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Biomedical subjects

B Levine

Publications and source records attributed to B Levine.

At least 235 records · Page 13Linked to original sources

PACS clinical experience at Georgetown University.

Georgetown University Hospital has been operating an image management and communications system (IMACS or PACS) for three-and-a-half years. This work was initially funded under the Army Medical Research and Development Command Digital Imaging Network Systems (DINS) project. The system was taken from a research system supporting only radiology tasks to one extended to clinical use, and has been used in clinical work for two-and-a-half years. This paper will summarize our PACS clinical experience and will describe the operational features implemented and those still necessary.

Computer Systems↗

Expression of a biologically active antiviral antibody using a sindbis virus vector system.

Monoclonal antibodies to the Sindbis virus E2 envelope glycoprotein protect mice against lethal encephalitis and mediate viral clearance from neurons. To facilitate structure-function analyses of anti-E2 mAbs, we developed an expression system that can be used for the construction of genetically engineered anti-E2 mAbs. We constructed recombinant Sindbis/immunoglobulin gene chimeric viruses that express heavy and light chains of an anti-E2 monoclonal antibody, R6. We used a PCR-based strategy to clone the entire rearranged heavy and light chain genes from R6 hybridoma cell cDNA into a double subgenomic Sindbis virus vector. The recombinant viruses, SIN/R6L and SIN/R6H, were generated by transfecting BHK-21 cells with in vitro transcribed RNA from Sindbis virus/R6 light chain and Sindbis virus/R6 heavy chain cDNA clones, respectively. Twelve hours after co-infection of BHK cells with SIN/R6L and SIN/R6H, the tissue culture supernatant contained up to 1.4 mg/ml of recombinant R6 IgG. The heavy and light chains of recombinant R6 were associated as judged by co-purification on protein A/G sepharose and co-electrophoresis of non-reduced proteins. The ELISA reactivity to Sindbis virus antigen was similar for recombinant R6 and R6 purified from ascites fluid. Furthermore, the in vivo biologic activity of recombinant R6 was similar to that of R6 purified from ascites; recombinant R6 treatment completely protected Balb/cJ mice from paralysis and death due to infection with neuroadapted Sindbis virus and also resulted in the clearance of infectious virus from the brains of immunodeficient scid mice persistently infected with wild-type Sindbis virus. Thus, the co-infection of BHK cells with SIN/R6L and SIN/R6H leads to the expression, assembly, and secretion of a biologically active recombinant antiviral antibody. Our results suggest that the Sindbis virus vector system is a simple and powerful tool for the production of functional, genetically engineered antibodies.

Amino Acid Sequence↗

Quality of well being in panic disorder: the assessment of psychiatric and general disability.

BACKGROUND: Panic disorder is a common and debilitating anxiety disorder which significantly disrupts the lives of patients and their family members. Recent epidemiological studies and analyses of data from clinical trials suggest that patients with panic disorder suffer significant work and social dysfunction. The authors hypothesized that this dysfunction could be characterized using both a well-validated, generalized scale of functioning and a specifically designed scale for assessing function in psychiatric patients and that these findings would correlate with symptomatology. METHOD: Fifty-six patients with panic disorder were characterized using the Sheehan Disability Scale, the Anxiety Sensitivity Index, and the Spielberger State Trait Anxiety Scale. Measures of health related quality of life from the Quality of Well Being Scale were compared with ratings for matched, historical, and population controls. RESULTS: Patients with panic disorder lost 39 quality-adjusted days for each year that they lived with the disorder. This decrease in quality of life is similar to what is observed in patients with non-insulin dependent diabetes. Diminished quality of life is correlated with the number of panic attacks, state anxiety, and depressive symptoms. These patients also demonstrated significant dysfunction in Sheehan total disability and subscale scores, including work-related functioning. CONCLUSIONS: This study demonstrates that the specific disabilities inherent in panic disorder can be linked to declines in quality of life as measured by the Quality of Well Being Scale and by measures of work-related dysfunction. Such an association between disease specific measures and a generalized measure of health related quality of life may offer clinicians a new tool to understand panic disorder and to conceptualize it within the broader context of disease and disability.

Adult↗

Deployable teleradiology and telemedicine for the US military.

The US military has been an effective proponent of digital imaging and teleradiology for the past 15 years. A digital imaging network that can eliminate the use of X-ray film can make the requirements simpler for military medicine. X-ray film requires the storage of new, unexposed films that have a fixed shelf life, and the storage and use of chemicals and water for processing. In some deployed situations, the chemical discharge has to be collected and shipped out of the deployed area. The technology of electronic imaging is therefore intrinsically important to military medicine. In December of 1995, the US government started to deploy 20000 US troops to Bosnia-Herzegovina as part of NATO's peace keeping operation (IFOR). A full complement of medical support facilities was to be established in the Bosnia region and Hungary where the deployment was staged. Primetime III was a project to deploy telemedicine and teleradiology capabilities linking these medical treatment facilities (MTF). The deployment of telemedicine was not the responsibility of our engineering team. This paper deals with the deployable teleradiology (DEPRAD) system that was installed by the ISIS Center at a number of facilities for filmless radiology and teleradiology services.

Evaluation Studies as Topic↗

Assessment of the acuteness of heroin deaths from the analysis of multiple blood specimens.

Data was compiled from 126 morphine-involved cases investigated by the Office of the Chief Medical Examiner, State of Maryland, USA. An investigation was conducted into whether comparison of morphine concentrations from a central and peripheral site could be used to determine whether a morphine death was acute or delayed. Fifty cases were identified as 'acute' because the urine free morphine concentration by radioimmunoassay (RIA) was less than 25 ng/mL; 76 cases were classified as 'random' because they had a urine morphine concentration greater than 25 ng/mL by RIA. The average heart blood to peripheral blood morphine concentration ratio in the acute deaths was 1.40. The average heart blood to peripheral blood morphine concentration ratio in the random deaths was 1.18. Because there was considerable overlap between the two groups of data, the authors conclude that it was not possible to predict 'acute' opiate intoxication deaths versus 'delayed' deaths when the only information available is heart and peripheral blood free morphine concentrations.

Drug Overdose↗

Alcohol concentration and the ability to form intent.

The ability to form intent to commit a particular act is often a significant issue in criminal litigation. Often, a complicating factor in the resolution of this issue is the presence of ethanol and drugs in the individual whose motives are to be ascertained. To determine whether an intoxicating blood ethanol concentration (BAC) in the absence of other information is sufficient to establish intent, we reviewed cases investigated by the Office of the Chief Medical Examiner, State of Maryland over a two-year period. Specifically, we identified cases of suicide with a suicide note, the presence of ethanol and the absence of other psychoactive drugs. The BACs ranged from 0.01 to 0.37 g/dL. The average BAC was 0.14 g/dL and the median BAC was 0.13 g/dL. Twenty-five of the 37 cases had a BAC greater than 0.08 g/dL. We conclude that a BAC alone is not sufficient to determine the capability of an individual to form intent to commit a particular act.

Alcohol Drinking↗

The analysis of ethanol in serum, blood, and urine: a comparison of the TDx REA ethanol assay with gas chromatography.

Studies were performed to evaluate two Abbott TDx ethanol assays, one which is commercially available (TDx-INT) and the other which is under experimental trial (TDx-MTT). Both assays employ radiative energy attenuation (REA) and differ only in the dye used for the chromogen. TDx-INT and TDx-MTT were compared to a headspace gas chromatographic method of analysis. Four types of specimens were studied: serum, urine, postmortem blood, and blood from intoxicated drivers (DWI). Specimens not containing ethanol were also analyzed. Statistical evaluation by least square regression analysis revealed good correlation (greater than 0.98) for each group when ethanol values obtained by either TDx method were compared to the value obtained by gas chromatography. The slopes of the lines ranged from 0.96 to 1.02.

Chromatography, Gas↗

Fatality resulting from methylphenidate overdose.

A case involving an accidental overdose fatality resulting from an intravenous injection of crushed Ritalin (methylphenidate) tablets is presented. The drug was quantified by gas chromatography/nitrogen-phosphorus detection and confirmed by gas chromatography/mass spectrometry. Concentrations of drug were as follows: blood, 2.8 mg/L; bile, 5.7 mg/L; kidney, 3.0 mg/kg; liver, 2.1 mg/kg; and stomach contents, 1.6 mg total. Other drugs and volatile substances were not detected.

Adult↗

Application of the Abbott TDx lidocaine, phenytoin, and phenobarbital assays to postmortem blood specimens.

The TDx fluorescence polarization immunoassays (FPIA) for some therapeutically monitored drugs (lidocaine, phenytoin, phenobarbital) were applied to the analysis of postmortem blood specimens. After an initial calibration using the appropriate TDx calibrators, blood bank blood fortified with known amounts of drug was analyzed by FPIA. Postmortem blood specimens containing the drugs, postmortem specimens not containing the drugs of interest (negatives), and randomly selected postmortem blood specimens fortified with known amounts of the drugs were analyzed by the FPIA and reference gas chromatographic (GC) methods. Concentrations determined in blood bank and postmortem blood specimens showed excellent correlation between the two methods and produced lines with slopes ranging from 0.98 to 1.08. In each case the correlation coefficient was greater than 0.97. Analysis of all negative specimens produced FPIA values below the limit of quantitation of the reference GC assay.

Autopsy↗

Abbott phencyclidine and barbiturates abused drug assays: evaluation and comparison of ADx FPIA, TDx FPIA, EMIT, and GC/MS methods.

This study evaluated the capability of the Abbott ADx assays to test for phencyclidine (PCP) and barbiturates in urine specimens by comparison to TDx, EMIT, and gas chromatographic/mass spectrometric (GC/MS) methods. Within-run and between-run precision were determined using three control samples (35, 100, and 250 ng/mL PCP; 0.4, 0.6, and 1.0 mg/L secobarbital) tested over a two-week period. Controls were analyzed in both single assay (batch) and multiple assay (combination) modes. Within-run coefficients of variation (CVs) for the three PCP controls were 2.4, 2.6, and 2.2%, respectively; the between-run CVs were 4.0, 3.5, and 2.8%, respectively. The within-run CVs for the three barbiturate controls were 3.0, 2.7, and 2.7%, respectively; the between-run CVs were 5.6, 4.7, and 4.5%, respectively. Fifty specimens not containing PCP or barbiturates, 50 specimens containing PCP, and 50 specimens containing barbiturates were tested by ADx, TDx, EMIT, and GC/MS. The methods compared favorably and no false positive or false negative results were obtained by any immunoassay method for any assay when compared to GC/MS.

Barbiturates↗

Vitreous humor in the evaluation of postmortem blood ethanol concentrations.

Many studies have been published comparing blood (B) ethanol (EtOH) and vitreous humor (VH) EtOH concentrations. We conducted a similar study of routinely collected specimens to determine (1) whether the reported average VH/B ratios are consistent, (2) the percentage of cases with VH/B ratios outside of the expected range, and (3) the magnitude of B EtOH that can be associated with negative VH EtOH (less than 0.01 g/dL). VH EtOH less than 0.01 g/dL was associated with 41 specimens; 34 specimens had B EtOH less than 0.03 g/dL while a B EtOH as high as 0.12 g/dL was measured. For B EtOH less than 0.10 g/dL, 67% had VH EtOH within 0.02 g/dL of B EtOH (N = 101). For B EtOH greater than or equal to 0.10 g/dL, the VH/B EtOH ratio ranged from 0.10 to 1.91; the mean ratio was 1.17 and the median ratio was 1.18 (N = 205); and 64% had a ratio between 1.00 and 1.39. Vitreous humor can be used to facilitate understanding the significance of postmortem blood EtOH concentrations.

Chromatography, Gas↗

Flecainide intoxication.

A fatal case attributed to flecainide intoxication is presented. Quantitation was by capillary gas chromatography with nitrogen-phosphorus detection. The flecainide concentration in the blood was 13 mg/L as compared to a therapeutic range in serum of 0.2-1.0 mg/L. Flecainide concentrations in other specimens were as follows: bile, 160 mg/L; urine, 54 mg/L; vitreous humor, 7.4 mg/L; liver, 180 mg/kg; kidney, 74 mg/kg; and stomach contents, 120 mg.

Adult↗

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↗

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↗

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↗

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↗

Simultaneous assay of buprenorphine and norbuprenorphine by negative chemical ionization tandem mass spectrometry.

A method for the simultaneous measurement of buprenorphine and its N-dealkylated metabolite, norbuprenorphine, in human plasma was developed with negative chemical ionization tandem mass spectrometry. Buprenorphine and norbuprenorphine were extracted from biological fluids by solid-phase extraction. The samples were derivatized with heptafluorobutyric anhydride and measured with negative chemical ionization tandem mass spectrometry. Buprenorphine formed a heptafluorobutyryl derivative and norbuprenorphine formed a bis-heptafluorobutyryl derivative; consequently, the sensitivity of norbuprenorphine was substantially higher than buprenorphine. The limit of quantitation (LOQ) for buprenorphine was 0.20 ng/mL, and the LOQ for norbuprenorphine was 0.03 ng/mL. Daily calibration curves were prepared. Buprenorphine was linear from 0.15 ng/mL to 20 ng/mL, and norbuprenorphine was linear between 0.016 ng/mL and 5 ng/mL. Between-run and within-run precision for buprenorphine at 0.5 ng/mL were 13.8% and 9.8%, respectively. Between-run and within-run precision for norbuprenorphine at 0.5 ng/mL were 23.1% and 17.9%, respectively. The molecular anion for buprenorphine was used as a precursor ion, whereas the [M-197]- was used as a precursor ion for norbuprenorphine in tandem mass spectrometry. Product ion spectra from collision-induced dissociation resulted principally from dissociations of the heptafluorobutyryl group. Monitoring select precursor to product ion reactions and using qualifier ion ratios increased the method's sensitivity and selectivity. The method was applied to samples collected from a patient who received oral and subcutaneous buprenorphine. Buprenorphine plasma concentrations ranged from less than 0.20 ng/mL to 8.7 ng/mL.

Adult↗

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↗