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Biomedical subjects

J J Saady

Publications and source records attributed to J J Saady.

28 records · Page 2Linked to original sources
PubMedDate not supplied

Demonstration of physical dependence following chronic continuous methadone delivery via osmotic minipumps in pregnant rats.

The effects of a 14-day (gestation days 7-20) chronic methadone (6.3-9.0 mg/kg/day) infusion via osmotic minipumps were studied on the induction of physical dependence in both pregnant and nonpregnant female rats. Following continued methadone exposure, an acute injection of naloxone (2.0 mg/kg, SC) produced the following symptoms of withdrawal in both pregnant and nonpregnant methadone-exposed rats: increased frequency of head shakes, teeth-chattering and face-rubbing episodes, as well as the induction of burrowing, diarrhea, facial tremor, squeaking and vaginal sniffing. Increased fetal movement in the maternal abdomen was also observed in the pregnant rats. In the saline-exposed pregnant controls, naloxone failed to induce a significant effect. In addition, brain and plasma methadone levels during the various stages of pregnancy (gestation days 8-20) were determined. The methadone levels in plasma were initially variable (gestation days 8-12) but became more constant (approximately 50 ng/ml) from gestation day 14 to 20. Methadone brain levels also followed a similar pattern, except that the brain methadone content was at least 20-fold greater than plasma concentrations at any given time. Thus, relative to the high brain levels, the present data suggest that acute changes in methadone plasma concentration may not be a good index of pharmacological effect.

Animals↗
PubMedDate not supplied

A case of nonfatal sodium fluoride ingestion.

A nonfatal case of sodium fluoride ingestion is presented. The quantity of sodium fluoride ingested is unknown. Initial serum and urine samples were taken 24 h after ingestion and contained 3.4 and 21.3 mg/L fluoride, respectively. At that time the patient was essentially asymptomatic, but it is clear that he survived a plasma concentration greater than that usually considered lethal, 3 mg/L serum fluoride. The case illustrates the lack of correlation between plasma fluoride concentration and toxic effects and the importance of obtaining a history of fluoride ingestion.

Humans↗
PubMedDate not supplied

Determination of atropine in blood by gas chromatography/mass spectrometry.

A gas chromatographic/mass spectrometric (GC/MS) method for the rapid quantitation of atropine (AT) in blood is presented. A 2.0-mL blood specimen containing deuterated N-methyl-atropine as the internal standard was alkaline-hydrolyzed to convert atropine to tropine. The tropine was extracted by organic solvent which was evaporated to dryness. Tropine in the residue was derivatized with pentafluoropropionic anhydride (PFPA) to the PFPA-tropine ester which was chromatographed on a 25-m cross-linked methyl silicone capillary column with temperature programming at 100 degrees C initially and increased by 20 degrees C/min. The retention time of atropine was 1.7 min. The GC/MS was operated in the SIM mode and the mass fragments monitored were 124 and 287 for AT and 127 and 290 for the internal standard. The assay was linear from 10-300 ng/mL. Replicate analysis of blood specimens containing 200 ng/mL gave a CV = 6.5% (n = 10). Recovery of AT at 75 and 150 ng/mL was 69% (n = 10). The limit of quantitation of AT was 10 ng/mL. Scopolamine may be simultaneously extracted and identified; the retention time was 1.8 min with mass ions 81 and 138.

Atropine↗
PubMedDate not supplied

Estimation of the body burden of arsenic in a child fatally poisoned by arsenite weedkiller.

A three-year-old child died after ingestion of a mouthful of an estimated 44% sodium arsenite solution. Litigation was initiated based on the quality of emergency treatment at a rural hospital. An issue raised in litigation was whether the child could have survived if he had received an additional dose of BAL (dimercaprol). BAL had been sent for from a neighboring city and arrived approximately 2.0 h after admission. The first 50-mg dose of BAL could have combined with a maximum of 30 mg arsenic; a second dose could have brought the total of chelated arsenic to 60 mg. To determine the total body burden of arsenic in the child, multiple tissues were analyzed. The total body burden was estimated at 113 mg, with 100 mg of this total attributable to the ingested solution. The actual body burden after two doses of BAL therefore would have been at least 40 mg, a fatal level.

Arsenic↗
PubMedDate not supplied

Determination of chlorinated hydrocarbon pesticides by solid-phase extraction and capillary GC with electron capture detection.

Pesticides and their metabolites are extracted and concentrated from serum using C18 solid-phase extraction cartridges. The internal standard aldrin is added to 4 mL of serum or plasma, treated with 2 mL of methanol, and the resultant supernatant applied to the C18 cartridge. After several washes, pesticides are eluted from the column with isoctane and the eluate quantified with capillary gas chromatography using electron capture detection. Extraction efficiency is from 70 to 75% and the method detection limit ranges from 0.1-0.7 ng/mL depending on the analyte. Precision studies demonstrate that CVs range from 3.5 to 25.2%. Standard curves are linear to at least 7 ng/mL for lindane and chlordane isomers, heptachlor, heptachlor epoxide, oxychlordane, trans-nonachlor, dieldrin, dichlorodiphenyldichloroethylene (p,p'-DDE), dichlorodiphenyldichloroethane (p,p'-DDD), and dichlorodiphenyltrichloroethylene (p,p'-DDT).

Chromatography, Gas↗
PubMedDate not supplied

Direct determination of benzoylecgonine in serum by EMIT d.a.u. cocaine metabolite immunoassay.

An EMIT d.a.u. immunoassay for urine testing was applied on the Syva ETS Plus analyzer for the detection of the cocaine metabolite, benzoylecgonine (BE), in human serum. Serum was analyzed without prior extraction, concentration, or matrix modification. Calibrators and serum controls were prepared from EMIT d.a.u. calibrators that were reconstituted and diluted with EMIT Tox serum calibrator. The assay cutoff concentration for BE was 50 ng/mL. The within-run and between-run precisions of the assay were both less than 5%. Analysis of 162 patient serums yielded 43 BE positive results. All EMIT positive serum BE results were confirmed by gas chromatography-mass spectrometry. All patients with positive BE serums also had BE positive urine samples. Serum bilirubin and triglycerides as high as 38 mg/dL and 319 mg/dL, respectively, did not interfere with the assay. Modification of the EMIT urine assay allowed for a simple, rapid, and reliable method for the detection of BE in serum.

Cocaine↗
PubMedDate not supplied

Cocaine, ecgonine methyl ester, and benzoylecgonine plasma profiles in rhesus monkeys.

From a public health point of view, cocaine (COC) presents serious clinical problems and deaths from overdose and lifelong addiction patterns, not to mention its involvement in crime, in the United States. This study subjected rhesus monkeys to one intravenous administration of COC (1 mg/kg), which closely imitates the smoking of "crack" COC with regard to dose and effect. We monitored plasma concentrations over time, beginning when the primates were in a state of hyperarousal. Blood was sampled at 1, 6, 12, and 40 min after dosing. Plasma concentrations of COC decreased rapidly with a half life of 15.7 min. Mean COC concentrations in the drug-treated group (n = 7) for the four timepoints were 296, 225, 187, and 80 ng/mL, respectively. Ecgonine methyl ester (EME) concentrations ranged from 57 to 91 ng/mL. When compared with the 1-min COC concentrations, the mean EME concentration was 30.7%. Benzoylecgonine (BZE) ranged from 34 to 42 ng/mL, and the mean concentration was 11.5% of the mean COC concentration at 1 min. EME and BZE concentrations did not vary appreciably over the time course of the study. Plasma norcocaine concentrations were less than the limit of detection of 25 ng/mL. Because a rapid decline in plasma COC concentrations over time was observed along with a very small change in EME and BZE concentrations, we attribute tissue redistribution of COC, particularly to the brain, as significant and metabolism or hydrolysis of COC as minor.

Animals↗
PubMedDate not supplied

Rapid, simultaneous quantification of morphine, codeine, and hydromorphone by GC/MS.

Morphine, codeine, and hydromorphone were extracted from blood or serum using a one step extraction. The extract was derivatized and the trifluoroacetyl opiates were quantified by GC/MS selected ion monitoring (SIM) using nalorphine as the internal standard. Calibration curves were linear and sensitivity as low as .02 mg/L for morphine and codeine, and .08 mg/L for hydromorphone, was achieved. Urine or tissue homogenates could be processed similarly after acid hydrolysis.

Autoanalysis↗
PubMedDate not supplied

Demonstration of major metabolic pathways for chlordecone (kepone) in humans.

The hypothesis that liver is the site of the previously demonstrated chlordecone alcohol formation in man was tested. Human bile obtained from chlordecone-poisoned factory workers contained substantial amounts of free chlordecone, but little free chlordecone alcohol. However, when the same bile specimens were pretreated with beta-glucuronidase before analysis by gas-liquid chromatography, large amounts of chlordecone alcohol appeared, accounting for 75% of total organochlorine compounds. Confirmation of the identity of chlordecone and chlordecone alcohol was made by using gas liquid chromatography-mass spectrometry. Whereas biliary chlordecone alcohol was present predominantly as its glucuronide conjugate (93%), chlordecone was excreted primarily as the unaltered compound (72%) with only a small portion conjugated with glucuronic acid (9%). The remaining fraction of the total chlordecone measured in bile appeared to be a stable polar metabolite resistant to beta-glucuronidase. This unidentified metabolite could be converted to free chlordecone only by acid hydrolysis under harsh conditions. In contrast to human bile, rat bile contained only trace amounts of chlordecone alcohol (less than 0.5% of total chlordecone), thus indicating that hepatic metabolism of chlordecone is species-specific. We conclude that in man, the major metabolic route for chlordecone is its reduction in the liver followed by glucuronidation.

Animals↗