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Biomedical subjects

J A Barone

Publications and source records attributed to J A Barone.

At least 19 recordsLinked to original sources
PubMed2005

Climatic unpredictability and parasitism of caterpillars: implications of global warming.

Insect outbreaks are expected to increase in frequency and intensity with projected changes in global climate through direct effects of climate change on insect populations and through disruption of community interactions. Although there is much concern about mean changes in global climate, the impact of climatic variability itself on species interactions has been little explored. Here, we compare caterpillar-parasitoid interactions across a broad gradient of climatic variability and find that the combined data in 15 geographically dispersed databases show a decrease in levels of parasitism as climatic variability increases. The dominant contribution to this pattern by relatively specialized parasitoid wasps suggests that climatic variability impairs the ability of parasitoids to track host populations. Given the important role of parasitoids in regulating insect herbivore populations in natural and managed systems, we predict an increase in the frequency and intensity of herbivore outbreaks through a disruption of enemy-herbivore dynamics as climates become more variable.

Animals↗
PubMed2001

Impact of presentation of research results on likelihood of prescribing medications to patients with left ventricular dysfunction.

This study was conducted to evaluate willingness to prescribe medication based on identical data presented in different outcome terms to health professionals of varied discipline, geographic location, and level of training. Cross-sectional survey using a self-administered questionnaire was performed in 400 health professionals (physicians, pharmacists, physicians-in-training, and pharmacy students) in the United States and Europe. Data reflecting a clinical trial were presented in 6 outcome terms: 3 terms describing identical mortality (relative risk reduction, absolute risk reduction, and number of patients needed to be treated to prevent 1 death); and 3 distractors (increased life expectancy, decreased hospitalization rate, and decreased cost). Willingness to prescribe and rank order of medication preference assuming willingness to prescribe were measured. The results of the study showed that willingness to prescribe and first choice preference were significantly greater when study results were presented as relative risk reduction than when identical mortality data were presented as absolute risk reduction or number of patients needed to be treated to avoid 1 death (p <0.001). Increase in life expectancy was the most influential distractor. In conclusion, this study, performed in the era of "evidence-based medicine," demonstrates that the method of reporting research trial results has significant influence on health professionals' willingness to prescribe. The high numerical value of relative risk reduction and the concrete and tangible quality of increased life expectancy exert greater influence on health professionals than other standard outcome terms.

Cardiovascular Agents↗
PubMed2001

Retrospective analysis of the effects of cisapride on the QT interval and QT dispersion in chronic hemodialysis patients.

Cisapride is contraindicated in patients with end-stage renal disease (ESRD) and gastrointestinal motility disorders. Ventricular arrhythmias have been associated with both cisapride and hemodialysis (HD). However, reports conflict regarding the safety of cisapride in HD patients. We undertook this study to characterize the effects of cisapride on QT intervals and QT dispersion (QTD) in HD patients. Baseline and steady-state electrocardiograms (ECGs) were retrospectively selected for calendar year 1999 for each patient administered cisapride if ECGs showed sinus rhythm, potassium level was 3.5 mEq/dL or greater, and there was no pharmacokinetic drug interaction. QT intervals were measured by two investigators, and QTDs were calculated (maximum [QT(max)] - minimum QT interval [QT(min)]). Averages between investigator measures (+/- SD), presented for each value, were evaluated using Wilcoxon's signed-rank test. Thirty-one HD patients were administered cisapride. Seventeen patients failed to meet entry criteria, and no patient had a pharmacokinetic drug interaction. In included patients (6 men, 8 women), heart rates were 86.71 +/- 20.87 beats/min at baseline and 86.57 +/- 14.23 beats/min during treatment (P = not significant). Serum potassium levels were 4.97 +/- 1.2 mEq/dL at baseline and 4.94 +/- 0.76 mEq/dL during treatment (P = not significant). Average baseline QT(max) and QT(min) were 391.07 +/- 42.43 and 330.71 +/- 40.94 milliseconds, respectively. Treatment QT(max) and QT(min) were 391.43 +/- 38.2 and 343.93 +/- 35.69 milliseconds, respectively (P = not significant for both). QTD was 60.36 +/- 17.59 milliseconds at baseline and 47.5 +/- 19.59 milliseconds during treatment (P = 0.074). Mean corrected QT (QTc) intervals increased from 426.57 +/- 26.62 to 431.71 +/- 29.98 milliseconds (P = 0.55) from baseline to treatment. No ventricular arrhythmia was observed during at least 160 days (range, 2 to 830 days) of cisapride exposure. Two patients died during this study, both of other causes 4 days after discontinuing cisapride therapy. Cisapride did not significantly increase mean QTc interval, QT(max), or QTD in patients with ESRD managed by HD when potassium levels were stable and pharmacokinetic drug interactions were avoided.

Arrhythmias, Cardiac↗
PubMed2001

Comparative pharmacology of proton pump inhibitors.

The PPIs are the most effective therapy to suppress gastric acid secretion. These agents decrease acid secretion by inhibiting parietal cell proton pumps. From chemical and pharmacodynamic points of view, subtle differences that exist among the PPIs may influence clinical activity.

Aryl Hydrocarbon Hydroxylases↗
PubMed1999

Factors contributing to trends in prescription drug expenditures.

Between 1970 and 1995, national prescription drug expenditures and Medicaid drug expenditures increased proportionately less than did total health care expenditures and total Medicaid expenditures, respectively, although they increased to a greater extent than did expenditures in other sectors of the economy. General inflation, which cannot be controlled by health care policy, has been the major factor contributing to the growth in national prescription drug expenditures. Other contributors were population growth, increases in per capita prescription use, increases in per-prescription intensity (ie, real drug expenditures), and the fact that prescription drug prices exceeded general inflation. Medicaid drug expenditures have increased mainly because of growth in the number of drug recipients, increases in prescription drug prices, and economy-wide inflation.

Data Collection↗
PubMed1999

Domperidone: a peripherally acting dopamine2-receptor antagonist.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of domperidone in the treatment of gastrointestinal motility disorders and emesis. DATA SOURCES: MEDLINE and Excerpta Medica online databases were searched to identify published reports. STUDY SELECTION: Domperidone has been marketed worldwide outside the US since 1978, and extensive clinical data for this drug are available. This review focuses on the clinical experience from controlled studies of domperidone in the treatment of motility disorders, particularly diabetic gastroparesis. Also, case reports are used in summarizing safety. The control comparator groups included placebo or other prokinetic drugs (metoclopramide and cisapride). Controlled clinical trials of domperidone's efficacy and safety as an antiemetic are also briefly examined. Although a variety of domperidone dosage forms have been marketed, data generated from trials using the 10-mg tablet are highlighted because this is the only dosage form available in Canada and is under investigation in the US. DATA EXTRACTION: Because symptoms do not correlate with objective measures of gastrointestinal motility and they are the primary reason that patients with motility disorders seek treatment, the primary outcome extracted from the clinical studies was symptomatic response to treatment. Safety and efficacy between domperidone and placebo, metoclopramide, or cisapride were compared. DATA SYNTHESIS: Domperidone, a peripheral dopamine2-receptor antagonist, regulates the motility of gastric and small intestinal smooth muscle and has been shown to have some effects on the motor function of the esophagus. It also has antiemetic activity as a result of blockade of dopamine receptors in the chemoreceptor trigger zone. In controlled clinical trials, domperidone provided better relief of symptoms (anorexia, nausea, vomiting, abdominal pain, early satiety, bloating, distension) than placebo in patients with symptoms of diabetic gastropathy; symptomatic improvement was similar with domperidone and metoclopramide or cisapride. Domperidone also provided short-term relief of symptoms in patients with dyspepsia or gastroesophageal reflux, prevented nausea and vomiting associated with emetogenic chemotherapy, and prevented the gastrointestinal and emetic adverse effects of antiparkinsonian drugs. Because very little domperidone crosses the blood-brain barrier, reports of central nervous system adverse effects, such as dystonic reactions, are rare. CONCLUSIONS: Domperidone is a unique gastrokinetic and antiemetic drug. Because of its favorable safety profile, domperidone appears to be an attractive alternative to metoclopramide. In the management of diabetic gastropathy, domperidone's antiemetic activity distinguishes it from cisapride.

Animals↗
PubMed1998

Enhanced bioavailability of itraconazole in hydroxypropyl-beta-cyclodextrin solution versus capsules in healthy volunteers.

The bioavailabilities and bioequivalences of single 200-mg doses of itraconazole solution and two capsule formulations were evaluated in a crossover study of 30 male volunteers. The two capsule formulations were bioequivalent. The bioavailabilities of the solutions itraconazole and hydroxyitraconazole were 30 to 33% and 35 to 37% greater, respectively, than those of either capsule. However, the maximum concentrations of the drug in plasma (Cmax), the times to Cmax, and the terminal half-lives were comparable for all three formulations. These data indicate that the bioavailabilities of itraconazole and hydroxyitraconazole are enhanced when administered as an oral solution instead of capsules.

Adolescent↗
PubMed1994

Cisapride: a gastrointestinal prokinetic drug.

OBJECTIVE: To summarize the pharmacology, pharmacokinetics, efficacy, and safety of cisapride, and to evaluate its potential therapeutic role. DATA SOURCES: A computerized search of the MEDLINE database was used to identify English-language publications of cisapride data in humans. The MEDLINE search was supplemented by review article bibliographies. There was no attempt to limit the search to a specific gastrointestinal motility disorder. STUDY SELECTION: The MEDLINE search alone identified 165 citations. Because of the volume of available human cisapride data, the focus of the efficacy section is on complete published reports of controlled clinical studies. Abstracts and uncontrolled data are discussed only when other information is unavailable to address important aspects. DATA EXTRACTION: Information regarding study design, study population, results, and safety was recorded from each publication. The placebo response to gastrointestinal complaints in patients with motility disorders is high. Therefore, objective evidence of improvement was emphasized when documentation was available. DATA SYNTHESIS: Cisapride stimulates the motility of smooth muscle lining the esophagus, stomach, small intestine, and colon, and increases the tone of gut sphincters in vitro and in vivo. In controlled investigations, cisapride was superior to placebo in relieving symptoms associated with reflux esophagitis, nonulcer dyspepsia, and gastroparesis. Similar symptom and healing effects were observed with cisapride and histamine (H)2-antagonists in reflux esophagitis. Cisapride was either equal to or superior to metoclopramide in relieving reflux symptoms. However, metoclopramide was associated with significantly more central nervous system adverse effects. Cisapride was well tolerated, with adverse effects limited primarily to the gastrointestinal tract. CONCLUSIONS: Cisapride represents an attractive alternative to metoclopramide for the treatment of a variety of motility disorders. Because it addresses a primary underlying cause of reflux esophagitis, cisapride may also prove to be an effective alternative to acid suppressants in the management of this disorder.

Adult↗
PubMed1993

Food interaction and steady-state pharmacokinetics of itraconazole capsules in healthy male volunteers.

The influence of food on itraconazole pharmacokinetics was evaluated for 27 healthy male volunteers in a single-dose (200 mg) crossover study with capsules containing itraconazole-coated sugar spheres. This study was followed by a study of the steady-state pharmacokinetics for the same subjects with 15 days of administration of itraconazole at 200 mg every 12 h. Concentrations of itraconazole and hydroxyitraconazole, the active main metabolite, were measured in plasma by high-performance liquid chromatography. The results of the food interaction segment showed that a meal significantly enhances the amount of itraconazole absorbed. The mean maximum concentration in plasma of unmetabolized itraconazole after fasting (140 ng/ml) was about 59% that after the standard meal (239 ng/ml). The rate of elimination was not affected (terminal half-life, approximately 21 h). The mean maximum concentration in plasma of hydroxyitraconazole after fasting was about 72% the postmeal concentration (287 and 397 ng/ml, respectively). The terminal half-life of hydroxyitraconazole was approximately 12 h. Steady-state concentrations of itraconazole and hydroxyitraconazole were reached after 14 or 15 days of daily dosing. The average steady-state concentrations were approximately 1,900 ng/ml for itraconazole and 3,200 ng/ml for hydroxyitraconazole. The shape of the elimination curve for itraconazole after the last dose was indicative of saturable elimination. This conclusion was confirmed by the sevenfold increase in the area under the curve from 0 to 12 h at steady state compared with the area under the curve from 0 h to infinity after a single dose. It was furthermore confirmed by the larger-than-expected number of half-lives required to achieve steady-state plasma drug levels.

Adult↗
PubMed1992

Comparative potency and dissolution performance of internationally available piroxicam products.

Generic drug products are marketed throughout the world and are generally regarded as being equivalent to the name brand product. Piroxicam is a widely prescribed nonsteroidal anti-inflammatory drug and is marketed under the Pfizer tradename Feldene or Felden . In countries with no patent laws or where the Feldene patent has expired, the drug is available under various trademarks by many different producers. Differences in formulations produced by different manufacturers can be assessed by measuring dissolution rate and potency. In this study, the United States Pharmacopeia (USP) dissolution and potency tests were applied to 85 generic piroxicam products obtained from 21 countries in an attempt to evaluate if the available formulations met standard quality assurance tests. The results show that of the 85 piroxicam products tested, 17 products met the USP dissolution standards and 68 products failed. Of the 85 products tested for potency as a percentage of label claim, 50 products failed the USP criteria. Overall, 91% of the generic piroxicam products evaluated failed to meet the routine in vitro USP quality assurance criteria for potency and/or dissolution. The substantial differences observed in this study regarding performance of piroxicam dosage forms available worldwide have possible implications in terms of product equivalency and standards at an international level. While these results cannot be used to draw clinical conclusions without bioavailability data, they should nonetheless be kept in mind by healthcare practitioners.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemistry, Pharmaceutical↗
PubMed1992

Features and treatment of rabies.

The epidemiology, virology, transmission, pathology, clinical manifestations, diagnosis, and treatment of rabies infection are described. The incidence of rabies is increasing. The virus is usually transmitted through the bite of an infected animal; however, corneal transplantation from an infected donor and viral inhalation may also result in infection. The clinical course of rabies occurs in five stages. Stage I is the incubation period, stage II is the prodromal period, stage III is the neurological period, stage IV is coma, and stage V, which occurs infrequently, is recovery. Early in the disease, constitutional symptoms and signs of local wound healing may be present. During the later stages, a wide array of clinical manifestations may occur, including hydrophobia and aerophobia, which are pathognomonic for rabies. Once inoculation with the rabies virus is suspected, prompt therapy, including appropriate wound care and rabies vaccination, is imperative, even in previously immunized individuals. Human diploid-cell vaccine and rabies vaccine adsorbed, which stimulate the production of antibodies, and human rabies immune globulin, which provides protective antibodies, are nearly 100% effective in preventing progression from stage I disease. If left untreated, rabies is usually fatal. However, treatment with human diploid-cell vaccine or rabies vaccine adsorbed and with human rabies immune globulin is nearly always curative if initiated early in the incubation period.

Animals↗
PubMed1990

Angiotensin-converting enzyme inhibitors: a comparative review.

The chemistry, pharmacology, pharmacokinetics, adverse effects, and dosages of the three currently available angiotensin-converting enzyme (ACE) inhibitors are reviewed. This class of agents effectively inhibits the conversion of angiotensin I to the active vasoconstrictor angiotensin II, a hormone that also promotes, via aldosterone stimulation, increased sodium and water retention. The ACE inhibitors, therefore, are capable of lowering blood pressure primarily by promoting vasodilatation and reducing intravascular fluid volume. Captopril, the first orally active, commercially available ACE inhibitor, is a sulfhydryl-containing compound. Captopril was followed by the introduction of enalapril and lisinopril, two non-sulfhydryl ACE inhibitors. The pharmacokinetic profiles of these three ACE inhibitors differ. Captopril has rapid onset with relatively short duration of action, whereas enalapril and lisinopril have slower onset and relatively long duration of action. Captopril is an active ACE inhibitor in its orally absorbable parent form. In contrast, enalapril must be deesterified in the liver to the metabolite enalaprilat in order to inhibit the converting enzyme; this accounts for its delayed onset of action. Lisinopril does not require metabolic activation to be effective; however, a slow and incomplete absorption pattern explains the delay in onset of activity. Captopril and its disulfide metabolites are primarily excreted in the urine with minor elimination in the feces. Approximately two-thirds of an administered enalapril dose is excreted in the urine as both the parent drug and the metabolite enalaprilat; the remainder of these two substances are excreted in the feces. Lisinopril does not undergo measurable metabolism and approximately one-third is excreted unchanged in the urine with the remaining parent drug being excreted in the feces. The ACE inhibitors lower systemic vascular resistance with a resultant decrease in blood pressure. Their efficacy is comparable to diuretics and beta-blockers in treating patients with mild, moderate, or severe essential and renovascular hypertension. In those patients with severe congestive heart failure (CHF) the ACE inhibitors produce a reduction in systemic vascular resistance, blood pressure, pulmonary capillary wedge pressure, and pulmonary artery pressure. These drugs may produce improvement in cardiac output and stroke volume and, with chronic administration, may promote regression of left ventricular hypertrophy. The antihypertensive effects of the ACE inhibitors are enhanced when these agents are combined with a diuretic. Captopril and enalapril have been shown to be of particular benefits as adjunctive therapy in patients with congestive heart failure, both in terms of subjective improvement of patient symptoms, and in improving overall hemodynamic status.(ABSTRACT TRUNCATED AT 400 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

Evaluation of the effects of multiple-dose activated charcoal on the absorption of orally administered salicylate in a simulated toxic ingestion model.

The effects of multiple-dose activated charcoal administration on the absorption of orally administered salicylate were evaluated in a simulated overdose model. Thirteen adult volunteers were each given 24 81-mg aspirin tablets during a control phase, and during three randomized treatment periods the volunteers received 50 g activated charcoal for one, two, or three doses (separated by four hours). The control phase and treatment periods were separated by a one-week interval. Urine was collected for 48 hours to determine percent total salicylate excretion. Ten subjects completed all four phases of the study. Mean +/- SD percent recovery of salicylate from urine was: control, 91.0 +/- 6.12; one-dose charcoal, 68.3 +/- 12.46; two-dose charcoal, 65.9 +/- 13.48; and three-dose charcoal, 49.2 +/- 12.48. Each charcoal treatment significantly lowered the absorption of aspirin as compared with the control (P less than .01). There was no significant difference between one-dose and two-dose charcoal regimens. There was a statistically significant decrease in salicylate absorption with the three-dose charcoal regimen as compared to one-dose and two-dose regimens (P less than .01). We conclude that activated charcoal is effective in inhibiting absorption of orally administered salicylate, in a small-dose aspirin ingestion model, with a three-dose multiple charcoal regimen being superior to either single-dose or two-dose regimens.

Administration, Oral↗
PubMed1988

Comparative dissolution performance of internationally available piroxicam products.

Piroxicam is a widely used nonsteroidal antiinflammatory drug available worldwide under various trade names by several manufacturers. Only one brand of piroxicam (Feldene) is currently marketed in the U.S., and the United States Pharmacopeial Convention established an official dissolution requirement for piroxicam in 1985. The purpose of this study was to evaluate and compare the dissolution performance of several internationally available piroxicam products using the United States Pharmacopeia (USP) dissolution test for piroxicam capsules. Of 25 brands of piroxicam capsules evaluated, 72 percent of the brands failed to meet the USP requirement, several by a wide margin. Although there is no specific USP dissolution test for tablets, the test for capsules was applied to five different brands of piroxicam tablets, and 80 percent of the tablet brands tested failed to meet the USP requirement. Although comparative bioavailability studies would be required to establish any definitive relationship between dissolution test performance and bioavailability, the failure of most of these products to meet the USP requirement for dissolution indicates formulation differences that could result in altered bioavailability. The substantial differences in dissolution performance observed among the piroxicam oral dosage forms tested have implications concerning the equivalency and standards of multisource products available on the international market, and should be taken into account by health care providers worldwide.

Biological Availability↗
PubMed1988

Effect of food and gastric acidity on absorption of orally administered ketoconazole.

Effects of food and gastric acidity on the bioavailability of ketoconazole tablets were investigated in 12 volunteers using a six-treatment, randomized, Latin-square crossover design. All volunteers received all treatments, as follows: (A) ketoconazole 200 mg administered after a fast; (B) ketoconazole 200 mg with a standardized high-fat meal; (C) ketoconazole 200 mg with a standardized high-carbohydrate meal; (D) ketoconazole 200 mg after pretreatment with glutamic acid hydrochloride 680 mg as capsules; (E) ketoconazole 200 mg in a simulated achlorhydric state induced with cimetidine and sodium bicarbonate; and (F) ketoconazole 200 mg administered with glutamic acid hydrochloride in a simulated achlorhydric state. Ketoconazole concentrations were measured by high-performance liquid chromatography in plasma samples drawn immediately before and at various times over 24 hours after drug administration. Bioavailability variables, including natural logarithm transformation for area under the concentration-time curve (AUC), were subjected to analysis of variance followed by Duncan's Multiple Range testing. Treatments B and C significantly prolonged the times required to achieve the peak plasma ketoconazole concentration, and treatment C also significantly reduced the peak plasma ketoconazole concentration (Cmax) compared with treatment A. There was a trend toward increased AUC values with treatment B and decreased AUC values with treatment C. Treatment D produced a higher Cmax compared with treatment A, and treatment E produced large, significant reductions in Cmax and AUC values compared with treatment A. Treatment F significantly increased AUC values and Cmax compared with treatment E.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗