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Biomedical subjects

J E Murphy

Publications and source records attributed to J E Murphy.

At least 73 records · Page 4Linked to original sources
PubMed1991

Elevated phenytoin concentration caused by sampling through the drug-administration catheter.

Elevated phenytoin concentrations are a problem due to the toxic effects that can result. When an elevated concentration is reported, it is important to determine the validity of the report because therapeutic action may include withholding further doses. If the concentration is falsely elevated, the potential for seizure activity as it falls is inherent. Assessing validity involves considering laboratory error and assays of blood samples drawn from the wrong patient. The capacity-limited biotransformation of phenytoin complicates the estimation of concentrations, making it more difficult to establish the accuracy of reported values. Our patient had a phenytoin concentration of 80.7 mg/L. It had been 13.4 mg/L the day before, and the patient received only an additional 400 mg prior to the reported high value. The pharmacokinetic team determined that the dose was administered through a triple-lumen catheter from which blood may have been withdrawn for phenytoin analysis the next day. Venous sampling 7 hours after the 80.7-mg/L value yielded a phenytoin concentration of 12.4 mg/L. Clinicians should consider this error potential in the differential evaluation of elevated concentration in apparently nontoxic patients.

Administration, Oral↗
PubMed1990

A comparison of venous versus capillary measurements of drug concentration.

Accessing patient's veins for drug level sampling is not always feasible. The use of capillary sampling techniques is often utilized when venous access is hampered. In the therapeutic monitoring of patients, unexpected drug level results often occur that can be caused by a number of different factors. The possibility that differences in assay results might occur if samples were collected by capillary stick vs. venous phlebotomy was examined by simultaneous sampling in 18 patients. Although correlation was very high (0.999) and percentage differences fairly low (range of 0 to 15.4%), a statistical difference was noted in the sampling methods. The precision was 6.5 +/- 6.58% and there was a slight negative bias (-3.76%), with capillary samples less than venous samples. Although there were statistical differences for the drugs studied in the concentration ranges evaluated, capillary samples should provide fairly small errors when compared to venous samples.

Adult↗
PubMed1990

Effect of cimetidine on oral digoxin absorption.

Cimetidine is a commonly prescribed histamine 2-receptor antagonist used in the treatment of gastric acid-related disorders. Cimetidine can interact with a number of drugs, including theophylline, benzodiazepine sedative hypnotics, warfarin, and antiarrhythmics. Problems may occur in patients receiving drugs with a narrow therapeutic index when combined with cimetidine. Contrasting reports have been published on the potential interaction between digoxin and cimetidine. This study focuses on cimetidine's effect on the pharmacokinetic disposition of chronic digoxin usage. Six hospitalized patients with stable congestive heart failure received their usual maintenance dose of digoxin 0.125-0.25 mg/d po. After confirming steady-state digoxin concentrations, cimetidine 300 mg po q6h was administered. Two patients were dropped from the study. Analysis of digoxin serum concentrations, area under the curve, and the rate of elimination suggested no significant differences in digoxin parameters when combined with cimetidine.

Administration, Oral↗
PubMed1990

Implementing and maintaining a private pharmacokinetics practice.

The development and maintenance of a private-practice pharmacokinetics service is described. A contracted pharmacokinetics service has been in place at Georgia Baptist Medical Center, a 525-bed hospital, for the past eight years. Physician support, inhouse study results, and literature documentation of the benefits of scheduling drug concentration determinations were used to convince hospital administrators of the value of a pharmacokinetics service. Services were reimbursed by increasing the fee charged for each drug concentration determination, with payment made to the pharmacokinetics service on a monthly basis. The service is associated with the pathology department for administrative purposes. Each member of the pharmacokinetics service is credentialed by the medical staff. The group trains part-time personnel to provide services when needed. Services provided by the group but not required by the contract include collecting quality assurance data, conducting research, serving on hospital committees, writing newsletter articles, conducting inservice-education programs, and providing clinical interventions for nonconsultation patients. This private-practice pharmacokinetics service provides high-quality services and is well accepted within the institution.

Drug Information Services↗
PubMed1990

Multidimensional work sampling to quantify a pharmacokinetics resident's duties.

A multidimensional work-sampling technique was used to quantify a pharmacokinetics resident's duties. Four dimensions were measured: activity, contact, function, and location. A code list of 47 variables was developed to encompass all activities of the resident being observed. A combination of self-reporting and observer reporting was used to test the veracity of the resident's report and to determine whether differences in reporting occurred. Observation was done 20 times a day over a five-week period (24 working days). Random time periods separated the observation points. The observer and the resident recorded 260 and 220 observations, respectively, for a total of 480. The overall reliability measure was 78%, indicating good interobserver agreement. The resident spent about 36% of his time doing work related to pharmacokinetics consultations and 23% of his time attending meetings. He spent a large proportion of time (48.5%) working alone. Much of his remaining time was spent with the Pharm.D. students and the preceptors. Multidimensional work sampling based on a combination of self-reporting and observer reporting is a useful tool for quantifying the work practices of pharmacokinetics residents.

Education, Pharmacy, Graduate↗
PubMed1989

Construction and analysis of deletion mutations in the U5 region of Moloney murine leukemia virus: effects on RNA packaging and reverse transcription.

A collection of deletion mutations was generated in the U5 region of cloned DNA copies of Moloney murine leukemia virus or a related retrovirus. Cell lines expressing the mutant DNAs were generated by cotransformation, and the virions released were characterized biochemically. Deletions in the 5' part of U5 profoundly reduced packaging of the viral RNA into virions; one deletion in the 3' part of U5 did not block packaging but affected reverse transcription. One mutant with a deletion in the central part of U5 was fully viable and served to separate the two functional parts of U5.

Animals↗
PubMed1989

The palindromic LTR-LTR junction of Moloney murine leukemia virus is not an efficient substrate for proviral integration.

We generated viral constructs to test the hypothesis that the major substrate on retroviral DNA that is utilized for proviral DNA integration is the palindromic sequence, termed the LTR-LTR junction, normally present in circular molecules formed by joining the two termini of linear proviral DNA. Recombinant viral genomes were built which carried a selectable marker and an extra copy of the LTR-LTR junction from a cloned circular provirus. The junction sequence in each case was positioned such that its use during integration would lead to an easily detected, aberrantly integrated proviral DNA. Analysis of DNA from cells infected with the virus constructs showed that the introduced junction sequence is used at least 1,000-fold less efficiently than the natural sequences at the ends of the genome. This suggests that a linear or more exotic DNA intermediate is most likely the true precursor for the integration reaction.

Animals↗
PubMed1989

Seven years of experience with a pharmacokinetic service.

There have been several reports describing the impact of pharmacokinetic services on cost containment. The purposes of this report are to describe seven years of experience with the operation of a pharmacokinetic service, and the processes used to implement and maintain the service along with a discussion of the impact of the service on hospital cost and patient charge containment. The major functions of the pharmacokinetic service are to; 1) provide clinical pharmacokinetic and pharmacology consultation upon physician request, 2) coordinate the scheduling of serum drug levels (SDLs), and 3) provide quality assurance and utilization review reports related to the service. Data gathered from the service are reported to the medical staff monthly and are incorporated into the hospital's on-going drug usage evaluation. The results of continuous review demonstrate that direct intervention of a pharmacokineticist and a systematic approach to drug level scheduling yielded less than 1% of inappropriately collected SDLs, and in the latest year, a yearly patient charge savings of +116,304. In another study evaluating the service, it was demonstrated that when aminoglycoside dosages are adjusted by a pharmacokineticist, a patient charge savings of +491 per patient is realized. This review of seven years of experience with a pharmacokinetic service supports the conclusion that these services can have a beneficial impact on hospital costs. Furthermore, data gathered from the service can be utilized for the hospital's overall quality assurance program.

Cost Control↗
PubMed1989

Falsely elevated digoxin levels: another look.

Digoxin therapy can cause important toxic events when elevated drug levels occur. Interpreting drug levels can be hampered by artifactual errors such as poor assay quality, incorrect timing or drawing of blood samples, and, as has been demonstrated for tobramycin, errors due to drawing blood through drug administration catheters. A case is reported in which a correctly timed and analyzed digoxin level of 33.60 ng/ml may have been due to drawing the blood sample through a line used to administer digoxin eight hours earlier. Subsequent measurements by venipuncture documented much lower concentrations.

Aged↗
PubMed1988

Piroxicam inhibits the growth of an adenocarcinoma isograft in Fischer rats.

The effect of piroxicam, a nonsteroidal anti-inflammatory drug, on a transplantable adenocarcinoma in Fischer rats was studied. Forty male Fischer rats were injected with 1 X 10(6) DMH-F317 adenocarcinoma cells, and after 2 weeks were assigned to be treated with piroxicam or carrier solution. The groups were as follows: Group 1, control; Group 2, 4.0 mg/kg piroxicam; Group 3, 6.0 mg/kg piroxicam; and Group 4, 8.0 mg/kg piroxicam. Thirty-nine of forty rats developed measurable tumors during this study. At the conclusion, 60% (6/10) of the rats in Group 2 were tumor free compared to 0/10 controls, 0/10 Group 3 rats, and 1/8 Group 4 rats. (P less than 0.005, chi 2). Mean tumor volumes (mm3) were calculated for each group and converted to log10. At Week 6, the mean log10 tumor volume (+/- SEM) for Group 2 was 1.5 +/- 0.6 vs 4.1 +/- 0.1 for Group 1 (P less than 0.05). The mean log10 volume for Group 3 was 3.8 +/- 0.1 (P less than 0.05 vs Group 2). The mean log10 volume for Group 4 was 3.4 +/- 0.05 and was not significantly different from that for Group 2 (P greater than 0.05). Plasma PGE2 levels for each treatment group were determined at the conclusion of the study and no statistical difference between treatment groups was found. It is concluded that piroxicam inhibits tumor growth in this model, and may have a role as a biological response modifier in cancer therapy.

Adenocarcinoma↗