia (greater than 750 cells/microliter) was present in 4 of 5 dogs; lymphocytosis (greater than 4,800 cells/microliter) was evident in 1 dog. Proteinuria (greater than or equal to 30 mg/dl) was detected in 3 of 4 dogs with chronic dipetalonemiasis.

Animals↗
PubMed1982

In vitro degradation of L-phenylalanine mustard (L-PAM).

L-Phenylalanine mustard (L-PAM), a bis-choroethylamine, is an important drug in the treatment of multiple myeloma and ovarian cancer. It undergoes rapid hydrolysis in vitro and in vivo, forming the mono-and dihydroxy degradation products. L-PAM's first-order disappearance rate in a phosphate-buffered solution did not differ statistically according to the presence or absence of activated rat liver microsomal enzymes. Furthermore, L-PAM's disappearance rate in a rat whole liver perfusion system was not greater than its hydrolysis rate in water. In vitro plasma recovery studies showed that up to 85% of the 14C L-PAM drug equivalents could be recovered as the parent compound and the mono- and dihydroxy degradation products. Thus, L-PAM in in vitro degradation was similar qualitatively and quantitatively to its reported in vivo degradation in animals and man. It is concluded that L-PAM does not undergo important, active in vivo metabolism.

Animals↗
PubMed1981

Methodologic problems in clonogenic assays of spontaneous human tumors.

Colony formation in soft agar was used to investigate growth properties and drug sensitivity in 102 tumor specimens from 91 patients. Sufficient colony growth for sensitivity testing with various drugs was obtained in 36 of 67 specimens (54%) with adequate cell yield and pathologically documented malignancy. Room temperature (20-24 degrees C) is superior to both 4 degrees C and 37 degrees C for 12-36 h storage and transport of malignant effusions. By contrast, fine mincing in sterile saline or balanced salt solution, and refrigerated storage (4 degrees C) appear optimal in experiments with three solid tumors. The use of buffered NH4Cl to lyse red blood cells markedly reduced plating efficiencies, and also reduced the percentage of tumors in which drug sensitivities could be tested from 64% to 38%. Several combinations of potential growth factors and culture media have been tested. Insulin enhanced plating efficiency (PE) in all six adenocarcinomas tested. Drug sensitivity of tumors was not affected by varying plating efficiency up to five-fold in two tumors. In eleven cases tumor cells were exposed to combinations of two or more drugs, and results assessed for evidence of drug interactions. In almost all cases, these two-drug combinations produced additive cell killing than either antagonistic or greater-than-additive effects.U

Adenocarcinoma↗
PubMed1980

Comparative pharmacokinetics of chlorambucil and melphalan in man.

We have studied the pharmacokinetics of orally administered chlorambucil and melphalan in patients with hematologic malignancies and solid tumors. With a standard oral dose of 0.6 mg/kg, chlorambucil showed much more rapid systemic appearance than did melphalan and had a mean peak plasma concentration and area under the plasma disappearance curve which was 3-4 times greater than that observed in patients receiving melphalan. Melphalan had extremely variable systemic availability which was not observed with chlorambucil, and was not related to problems in tablet formulation. Chlorambucil undergoes extensive active metabolism to phenylacetic acid mustard, whereas melphalan undergoes rapid chemical degradation and has little, if any, active metabolism. On a pharmacokinetic basis, chlorambucil's greater in vitro stability, its more rapid and predictable systemic availability after oral dosing, and its extremely low urinary excretion make it a more predictable alkylating agent for clinical use than melphalan, especially for patients with reduced renal function.

Biotransformation↗
PubMed1980

Concentration profile for the dissolution of drug tablets undergoing simultaneous degradation.

An empirical approach to the concentration-time history of a dissolving drug has resulted in a cube-root equation in which the characteristic constant of the equation embodies the important physical variables of the system. This expression has been used to study the dissolution of a drug that degrades simultaneously in the test solution. An alternative representation of the dissolution process is first-order kinetics. These two approaches are compared by fitting the experimental data of the dissolution of digoxin and melphalan tablets in various media, and a new method for the proper analysis of data for the dissolution of tablets that simultaneously degrade in the test solution is presented.

Chemistry, Pharmaceutical↗
PubMed1979

Kinetics of intravenous melphalan.

We have studied the disposition and elimination of melphalan after intravenous administration in 9 patients with cancer. High-pressure liquid chromatography and 14C-melphalan were used to assay drug concentration in plasma and urine. Composite plasma t1/2alpha was 7.7 +/- 3.3 and t1/2beta was 108 +/- 20.8 min for 8 of the patients. The mean 24-hr urinary excretion of melphalan was 13.0 +/- 5.4% of the administered dose. In 2 patients, 80% to 100% of the measured 14C counts in plasma and urine samples at each study interval, up to 24 hr after drug administration, could be accounted for by the sum of parent compound, monohydroxy and dihydroxy products, and methanol nonextractable radioactivity (i.e., protein-bound activity). These data and evidence of rapid disappearance from plasma at 37 degrees in vitro suggest that spontaneous degradation, and not enzymatic metabolism, is the major determinant of the t1/2 of melphalan in vivo.

Adult↗