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Biomedical subjects

R J Arnold

Publications and source records attributed to R J Arnold.

At least 19 recordsLinked to original sources
PubMed2001

Use of a decision-analytic model to support the use of a new oral US contrast agent in patients with abdominal pain.

RATIONALE AND OBJECTIVES: The authors performed this study to compare the cost and diagnostic abilities of ultrasound (US) performed with and without the use of an oral contrast material recently approved by the U.S. Food and Drug Administration. MATERIALS AND METHODS: An interactive decision-analytic model was constructed to compare US performed with and without contrast material (SonoRx; Bracco Diagnostics) for the evaluation of patients with abdominal pain who were suspected of having pancreatic disease. The model considered all resources that might be used to evaluate a patient suspected of having pancreatic disease (eg, US, computed tomography [CT], endoscopic retrograde cholangiopancreatography, fine-needle aspiration biopsy, and open biopsy). The literature and an expert panel were the clinical data sources. Cost estimates were based on Medicare and non-Medicare reimbursements. The primary cost-effectiveness measure was the cost to achieve a diagnosis. RESULTS: SonoRx-enhanced US was less expensive than unenhanced US ($714 vs $808, respectively, with Medicare costs; $1,612 vs $1,878, respectively, with non-Medicare costs) and as effective (0.785 vs 0.782, respectively). SonoRx-enhanced US was more cost-effective than unenhanced US ($909 vs $1,034, respectively, with Medicare costs; $2,052 vs $2,401, respectively, with non-Medicare costs). This relationship was maintained throughout extensive sensitivity analyses. CONCLUSION: SonoRx-enhanced US is more cost-effective than unenhanced US, primarily because it avoids the need for CT. CT may be avoided owing to the higher probability of obtaining optimal US scans with oral contrast material.

Abdominal Pain↗
PubMed2000

Improved calibration of time-of-flight mass spectra by simplex optimization of electrostatic ion calculations.

A novel time-of-flight mass calibration method has been developed. In contrast to conventional methods, where the relationship between ion flight time and mass is an arbitrary polynomial equation, this method is based on the physics of ion motion. Parameters needed to describe the physics are numerically optimized using a simplex algorithm. Once these parameters are established, unknown masses can be determined from their times-of-flight. This calibration method gives intrinsically well-behaved results, since nonlinearities (due to extraction delay, desorption velocity, etc.) are properly taken into account in the time-of-flight calculation. The simplex method is compared to curve fitting for the analysis of time-of-flight data, and some significant advantages are demonstrated. Salient features of the method include greatly improved mass extrapolation accuracy, no loss of interpolated calibration accuracy, the ability to obtain an accurate calibration with a minimal number of calibrants, and the ability to extract unknown parameters such as desorption velocities.

Algorithms↗
PubMed2000

Observation of tetrahydrofolylpolyglutamic acid in bacteria cells by matrix-assisted laser desorption/ionization mass spectrometry.

Tetrahydrofolylpolyglutamic acid in whole bacteria cells and cell lysates is analyzed by matrix-assisted laser desorption/ionization mass spectrometry. The speed, mass information, and tolerance to impurities of this technique make it ideal for monitoring the glutamation levels of folic acid in biological systems. Folylpolyglutamic acid is observed in a few strains of E. coli and two species of Staphylococcus bacteria. The effects of growth time, growth media, and the addition of methotrexate, a dihydrofolate reductase inhibitor, are also studied.

Antimetabolites, Antineoplastic↗
PubMed1999

The action of N-terminal acetyltransferases on yeast ribosomal proteins.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used to determine the state of N-terminal acetylation of 68 ribosomal proteins from a normal strain of Saccharomyces cerevisiae and from the ard1-Delta, nat3-Delta, and mak3-Delta mutants (), each lacking a catalytic subunit of three different N-terminal acetyltransferases. A total 30 of the of 68 ribosomal proteins were N-terminal-acetylated, and 24 of these (80%) were NatA substrates, unacetylated in solely the ard1-Delta mutant and having mainly Ac-Ser- termini and a few with Ac-Ala- or Ac-Thr- termini. Only 4 (13%) were NatB substrates, unacetylated in solely the nat3-Delta mutant, and having Ac-Met-Asp- or Ac-Met-Glu- termini. No NatC substrates were uncovered, e.g. unacetylated in solely mak3-Delta mutants, consistent with finding that none of the ribosomal proteins had Ac-Met-Ile-, Ac-Met-Leu-, or Ac-Met-Phe- termini. Interestingly, two new types of the unusual NatD substrates were uncovered, having either Ac-Ser-Asp-Phe- or Ac-Ser-Asp-Ala- termini that were unacetylated in the ard1-Delta mutant, and only partially acetylated in the mak3-Delta mutant and, for one case, also only partially in the nat3-Delta mutant. We suggest that the acetylation of NatD substrates requires not only Ard1p and Nat1p, but also auxiliary factors that are acetylated by the Mak3p and Nat3p N-terminal acetyltransferases.

Acetylation↗
PubMed1999

Monitoring the growth of a bacteria culture by MALDI-MS of whole cells.

We have probed the time evolution of a growing bacteria culture by extracting samples periodically and performing matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) on whole cells. The mass spectra generated by this method contain tens of peaks in the 3-11-kDa mass range. Cultures of E. coli strain K-12 were grown in two types of containers and at two nutrient concentrations and sampled periodically from 6 to 84 h after inoculation. The relative intensities of several of the stronger peaks vary quite dramatically as a function of time. These temporal characteristics must be taken into account when MALDI-MS is applied to identify bacteria. The results also suggest that MALDI-MS can be used to follow the aging of a bacteria culture.

Escherichia coli↗
PubMed1999

Observation of Escherichia coli ribosomal proteins and their posttranslational modifications by mass spectrometry.

Ribosomes from the K-12 strain of Escherichia coli were analyzed with good sensitivity and high mass accuracy using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Fifty-five of the 56 subunit proteins were observable. Mass spectral peak locations were consistent with previously reported post-translational modifications involving N-terminal methionine loss, methylation, thiomethylation, and acetylation for all but one case. The speed and accuracy of mass spectrometry make it a good candidate for phylogenetic studies of ribosomes and the observation of posttranslational modifications in other organisms.

Escherichia coli↗
PubMed1998

Fingerprint matching of E. coli strains with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of whole cells using a modified correlation approach.

We have developed a mathematical algorithm to compare and distinguish matrix-assisted laser desorption/ionization (MALDI) mass spectra of whole bacteria cells. This fingerprint matching technique eliminates the subjectivity involved in visually comparing two spectra to determine whether they match and it provides a quantitative measure of spectral similarity. Using it, we have distinguished twenty five different strains of a single bacteria species, E. coli. Cells are grown in culture, samples are prepared, and MALDI-TOF mass spectra are recorded for each strain. Pairs of spectra are compared by a modified cross-correlation procedure. This modified approach increases the sensitivity of correlation analysis to small spectral differences. The technique can be fine-tuned by varying the number of intervals into which spectra are divided.

DNA Fingerprinting↗
PubMed1997

Pharmacoeconomic analysis of selected antibiotics in lower respiratory tract infection.

An interactive pharmacoeconomic model was designed to evaluate the effects of clinical response and adverse drug events on the comparative cost and cost-effectiveness of a relatively new antibiotic, clarithromycin, compared with those of six other antibiotics used to treat community-acquired lower respiratory tract infection. The cost and cost-effectiveness analyses were based don 12 randomized, double-blind, controlled clinical trials conducted between 1987 and 1992 in regionally distributed outpatient clinics in the United States. The trials enrolled a total of 2377 patients. Of the 2377, 1102 patients were treated for acute exacerbation of chronic bronchitis, 591 for pneumonia, and 201 for either of the two conditions. Safety data for one of the antibiotics was obtained from a trial of patients with sinusitis (N = 483). The antibiotics included in the analysis were amoxicillin/clavulanate, ampicillin, cefaclor, cefixime, cefuroxime, clarithromycin, and erythromycin. The main outcome measures were the costs of resources to achieve a clinical response, costs related to managing adverse drug events, and costs of antibiotic treatment from the perspective of managed care. The mean total cost per episode ranged from approximately $137 to $267. The drug acquisition cost typically contributed a small amount to the overall cost. For the cost-effectiveness analysis, in which complication-free cure was used as a proxy for patient satisfaction, the range of mean cost per complication-free cure varied from approximately $307 for clarithromycin to $612 for cefaclor. When ranked from most to least cost-effective, the order was as follows: clarithromycin, cefixime, amoxicillin/clavulanate, erythromycin, cefuroxime, ampicillin, and cefaclor. The costs associated with clinical management (including treatment failure) and managing adverse drug events significantly contribute to the total cost and cost-effectiveness of antibiotics in the outpatient setting. Cost-effectiveness analyses are valuable in analyzing the various costs associated with the treatment of lower respiratory tract infection (acute exacerbation of chronic bronchitis or pneumonia) and may be useful tools for physicians managing patients, members of pharmacy and therapeutics committees developing formularies, and medical staff implementing practice guidelines.

Anti-Bacterial Agents↗
PubMed1995

High resolution matrix-assisted laser desorption/ionization time-of-flight analysis of single-stranded DNA of 27 to 68 nucleotides in length.

Mass spectra of single-stranded DNA oligonucleotides were acquired using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). Resolution enhancement using space-velocity correlation focusing allows for facile observation of different oligomers, the direct observation of individual DNA-metal adducts, and investigation of counter ion structure.

Base Sequence↗
PubMed1993

Integrating worldwide marketing needs and clinical research.

In this era of globalization, expanding research needs, and the necessity of sharing global technologies and worldwide data evaluation techniques, a challenging environment has been created for multinational drug development, clinical testing, and marketing. Integrating worldwide marketing needs and clinical research will become even more significant in the future as harmonization of pharmaceutical industry research and regulatory requirements increase with the unification of the European Economic Community. Marketing and research teams within a pharmaceutical company must work closely together to make the drug being developed appropriate to a global market.

Drug Industry↗
PubMed1993

Selection of oral controlled-release drugs: a critical decision for the physician.

Controlled-oral release dosage formulations of medications have become relatively prevalent in medicine today because of their ability to reduce noncompliance and, perhaps, to increase efficacy. However, there are many patient- and drug-related factors that may present special problems in product selection. For example, interchange of controlled-release brands that may have different absorption characteristics can result in therapeutic failure and/or toxicity. Especially in light of recent events associated with Food and Drug Administration product reviews, this paper outlines concepts that will assist physicians in making informed decisions regarding generic substitution of oral controlled-release products.

Absorption↗
PubMed1993

Comparative cost-effectiveness analysis of theophylline and ipratropium bromide in chronic obstructive pulmonary disease. A three-center study.

The charts of 311 patients receiving theophylline (T) and 289 patients receiving ipratropium bromide (IB) for COPD were reviewed to determine the total costs and cost-effectiveness of these 2 agents in 3 different health-care settings. A direct cost-accounting method assessed cost, and a Markov decision-analysis model calculated cost-effectiveness. Costs to treat toxic effects were greater for T versus IB. The types and incidences of toxic effects, by drug, were similar among the three centers. Overall costs for T were $121.40 per patient per therapy-month versus $84.56 per patient per therapy-month for IB, as determined by the cost-accounting method. The marginal cost was $366 for T over IB when extrapolated over 1 year using the Markov model. The Markov model also predicted that patients receiving IB had a greater number of complication-free therapy-months (measurement of effectiveness) than patients receiving T. We conclude that treatment with IB was less costly and more cost-effective than T.

Aged↗
PubMed1992

Pharmacoeconomic considerations in antiarrhythmic therapy.

Recently, the Cardiac Arrhythmia Suppression Trial (CAST) has focused attention on the morbidity and mortality that may be associated with pharmacological antiarrhythmic therapies. While the severity and frequency of adverse effects vary among the available agents, it is uncertain whether initial therapy with one agent is preferable to that with another when efficacy, incidence of adverse effects and costs of treating these adverse effects are examined. Moreover, it is uncertain whether pharmacotherapy is more cost-effective than other strategies.

Anti-Arrhythmia Agents↗
PubMed1991

Comparative cost-effectiveness analysis of quinidine, procainamide and mexiletine.

Quinidine and procainamide have the potential for major organ toxicity, whereas mexiletine has been reported to have little risk of organ toxicity, serious proarrhythmia or congestive heart failure, but a relatively high incidence of nuisance side effects. In light of the potential adverse effects of all antiarrhythmic agents as highlighted by the Cardiac Arrhythmia Suppression Trial, the relative cost-effectiveness of these 3 agents was assessed. Based on a review of greater than 1,000 published reports, studies included in the analysis examined greater than or equal to 1 of these agents in adults, with adequate efficacy or safety data, or both. The majority of studies assessed patients with symptomatic or malignant arrhythmias, or both. Data were analyzed using a decision analysis/cost-effectiveness model. Probabilities were averaged using techniques of meta-analysis. Costs were obtained from a university medical center cost-accounting system and from expected follow-up visits to university clinics. Thirty-seven separate side effects were included in the analysis. In terms of overall cost, 12 months of mexiletine would engender $875, quinidine $1,239 and procainamide $1,911 of expenses. Mexiletine dominates the older agents in terms of cost per successful drug response, a result that holds over a wide range of efficacy and safety data. Analyses demonstrated no increase in all-cause mortality for quinidine and mexiletine over placebo, but a trend toward higher mortality with procainamide. The results suggest that mexiletine is a cost-saving alternative therapy for ventricular arrhythmias when adverse reactions are considered in addition to pharmaceutical costs and treatment efficacy.

Ambulatory Care↗
PubMed1982

Tissue glycogen levels in dams and fetuses as affected by fasting and refeeding pregnant sows.

Nineteen Landrace sows mated to Landrace boars were randomly assigned, on d 91 of pregnancy, to three groups: (1) control (six sows)--fed standard 13% protein corn-soybean meal gestation diet at 1.82 kg/d to d 112 of pregnancy; (2) 4-d fast (seven sows)--fed standard gestation diet to d 94 of pregnancy, fasted from d 95 to 98 of pregnancy and then refed a semipurified fat-free diet ad libitum until d 112 of pregnancy, and (3) 8-d fast (six sows)--treated the same as groups 2, except that the fast began on d 91 and extended through d 98 of pregnancy. The fat-free diet consisted of dextrose and soybean meal and was fortified with minerals and vitamins. On d 112 of pregnancy, all fetuses were removed by Caesarean section and determinations were made of fetal body and liver weights, fetal liver and gastrocnemius muscle glycogen concentrations, and maternal uterus and peritoneal adipose tissue glycogen levels. Sows in groups 2 and 3 consumed more (P less than .01) average daily feed during the refeeding period than did the control sows. Fasting and refeeding failed to affect maternal or fetal tissue glycogen concentration, or fetal body or liver weight. Average sow tissue glycogen concentrations were .23 and 3.0 mg/g tissue for peritoneal adipose tissue and uterus, respectively. Average fetal liver and gastrocnemius muscle glycogen concentrations were, 87 and 62 mg/g tissue, respectively. Average fetal body and liver weights were 1,287 and 39.5 g/fetus, respectively. We conclude that fasting followed by refeeding of a fat-free diet to pregnant sows during late gestation does not increase maternal or fetal tissue glycogen content and appears to be of no value in enhancing pig survival in early postnatal life.

Animal Feed↗