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Biomedical subjects

S D Pearson

Publications and source records attributed to S D Pearson.

50 records · Page 3Linked to original sources

Leaching of diethylhexyl phthalate from polyvinyl chloride containers by selected drugs and formulation components.

The extent of leaching of diethylhexyl phthalate (DEHP) from polyvinyl chloride (PVC) bags by several organic solvents and surfactants used as formulation components and by 12 drug products containing these solvents and surfactants was studied. The organic solvents ethanol, polyethylene glycol, and propylene glycol, the surfactants polysorbate 80 and polyoxyethylated castor oil, and the 12 drugs were admixed separately in PVC bags of 5% dextrose injection. At the time of preparation and after 4, 8, and 24 hours at 24 degrees C, the concentration of DEHP in duplicate samples was determined in duplicate by high-performance liquid chromatography. Ethanol, polyethylene glycol, and propylene glycol at concentrations of 25% and the drugs containing these components did not leach DEHP within the study period. Polysorbate 80 1% to 25% leached detectable amounts of DEHP in as little as one hour at the high concentration and within four hours at the lower concentrations; at 24 hours, DEHP concentrations ranged from 36 micrograms/mL for 1% polysorbate 80 to 237 micrograms/mL for 25% polysorbate 80. Similar results were observed for polysorbate 80 plus ethanol and for polyoxyethylated castor oil plus ethanol. Drug products containing surfactants, including cyclosporine, miconazole, and teniposide, and the vehicles used in formulating taxol and taxotere, leached relatively large amounts of DEHP in 24 hours. Smaller amounts were leached by chlordiazepoxide hydrochloride and etoposide. DEHP was leached from PVC containers by a variety of surfactants and drug products containing these surfactants. Drugs that leach DEHP should be prepared in non-PVC containers and administered through non-PVC tubing.

Chemistry, Pharmaceutical↗

Stability and compatibility of minocycline hydrochloride and rifampin in intravenous solutions at various temperatures.

The stability and compatibility of minocycline hydrochloride and rifampin in intravenous solutions at several temperatures were studied. Triplicate test solutions of (1) minocycline hydrochloride 0.1 mg/mL or rifampin 0.1 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection and (2) minocycline hydrochloride 0.1 mg/mL admixed with rifampin 0.1 mg/mL in 0.9% sodium chloride injection were prepared and stored at various temperatures. Samples were removed at intervals for up to seven days and stored at -70 degrees C until analyzed. Drug concentration was measured by stability-indicating high-performance liquid chromatography. Compatibility was assessed by visual and turbidimetric examination. For the solutions containing the drugs separately, minocycline hydrochloride was stable in both diluents, with the initial concentration declining by 8% at 24 degrees C and 2% at 4 degrees C over seven days. Rifampin was less stable, losing 6-8% of the initial concentration in three days at 4 degrees C and 5-7% in 8 hours and 13-17% in 24 hours at 24 degrees C. There was no change in turbidity in the solutions containing either minocycline hydrochloride or rifampin. The admixture, however, was turbid after 72 hours at 37 degrees C. Minocycline hydrochloride in the admixture was stable for seven days at 24 and 4 degrees C but not for three days at 37 degrees C. The concentration of rifampin decreased 20% in one day at 24 degrees C, 8-10% in three days at 4 degrees C, and 14% in 4 hours and 40% and in 24 hours at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗

The energetics of embryonic growth and development. I. Oxygen consumption, biomass growth, and heat production.

A quantitative phenomenological model to describe the relationships between biomass growth rate, oxygen consumption, and heat production in developing embryos has been developed and tested using a wide range of experimental data. The model employs generalized material and energy balances, principles of enzyme kinetics, and an overall metabolic model scheme based on known biochemical principles. The phosphorylation concentration ratio of ATP and ADP occurs naturally and becomes a significant parameter in the analysis. The model is applied to the growth of Escherichia coli, Oryzias latipes, chick spinal cord, and whole chicken eggs. Excellent agreement between the model and the experimental data is obtained. In a succeeding paper (Part II) environmental effects and growth efficiency are discussed.

Animals↗

Mechanism of false-negative urine cannabinoid immunoassay screens by Visine eyedrops.

To drug-free urine specimens, we added the following drugs of abuse to give concentrations twice the cutoff value for positive test results: 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (9-carboxy-THC), oxazepam, secobarbital, morphine, benzoylecgonine, amphetamine, or phencyclidine (PCP). Visine was then added. Although measured concentrations of several drugs were decreased in the presence of Visine, false-negative results were obtained only for 9-carboxy-THC for the EMIT-d.a.u. and TDx urine cannabinoid assays. Visine also decreased 9-carboxy-THC as measured by the Abuscreen assay. At low concentrations of Visine, false-negative cannabinoid results were attributable to the benzalkonium chloride ingredient of Visine. The added Visine was not detectable by routine urine analysis and had no effect on the activity of the glucose-6-phosphate dehydrogenase-drug conjugate used in the EMIT-d.a.u. assays. Moreover, analysis by gas chromatography/mass spectrometry showed no chemical modification or loss of 9-carboxy-THC in the Visine-adulterated urine specimens. However, Visine did increase the adhesion of 9-carboxy-THC to the borosilicate glass specimen containers. Results of ultrafiltration studies with Visine suggest that 9-carboxy-THC partitions between the aqueous solvent and the hydrophobic interior of benzalkonium chloride micelles, thereby reducing the availability of 9-carboxy-THC in antibody-based assays.

Amphetamine↗

Isolation of high-specific-activity subunits of cholera toxin by reversed-phase high-performance liquid chromatography.

Facile, rapid procedures for the separation of active cholera toxin subunits were developed, based on high-performance liquid chromatography (HPLC) with a Nucleosil C8 reversed-phase column. These procedures were capable of completely resolving subunits A and B as well as S-carboxymethylated or reduced alpha-, gamma-, and beta-chains. The binding of HPLC-purified B subunit to GM1 ganglioside was essentially identical to that of cholera toxin when compared on a molar basis. The adenosine 5'-diphosphate-ribosyltransferase activity of HPLC-purified A subunit, reduced alpha-chain, or carboxymethyl alpha-chain was also determined to be reasonably high compared to that of cholera toxin or commercially prepared A subunit.

Alkylation↗

The inactivation of plasma alpha 1-proteinase inhibitor by nitrous acid.

Exposure of alpha 1-PI to nitrous acid resulted in a complete inactivation of either of its elastase or trypsin inhibitors activities. Amino acid analyses of the nitrous acid treated inhibitor revealed only losses of one tryphanyl and three lysyl residues. Reductive methylation of alpha 1-PI offered no protection against loss of activity by nitrous acid. Since no further loss of lysyl residues was observed upon exposure of fully active reductively methylated alpha 1-PI to nitrous acid, modification of one tryptophanyl residue appears to be responsible for the inhibitor's sensitivity to nitrous acid. Absorption spectral studies of the nitrous acid treated alpha 1-PI indicated that the tryptophanyl residue was modified to its N-nitroso derivative.

Blood Proteins↗

The clinical algorithm nosology: a method for comparing algorithmic guidelines.

Concern regarding the cost and quality of medical care has led to a proliferation of competing clinical practice guidelines. No technique has been described for determining objectively the degree of similarity between alternative guidelines for the same clinical problem. The authors describe the development of the Clinical Algorithm Nosology (CAN), a new method to compare one form of guideline: the clinical algorithm. The CAN measures overall design complexity independent of algorithm content, qualitatively describes the clinical differences between two alternative algorithms, and then scores the degree of similarity between them. CAN algorithm design-complexity scores correlated highly with clinicians' estimates of complexity on an ordinal scale (r = 0.86). Five pairs of clinical algorithms addressing three topics (gallstone lithotripsy, thyroid nodule, and sinusitis) were selected for interrater reliability testing of the CAN clinical-similarity scoring system. Raters categorized the similarity of algorithm pathways in alternative algorithms as "identical," "similar," or "different." Interrater agreement was achieved on 85/109 scores (80%), weighted kappa statistic, k = 0.73. It is concluded that the CAN is a valid method for determining the structural complexity of clinical algorithms, and a reliable method for describing differences and scoring the similarity between algorithms for the same clinical problem. In the future, the CAN may serve to evaluate the reliability of algorithm development programs, and to support providers and purchasers in choosing among alternative clinical guidelines.

Algorithms↗

How managed care can be ethical.

The growth of managed care in the United States has been paralleled by a rising tide of anti-managed care sentiment. The "managed care problem" is understood generally as the need to protect individuals against large companies that care more about their bottom line than about people. The premise of the BEST (Best Ethical Strategies for Managed Care) project is that the "managed care problem" is best understood as an ethical problem--a conflict of values that arises as the country changes from a patient-centered to a population-centered approach to health care. The BEST project team worked with nine managed care organizations to identify their most intractable problems. The team redefined these problems in terms of ethical dilemmas, then studied each organization in search of innovative, exemplary approaches. These exemplary approaches are being shared publicly with the aim that they be adapted and adopted by other organizations facing similar difficulties and by regulators and legislators hoping to improve the health care system.

Benchmarking↗

Direct admission to an extended-care facility from the emergency department.

BACKGROUND: Many patients are admitted to acute-care hospitals when their medical needs might be more appropriately met in an extended-care facility (ECF). OBJECTIVE: To describe a cohort of patients who were admitted from an emergency department to an ECF. DESIGN: Observational cohort study. PARTICIPANTS: 121 enrollees of Harvard Vanguard Medical Associates who were admitted directly from an emergency department to an ECF between October 1, 1994, and December 31, 1997. OUTCOME MEASURES: Mean length of stay, charges per patient, and discharge disposition (discharged to home, discharged to a long-term-care facility, died, or transferred to an acute-care hospital within 30 days of ECF admission). RESULTS: Patients admitted directly to an ECF were generally frail and elderly (median age, 75 years). Mean length of stay in the ECF was 11 days; the mean per-patient charge was $3290. Three quarters of patients were discharged from the ECF to their homes. Six percent (seven patients) were transferred from the ECF to an acute-care hospital within 30 days of ECF admission. None of these transfers clearly suggested that the initial decision to directly admit a patient to the ECF was inappropriate. Most patients were satisfied with direct ECF admission: Of the surviving, cognitively intact patients admitted to an ECF in 1997, 71% stated that they would choose direct admission to an ECF over admission to an acute-care hospital if they were "in a similar situation in the future." CONCLUSIONS: For selected patients, direct admission to an ECF seems to be feasible, safe, and acceptable. A randomized, clinical trial is needed to fully assess the safety and cost implications of direct ECF admission.

Boston↗

An outpatient program to treat deep venous thrombosis with low-molecular-weight heparin.

CONTEXT: Although recent trials have demonstrated the safety and efficacy of low-molecular-weight (LMW) heparin, clinicians may need help incorporating this drug into routine practice. OBJECTIVE: To describe the development, implementation, and early results of an outpatient LMW heparin program for acute deep venous thrombosis (DVT). DESIGN: Before-after study. SETTING: Eight health centers of Harvard Vanguard Medical Associates, a multispecialty group practice in Boston. PATIENTS: Patients with confirmed acute, lower-extremity DVT before (40 patients given a diagnosis from January to August 1996) and after (67 patients given a diagnosis from September 1996 to April 1997) implementation of the LMW heparin program. INTERVENTION: A centrally coordinated outpatient LMW heparin program. DATA SOURCES: Hospital and HMO financial databases; electronic patient medical records. OUTCOME MEASURES: Costs of care for 2-week episodes and short-term clinical outcomes. RESULTS: The proportion of patients with DVT treated in the hospital decreased from 90% to 46% after the introduction of the LMW heparin program. The mean cost of treatment for all patients with DVT decreased from $5465 to $3719 per patient. For the subset of patients actually treated in the outpatient program, the average cost was $1402 per patient. There were no deaths, no clinically recognized pulmonary emboli, and no cases of significant bleeding among patients treated in the program, although 3 patients were subsequently hospitalized for worsening leg pain. CONCLUSIONS: The cost of caring for patients with DVT decreased after introduction of the outpatient LMW heparin program. Given explicit selection criteria, short-term clinical outcomes after outpatient management have been excellent. This program may serve as a model for physicians and health plans interested in establishing a program for treating acute DVT in the outpatient setting.

Ambulatory Care↗