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Biomedical subjects

A Poklis

Publications and source records attributed to A Poklis.

At least 55 records · Page 3Linked to original sources

Disposition of cocaine and norcocaine in blood and tissues of B6C3F1 mice.

The biodisposition of cocaine and norcocaine in blood and tissues of immunological importance in B6C3F1 mice following exposure to cocaine or cocaine plus an organophosphate esterase inhibitor, diazinon, is presented. Analysis of specimens was by gas chromatography-mass spectrometry. Results from these studies indicate that pretreatment with diazinon significantly increases cocaine and norcocaine concentrations in the blood, spleen, thymus, and liver. Following acute exposure to cocaine-diazinon, cocaine was found in the spleen and thymus up to 1 hour after exposure. Norcocaine was not detected at this time. Following 7-day exposure to cocaine-diazinon, both cocaine and norcocaine were found in liver, blood, and spleen up to 1 hour after the last exposure; however, only cocaine was detected in the thymus at 1 hour. Cocaine and norcocaine were not detected in any tissues 24 hours after the last exposure.

Animals↗

Hepatic lidocaine metabolism and liver histology in patients with chronic hepatitis and cirrhosis.

Recent advances in the medical and surgical treatment of chronic hepatitis and cirrhosis have made it increasingly important to develop noninvasive tests of liver function. Our study has evaluated the hepatic conversion of lidocaine to its primary metabolite monoethylglycinexylodide and compared this with liver histological findings in 225 patients with chronic hepatitis (161 with hepatitis C, 23 with hepatitis B, 21 with autoimmune hepatitis and 20 with cryptogenic hepatitis). One hundred seven (47.7%) patients had cirrhosis at the time of evaluation. A decline in monoethylglycinexylodide production was observed with worsening liver histological conditions from a mean of 81.5 +/- 7.0 ng/ml in patients with chronic persistent hepatitis to 61.2 +/- 5.5 ng/ml for chronic active hepatitis and 20.9 +/- 1.5 ng/ml in patients with cirrhosis (p < 0.05). A further stepwise decline in monoethylglycine xylodide production was observed with worsening Child class: from 25.5 +/- 2.2 ng/ml for class A patients to 8.9 +/- 1.4 ng/ml for patients with Child class C disease (p < 0.05). All patients with monoethylglycinexylodide production less than 20 ng/ml had cirrhosis confirmed on histological examination. In contrast, no relationship was observed between liver histological status and serum transaminases (AST or ALT), bilirubin, albumin and prothrombin time. Thirty-five patients underwent repeat histological evaluation and monoethylglycinexylodide testing after receiving at least 6 mo treatment for chronic hepatitis (interferon for hepatitis B and C and corticosteroids for autoimmune hepatitis). The change in monoethylglycinexylodide production observed in these patients was a linear function of the change in Knodell histological index (r = 0.73, p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

EMIT-d.a.u. monoclonal amphetamine/methamphetamine assay. I. Stereoselectivity and clinical evaluation.

The stereoselectivity, cross-reactivity and clinical performance of the EMIT-d.a.u. monoclonal amphetamine(A)/methamphetamine (MA) immunoassay (EM) were evaluated. The cut-off calibrator of the assay was 1000 ng/ml S(+)MA. Analysis of drug-added urines and 72 clinical specimens demonstrated a cut-off for S(+)-amphetamine of approximately 400 ng/ml. The stereoisomeric selectivity of the assay was determined in a concentration vs. response manner by adding pure S(+) or R(-)isomers of A and MA, to drug free urine. The EM assay demonstrated a high selectivity for S(+)-isomers with only one of 16 urine specimens collected following excessive use of nasal inhalers yielding a positive result. This specimen contained 6000 ng/ml R(-)MA. Five-hundred clinical urine specimens were simultaneously analyzed for A or MA by the EM and EMIT-d.a.u. polyclonal (EP) amphetamine assay with 131 positive results confirmed by GC/MS. In five specimens negative by EM while positive by EP, MA was present at concentrations below the 1000 ng/ml cut-off. Two ME false positive results were apparently caused by chlorpromazine (CPZ) metabolites. A study of other phenothiazines or their metabolites gave no false positive results. The possible cross reactivity of the EM assay was further studied for phenyl-isopropylamine analogs or drugs previously reported to react with the EP assay. The EM assay showed much less cross-reactivity than EP to all drugs tested.

Amphetamine↗

EMIT-d.a.u. monoclonal amphetamine/methamphetamine assay. II. Detection of methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA).

The cross-reactivity, stereoselectivity and clinical performance of the EMIT-d.a.u. monoclonal amphetamine/methamphetamine immunoassay (EM) for the detection of methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) in urine was evaluated. The cut-off concentrations of racemic MDA and MDMA were found to be approximately 800 ng/ml and 3000 ng/ml, respectively. The EM assay demonstrated a high selectivity for the S(+) isomer of both MDA and MDMA. Urines collected over a 24-h period from rats administered 20 mg i.v. racemic MDMA were all positive when analyzed by the EM assay. The EM was found vastly superior to the EMIT d.a.u. polyclonal amphetamine/methamphetamine assay for the detection of MDA and MDMA. The EM assay displayed sufficient sensitivity for detection of these drugs following clinical intoxication.

3,4-Methylenedioxyamphetamine↗

Response of the Emit II amphetamine/methamphetamine assay to specimens collected following use of Vicks inhalers.

The possible cross-reactivity of l-methamphetamine (desoxyephedrine) to the Syva Emit II amphetamine/methamphetamine assay was evaluated in urine specimens collected from seven subjects using Vicks Inhalers. The subjects were six males and one female ranging from 24 to 47 years of age. Four subjects used the inhaler every two waking hours for five consecutive days, while three subjects inhaled hourly for three consecutive days. All urine voids were collected, totaling 150 specimens. All specimens were analyzed by the Emit II assay on a Hitachi 717 automatic analyzer with a 1000-ng/mL d-methamphetamine cutoff calibrator. None of the inhaler specimens produced an Emit II response equal to or greater than the cutoff calibrator; all were negative. Specimens producing the highest rates were further analyzed by chiral GC/MS. The highest concentrations of l-methamphetamine were observed in urines from two subjects inhaling hourly: 1390, 1290, and 740 ng/mL. These specimens were collected the evenings of the second and third day. When used as directed or even with double the daily dose, Vicks Inhalers did not cause false-positive results in urine tested with the Emit II Amphetamine/Methamphetamine assay.

Administration, Inhalation↗

Evaluation of the ADx REA assay for determination of ethanol in serum and urine.

The Abbott ADx REA assay (ADx) for the determination of ethanol in human serum and urine was evaluated. The within-run precision of a urine sample containing 3.00 g/L ethanol resulted in a coefficient of variance (CV) of 2.1% (n = 20). The within-run precision of a serum sample containing 1.47 g/L ethanol resulted in a CV of 2.3% (n = 20). The between-run precision of the TDx REA ethanol assay controls yielded 0.50 +/- 0.02 g/L ethanol (target value, 0.50 g/L) with a CV of 3.0% (n = 6); 1.03 +/- 0.03 g/L ethanol (target value, 1.00 g/L) with a CV of 2.7% (n = 6); and 2.56 +/- 0.07 g/L ethanol (target value, 2.50 g/L) with a CV of 2.8% (n = 6). Results of an intermethod comparison study of clinical serum and urine ethanol determinations by gas chromatography (x) and ADx (y) yielded by regression analysis y = 0.993x - 0.04 g/L (r = 0.985; n = 92) for serums and y = 0.974x - 0.02 g/L, (r = 0.991; n = 75) for urines. No significant interference was seen with low molecular weight alcohols or ketones.

Chemistry, Clinical↗

Determination of thioridazine enantiomers in human serum by sequential achiral and chiral high-performance liquid chromatography.

Quantitation of thioridazine (TRZ) enantiomers, (+)-TRZ and (-)-TRZ, in patient serums was performed by a sequential achiral and chiral HPLC method. The lower limit of quantitation was 50 ng/mL for each enantiomer, and the method was linear up to 1000 ng/mL. The within-run and between-run precision at 125 and 500 ng/mL of each enantiomer yielded coefficients of variation (CV) of less than 10% and less than 12%, respectively. Absolute recovery of 250 ng/mL racemic TRZ added to serum (n = 9) yielded mean recoveries of 77.2% and 77.8% for (+)-TRZ and (-)-TRZ, respectively. Absolute recovery of 1000 ng/mL racemic TRZ added to serum (n = 9) yielded mean recoveries of 74.0% and 74.7% for (+)-TRZ and (-)-TRZ, respectively. Significantly different TRZ enantiomer concentrations were present in patient serums. The mean serum concentration was 110 ng/mL for (+)-TRZ (n = 18), and 317 ng/mL for (-)-TRZ (n = 21). The ratios of (-)-TRZ to (+)-TRZ ranged from 2.2 to 5.3, with a mean of 3.3. Variations in the concentration of TRZ enantiomers may contribute to the lack of correlation between serum TRZ values and therapeutic effect.

Chromatography, High Pressure Liquid↗

Production of urinary ethanol after sample collection.

As the interest in urine drug testing grows, ethanol is frequently included in drug-abuse screening. Collection of urine for drug testing is less invasive than blood collection and is used to screen employees in a large cross-section of occupations. Because alcohol can be produced from carbohydrates via fermentation, our interest was to determine: (1) if ethanol could be produced in glucose-positive urine (2) under what microbiological conditions would this process occur, and (3) would the urine ethanol concentration be significant. Fourteen urine specimens were selected from the Urinalysis Laboratory of a large medical center. All specimens were tested for ethanol concentration on the day of voiding and were found to be negative (< 0.01 mg/100 mL). Urine glucose concentrations ranged from 0 to > or = 2000 mg/dL. Microbiological examinations were performed on all specimens. Storing the samples at room temperature, five of the specimens produced ethanol over the time course of the study (1 to 21 days) in concentrations ranging from 0.036 to 2.327 g/100 mL. Yeast was identified in the five glucose positive urine samples producing ethanol. Six glucose positive urine samples that did not produce ethanol were found to be yeast negative. Findings indicate that significant ethanol concentrations can develop from glucose and yeast positive urine, after the day of voiding.

Ethanol↗

Determination of ethylene glycol in serum utilizing direct injection on a wide-bore capillary column.

A simple, rapid, and reliable procedure for the determination of ethylene glycol (EG) and other diol compounds utilizing direct injection of diluted serum on a unique wide-bore capillary column containing a highly polar stationary phase (Nukol column) is presented. The method uses 1,4-butanediol as the internal standard (IS) and resolves propylene glycol, EG, 1,3-butanediol, and diethylene glycol. The within-run precision of the method yielded at 27.5 mg/L EG, CV = 9.4% (n = 10) and at 222 mg/L EG, CV = 7.3% (n = 10). Absolute recovery of EG at 222 mg/L was 95.9 +/- 7.1% (n = 10). At the limit of quantitation, 27.5 mg/L EG, the absolute recovery was 115 +/- 13.1% (n = 10). The method was free of interference from common volatile intoxicants, organic acid metabolites, and polar drugs. However, valproic acid was not completely resolved from the IS. The Nukol column has demonstrated an extended column lifetime and versatility for analysis of other polar compounds.

Chromatography, Gas↗

Postinjury scopolamine administration in experimental traumatic brain injury.

A single bolus dose of scopolamine (1.0 mg/kg) or saline (equal volume) was injected (i.p.) at 15, 30 or 60 min after fluid percussion traumatic brain injury in the rat. Scopolamine administered at 15 min postinjury significantly reduced beam walking deficits and body weight loss assessed for 5 days after injury. Scopolamine treatment at 30 or 60 min postinjury had no effect on behavioral outcome assessed for 5 days after injury. Plasma concentrations of scopolamine were measured with a radioreceptor assay. The plasma half-life for scopolamine was 21.6 min in injured rats and 17.3 min in normal rats (P less than 0.05). These results, along with evidence from previous studies, suggest that a brief period of excessive neuronal excitation can produce relatively long-lasting behavioral deficits. The temporal effectiveness of receptor antagonist intervention in this process appears to be brief.

Animals↗

Evaluation of the Vision Theophylline assays in the emergency department setting.

STUDY OBJECTIVES: To determine whether the use of fingerstick blood samples or venipuncture blood samples affect the accuracy and the precision of the Vision Theophylline I assay and the Vision Theophylline II assay in the emergency department setting. DESIGN: Prospective clinical trial. SETTING: ED in a university teaching hospital. SUBJECTS/INTERVENTIONS: Simultaneous fingerstick and venipuncture blood samples were obtained from adult patients who required baseline theophylline levels in the ED. MEASUREMENTS: The Vision system was used in the ED to measure theophylline concentrations from fingerstick and venipuncture samples. Vision samples were drawn and analyzed by one of three pharmacists rounding within the ED between March and October 1990. These pharmacists were instructed by laboratory personnel concerning pertinent operating procedures. The vision Theophylline I and Theophylline II assays are enzyme-inhibitor immunoassays contained within a multi-chamber test packet. The high-performance liquid chromatography (HPLC) theophylline assay was used as the reference method. MAIN RESULTS: Linear regression of theophylline concentrations determined by the Vision Theophylline I assay versus HPLC revealed a significant correlation for fingerstick samples (r = .9440; P less than .05) and for venipuncture samples (r = .9750; P less than .05). The accuracy values for Vision Theophylline I assay venipuncture and fingerstick samples versus HPLC were -0.63 +/- 1.2 mg/l and 0.22 +/- 1.8 mg/L, respectively. The precision for Vision Theophylline I assay venipuncture and fingerstick samples versus HPLC were 0.27 and 0.38, respectively. Linear regression of theophylline concentrations determined by the Vision Theophylline II assay versus HPLC revealed a significant correlation for fingerstick samples (r = .9804; P less than .05) and for venipuncture samples (r = .9875; P less than .05). Accuracy values for Vision Theophylline II fingerstick and venipuncture samples versus HPLC were -0.53 +/- 1.4 mg/L and -0.65 +/- 1.3 mg/L, respectively. Precision values for Vision Theophylline II fingerstick and venipuncture samples versus HPLC were 0.34 and 0.29, respectively. CONCLUSION: There is a strong correlation between theophylline concentrations measured by Vision Theophylline assay versus HPLC, regardless of whether the Vision Theophylline assay is performed on a fingerstick or venipuncture sample. Vision fingerstick samples were more accurate than Vision venipuncture samples for both Vision Theophylline I and II assays. Theophylline concentrations measured by the Vision system using venipuncture samples were slightly more precise than those using fingerstick samples when compared with HPLC analysis. These differences in accuracy and precision were not clinically relevant.

Blood Specimen Collection↗

Determination of serum acetaminophen in emergency toxicology: evaluation of newer methods: Abbott TDx and second derivative ultraviolet spectrophotometry.

Newer methods for the determination of serum acetaminophen in emergency toxicology, the Abbott TDx immunoassay and second derivative ultraviolet spectrophotometry, were evaluated and compared to a high pressure liquid chromatographic procedure. The Abbott TDx immunoassay within-run and day to day precision yielded coefficients of variance below 2.7% and 7.2% respectively: Abbott TDx immunoassay results correlated well with those of high pressure liquid chromatographic in patient serums 15.0 to 333 mg/L acetaminophen; r2 = 0.954, n = 40. The Abbott TDx immunoassay assay was rapid, easy to perform, free of interferences from other drugs and exhibited no carryover from previous samples. The within run precision of the second derivative ultraviolet spectrophotometry method yielded coefficients of variance of less than 7.0%. Second derivative ultraviolet spectrophotometry results demonstrated good correlation with high pressure liquid chromatographic results in patient sera; r2 = 0.923, n = 40; however, performance deteriorated below 50.0 mg/L acetaminophen. Spectral interferences were noted at high concentrations of some drugs.

Acetaminophen↗

Fatal acetaminophen poisoning with evidence of subendocardial necrosis of the heart.

The authors describe a case of fatal acetaminophen overdose which occurred in a 16-year-old female. Her serum acetaminophen concentration 11.5 h postingestion was 154 mg/L. Antidotal therapy was unsuccessful, and after 9 days she died. Autopsy findings included centrilobular zonal liver necrosis, acute proximal renal tubular necrosis, and diffuse alveolar pulmonary damage. Her heart was transplanted into a young woman with congenital heart disease. The recipient expired 14 days after the transplant as a result of sepsis complicating bowel ischemia. The transplanted heart showed extensive subendocardial myocyte necrosis related to acetaminophen toxicity and not rejection.

Acetaminophen↗

Stereoselective pharmacokinetics of 3,4-methylenedioxymethamphetamine in the rat.

Studies to characterize the pharmacokinetics of the enantiomers of MDMA were conducted in rats using the iliac arterial cannulation. Two routes of administration, intravenous and subcutaneous, were evaluated at two dose levels for each route [20 and 40 mg/kg (+/-)-MDMA for subcutaneous, 10 and 20 mg/kg (+/-)-MDMA for intravenous administrations]. The average half-life (+/- SD) for all dosing groups was 2.5 +/- 0.8 h for (-)-(R)-MDMA and 2.2 +/- 0.8 h for (+)-(S)-MDMA. The more rapid clearance of (+)-(S)-MDMA compared with (-)-(R)-MDMA is consistent with the area under the curve (AUC) data of the parent drug and its primary metabolite MDA. The mean (+/- SD) AUC S/R ratios of MDMA and MDA were 0.70 +/- 0.05 and 3.1 +/- 0.8, respectively. Following a 20 mg/kg dose of racemic MDMA iv the mean (+/- SD) of the percent dose excreted as (-)-(R)-MDMA, (+)-(S)-MDMA, (-)-(R)-MDA, and (+)-(S)-MDA were 20 +/- 10, 12 +/- 6, 3 +/- 1, and 6 +/- 2, respectively.

3,4-Methylenedioxyamphetamine↗

Phencyclidine and violent deaths in St. Louis, Missouri: a survey of medical examiners' cases from 1977 through 1986.

A survey of 104 deaths involving phencyclidine (PCP) occurring from 1981 through 1986 in metropolitan St. Louis, Missouri, is presented. Four black males (22-33 yr) died from fatal PCP intoxication. PCP was detected in an additional 100 deaths: 81 homicides, 13 suicides, and 6 accidental deaths. Seventy-five of these deaths were homicides of Black males (mean age 27 years) typically dying from gunshot wounds, 64 cases. In 50% of deaths where PCP was detected, other drugs were co-administered: ethanol (35%) and cocaine (20%) being the most common mixtures. A dramatic continuous increase in PCP abuse from 1984 through 1986 was demonstrated by drug abuse indicator data: treatment admissions, emergency room episodes, police exhibits, and driving under the influence of PCP arrests. Increased abuse of PCP in St. Louis has been associated with increased medical emergencies and violence against persons.

Accidents↗

Evaluation of the Abbott ADx total serum tricyclic immunoassay.

The ADx total serum tricyclic antidepressant (TCA) fluorescence polarization immunoassay (Abbott Diagnostics) for the semi-quantitation of imipramine or amitriptyline and their respective N-demethylated metabolites in cases of TCA overdose was evaluated. The assay is linear from 75-1000 ng/mL total TCA in serum, and flaggs as "HI" all results exceeding 300 ng/mL. The within and between run precision of the assay for patient serum containing imipramine or amitriptyline and their metabolites gave CV's of less than 5.5% and 8.9%, respectively. A good correlation between the results of patient serum containing imipramine and desipramine simultaneously analyzed by ADx and gas liquid chromatography (GC) was observed, r2 = 0.964, n = 32. Results of patient serum containing amitriptyline and nortriptyline or doxepin and desmethyldoxepin analyzed by ADx and GC or GC-mass spectrometry were not well correlated; r2 = 0.738, n = 44 and r2 = 0.695, n = 21, respectively. The assay consistently flagged as "HI" serum with total imipramine and desipramine concentrations above 300 ng/mL by GC, and serum with greater than 360 ng/mL of amitriptyline and nortriptyline by GC/MS. No significant cross-reactivity was observed for drugs other than the TCA.

Antidepressive Agents, Tricyclic↗