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Biomedical subjects

T P Murphy

Publications and source records attributed to T P Murphy.

At least 19 recordsLinked to original sources
PubMed2001

GC-MS determination of heroin metabolites in meconium: evaluation of four solid-phase extraction cartridges.

A procedure for extraction of heroin and metabolites for gas chromatography-mass spectrometry (GC-MS) analysis of meconium specimens that would allow detection of these analytes at low levels was needed. Solid-phase extraction (SPE) cartridges were therefore evaluated for their effectiveness in sample preparation. Four different types of commercially available extraction cartridges were used. Heroin, 6-monoacetylmorphine (6-MAM), morphine, and codeine were extracted from meconium samples using these SPE cartridges and then simultaneously analyzed using GC-MS. In each case, the extraction efficiency, linearity range, limit of detection (LOD), limit of quantitation (LOQ), between-run precision, and within-run precision were determined. Although satisfactory results were obtained with the four different types of SPE cartridges, best overall performance was observed using Clean Screen columns following the procedures outlined here. LODs as low as 20 ng/g for codeine, 10 ng/g for morphine, and 2.5 ng/g for 6-MAM were obtained, and LOQs as low as 20 ng/g for codeine, 10 ng/g for morphine, and 5 ng/g for 6-MAM were obtained. In all cases linearities were observed (r = > 0.99) for codeine, morphine, and 6-MAM over a wide concentration range (100-2000, 100-2000, and 5-100, respectively). At 50 ng/g codeine and morphine and 10 ng/g 6-MAM, the precision of analysis using these cartridges showed coefficients of variation ranging from 4.75% to 15.5%.

Codeine↗
PubMed2001

Identification and quantitation of 11-nor-delta9-tetrahydrocannabivarin-9-carboxylic acid, a major metabolite of delta9-tetrahydrocannabivarin.

After incubation of delta9-tetrahydrocannabivarin with human hepatocytes, a major metabolic product was detected by gas chromatography-mass spectrometry that showed identical retention time and mass spectrum to the synthetic 11-nor-delta9-tetrahydrocannabivarin-9-carboxylic acid (11-nor-delta9-THCV-9-COOH). Analysis of human urine specimens from marijuana users and plasma samples from Marinol users showed that 11-nor-delta9-THCV-9-COOH was only present in urine specimens of marijuana users. These results supported the conclusion that identification of 11-nor-delta9-THCV-9-COOH in a donor's urine specimen indicates the use or ingestion of cannabis-related product(s) and would not explain the sole use of Marinol.

Chromatography, High Pressure Liquid↗
PubMed2001

Delta9-tetrahydrocannabivarin as a marker for the ingestion of marijuana versus Marinol: results of a clinical study.

Delta9-tetrahydrocannabinol (THC), the main psychologically active ingredient of the cannabis plant (marijuana), has been prepared synthetically and used as the bulk active ingredient of Marinol, which was approved by the FDA for the control of nausea and vomiting in cancer patients receiving chemotherapy and as an appetite stimulant for AIDS patients. Because the natural and the synthetic THC are identical in all respects, it is impossible to determine the source of the urinary metabolite of THC, 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), in a urine specimen provided in a drug-testing program. Over the last few years there has been a need to determine whether a marijuana positive drug test is the result of the ingestion of marijuana (or a related product) or whether it results from the sole use of Marinol. We have previously proposed the use of delta9-tetrahydrocannabivarin (THCV, the C3 homologue of THC) as a marker for the ingestion of marijuana (or a related product) because THCV is a natural component of most cannabis products along with THC and does not exist in Marinol. We have also reported that THCV is metabolized by human hepatocytes to 11-nor-delta9-tetrahydrocannabivarin-9-carboxylic acid (THCV-COOH); therefore, the presence of the latter in a urine specimen would indicate that the donor must have used marijuana or a related product (with or without Marinol). In this study, we provide clinical data showing that THCV-COOH is detected in urine specimens collected from human subjects only after the ingestion of marijuana and not after the ingestion of Marinol (whether the latter is ingested orally or by smoking). Four subjects (male and female) participated in the study in a three-session, within-subject, crossover design. The sessions were conducted at one-week intervals. Each subject received, in separate sessions and in randomized order, an oral dose of Marinol (15 mg), a smoked dose of THC (16.88 mg) in a placebo marijuana cigarette, or a smoked dose of marijuana (2.11% THC and 0.12% THCV). Urine samples were collected and vital signs were monitored every 2 h for a 6-h period following drug administration. Subjects were then transported home, were given sample collection containers and logbooks, and were instructed to record at home the volume and time of every urine collection for 24 h, and once a day for the remainder of a week (6 days). Subjects were also instructed to freeze the urine samples until the next session. All urine samples were analyzed by GC-MS for THC-COOH and THCV-COOH using solid-phase extraction and derivatization procedure on RapidTrace and TBDMS as the derivative. The method had a limit of detection of 1.0 ng/mL and 1.0 ng/mL for THCV-COOH and THC-COOH, respectively.

Administration, Oral↗
PubMed2000

Fibrin sheath stripping versus catheter exchange for the treatment of failed tunneled hemodialysis catheters: randomized clinical trial.

PURPOSE: To compare the effectiveness of two treatments for tunneled hemodialysis catheter malfunction: percutaneous fibrin sheath stripping (PFSS) and over-the-wire catheter exchange (EX). MATERIALS AND METHODS: Adult patients with poorly functioning tunneled hemodialysis catheters (flow rates < 200 mL/min) were randomly assigned to receive either PFSS or EX. Over the course of 20 months, 30 patients (37 encounters) referred to a single institution met the inclusion criteria and consented to participate. PFSS employed transcatheter snares via femoral vein puncture, whereas EX was performed over a guide wire with use of fluoroscopic guidance. Patients were followed up to determine the duration of continued adequate hemodialysis via manipulated catheters for up to 4 months (primary outcome measure). RESULTS: Overall technical success rate was 97%. Mean catheter patency for the PFSS group was 24.5 +/- 29.3 days, and 52.2 +/- 43 days for the EX group (P < .0001). After EX, patency rates at 1, 2, 3, and 4 months were 71%, 33%, 27%, and 27%, compared to 31%, 16%, 7%, and 0% after PFSS (P = .04, logrank test). Exchanged catheters were significantly more likely to be patent for as long as 4 months (23% versus 0%; P < .05, chi2 test). CONCLUSIONS: Malfunctioning tunneled hemodialysis catheters treated by means of EX are significantly more likely to remain patent for up to 4 months than are those treated by means of PFSS. According to the results of this trial, PFSS should not be performed as a routine therapy for catheter malfunction.

Adult↗
PubMed2000

Thrombolytic therapy with use of alteplase (rt-PA) in peripheral arterial occlusive disease: review of the clinical literature. The Advisory Panel.

PURPOSE: The clinical literature describing the use of alteplase in the treatment of peripheral arterial occlusive (PAO) disease is reviewed. MATERIALS AND METHODS: The literature database was acquired by a MEDLINE search using the Boolean keyword string: tissue plasminogen activator and/or rt-PA and peripheral not animal. A review was performed to identify the dose range of alteplase, technique of infusion, use of anticoagulation, clinical success rates, and risk of complications. RESULTS: Forty-six clinical studies were identified. There are few prospective, randomized clinical trials and a lack of standardized protocols and endpoints. Use of catheter-directed infusions of recombinant tissue plasminogen activator (rt-PA) may be beneficial versus surgery in the initial management of acute limb ischemia (< 14 days) and in reducing the magnitude of subsequent surgical or percutaneous revascularization. For patients with chronic limb ischemia (> 14 days), irreversible acute limb ischemia, or advanced diabetic arteriopathy, catheter-directed infusion of rt-PA or other plasminogen activators may be unsuitable. The risk of adverse bleeding appears related to the overall dose and duration of infusion. These risks appear similar to those of urokinase. The role of heparin in increasing adverse bleeding during rt-PA therapy is unclear. CONCLUSIONS: There is no generally accepted dose or technique for administering catheter-directed thrombolysis using alteplase; however, several studies have demonstrated its clinical safety and efficacy. Formal studies will be required to determine the optimal dose, technique of infusion, the role of anticoagulation, and complication rates when alteplase is used for PAO disease.

Arterial Occlusive Diseases↗
PubMed2000

Hearing results in pediatric patients with chronic otitis media after ossicular reconstruction with partial ossicular replacement prostheses and total ossicular replacement prostheses.

OBJECTIVE: To examine hearing results in pediatric patients after ossicular reconstruction with partial ossicular replacement prostheses (PORPs) and total ossicular replacement prostheses (TORPs) in children with chronic otitis media. METHODS: A retrospective chart review was performed on 55 pediatric patients with chronic otitis media who underwent ossicular reconstruction from 1991 to 1998. Patients' audiograms were evaluated preoperatively and postoperatively for pure-tone average (PTA), air-bone gap (ABG), speech reception threshold (SRT), method of ossicular reconstruction, and management of the mastoid. RESULTS: Twenty-seven patients underwent ossicular reconstruction with TORPs. The average preoperative ABG was 40.1 dB, and the average postoperative ABG was 31.6 dB. Forty-one percent of the children improved their PTA greater than 10 dB postoperatively, and 52% of children did not change their ABG by more than 10 dB postoperatively. Nineteen percent of children with TORPs had a postoperative ABG less than 20 dB, and 44% of children with TORPs had a postoperative ABG less than 30 dB. Twenty-eight patients underwent ossicular reconstruction with PORPs. The average preoperative ABG was 29.7 dB, and the average postoperative ABG was 22.5 dB. Thirty-two percent of patients improved their PTA by greater than 10 dB, while 57% of children with PORPs did not change their ABG by more than 10 dB postoperatively. Forty-three percent of children with PORPs had an ABG of less than 20 dB postoperatively, and 71% of children with PORPs had a postoperative ABG less than or equal to 30 dB. CONCLUSIONS: Children who underwent ossicular reconstruction with PORPs had slightly better postoperative hearing than did children with TORPs. Postoperative hearing was essentially unchanged in approximately 55% of both groups. Preoperative hearing levels may be the most important factor determining postoperative hearing in nonstaged surgery for children with chronic otitis media Long-term hearing results in children with single-stage surgery were not as good as those reported in the literature for staged surgery. Severe mucosal disease and eustachian tube dysfunction may contribute to poorer hearing results in children.

Audiometry, Pure-Tone↗
PubMed1999

Immunoassay and GC-MS procedures for the analysis of drugs of abuse in meconium.

The analysis of meconium specimens for metabolites of substances of abuse is a relatively accurate method for the detection of fetal exposure to drugs. Most of the methods reported in the literature before the early 1990s relied on radioimmunoassays. The purpose of this study was to develop and validate methods for meconium sample preparation for the screening and gas chromatography-mass spectrometry (GC-MS) confirmation of meconium extracts for cannabinoids, cocaine, opiates, amphetamines, and phencyclidine. EMIT and TDx immunoassays were evaluated as screening methods. The sample preparation method developed for screening included extraction and purification prior to analysis. Cutoff levels were administratively set at 20 ng/g for 11-nor-delta9-THC-9-COOH (THCCOOH) and phencyclidine and at 200 ng/g for benzoylecgonine, morphine, and amphetamines, although lower levels could be detected in meconium using the EMIT-ETS system. Ninety-five meconium specimens were subjected to the screening procedure with GC-MS confirmation of presumptive positives. In addition, 30 (40 for cocaine) meconium specimens were subjected to GC-MS analysis for all analytes regardless of the screening results to determine the false-negative rate, if any, of the immunoassay. Although there were no false negatives detected, the GC-MS confirmation rate for the immunoassay-positive specimens was generally low, ranging from 0% for amphetamines to 75% for opiates. The lowest rate of confirmed positives was found with the cannabinoids, suggesting that tetrahydrocannabinol (THC) metabolites other than free 11-nor-9-carboxy-delta9-THC may be major contributors to the immunoassay response in meconium.

Amphetamine↗
PubMed1999

Identification and analysis of the major metabolites of cocaine in meconium.

A gas chromatographic-mass spectrometric (GC-MS) method was used for the simultaneous analysis of cocaine and its metabolites (norcocaine, benzoylecgonine, norbenzoylecgonine, ecgonine methylester, cocaethylene, and the o-, m, and p-hydroxy derivatives of cocaine and benzoylecgonine) in meconium specimens collected from newborns prenatally exposed to the drug in an effort to determine which of these metabolites are more relevant in the confirmation of immunoassay-positive specimens. Significant metabolites included benzoylecgonine and its m- and p-hydroxy derivatives. Reanalysis of immunoassay-positive meconium specimens that previously failed to confirm by GC-MS for benzoylecgonine revealed that the GC-MS confirmation rate could be substantially enhanced by inclusion of m- and p-hydroxybenzoylecgonine in the analysis along with benzoylecgonine. Several specimens were found to be positive for hydroxylated derivative(s) in the absence of benzoylecgonine itself.

Cocaine↗
PubMed1999

An inquiry-based teaching tool for understanding arterial blood pressure regulation and cardiovascular function.

Educators are placing a greater emphasis on the development of cooperative laboratory experiences that supplement the traditional lecture format. The new laboratory materials should encourage active learning, problem-solving, and inquiry-based approaches. To address these goals, we developed a laboratory exercise designed to introduce students to the hemodynamic variables (heart rate, stroke volume, total peripheral resistance, and compliance) that alter arterial pressure. For this experience, students are presented with "unknown" chart recordings illustrating pulsatile arterial pressure before and in response to several interventions. Students must analyze and interpret these unknown recordings and match each recording with the appropriate intervention. These active learning procedures help students understand and apply basic science concepts in a challenging and interactive format. Furthermore, laboratory experiences may enhance the students' level of understanding and ability to synthesize and apply information. In conducting this exercise, students are introduced to the joys and excitement of inquiry-based learning through experimentation.

Blood Pressure↗
PubMed1999

Acute vertebrobasilar occlusion: treatment with high-dose intraarterial urokinase.

OBJECTIVE: The purpose of this study was to describe our successful experience with high-dose intraarterial urokinase therapy in treating acute, life-threatening vertebrobasilar occlusion. CONCLUSION: We successfully treated five patients with acute vertebrobasilar occlusion who presented up to 24 hr after the onset of symptoms. Higher doses of urokinase than are commonly reported in the literature were used in this series at a rapid infusion rate with a "pulse-spray" technique. The result was prompt thrombolysis and good clinical outcome.

Acute Disease↗