Biomedical subjects

M L Smith

Publications and source records attributed to M L Smith.

At least 505 records · Page 28Linked to original sources

PubMedDate not supplied

Experience with a sulfonamide diuretic in a large urine drug testing program.

Gas chromatography/mass spectrometry (GC/MS) with selected ion monitoring is a common confirmation method for tetrahydrocannabinol (THC) metabolites in urine. Department of Defense laboratories use this method for analysis of 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THCA) following ion exchange column purification and methylation. Furosemide, a common diuretic which is excreted into urine, will be isolated with THCA in the extraction procedure, will appear in the chromatographic window [retention time relative to 11-nor-delta-9-tetrahydrocannabinolmethyl ether-9-carboxylic acid methyl ester (THCA-Me) of 1.13], and will exhibit the six ions monitored for THCA-Me and its trideuterated analog. The results indicate that methylated furosemide and other common diuretics can easily be distinguished from THCA-Me. They also allow one to explain in court the extraneous peaks in a chromatogram and to correct for the overutilization of derivatizing reagent.

Diuretics↗

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Detection of amphetamine and methamphetamine in urine by gas chromatography/mass spectrometry following derivatization with (-)-menthyl chloroformate.

A gas chromatography/mass spectrometry assay was developed for the detection of amphetamine and methamphetamine in urine. These drugs were detected as carbamate derivatives following reaction with (-)-menthyl chloroformate. Selected ion monitoring of the 226, 182, and 227 dalton ions for amphetamine and the 240, 102, and 196 dalton ions for methamphetamine provided positive analyte identification. Quantitative values obtained by isotope dilution mass spectrometry displayed a linear response from below 50 to above 6,000 ng/mL. Differentiation of over-the-counter (R)-methamphetamine from illicit (S)-methamphetamine was accomplished by chromatographic separation of the diastereomeric derivatives on an achiral column. No interferences were observed from ephedrine, pseudoephedrine, phentermine, phenylpropanolamine, or 2-phenylethylamine.

Amphetamine↗

PubMedDate not supplied

Analysis of spleen specimens for carbon monoxide.

Crucial to the investigation of aircraft fatalities is the analysis of biological specimens for carbon monoxide (CO). In many cases, blood specimens are unavailable or unsuitable for analysis, and the testing of an alternate specimen for CO becomes necessary. Spleen specimens provide a rich source of red blood cells and hence can be a primary substitute for blood. To verify this, 40 paired blood and spleen specimens were analyzed for CO by using a gas chromatographic method. Ten specimens with a spleen CO saturation level (sat.) of less than 10% were associated with corresponding blood specimens with CO sat. less than 10%. Fifteen of the 18 spleen specimens with CO sat. greater than 29% were associated with blood specimens with greater than 48% sat. Results were inconclusive when the spleen CO sat. was between 10 and 29%. We concluded that spleen CO sat. can reflect blood CO sat. in certain situations, particularly when spleen CO sat. is high.

Carbon Monoxide↗

PubMedDate not supplied

Evaluation of six commercial amphetamine and methamphetamine immunoassays for cross-reactivity to phenylpropanolamine and ephedrine in urine.

We evaluated six commercially available amphetamine (A) and methamphetamine (MA) immunoassays for their relative cross-reactivities to isomers of phenylpropanolamine (PPA) and ephedrine (E) in urine: Syva EMIT, Abbott fluorescence polarization (FPIA), Roche, and Diagnostic Products Corporation (DPC) radioimmunoassays for A and MA. Two stereoisomers of PPA and four stereoisomers of E were tested using (1) drug-free urine spiked at 1,000 mg/L or 100 mg/L of each compound and (2) 60 clinical urine specimens not containing A or MA but having varying amounts of PPA and/or E. Specimens responding greater than the 1-mg/L A or MA cutoff were defined as positive. All specimens spiked at 100 mg/L were negative by all immunoassays. All specimens spiked at 1,000 mg/L were positive by EMIT and negative by FPIA, Roche A, and DPC A; 1,000 mg/L/-E and d-pseudoephedrine were also positive by Roche MA and DPC MA. Three of the 60 clinical specimens tested positive by EMIT and one specimen tested positive by DPC A and DPC MA.

Amphetamine↗

PubMedDate not supplied

Feasibility of using GC/FT-IR for drug analysis in the forensic toxicology laboratory.

New developments in cryogenic sample deposition for gas chromatography/Fourier transform infrared (GC/FT-IR) spectroscopy have increased the sensitivity of the technique 100-1000-fold, to match or surpass that of gas chromatography/mass spectrometry (GC/MS). The current methods of GC/MS have led to some false positive identifications in drug testing labs. New methods employing GC/FT-IR will provide absolute identification through infrared fingerprinting with routine detection in the ppb range. GC/FT-IR methods are being developed which indicate low picogram amounts of material are detectable. Some preliminary data have shown that reference-quality spectra can be obtained from samples containing 200 ng/mL of amphetamines, and spectra from samples below the 25 ng/mL level for amphetamines can be obtained for identification purposes. These and other applications will be addressed along with limit of detection (LOD), limit of quantitation (LOQ), and linearity in comparison to commonly used techniques.

Chromatography, Gas↗

PubMedDate not supplied

Forensic drug testing for opiates. VI. Urine testing for hydromorphone, hydrocodone, oxymorphone, and oxycodone with commercial opiate immunoassays and gas chromatography-mass spectrometry.

Opiate testing for morphine and codeine is performed routinely in forensic urine drug-testing laboratories in an effort to identify illicit opiate abusers. In addition to heroin, the 6-keto-opioids, including hydromorphone, hydrocodone, oxymorphone, and oxycodone, have high abuse liability and are self-administered by opiate abusers, but only limited information is available on detection of these compounds by current immunoassay and gas chromatographic-mass spectrometric (GC-MS) methods. In this study, single doses of hydromorphone, hydrocodone, oxymorphone, and oxycodone were administered to human subjects, and urine samples were collected before and periodically after dosing. Opiate levels were determined in a quantitative mode with four commercial immunoassays, TDx opiates (TDx), Abuscreen radioimmunoassay (ABUS), Coat-A-Count morphine in urine (CAC), and EMIT d.a.u. opiate assay (EMIT), and by GC-MS. GC-MS assay results indicated that hydromorphone, hydrocodone, oxymorphone, and oxycodone administration resulted in rapid excretion of parent drug and O-demethylated metabolites in urine. Peak concentrations occurred within 8 h after drug administration and declined below 300 ng/mL within 24-48 h. Immunoassay testing indicated that hydromorphone, hydrocodone, and oxycodone, but not oxymorphone, were detectable in urine by TDx and EMIT (300-ng/mL cutoff) for 6-24 h. ABUS detected only hydrocodone, and CAC failed to detect any of the four 6-keto-opioid analgesics. Generally, immunoassays for opiates in urine displayed substantially lower sensitivities for 6-keto-opioids compared with GC-MS. Consequently, urine samples containing low to moderate concentrations of hydromorphone, hydrocodone, oxymorphone, and oxycodone will likely go undetected when tested by conventional immunoassays.

Enzyme Multiplied Immunoassay Technique↗

PubMedDate not supplied

MDA-MDMA concentrations in urine specimens.

Urine specimens collected from active-duty U.S. Army personnel were submitted for analysis to the Tripler Army Medical Center, Forensic Toxicology Drug Testing Laboratory as part of the random drug testing program. During an 18-month drug-screening period, 34 specimens tested positive for amphetamines with the Roche Abuscreen Radioimmunoassay for Methamphetamine (High Specificity); based on gas chromatographic-mass spectrometric (GC-MS) analysis, the presence of 3,4-methylenedioxymethamphetamine (MDMA) was suspected. These samples were subsequently submitted to the Division of Forensic Toxicology, Office of the Armed Forces Medical Examiner, Armed Forces Institute of Pathology for further testing. All 34 samples screened positive using both the Abbott TDx Amphetamine/ Methamphetamine II assay and the Amphetamine class assay. Confirmation and quantitation by GC-MS revealed the presence of both MDMA and 3,4-methylenedioxyamphetamine (MDA) in all samples. The MDMA concentrations ranged from 0.38 to 96.2 mg/L (mean, 13.4 mg/L) and the MDA concentrations ranged from 0.15 to 8.6 mg/L (mean, 1.6 mg/L). The mean ratio of MDA, the N-demethylation metabolite of MDMA, to MDMA was 0.15, similar to the ratio of amphetamine, the N-demethylation metabolite of methamphetamine, to methamphetamine of 0.10. The presence of MDA in urine specimens at a concentration approximately 10-15% that of the MDMA present is consistent with MDMA metabolism, which may be indicative of the use of MDMA only, as compared with the combined use of both drugs.

3,4-Methylenedioxyamphetamine↗

PubMedDate not supplied

Methylephedrine concentrations in blood and urine specimens.

Methylephedrine is a sympathomimetic amine that appears in many over-the-counter cough and cold medications throughout the world. The abuse of methylephedrine-containing medications has been reported in Japan. Although methylephedrine is not available in the United States, it was identified in 15 cases received by the Forensic Toxicology Laboratory, Division of Forensic Toxicology, Office of the Armed Forces Medical Examiner, Armed Forces Institute of Pathology over a two-year period; 12 of the 15 cases were collected from patients or decedents located within the confines of the continental United States. Methylephedrine was identified in each case by gas chromatography-nitrogen-phosphorus detection following an alkaline extraction and subsequently confirmed using full scan electron impact mass spectrometry. Quantitation of underivatized methylephedrine was performed using the same technique. Blood methylephedrine concentrations ranged from less than 0.05 to 0.28 mg/L (n = 14), and the mean methylephedrine concentration in urine was 1.6 mg/L (range, 0.15-6.8, n = 11 [excluding case 6]). A literature search revealed little information pertaining to the interpretation of methylephedrine concentrations in the blood. Six of the 15 cases presented here were positive for methylephedrine in the blood. Three of these cases were postmortem cases, and the other three cases were nonfatal aircraft mishaps. There is no evidence in any of these cases that methylephedrine was present at toxic concentrations; therefore, it appears from the cases reviewed in this study that blood methylephedrine concentrations less than 0.3 mg/L are not associated with significant toxicity.

Cause of Death↗

PubMedDate not supplied

Effects of pyridinium chlorochromate adulterant (urine luck) on testing for drugs of abuse and a method for quantitative detection of chromium (VI) in urine.

Pyridinium chlorochromate (PCC) as an adulterant is popular for concealing drug-positive results. When 11-nor-delta9-THC-9-carboxylic acid (THC-acid) in urine was treated with 2 mmol/L of PCC (Cr6+ 104 microg/mL), 58-100% of the THC-acid was lost. The loss increased with decreasing pH and increasing reaction time (0-3 days). Free codeine and free morphine remained unaffected by PCC at pH within the physiological range of the urine (pH 5-7). At lower pH, the loss of free morphine varied from 0 to 100%. Amphetamine, methamphetamine, benzoylecgonine, and PCP remained unaffected by PCC when exposed to the oxidant for three days in urine pH of 3-7. Chromium (VI) from PCC in a urine solution was detected by a color reaction with 1,5-diphenylcarbazide (DPC). When the reagent was added to the urine, an immediate red-violet color appeared. The chromium-DPC complex showed a characteristic absorption peak at wavelength 544 nm with a shoulder at wavelength 575 nm. The ratio of absorption was used to identify the chromium compound. The concentration of chromium (VI) was determined by measuring absorption at wavelength 544 nm and was linear over 0.5-20 microg/mL. The limit of detection of the procedure was 0.37 microg/mL.

Anti-Infective Agents↗

PubMedDate not supplied

Language and behavior in children with Sotos syndrome.

OBJECTIVE: To examine language and behavior in children with Sotos syndrome, an overgrowth syndrome involving advanced bone age, characteristic facies, and developmental disability. METHOD: Twenty-seven children with Sotos syndrome were compared with 20 children with overgrowth, intellectual disability, and facies not characteristic of Sotos syndrome. Ages ranged from 5 to 16 years. Direct assessment was undertaken with standardized measures of intelligence and language abilities. Behavior was examined by parent and teacher report. RESULTS: Children with Sotos syndrome had levels of intelligence in the severely disabled to average range, with the majority falling in the borderline range. Mean level of intelligence was significantly higher than that observed for children in the comparison group. Language abilities were developed to a level consistent with overall level of intelligence. Rates of parent- and teacher-reported behavior problems were significantly higher than normal, but, with the exception of temper tantrums, did not differ from those observed in children in the comparison group. Attention-deficit hyperactivity disorder was observed in 38% of children with Sotos syndrome. They were more irritable and had more stereotypic behavior and inappropriate speech than is expected in children with intellectual disabilities, and they were more withdrawn and had more stereotypic behavior than children in the comparison group. CONCLUSIONS: Assessment of language abilities revealed no specific language impairment. High rates of behavior problems were observed, but these were not higher than those observed for other large, delayed, dysmorphic children.

Abnormalities, Multiple↗

PubMedDate not supplied

Seminal fluid androgen binding protein.

The following study was undertaken to determine the presence of an androgen binding protein (ABP) in the ejaculate. Seminal fluid was obtained from ten fertile subjects. Sperm counts ranged from 20 x 106/cc to 80 x 106/cc. Each sample was preincubated with tritiated dihydrotestosterone (DHT) and examined by polyacrylamide gel electrophoresis (PAGE). Second, after preincubation of the samples with tritiated DHT, the samples were mixed with Concanavalin-A bound to sepharose-D (C-S) and the supernate separated and counted. Finally, saturation analysis of the samples using dextran-coated charcoal for separation and counted. Finally, saturation analysis of the samples using dextran-coated charcoal for separation was performed and Scatchard analysis was used to determine the concentration of ABP present. PAGE demonstrated ABP in seven of ten samples studied. The bound counts of DHT were removed by C-S. The concentrations of ABP ranged from 0.132 to 0.468 nanomoles ABP/dl semen. These data indicate there is an ABP in seminal fluid similar to that from the Sertoli cell.

Androgen-Binding Protein↗

PubMedDate not supplied

Chronic carbamazepine treatment in the rat: efficacy, toxicity, and effect on plasma and tissue folate concentrations.

Folate depletion has often been a problem in chronic antiepileptic drug (AED) therapy. Carbamazepine (CBZ), a commonly used AED, has been implicated in some clinical studies. A rat model was developed to examine the effects of chronic CBZ treatment on folate concentrations in the rat. In the course of developing this model, a common vehicle, propylene glycol, by itself in high doses, was found to exhibit protective properties against induced seizures and inhibited weight gain. Seizures induced by hexafluorodiethyl ether (HFDE) were also found to be a more sensitive measure of protection by CBZ than seizures induced by maximal electroshock (MES). Oral administration of CBZ as an aqueous suspension every 8 h at a dose of 250 mg/kg was continuously protective against HFDE-induced seizures and was minimally toxic as measured by weight gain over 8 weeks of treatment. The CBZ levels measured in plasma and brain of these animals, however, were below those normally considered protective. This treatment with CBZ had no apparent adverse effect on folate concentrations in the rat, and, indeed, the folate concentration increased in liver after 6 weeks of treatment and in plasma at 8 weeks of treatment.

Aging↗

PubMedDate not supplied

Phenytoin-folate interactions: differing effects of the sodium salt and the free acid of phenytoin.

Chronic phenytoin (PHT) treatment has long been associated with folate deficiency. It has been suggested that pH changes in the gut associated with PHT ingestion may be responsible for decreased folate uptake either by direct inhibition of folate transport into the intestinal mucosa or by inhibition of folate conjugase activity. To examine these possibilities, rats were gavaged chronically with PHT using either the sodium salt (NaPHT) or the free acid (HPHT) in the presence of folic acid as the dietary source of folate. The NaPHT caused a greater depletion of folate in the liver and brain and a significant increase in methylenetetrahydrofolate reductase activity in the liver. The HPHT caused a significantly decreased weight gain over the 8 weeks of treatment and resulted in a much higher liver PHT concentration and a slightly lower plasma PHT concentration. These data support the hypothesis that PHT-induced changes in pH in the gut affect the enterohepatic circulation of folate.

Animals↗

PubMedDate not supplied

From the other side.

Explore the source record for details and available documents.

Coronary Care Units↗

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Ischemia in normo- and hyperglycemic rats: effects on brain water and electrolytes.

Previous investigations have shown that preischemic hyperglycemia worsens cerebral outcome. This study sought to delineate the temporal relations between postischemic brain edema and the development of spontaneous epileptic activity. Fasted rats were subjected to 10 minutes of forebrain ischemia. One-half of the animals were made hyperglycemic by glucose infusion prior to ischemia. At serial recirculation intervals regional specific gravity and cortical electrolytes were measured. Normoglycemic animals showed a biphasic increase in brain water content that was fully resolved by 96 hours and had no convulsive activities. Hyperglycemic brains, although displaying a slower resolution from an initial transient decrease in specific gravity, also developed an interval with normal water content that persisted at 18 hours postischemia. At 24 hours, an increase in water content recurred and was soon followed by the onset of seizure activity. Cortical electrolyte changes were unremarkable until seizures occurred. Significant increases in total Na+, Cl-, and Ca2+ and a decrease in K+ were then seen. We conclude that while the normoglycemic brain is capable of resolving postischemic edema in this model, the hyperglycemic brain develops a delayed secondary increase in water content followed by the onset of seizure activity accompanied by a deterioration of ionic homeostasis.

Animals↗

PubMedDate not supplied

A guideline for cardiopulmonary conditioning in the middle-aged recreational athlete. A physiologic base.

The aging process predisposes man to a greater concern for and sensitivity to his health and fitness. Regular exercise can improve and maintain an individual's general health regardless of the fitness level at the onset of the exercise regimen. We have noted that age does not significantly reduce the benefits (trainability) attained from exercise; however, it does appear that a prolonged sedentary lifestyle will diminish the fitness level that can be achieved. Cardiopulmonary fitness is primarily a function of the oxygen transport system and, therefore, is monitored by determining maximal aerobic capacity (VO2max). The VO2max is a highly reproducible parameter related to cardiac output and the arteriovenous oxygen difference. Exercise conditioning can improve the VO2max by augmenting both the cardiac output and the oxygen extraction within the capillaries. Resting stroke volume is increased by a conditioning effect and resting bradycardia is common. Changes in total peripheral resistance (TPR) and blood pressure are not as readily demonstrable. To produce a conditioning effect and maintain fitness it is recommended that dynamic exercise at intensities of 60 to 90% of the maximum heart rate reserve for at least 15 minutes should be performed at least 3 days/week. The total work load (as a function of intensity and duration) appears to be the most important criterion for producing a conditioning effect. Proper testing and evaluation is necessary for a clinician in prescribing an exercise program that is safe and effective. With the middle-aged individual precautions must be taken to discern any risks for a cardiovascular event or structural injury.

Adult↗

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A good death: is euthanasia the answer?

Euthanasia--particularly active voluntary euthanasia--and assisted suicide are subjects of continuing controversy. Historical attitudes, current concerns, the situation in the Netherlands, and the positions of various medical associations are reviewed. Major arguments for and against active euthanasia are presented, with special consideration to the role that health care providers might be asked to perform should active euthanasia and assisted suicide be given societal sanction. The authors conclude that better pain management and A willingness to provide care within already established ethical and legal guidelines, not the legalization of active euthanasia and assisted suicide, are the appropriate responses to current proposals for assistance in dying.

Attitude↗

PubMedDate not supplied

Futile medical treatment and patient consent.

What are a physician's ethical responsibilities when a patient or surrogate demands futile life-saving treatment? Recent attempts to define medical futility have implications for physician responsibility and may create exceptions to acquiring patient consent. Wording is proposed for a "futility clause" for use in do-not-resuscitate policies.

Consensus↗