A comparison of ONTRAK TESTCUP, abuscreen ONTRAK, abuscreen ONLINE, and GC/MS urinalysis test results.

This study was designed to compare results obtained from two separate on-site drug testing kits (ONTRAK TESTCUP and Abuscreen ONTRAK) with those obtained from laboratory based immunoassay and GC/MS. Abuscreen ONLINE immunoassay was used to select 250 negative samples and 100 presumptive-positive samples each for cocaine/metabolites, opiates and cannabinoids. Presumptive-positive samples were selected if the immunoassay response was > or = 300 ng/mL for cocaine/metabolites (BZE), > or = 300 ng/mL for opiates or > or = 50 ng/mL for cannabinoids (THC-COOH). GC/MS was used to confirm that each selected sample contained > or = 150 ng/mL BZE, > or = 300 ng/mL morphine/codeine or > or = ng/mL THC-COOH. TESTCUP results had a 100% agreement with GC/MS and a > 99% agreement with ONLINE when testing negative samples. The agreement between TESTCUP and ONLINE results for samples containing opiates was 100%. Results of testing samples containing BZE with TESTCUP demonstrated a 98% agreement with both GC/MS and ONLINE. Both discrepant samples contained BZE at concentrations < or = 300 ng/mL. The least agreement between TESTCUP and ONLINE results was found when testing samples containing THC-COOH. The agreement with ONLINE and GC/MS was 92% and all discrepant samples had GC/MS determined THC-COOH concentrations less than 50 ng/mL. A 100% agreement was obtained between expected and recorded TESTCUP results for QC samples fortified to contained BZE, morphine or THC-COOH at concentrations within 120% of the screening cutoffs. ONTRAK had a 100% agreement with both GC/MS and ONLINE when testing negative samples and samples that contained opiates. ONTRAK had a 91% agreement with GC/MS and ONLINE for testing of samples that contained BZE. The least agreement between ONTRAK and ONLINE results was found when testing samples that contained THC-COOH. The agreement was 89%, however, all discrepant samples contained GC/MS concentrations of THC-COOH less that the 50 ng/mL cutoff. With ONTRAK, a 100% agreement was obtained between expected and recorded results QC samples that contained morphine or THC-COOH and a 97.7% agreement was obtained between expected and recorded results on QC samples that contained BZE.

Metabolic aspects of the toxicology of mixtures of parathion, toxaphene and/or 2,4-D in mice.

The effects of mixtures of parathion (PA;5 mg kg-1), toxaphene (TOX; 50 mg kg-1)and/or 2,4-dichlorophenoxyacetic acid (2,4-D; 50 mg kg-1) on the hepatic mixed-function oxygenase (MFO) system were studied in ICR male mice (21-24 g) by oral intubation daily for 7 days. In general, TOX and TOX-containing mixtures were found to induce the metabolism of amidopyrine (21-52%), aniline (58-72%), phenacetin (239-307%), pentobarbital (104-148%) and benzo[a]pyrene (143-304%) in the 9000 g liver supernatants and to increase the hepatic cytochrome P-450 contents (57-80%). Furthermore, the TOX pretreatment was effective in enhancing the biotransformation of PA or paraoxon (PO) in the supernatants. This enhancement was not altered significantly by 5 mM EDTA. Although TOX increased the aliesterase activity in the serum and liver homogenates and supernatants by 31-158%, the activity of paraoxonase was not affected in these preparations. The TOX-induced increase in the metabolism of PA or PO was, at least in part, associated with the MFO system, and paraoxonase did not have significant involvement in the increase. These findings suggest that the toxicity of the PA + TOX mixture would be lower than that of PA, as TOX has the ability to increase the biotransformation of PA, as well as of PO, and the levels of aliesterase, thereby providing a pool of noncritical enzymes for the binding of PO. Because of these properties of TOX, it is anticipated that the toxicity of the PA + TOX + 2,4-D mixture also would be lower than that of PA.

Toxicity of mixtures of parathion, toxaphene and/or 2,4-D in mice.

The toxicity of the mixtures of parathion (PA), toxaphene (TOX) and/or 2,4-dichlorophenoxyacetic acid (2,4-D) was studied in ICR male mice (21-24 g) by oral intubation, in corn oil, daily for up to 14 days. On Day 15, the exposure was discontinued, and animals were monitored for an additional period of 7 days for the possible reversibility of the toxicity. The body weight gain decreased with the mixtures, as well as with the individual agricultural chemicals (ACs), during the 14-day period. The cholinesterase (ChE) activity in the serum and brain was inhibited in the animals of the groups of PA (1-10 mg kg-1) and PA (5 mg kg-1)-containing mixtures. TOX (50-200 mg kg-1) caused initial inhibitory effects of 20-65% on the serum ChE (Day 1) before producing increases of 53-64% in the enzyme activity by Day 15, with little effects on the brain ChE levels. 2,4-D (50-200 mg kg-1) resulted in significantly elevated levels of the serum ChE, with substantial decreased in the brain ChE activity. The serum glutamic pyruvic transaminase level was up (38-630%) in TOX (50 mg kg-1), 2,4-D (50 mg kg-1) or their mixture group. No pathological changes at the light microscopic level in the brain and liver were noticed. TOX and TOX-containing mixtures significantly increased the liver/body weight ratio and decreased the pentobarbital (60 mg kg-1, i.p., in saline)-induced sleep.(ABSTRACT TRUNCATED AT 250 WORDS)

Organ-selective switching of 3-methylindole toxicity by glutathione depletion.

A high dose (550 mg/kg) of 3-methylindole (3MI) specifically damaged pulmonary tissue in Swiss-Webster mice without causing any hepatic or renal necrosis. When a glutathione depleter, L-buthionine-(S,R)-sulfoximine (BSO, 1.0 mmol/kg), was administered to mice 3 hr before a low dose of 3-methylindole (75 mg/kg), significant renal damage was observed by histopathological examination after 4 hr. The nephrotoxicity occurred without any observable pathological damage to lung tissues. Increased doses of BSO caused dose-dependent increases in renal toxicity. A low dose of BSO (1.0 mmol/kg) caused no depletion of renal glutathione levels, a large depletion of hepatic glutathione levels (60% of control values), and much larger increases in covalent binding of [methyl-14C]3-methylindole to renal tissues (3.4-fold) than to hepatic tissues (1.5-fold) or pulmonary tissues (2.1-fold). No evidence of hepatic or pulmonary histopathological damage was observed at any dose of BSO with 75 mg/kg 3MI. These results indicate that a shift in organ selectivity of 3MI-induced toxicity from pulmonary to renal sites occurs as a result of glutathione depletion in hepatic tissues. The production of a toxic metabolite in the livers of glutathione-depleted mice that is circulated to susceptible renal cells may be the mechanism of this interesting organ-selective shift in toxicity of 3MI.

Interaction between phencyclidine and its pyrolysis product, 1-phenylcyclohexene.

The interaction between phencyclidine (PCP) and its pyrolysis product, 1-phenylcyclohexene (PC), at metabolic level was evaluated in Swiss male mice (21-24 g). PC (1.1, 2.2 and 4.4 mmol/kg/day for 4 days, IP, in corn oil) treatment to mice induced the in vitro metabolism (p less than 0.05) of amidopyrine (17%), aniline (12%), phenacetin (62-100%), pentobarbital (20-26%), PCP (25-80%) and benzo[a]pyrene (81-147%) in the 9000 g liver fraction and the hepatic microsomal contents of cytochrome P-450 (18-42%). The induction of the mixed function oxygenase (MFO) system was consistent with the decreases in the concentrations of IP administered pentobarbital (0.27 mmol/kg, in saline) and PCP (16.4, 32.8 and 65.6 mumol/kg, in saline) in the serum, brain, liver and kidneys of PC pretreated mice. At 1 hr after the above doses of PC, the in vitro metabolism of amidopyrine, aniline, or phenacetin was not inhibited. However, the biotransformation of benzo[a]pyrene was inhibited by 33 to 45%. Though PC after a single dose did not alter the tissue concentrations of PCP, it increased the pentobarbital concentrations in the tissues studied (p less than 0.05). These results indicate that PC has a potential to induce the MFO system after the 4-day treatment. This property of PC plays an important role in the reduction of the action of PCP by enhancing its metabolism, thereby decreasing its tissue levels.

An evaluation of diagnostic techniques utilized in the initial workup of pediatric patients with acute lymphocytic leukemia.

The records of 32 pediatric patients with acute lymphocytic leukemia (ALL) were reviewed to evaluate the role of various diagnostic techniques used to assess the extent of extramedullary disease. Our findings indicate that adequate screening for hepatosplenomegaly is obtained by clinical assessment and for bone and renal involvement by bone scintigraphy including concomitant renal imaging. We recommend that radiographs be restricted to scintigraphically abnormal areas and/or sites of bone pain. Liver-spleen scintigraphy, gallium studies, intravenous pyelography, and ultrasound studies of the abdomen and pelvis should be utilized only to answer specific clinical questions. Evaluation in this manner reduces both radiation exposure and patient expense, while it adequately defines the extent of disease in these organs.

Extraction and identification of a human pancreatic-tumor-associated antigen.

In attempting to develop an immunoassay to aid in the early diagnosis of cancer of the pancreas, a pancreatic-tumor-associated antigen (TAA) was identified and partially purified. The antigen has a molecular weight of approximately 380,000, does not cross-react with carcinoembryonic antigen (CEA), and is apparently either not present or not readily detectable in normal pancreatic tissue. The development of an immunoassay employing such an antigen to aid in the diagnosis of cancer of the pancreas at an early stage of development is discussed.