Performance evaluation of 26 combinations of chemical protective clothing materials and chemicals after repeated exposures and decontaminations.

Effective decontamination of chemical protective clothing (CPC) is essential for reducing occupational skin diseases and disorders during a reuse scenario. To protect the workforce, the efficacy of decontamination methods and the reusability of CPC need to be evaluated. In this study, performance of 14 CPC materials against 12 liquid chemicals was evaluated based on standardized breakthrough time (BT) and steady-state permeation rate (SSPR).

Development of a computer program for permeation testing data analysis.

A Microsoft Windows-compatible computer program, referred to as "Permeation Calculator," was developed at the National Institute for Occupational Safety and Health (NIOSH) to automate and standardize permeation testing data analysis. The program imports the data file collected during a permeation test and calculates relevant permeation parameters within a few seconds, based on a series of algorithms, strategies, and automated decision-making processes. It allows calculations of all the permeation parameters related to American Society for Testing and Materials (ASTM) F 739, International Organization for Standardization (ISO) 6529, and ASTM D 6978 standards, including standardized breakthrough time, normalized breakthrough time, breakthrough detection time, steady-state permeation rate, cumulative permeation mass at a given elapsed time, and elapsed time at a given cumulative permeation mass for either a closed-loop or an open-loop permeation test.

Change in tensile properties of neoprene and nitrile gloves after repeated exposures to acetone and thermal decontamination.

This study investigated the change in tensile properties of neoprene and nitrile gloves after repeated cycles of exposure to acetone, followed by thermal decontamination. The glove was exposed to acetone (outer surface in contact with chemical), subjected to thermal decontamination, and tested for the tensile strength and the ultimate elongation. Thermal decontamination was carried out inside an oven for 16 hours at 100 degrees C.

[Effect of chronic Chlamydia infection with non-specific inflammation on cardiovascular complications in acute myocardial infarct].

It is known that local and systemic inflammatory processes play an important role in the genesis and development of atheroclerotic lesions and in the pathophysiology of acute coronary syndromes. This hypothesis is supported by findings of elevated parameters of the "inflammatory" reaction in the affected blood vessels but also in the blood of atherosclerotic patients. Known risk factors do not explain quite satisfactorily epidemiological cardiovascular phenomena and different manifestations of coronary heart disease.

Intraperitoneal adoptive immunotherapy of ovarian carcinoma with tumor-infiltrating lymphocytes and low-dose recombinant interleukin-2: a pilot trial.

A pilot study was conducted in patients who had advanced epithelial ovarian carcinoma, and who were refractory to platinum-based chemotherapy, to determine the feasibility and clinical effects of a schedule of intraperitoneal (IP) tumor-infiltrating lymphocytes (TIL) expanded in recombinant interleukin-2 (rIL-2), and low-dose rIL-2 IP. TIL were expanded from solid metastases or malignant effusions in serum-free AIM V medium supplemented with low concentrations (600 IU/ml) or rIL-2 using a four-step method of expansion that included a hollow fiber bioreactor (artificial capillary culture system). Patients received IP TIL suspended in dextrose 5% in sodium chloride 0.

Large-scale expansion in interleukin-2 of tumor-infiltrating lymphocytes from patients with ovarian carcinoma for adoptive immunotherapy.

Tumor infiltrating lymphocytes (TIL) from malignant ascites or solid tumor specimens obtained from patients with ovarian carcinoma were expanded to large numbers in vitro (10(10)-10(11)) by a four-step method using AIM V medium and low concentrations of recombinant interleukin-2 (rIL-2). The expansion procedure employed 24-well culture plates, T-flasks, polyolefin gas-permeable bags (PGPB), and an artificial capillary culture system (ACCS). The mean number of mononuclear leukocytes introduced into the 24-well plates was 16.

Induction of interleukin-2 receptor by tumor necrosis factor alpha on cultured ovarian tumor-associated lymphocytes.

We have recently reported that autologous tumor-specific cytotoxic T lymphocyte (CTL) lines and clones can be developed from lymphocytes infiltrating ovarian malignant ascites (TAL). In this study, we investigated the biological effects of tumor necrosis factor alpha (TNF alpha) in the induction, expansion, long-term proliferation and lytic function of CD8+ TAL. TNF alpha up-regulated the IL-2 receptor (IL-2R) alpha chain (Tac antigen) on the surface of CD3+ CD8+ CD4- TAL, enhanced the proliferation of autologous tumor-specific CTL, and potentiated their lytic function in long-term cultures.

Development of a cell surface reacting human monoclonal antibody recognizing ovarian and certain other malignancies.

A human monoclonal antibody designated AC6C3 was developed by fusing regional lymph node lymphocytes from a patient with epithelial ovarian carcinoma with cells of the hybrid myeloma SPAZ 4. This monoclonal antibody recognized a determinant expressed on the cell surface of ovarian tumor cell lines. The AC6C3 hybridoma has been maintained for more than 24 months by repeated cloning and secretes IgM at concentrations of 2-8 micrograms/10(6) cells/24h.

Antitumor activity against human tumor samples of cis-diamminedichloroplatinum(II) and analogues at equivalent in vitro myelotoxic concentrations.

We compared the antitumor activity of cis-diamminedichloroplatinum(II) (cisplatin; CDDP) with three CDDP analogues: cis-diammine-1,1-cyclobutanedicarboxylateplatinum(II) (CBDCA), N-methyliminodiacetato-1,2-diamino(cyclohexane)platinum(II) (MIDP), and N-(2-hydroxyethyl)-iminodiacetato-1,2-diamino(cyclohexane)platinum (II) (HIDP). Fresh human tumor samples in the adhesive tumor culture system were utilized for this comparison. The equitoxic concentrations of all four drugs were derived based on their inhibitory activity against human bone marrow samples.

High colony-forming efficiency of primary human tumor cells cultured in the adhesive-tumor-cell culture system: improvements with medium and serum alterations.

The colony-forming efficiency (CFE) of primary human tumor cells cultured in the adhesive-tumor-cell culture system (ATCCS) using Ham's F12 (F12) or Eagle's minimum essential medium, alpha modification (alphaMEM) and culture medium supplemented with either swine, equine or bovine sera were compared. AlphaMEM supplemented with equine serum provided the highest CFE of the combinations. The CFE increase due to the change from F12 to alphaMEM was approximately 5-fold, and the increase due to the change in serum from swine to equine was approximately 2-fold.

Comparison between clinical response and in vitro drug sensitivity of primary human tumors in the adhesive tumor cell culture system.

The newly described adhesive tumor cell culture system (ATCCS) offers a distinct advantage over other assays in that it has a high plating efficiency requiring low cell inoculum, it affords workable assays in approximately 70% of specimens from the heterogenous tumor types, and it has the ability to assay up to nine drugs at four different concentrations. Clinical correlations based on the ATCCS were obtained in 65 patients undergoing 71 clinical trials. Patients with melanoma, lung cancer, and sarcoma dominated the group.

Involvement of chromosome 7 in primary lung tumor and nonmalignant normal lung tissue.

By using the newly developed adhesive tumor cell culture system, we analyzed the chromosomal constitutions of primary lung tumor and nonmalignant normal lung tissue from 10 previously untreated patients with non-small cell lung cancer. Chromosomal analyses were successfully carried out in banded chromosome preparations from 10 tumor and 8 normal lung tissue samples. All analyzed tumor and normal lung tissue samples had a predominantly normal diploid chromosome number.

Comparison of antitumor activity of standard and investigational drugs at equivalent granulocyte-macrophage colony-forming cell inhibitory concentrations in the adhesive tumor cell culture system: an in vitro method of screening new drugs.

We compared the in vitro growth inhibition of primary human tumor cells in the adhesive tumor cell culture system (ATCCS), exposed to the investigational agents caracemide, spirogermanium and taxol and to standard chemotherapy agents at equitoxic concentrations for granulocyte-macrophage colony-forming cells (GM-CFC) in vitro. Clinically active standard agents tested at up to GM-CFC 90% inhibitory concentrations (IC90) resulted in in vitro activity (greater than or equal to 50% tumor growth inhibition) in at least 30% of tumors tested. In vitro responses for taxol, caracemide and spirogermanium were 78%, 9% and 7%, respectively.

Biological effect of epidermal growth factor on the in vitro growth of human tumors.

The effect of epidermal growth factor (EGF) on the in vitro growth of 186 malignant human tumor specimens (45 melanomas, 32 sarcomas, and 56 lung, 16 gynecological, 14 breast, 12 genitourinary, and 11 gastrointestinal carcinomas) was evaluated in the cellular adhesive matrix human tumor culture system supplemented with transferrin, insulin, hydrocortisone, and estradiol. EGF increased tumor growth by at least 50% in 81% of the 186 tumors and by over 100% in 54%. The enhanced growth induced by EGF was related to an accelerated cellular division independent of tumor type and not to an increase in the actual number of clonogenic units.

In vitro cytotoxicity patterns of standard and investigational agents on human bone marrow granulocyte-macrophage progenitor cells.

Inhibitory concentrations (ICs) against human bone marrow granulocyte-macrophage colony forming cells (GM-CFC) were established for 26 cancer chemotherapy agents, including seven investigational agents by ten day exposure. Each drug was tested at four or more concentrations to generate reliable survival curves. The analysis of the survival curves produced three patterns according to which drugs were classified: class A drugs had a shouldered curve with terminal exponential kill of GM-CFC, class B drugs produced initial exponential component followed by a plateau, and class C drugs produced linear curves.

An improved cytogenetic technique for human solid tumors grown in adhesive-tumor-cell culture system.

An improved technique for cytogenetic analysis of primary human solid tumors has been developed using an adhesive-tumor-cell culture system. While the previously described in situ harvesting procedure yielded highly condensed chromosome morphology and inadequate metaphase spread, the newly described harvesting procedures have yielded superior quality metaphase morphology and banding patterns. Cytogenetic analysis was successfully carried out on ten primary lung tumors and eight nonmalignant "normal" lung tissues.

Drug and radiation sensitivity measurements of successful primary monolayer culturing of human tumor cells using cell-adhesive matrix and supplemented medium.

The limitations of the agar suspension culture method for primary culturing of human tumor cells prompted development of a monolayer system optimized for cell adhesion and growth. This method grew 83% of fresh human tumor cell biopsy specimens, cultured and not contaminated, from a heterogeneous group of 396 tumors including lung cancer (93 of 114, 82%); melanoma (54 of 72, 75%); sarcoma (46 of 59, 78%); breast cancer (35 of 39, 90%); ovarian cancer (16 of 21, 76%); and a miscellaneous group consisting of gastrointestinal, genitourinary, mesothelioma, and unknown primaries (78 of 91, 86%). Cell growth was characterized morphologically with Papanicolaoustained coverslip cultures and cytogenetically with Giemsastained metaphase spreads.

Activity of 2-fluoro-Ara AMP against gynecologic tumors in the soft agar assay.

To characterize in vitro activity of 2-fluoro-Ara AMP and its relation to the activities of cisplatin and doxorubicin, 28 specimens from patients wit gynecologic tumors (predominantly ovarian) were tested in a soft agar assay. Twenty-six of 28 (93%) grew when the medium was supplemented with four hormones (epidermal growth factor, hydrocortisone, estradiol-17, and insulin). Normal bone marrow cells were utilized as a biologic control to define in vitro concentrations of the three drugs.

Effects and interactions of epidermal growth factor, insulin, hydrocortisone, and estradiol on the cloning of human tumor cells.

We investigated the effects and interactions of epidermal growth factor (EGF), insulin, hydrocortisone, and estradiol on the growth of 18 freshly obtained human tumors in our human tumor stem cell assay (HTSCA) cultured at a reduced serum concentration (8.5% ml). All possible combinations of these four supplement factors were added to the assay to determine the ability of each component to enhance colony formation.

The human tumor stem cell assay revisited.

The human tumor stem cell assay (HTSCA) is a bilayer soft agar system for growing fresh human tumor specimens in vitro to determine drug sensitivity and improve our understanding of tumor biology. Recent clinical correlations of 60% accuracy for predicting a positive clinical response and a 90% accuracy for predicting a lack of response to therapeutic agents suggest promising clinical usefulness. However, the clinician should be aware of the assay's inherent pitfalls, such as heterogeneity of the tumor specimen, inability to obtain pure single-cell suspensions, low cloning efficiency, unusual drug dose-dependent survival curves, uncertain validity of in vitro pharmacology, non-standardized criteria for in vitro sensitivity, and the variability of in vitro results.

Survival of human bone marrow cells after in vitro treatment with 12 anticancer drugs and implications for tumor drug sensitivity assays.

We investigated the responsiveness of human normal granulocyte-macrophage colony-forming units in culture (GM-CFUC) continuously exposed in vitro to 1 of 12 anticancer drugs. All drugs except bleomycin showed a simple negative exponential dose-survival curve. The in vitro toxicity of drugs in GM-CFUC did not always correlate with the relative myelosuppressive potency observed in vivo.

Differential cytotoxic activity of chemotherapy agents on colony-forming cells from human tumors and normal bone marrow in vitro.

We have compared the in vitro differential killing efficacy of doxorubicin, 5-fluorouracil, cis-platinum, etoposide, and bleomycin on human tumor cells in a new adhesive tumor cell culture system (ATCCS), and on normal bone marrow granulocyte-macrophage colony-forming units (GM-CFUC) in culture. All of the above chemotherapy agents were tested with continuous exposure against tumor cells and GM-CFUC. In addition, bleomycin was also tested with a short (60 min) exposure against GM-CFUC.

Dose-survival curves of cis-platinum, melphalan, and velban in human granulocyte/macrophage progenitor cells.

To optimize the in vitro concentrations of anticancer agents with clinical dose-limiting myelosuppression in the human tumor stem cell assay, we established dose-survival curves for cis-platinum, melphalan, and velban in normal human granulocyte/macrophage colony-forming units (CFU-gm) in a bilayer agar system. The LD50 (drug concentration capable of killing 50% of CFU-gm) of cis-platinum, melphalan, and velban for one-hour exposure was (a) greater than 10 micrograms/ml, (b) 0.9 microgram/ml, and 1.