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At least 19 recordsLinked to original sources

PubMed1992

Regulation of smooth muscle alpha-actin promoter in ras-transformed cells: usefulness for setting up reporter gene-based assay system for drug screening.

Oncogenic activation of ras results in changes in the transcription of several genes leading to uncontrolled cell growth. In this paper, we demonstrate that transformation of fibroblast cells by the ras oncogene leads to transcriptional repression of the smooth muscle alpha-actin promoter. Transient transfection analysis of plasmids containing the 5' upstream region of the human alpha-actin gene fused to human growth hormone or bacterial chloramphenicol acetyltransferase coding sequences into Rat-2 and ras-transformed Rat-2 (HO6) cells indicates that alpha-actin promoter is repressed in ras-transformed cells. In addition, stable rat fibroblast cell lines expressing human growth hormone or beta-galactosidase under the control of alpha-actin promoter exhibit repressed reporter gene activity following transformation by the ras oncogene. alpha-Actin promoter-driven beta-galactosidase activity is derepressed in revertants of ras-transformed stable cell lines. This revertant cell line expresses elevated levels of ras p21 protein and is resistant to retransformation by Ki and Ha-ras oncogenes. The revertant may have either a defective target protein whose activity is essential for the transforming activity of ras or an activated tumor suppressor gene which can suppress the activity of ras. These results indicate that smooth muscle alpha-actin promoter activity is a sensitive marker to follow phenotypic changes following transformation by ras and subsequent reversion. The advantages of this alpha-actin promoter-reporter gene assay system to screen for drugs that inhibit the transforming activity of ras, either directly or indirectly, are discussed.

Actins↗

PubMed1992

Preemployment drug screening. The epidemiologic issues.

Deciding to test applicants for employment for drugs raises complex, legal, moral, economic, and technical issues. However, we focus here on three epidemiologic issues germane to this decision. In one industry, the United States Postal Service, two recent studies suggest associations between positive preemployment drug screens and turnover, absenteeism, accidents, injuries, and discipline, but these associations are weaker than had been assumed. Cost-benefit analyses show that whether drug screening saves money depends both on the costs associated with adverse outcomes such as accidents and on the prevalence of drug use in the population screened. Finally, the predictive value of a positive drug screen also depends crucially on the prevalence of drug use. In populations with low prevalence of drug use, a large proportion of the positives may be false positives.

Absenteeism↗

PubMed1992

Drug screening of newborns by meconium analysis: a large-scale, prospective, epidemiologic study.

A large-scale, prospective drug screening of newborns by meconium analysis was done to determine more accurately the prevalence and epidemiologic characteristics of drug use in a high-risk urban, obstetric population. Every other neonate delivered in a perinatal center from November 1988 to September 1989 was prospectively enrolled and their meconium was analyzed by radioimmunoassay for the metabolites of three commonly abused drugs--cocaine, morphine (opiates), and cannabinoid. In 3010 subjects studied, 44% were positive for cocaine, morphine, or cannabinoid; 31% were positive for cocaine, 21% for morphine, and 12% for cannabinoid. In contrast, only 335 (11%) mothers admitted to illicit drug use: 52% of their newborns had a positive urine drug screen and 88% had a positive meconium drug screen. Prevalence of drug use among the pregnant women varied per month. A profile of the pregnant addict in the population studied was noted (P less than .001): service patient, single, multigravid (greater than 3), and little or no prenatal care. The major problems associated with drug use during pregnancy were principally noted in the group that was exposed to cocaine and opiates and in the group where the mothers admitted to the use of illicit drugs. On the other hand, a large number of neonates who have been exposed to drugs in utero, particularly those whose mothers denied the use of drugs, appear normal at birth and may not be recognized. Improved detection of these newborns at risk can be achieved with a high index of suspicion and meconium drug analysis.

Cannabis↗

PubMed1992

Costs and benefits of preemployment drug screening.

OBJECTIVE: This study provides a cost-benefit analysis of preemployment drug screening and evaluates the sensitivity of this analysis to variation in its underlying assumptions. DESIGN: Cost-benefit analysis, based on a cohort analytic study previously reported. SETTING: Employees of the US Postal Service in Boston, Mass. PARTICIPANTS: Estimates of costs and benefit are based on a cohort of 2533 postal workers in Boston and on average costs for the Postal Service in Boston and nationwide. RESULTS: Drug screening would have saved the Postal Service $162 per applicant hired. However, these results were sensitive to the assumptions in the model. If the prevalence of drug use in the population screened were 1% rather than 12%, the program would lose money. Similarly, if the cost per urine sample screened were $95 rather than the $49 assumed, then the program would lose money, even if the prevalence of drug positives was as high as 9%. CONCLUSIONS: Because of the sensitivity of this analysis to changes in its underlying assumptions, any company considering preemployment drug screening should carefully weigh the costs and benefits in its own industry.

Adult↗

PubMed1976

A procedure for drug screening without the need to transport urines: use of ion exchange papers and hemagglutination inhibition.

A procedure was devised for screening for drug abuse in urine specimens by adsorbing the drugs onto papers loaded with ion-exchange resin. The drugs were then eluted from the papers into aqueous saline buffers, which were analyzed by hemagglutination inhibition with antisera specific for morphine, methadone, or barbiturates. The procedure combines the convenience of the ion-exchange papers with the precision and sensitivity of the immunoassay. The preliminary treatment consists of local treatment of urine specimens collected at many distant clinics with ion exchange papers that adsorb 50-65% of alkaloid drugs and 25% of barbiturates and can be shipped, after drying, in simple envelopes by regular mail to a central analytical laboratory for processing. At the central laboratory, portions of specimens are reconstituted in aqueous saline buffers, while drugs from other portions are extracted with solvents at appropriate pH. Drugs are detected in the reconstituted aqueous media by hemagglutination inhibition and spectrophotofluorimetry and confirmed in the solvent extracts by thin-layer chromatography. Recovery of labeled drugs after this treatment and urine screening data showed that the procedure is safe, convenient, and reliable in the case of opiate alkaloids, methadone, amphetamines, and phenothiazine tranquilizers but is less suitable for detection of barbiturates.

Chromatography, Ion Exchange↗

PubMed1992

Routine urine drug screening at the first prenatal visit.

OBJECTIVE: The purpose of this study is to determine whether routine urine drug screening at the first prenatal visit will identify and permit early intervention for those at risk for poor outcome. STUDY DESIGN: Comparisons of maternal and neonatal outcomes between 166 randomly chosen patients with positive and 150 randomly chosen patients with negative drug screens identified by the enzyme multiplied immunoassay test were made by unpaired t test, chi 2 test, probit analysis, and tests of independent Poisson distributions. RESULTS: Forty percent of those identified denied drug use. Antepartum (p less than 0.01) and postpartum (p less than 0.05) complications were increased among drug users. Birth weight (p less than 0.001), gestational age (p less than 0.03), and head circumference (p less than 0.05) were decreased among neonates. CONCLUSION: Because of difficulty in identifying illicit substance--using patients, consideration should be given to the implementation of routine urine drug screening at the first prenatal visit in populations with a high rate of illicit substance use.

Chi-Square Distribution↗

PubMed1975

The chemotherapy of rodent malaria, XXIII Causal prophylaxis, part II: Practical experience with Plasmodium yoelii nigeriensis in drug screening.

Data are presented on the causal prophylactic action of about 100 compounds of various types against Plasmodium yoelii nigeriensis N67 in mice. Examples are given to show how action against pre-erythrocytic schizonts may be differentiated from action on emerging erythrocytic stages. In a series of 35 8-aminoquinolines, all but 10 showed definite causal prophylactic activity at tolerated doses. The data permit the compounds to be ranked in order of activity, and many are shown to be more active in this test system than primaquine. Marked causal prophylactic activity is displayed by a variety of quinone structures, several of which show a significant residual action on blood stages. A high level of activity is found in dihydrofolate reductase inhibitors within several chemical classes. Rorguanil is more effective as a causal prophylactic than a blood schizontocide in the mouse as in man. Sulphonamides and sulphones are also effective in this system. The active levels are influenced by the content of PABA in the diet of the hosts. Causal prophylactic action has been detected in a number of experimental compounds including some antibiotics (such as tetracycline and clindamycin). The pyrocatechol RC 12 shows only slight activity at the maximum tolerated dose. Chloroquine, mepacrine, quinine, quinolinemethanols and phenanthrenemethanols are inactive as causal prophylactics. It is concluded that a rodent malaria-mouse model does provide a relatively simple model for the screening of drugs for causal prophylaxis, and the data so obtained are of relevance to the detection of causal prophylactics against human malaria.

Amidines↗

PubMed1992

Training and proficiency in the medical review of job applicant drug screens.

A survey was performed to examine the proficiency of urine drug screen medical review officers (MROs) and the effect of training upon their performance. One hundred thirty-nine attendees of the ACOEM basic MRO training course, and 82 attendees of the advanced course completed both pre- and postcourse surveys. The questionnaires included 10 vignettes with positive analytical results; of which only half should be reported as positive to management. The mean number of correct responses among the 10 cases presented were: basic pre-test--4.91; basic post-test--7.45; advanced pre-test--6.68; advanced post-test--7.33. Differences between all four groups were significant (P < .001 to P = .003), except for the basic post-test versus the advanced post-test, for which there was no significant difference. It is concluded that 1) inadequate knowledge and skill in the medical review of drug screens may contribute to errors in reports to management, 2) physician's performance can be improved with training, and 3) certification of MROs in both the private and public sectors should be considered.

Clinical Competence↗

PubMed1992

Multidrug-resistant phenotype of disease-oriented panels of human tumor cell lines used for anticancer drug screening.

Disease-oriented panels of human tumor cell lines used by the National Cancer Institute for large-scale in vitro anticancer drug screening were evaluated for multidrug-resistant phenotype at the functional (in vitro drug sensitivity) and molecular levels. The cell line panels manifested a broad range of sensitivities to drugs typically associated with multidrug resistance (MDR) as well as to drugs not associated with MDR. Individual cell lines displayed unique and characteristic profiles of response. Patterns of correlated response were observed among, but not between, MDR and non-MDR drugs. Strong evidence of correlated response was limited to drugs sharing an intracellular mechanism of action. Several tumor cell lines exhibited a high degree of resistance to MDR drugs and relative sensitivity to non-MDR drugs, contained high levels of MDR-1 mRNA, and expressed cell surface P-glycoprotein detectable with one or more monoclonal antibodies. Parallel expression of all of these features representing the classic MDR phenotype was observed among members of the colon and renal tumor panels. Certain individual cell lines among other panels (lung, ovarian, melanoma, and central nervous system) also manifested some aspects of the MDR phenotype to various extents. Identification of MDR cell lines used for large-scale in vitro anticancer drug screening will facilitate interpretation of data in a way which may allow identification of new drug leads of potential value in treatment of MDR tumor cell populations.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1992

A method for screening drugs against the liver stages of malaria using Plasmodium gallinaceum and Aedes mosquitos.

1. The radical cure of human malaria caused by Plasmodium vivax requires two drugs, i.e., a blood schizontocide such as chloroquine to clear the circulating parasites, and primaquine aimed at the liver stages (hyponozoites) responsible for the late relapses of this parasite. Primaquine is unique as a radical curative drug but is highly toxic. The only useful model currently available for screening drugs to replace primaquine is Plasmodium cynomolgi-induced malaria in Rhesus monkeys. Because of the limited availability and cost of these animals, the development of non-primate models for such screening would be of considerable value. 2. We used a drug-screening assay for the liver stage malaria parasite based on the ability of such drugs to stop development of gametocytes in the mosquito vector. The inhibition of the sporogonic cycle of malaria in the mosquito by primaquine (15 mg/kg) was confirmed here and used for re-evaluation of the gametocyte method. 3. We observed that the level of parasitemia in the untreated control chicken used to infect mosquitos was a crucial factor affecting the subsequent development of sporogony. Thus, parasitemia was carefully controlled in the studies involving oocyst development. Parasitemias lower than 6% at the beginning of the experiment and increasing were found to be most appropriate for the production of the infectious gametocytes during a period of 8 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Aedes↗

PubMedDate not supplied

Morphological and immunocytochemical characteristics of human tumor cell lines for use in a disease-oriented anticancer drug screen.

A panel of 60 human tumor cell lines is currently being used in the U.S. National Cancer Institute's in vitro anticancer drug screen. The panel is organized into 7 subpanels; 6 leukemia/lymphoma lines comprise one subpanel, and 54 other lines are organized into subpanels representing solid tumors of the central nervous system (CNS), colon, lung, ovaries, kidneys and melanomas. In the present study, the leukemia and lymphoma cell lines were analyzed by flow cytometry for appropriate CD antigens; all but 1 line showed patterns of expression consistent with their reported derivations. The solid tumor lines were characterized individually using morphological and immunocytochemical techniques to determine their relative degrees of representativity for the subpanels within which they are currently grouped. Histological, histochemical and ultrastructural examinations were performed on cell lines grown under identical conventional culture conditions and as xenografts in nude mice. Immunocytochemistry using panels of antibodies raised against 6 types of intermediate filaments, 7 adenocarcinoma-associated antigens, 7 melanoma/neuro-ectodermal-associated antigens, 3 neuroendocrine-associated antigens, 9 urinary tract associated antigens, and 4 markers of muscle differentiation was done on cells grown in monolayer culture. Central nervous system (CNS) cell lines lacked expression of glial fibrillary acidic protein, but all had other features consistent with derivation from glioblastoma. Lines derived from adenocarcinomas of the colon, lung and ovary, for the most part, expressed adenocarcinoma-associated antigens and showed histological and/or ultrastructural evidence of gland formation and other adenomatous features. Most of these lines were poorly differentiated. Lines derived from large-cell and squamous-cell cancers also showed some characteristics consistent with their reported origins, except for one line which showed immunocytochemical and morphologic characteristics consistent with rhabdomyosarcoma. The 2 lines derived from small cell lung cancer (SCLC) lacked neurosecretory granules and 3 other SCLC markers but showed morphologic features consistent with SCLC. Most melanoma cell lines strongly expressed melanoma-associated antigens and were morphologically similar to human melanoma. Five lines produced premelanosomes, melanosomes or melanin. Most of the renal cancer cell lines showed morphologic or immunocytochemical features consistent with renal clear cell carcinoma. Collectively, these morphological and immunocytochemical analyses provide information concerning tissue of origin, tumor type, degree of differentiation and other biologic features essential to the use of these lines in a disease-oriented in vitro antitumor drug screen and to the interpretation of data derived therefrom.

Antibody Specificity↗

PubMed1992

The effectiveness of preemployment drug screening in the prediction of employment outcome.

Studies of adverse employment outcomes associated with positive preemployment drug screens have tracked employees for only about 1 year. Changes in drug use after hire may invalidate the predictions of employment outcome in later years which are essential for cost-benefit analyses. This blinded, prospective cohort study tracks absence, industrial accidents, occupational injuries, discipline, and turnover in 2537 screened employees through an average of 2 years. Marijuana-positive urines predicted increased turnover, accidents, injuries, discipline, and absence, but these risks appeared lower in the second year than the first. Cocaine-positive urines predicted increased turnover, accidents, injuries, discipline, and absence at levels not consistently different than the first year. Cost-benefit analyses of drug screening project employment risks throughout employees' careers. This study raises the possibility that elevated risks may decrease after the first year.

Boston↗

PubMedDate not supplied

Preemployment drug screening in a large metropolitan medical center: a one-month trial.

To assess the prevalence of illicit drug use among job applicants, a large metropolitan medical center conducted preemployment drug screening of all applicants during January 1988. Urine samples from 172 preinformed applicants were screened using Enzyme Multiplied Immunoassay Technique (Emit d.a.u.) followed by confirmatory gas chromatography/mass spectrophotometry. 4.1% of tests were positive for marijuana and/or cocaine and none was positive for heroin. Positive findings increased with decreasing socioeconomic status. The findings suggest that applicants for jobs in large medical centers in metropolitan areas are no different from those in other sectors of the economy with respect to illicit drug use.

Adult↗

PubMed1992

Phase II preclinical drug screening in human tumor xenografts: a first European multicenter collaborative study.

In a European joint project carried out in 6 laboratories a disease-oriented program was set up consisting of a panel of 7 tumor types, each represented by 4 to 8 different human tumor lines, for secondary screening of promising anticancer drugs. Human tumor lines were selected on the basis of differences in histology, growth rate, and sensitivity to conventional cytostatic agents. Xenografts were grown s.c. in nude mice, and treatment was started when tumors reached a mean diameter of 6 mm in groups of mice where at least 6 tumors were evaluable. Drugs were given at the maximum tolerated dose. For evaluation of drug efficacy, median tumor growth curves were drawn, and specific growth delay and treated/control x 100% were calculated. Doxorubicin (8 mg/kg i.v. days 1 and 8) was effective (treated/control < 50%, and specific growth delay > 1.0) in 0 of 2 breast cancers, 1 of 3 colorectal cancers, 2 of 5 head and neck cancers, 3 of 6 non-small cell lung cancers, 4 of 6 small cell lung cancers, 0 of 3 melanomas, and 3 of 6 ovarian cancer lines. Amsacrine (8 mg/kg i.v. days 1 and 8) was not effective, while datelliptium (35 mg/kg i.p. days 1 and 8) was active against 2 of 6 small cell lung cancer lines. Brequinar sodium (50 mg/kg i.p. days 1-5) showed efficacy in 4 of 5 head and neck cancers, 5 of 8 non-small cell lung cancers, and 4 of 5 small cell lung cancer lines. The project has been shown to be a feasible approach. Clinical activity for doxorubicin and inactivity for amsacrine against solid tumor types was confirmed in the human tumor xenograft panel. Additional anticancer drugs will be studied in the European joint project to further define the reliability of this novel, promising screening approach.

Amsacrine↗

PubMed1992

Passive exposure to cocaine in medical personnel and its effect on urine drug screening tests.

This report studies the importance of passive exposure of medical personnel to cocaine hydrochloride and its impact on urine screening testing. Eleven medical staff members were exposed to cocaine hydrochloride by means of aerosol and cutaneous application, similar to that which may occur in medical practice. Urine drug screening tests were negative for everyone tested. This finding is supported by known drug kinetics. It is unlikely that a single passive exposure of medical staff to cocaine hydrochloride will produce a positive urine screening test. In all cases of positive urine tests, contaminants should be tested for which may indicate a source of the drug. The routine use of gloves and masks--which is recommended to prevent HIV infection--should further decrease medical personnel's passive exposure to cocaine hydrochloride.

Administration, Cutaneous↗

PubMed1977

A random survey of drug screening proficiency.

There is little evidence of uniformity of standards of performance as influenced by technical capability and priority of concern for drug-screening proficiency. The objective of this quality-control survey was to illustrate the degree of error associated with toxicological analyses and encourage the use of controls to decrease the possibility of reporting erroneous findings.

Adolescent↗

PubMed1977

Ceramic hydroxylapatite as a plaque growth and drug screening substrate.

A new polycrystalline form of hydroxylapatite, CHA, has been shown to closely mimic dental enamel, in vitro, in regard to rate and degree of plaque formation and effectiveness of antiplaque drugs. The material has successfully been exploited as a standardized hydroxylapatite plaque growth substrate in conjuntion with a mass antidental plaque drug screening program.

Apatites↗

PubMed1992

Effect of intranasal cocaine on the urine drug screen for benzoylecgonine.

Otolaryngologists have long recognized the value of cocaine as a topical anesthetic and vasoconstricting agent. It is used in nasal surgery and as a vasoconstrictor before examination. As drug abuse has increased, screening for drugs of abuse has become common. This study was designed to determine how medicinal cocaine affects the urine test for the metabolite benzoylecgonine, the most common screening test for cocaine. Group I consisted of 12 patients scheduled for elective nasal surgery. Cocaine was given in our usual preoperative manner as 4 ml of 4% solution on cottonoids. Group II consisted of 30 volunteers in whom approximately 1 ml of 4% solution was sprayed intranasally. In both groups, a urine sample was collected before dosing and at regular intervals afterwards. All samples were negative before application of cocaine and all were positive 24 hours later. The duration of the positive result had some variability, but all were negative by 72 hours. The results show that medicinally used cocaine does make a drug screen positive. Patients should be informed that cocaine is being used and could cause a positive test for several days.

Administration, Intranasal↗