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Biomedical subjects

P Larson

Publications and source records attributed to P Larson.

At least 19 recordsLinked to original sources
PubMed2001

Health and loyalty promotion visits for new enrollees: results of a randomized controlled trial.

Managed care needs effective and efficient ways to orient new members, enhance trust and loyalty, and offer prevention and self-care education and services. Recent adult enrollees of Kaiser Permanente (Northern California) were randomly assigned to one of three intervention conditions (n = 286) (individual visit with a physician, physician visit plus a visit with a health educator, a group visit of eight new members led by a physician and health educator) or a random control group (n = 278). Outcomes were gauged via pre- and post-visit questionnaires and a 20-min telephone survey at baseline and at a 6-month follow-up. Compared to controls, attendees of the three interventions had higher satisfaction, self-rated prevention knowledge, acceptance of health plan guidelines, and were more likely to plan to remain in the health plan. Group visit attendees stood out as experiencing the greatest benefits and were especially likely to report saving a telephone call or visit to their doctor by using a self-care handbook.

Adult↗
PubMed2001

Montelukast dose selection in children ages 2 to 5 years: comparison of population pharmacokinetics between children and adults.

Montelukast, a leukotriene receptor antagonist, has demonstrated efficacy and tolerability in the treatment of asthma in patients age 6 years and older. The purpose of this open, one-period, multicenter population pharmacokinetic study was to identify a chewable tablet (CT) dose of montelukast for administration to children ages 2 to 5 years with asthma, yielding a single-dose pharmacokinetic profile (area under the plasma concentration-time curve [AUC]) comparable to that of the 10 mg film-coated tablet (FCT) dose in adults. Because patient numbers were small and the volume of blood that could be collected from individual 2- to 5-year-old patients was limited, a population pharmacokinetic approach was used to estimate population AUC (AUCpop). The 4 mg CT dose of montelukast was well tolerated and yielded an AUCpop (2721 ng.h/mL) similar to that of the adult AUCpop (2595 ng.h/mL) observed after a 10 mg FCT dose. These results support the selection of a 4 mg once-daily CT dose of montelukast for future efficacy and safety studies in children ages 2 to 5 years with asthma.

Acetates↗
PubMed2000

Single dose methodology to assess the influence of an alpha1-adrenoceptor antagonist on uroflowmetric parameters in patients with benign prostatic hyperplasia.

AIMS: To establish methodology which rapidly and reliably assesses the effect of an alpha1-adrenoceptor antagonist on peak urine flow rates in men with benign prostatic hyperplasia (BPH). This methodology could then be applied to screening new drugs to treat BPH. METHODS: Twenty-five patients with BPH enrolled in a double-blind, placebo-controlled, two-period crossover study. Patients were either withdrawn from their current alpha1-adrenoceptor antagonist therapy (n = 22) or were untreated prestudy (n = 3) and all met prespecified uroflowmetric criteria including: (1) a peak urine flow rate (Qmax) < 12 ml s-1 off therapy (or < 10 ml s-1 if untreated prestudy) and (2) a decrease in peak urine flow rate (Qmax) of > 2 ml s-1 after withdrawal from therapy. Study treatment consisted of tamsulosin 0.4 mg (or matching placebo) once daily for 8 days in a two-period crossover. Uroflowmetry was performed predose and once postdose (4.5-5.5 h postdose) on day 1, and once postdose (4.5-5.5 h postdose) on day 8 of each treatment period. RESULTS: After a single dose of tamsulosin, the least-square mean difference between tamsulosin and placebo in the change from baseline Qmax was 2.8 ml s-1 (P = 0.017 vs placebo). After 8 days dosing of tamsulosin, the least-square mean difference between tamsulosin and placebo in the change from baseline Qmax was also 2.8 ml s-1 (P = 0.044 vs placebo). Additionally, there was no significant difference observed between the single and multiple dose results (P > 0.200 for between group difference). CONCLUSIONS: Both single and multiple doses of tamsulosin 0.4 mg increased Qmax in men with BPH. A single dose produced a comparable response to multiple dose administration. The magnitude of the effect was greater than the effect generally seen in longer term clinical trials, but this difference may be explained by the patient population in this study which was preselected for 'responsiveness' to an alpha1-adrenoceptor antagonist. These results support the utility of single dose uroflowmetric measurements in rapidly providing preliminary data on new investigational agents, specifically agents which act to increase urine flow in men with BPH. However, clinical efficacy would still need to be confirmed with longer term clinical trials.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2000

Randomized clinical trial of the effectiveness of 3 commonly used mouthwashes to treat chemotherapy-induced mucositis.

OBJECTIVE: To test the effectiveness of 3 mouthwashes used to treat chemotherapy-induced mucositis. The mouthwashes were as follows: salt and soda, chlorhexidine, and "magic" mouthwash (lidocaine, Benadryl, and Maalox). STUDY DESIGN: A randomized, double-blind clinical trial was implemented in 23 outpatient and office settings. Participants were monitored from the time they developed mucositis until cessation of the signs and symptoms of mucositis, or until they finished their 12-day supply of mouthwash. All participants followed a prescribed oral hygiene program and were randomly assigned a mouthwash. Nurses used the Oral Assessment Guide for initial assessment and taught patients how to assess their own mouths, then phoned the patients every other day to gather status reports. RESULTS: In 142 of 200 patients, there was a cessation of the signs and symptoms of mucositis within 12 days. No significant differences in time for the cessation of the signs and symptoms were observed among the 3 groups. CONCLUSIONS: Given the comparable effectiveness of the mouthwashes, the least costly was salt and soda mouthwash.

Aluminum Hydroxide↗
PubMed2000

A new cyclooxygenase-2 inhibitor, rofecoxib (VIOXX), did not alter the antiplatelet effects of low-dose aspirin in healthy volunteers.

The present study examined whether rofecoxib (VIOXX), a new specific inhibitor of cyclooxygenase-2 (COX-2), would interfere with the desired antiplatelet effects of aspirin. Thus, the effects of rofecoxib on inhibition of ex vivo serum-generated thromboxane B2 (TXB2) and platelet aggregation by low doses (81 mg) of aspirin were examined in healthy volunteers. This was a double-blind, randomized, placebo-controlled, parallel study of two treatment groups (n = 12 per group) in which subjects received 50 mg of rofecoxib or placebo for 10 days in a blinded fashion. Subjects also received 81 mg aspirin once on each of days 4 through 10 in an open-label fashion. Blood for measurement of serum TXB2 production and platelet aggregation studies was collected on day 1 (prior to rofecoxib/placebo), on day 4 (prior to aspirin), and on day 10 (before and 4 hours following the seventh dose of aspirin). Platelet-derived serum TXB2 (COX-1 assay) was measured in blood clotted for 1 hour at 37 degrees C. Platelet aggregation was independently induced employing 1 mM arachidonic acid and 1 microgram/mL collagen as agonists. Rofecoxib administered alone had no significant effect on serum TXB2 production or platelet aggregation (day 4). TXB2 production was inhibited 98.4% by aspirin coadministered with either rofecoxib or placebo (day 10). Similarly, platelet aggregation induced by arachidonic acid was inhibited 93.7% and 93.5% by aspirin coadministered with either rofecoxib or placebo, respectively (day 10). The comparable values for inhibition of collagen-induced platelet aggregation were 86.8% and 90.8%, respectively. No important clinical or laboratory adverse experiences were observed. In conclusion, rofecoxib alone (50 mg QD for 4 days) did not inhibit serum TXB2 production or platelet aggregation. In addition, rofecoxib (50 mg QD for 10 days) did not alter the antiplatelet effects of low-dose aspirin (inhibition of platelet aggregation and TXB2 production). Rofecoxib was generally well tolerated when administered alone or in combination with low-dose aspirin.

Adolescent↗
PubMed1999

Montelukast dose selection in 6- to 14-year-olds: comparison of single-dose pharmacokinetics in children and adults.

Montelukast, an oral leukotriene-receptor antagonist, has demonstrated efficacy and tolerability for the treatment of chronic asthma in adults. A once-daily 10 mg dose (film-coated tablet) was selected as the optimal adult dose based on dose-ranging studies. Asthma is a similar disease and is treated with the same medications in children and adults. These observations suggested that a dose of montelukast in children providing overall drug exposure (i.e., montelukast plasma concentrations) similar to that of the 10 mg film-coated tablet dose in adults would be efficacious, well tolerated, and obviate the need for separate dose-ranging studies in children. Therefore, the dose of montelukast for 6- to 14-year-old children was selected by identifying the chewable tablet dose of montelukast yielding a single-dose area under the plasma concentration-time curve (AUC) comparable to that achieved with the adult 10 mg film-coated tablet dose. Based on this approach, which included dose normalization of data from several pediatric pharmacokinetic studies, a 5 mg chewable tablet dose of montelukast was selected for use in clinical efficacy studies in 6- to 14-year-old children with asthma.

Acetates↗
PubMed1999

Risk factors for chemotherapy-induced oral mucositis: dental appliances, oral hygiene, previous oral lesions, and history of smoking.

Oral mucositis is one of the dose-limiting toxicities of several chemotherapy (CTX) agents. There are suggested risk factors that could influence the development of mucositis. The presence of dental appliances, history of oral lesions, or smoking have the potential to irritate the oral mucosa and produce breaks in the integrity of the mucosa. The purposes of this study were to determine if there were differences in the incidence, severity, and time to onset of CTX-induced mucositis in oncology outpatients who wore dental appliances, had a history of oral lesions, had varying oral hygiene/care practices, and had a history of smoking and those who did not. Patients who were initiated a course of CTX that included stomatotoxic agents were followed for three complete cycles of CTX. They were instructed on how to examine their mouths for mucositis, to contact, and then visit their outpatient settings if it occurred. Clinicians corroborated the presence of mucositis, and the Eiler's Oral Assessment Guide was used by clinicians to determine the severity. Of 332 outpatients, almost half (46%) wore some type of dental appliance, 32% had a history of oral lesions, 10% were currently smoking, and 63% had a history of smoking. Oral hygiene/care practices varied: 81% brushed their teeth two or more times a day, 29% flossed at least daily, 11% had visited their dentist within 2 months of beginning CTX, and 10% had their teeth professionally cleaned within two months of beginning CTX. There was a 31% (n = 104) incidence of CTX-induced mucositis. No significant differences were found in the incidence between patients who wore dental appliances, had a history of oral lesions, had a history of smoking, and practiced different hygiene/care and patients who did not. Of 104 patients who developed mucositis, the average severity rating was 13.05 +/- 2.88 (+/-SD) (a normal mouth is rated at 8) and the average time to onset was 22.3 +/- 21.46 days. There were no significant differences found in severity or time to onset of mucositis between patients who wore dental appliances, had a history of oral lesions, had a history of smoking, and practiced different dental hygiene/care and patients who did not. Although not significant, there were interesting differences in the time to onset across the suggested risk factors (e.g., patients who had visited a dentist or who had their teeth professionally cleaned within 2 months before beginning before CTX developed mucositis 7.4 and 10.6 days sooner, respectively, than patients who did not). These findings suggest that risk factors for the development of CTX-induced mucositis are not as simple and direct as clinicians may believe.

Adult↗
PubMed1998

Effect of montelukast on single-dose theophylline pharmacokinetics.

The effect of montelukast (MK-0476), a cysteinyl leukotriene receptor antagonist in development for treatment of asthma, on single-dose theophylline plasma concentrations was studied in three separate clinical trials. Montelukast was evaluated at 10 mg once daily (the clinical dosage), 200 mg once daily, and 600 mg (200 mg three times daily). At the clinical dosage, montelukast did not change single-dose theophylline plasma concentration in a clinically important manner. The geometric mean ratios for theophylline area under the plasma concentration versus time curve (AUC0-->infinity ) (0.92) and maximal plasma concentration (Cmax ) (1.04) were well within the predefined and generally accepted bioequivalence range of 0.80 and 1.25. Montelukast decreased theophylline Cmax by 12% and 10%, AUC0-->infinity by 43% and 44%, and elimination half-time by 44% and 39% at 200 mg/d (oral and intravenous, respectively), and at 600 mg/d, montelukast decreased theophylline Cmax by 25%, AUC0-->infinity by 66%, and elimination half-time by 63%. These results show that montelukast at the clinical dosage did not change theophylline pharmacokinetics in a clinically important manner, but at 20- to 60-fold higher dosages, montelukast significantly reduced the theophylline pharmacokinetics parameters; an apparent dosage dependence is suggested.

Acetates↗
PubMed1998

Pharmacokinetic and pharmacodynamic interaction between the lipoxygenase inhibitor MK-0591 and the cyclooxygenase inhibitor ibuprofen in man.

Twelve healthy male subjects participated in a double-blind, placebo-controlled, randomized, three-period, crossover study to investigate the safety, tolerability, biochemical activity and pharmacokinetics of ibuprofen, a cyclooxygenase inhibitor and MK-0591, a 5-lipoxygenase inhibitor, given as single entities and in combination. Each subject received for three consecutive 8-day periods, separated by 1 week washout, each of the following treatments: ibuprofen 600 mg three times a day with 125 mg MK-0591 twice a day, ibuprofen 600 mg three times a day with placebo for MK-0591 and MK-0591 125 mg twice a day with placebo for ibuprofen. Cyclooxygenase inhibition was measured by platelet thromboxane (TxB2) generation test, and 5-lipoxygenase inhibition was measured by urinary leukotriene E4 excretion and ex vivo LTB4 generation in calcium-ionophore-stimulated blood. TxB2 suppression on day 8 by ibuprofen was not affected by concomitant treatment with MK-0591. MK-0591 alone had no effect on TxB2 generation. Leukotriene biosynthesis was inhibited by more than 90% by MK-0591 alone and by combined treatment, while ibuprofen alone had no effect. Coadministration appears to affect the pharmacokinetics of MK-0591 (decrease of area under the plasma concentration-vs-time curve [AUC] and maximum plasma concentrations [Cmax]) and of ibuprofen (increase of AUC and half-lives of elimination (t1/2) of the (S)-enantiomer, increase of t1/2 the (R)-enantiomer). Combined treatment had no effect on creatinine clearance nor on the number and intensity of the reported adverse experiences.

Adult↗
PubMed1997

Pharmacokinetics and bioavailability of montelukast sodium (MK-0476) in healthy young and elderly volunteers.

A study was conducted to (i) characterize the multiple-dose pharmacokinetics of oral montelukast sodium (MK-0476), 10 mg d-1 in healthy young subjects (N = 12), (ii) evaluate the pharmacokinetics of montelukast in healthy elderly subjects (N = 12), and (iii) compare the pharmacokinetics and oral bioavailability of montelukast between elderly and young subjects. Following oral administration of montelukast sodium, 10 mg d-1 (the therapeutic regimen for montelukast sodium) for 7 d, there was little difference in the plasma concentration-time profiles of montelukast in young subjects between day 1 and day 7 dosing. On average, trough plasma concentrations of montelukast were nearly constant, ranging from 18 to 24 ng mL-1 on days 3-7, indicating that the steady state of montelukast was attained on day 2. The mean accumulation ratio was 1.14, indicating that this dose regimen results in a 14% accumulation of montelukast. In elderly subjects, mean values of plasma clearance (Cl), steady-state volume of distribution (Vss), plasma terminal half-life (t1/2), and mean residence time in the body (MRTIV) following a 7 mg intravenous (5 min infusion) administration of montelukast sodium in the elderly were 30.8 mL min-1, 9.7 L, 6.7 h, and 5.4 h, respectively. Following a 10 mg oral dose, the bioavailability of montelukast in healthy elderly averaged 61%, very close to that (62%) determined previously in healthy young subjects. Also following the 10 mg oral administration, the mean values of AUC0-->infinity, Cmax, tmax, and t1/2, and the mean plasma concentration-time profile of montelukast in the elderly, were generally similar to those in young subjects, indicating that age has little or no effect on the pharmacokinetics of montelukast. There is no need to modify dosage as a function of age.

Acetates↗
PubMed1996

Ethical and practice considerations for biofeedback therapists in the treatment of urinary incontinence.

The treatment of incontinence presents many unique issues for biofeedback therapists that are routine for professionals in fields such as nursing or medicine. Although all professional practice is guided by ethical standards, the unique circumstances encountered during biofeedback treatments for this disorder warrant the development of specific guidelines. This is true whether insertable or surface EMG devices are used. Therefore, the purpose of this article is to propose a set of ethical guidelines for biofeedback therapists. The intended audience includes professionals such as psychologists, clinical psychophysiologists, and other mental health-care providers who use biofeedback techniques. These are not formally endorsed by any professional organizations (e.g., APA, AAPB) at this time. Ethical considerations include proper medical evaluation, informed consent, patient instruction, disrobing, nonerotic physical contact, patient safety, and patient satisfaction.

Biofeedback, Psychology↗
PubMed1995

Single dose pharmacokinetics, safety and tolerability of MK-0476, a new leukotriene D4-receptor antagonist, in healthy volunteers.

MK-4076 or sodium 1-(1(R)-(3-(2-(7-chloro-2-quinolinyl)-(E)- ethenyl)phenyl) 3-(1-hydroxy-1-methylethyl)phenyl)propyl)thio)methyl) cycloproprane) acetate is a novel, potent, and specific LTD4-receptor antagonist. The safety, tolerability and plasma drug profiles of single oral doses of MK-0476 (capsules) were evaluated in 18 healthy male volunteers assigned to one of the two parallel 9-subject panels. Under fasting conditions, increasing single doses of 20 to 800 mg were administered in a first part of the study and in a second part, 200 mg MK-0476 was given either as a solution, under fasting conditions, or as capsules, after a standard breakfast. All volunteers completed the study. Side effects, reported by the investigator to be related to study drug, were mild and transient. No laboratory abnormalities were noted. In the evaluated dose range of MK-0476 (20 to 800 mg) the median value of tmax ranged from 2 to 4 h, while the apparent t1/2 value averaged 4 to 5 h. The median tmax value of the 200 mg capsule dose was not significantly different from the median tmax of the 200 mg oral solution dose indicating that neither disintegration nor dissolution is a rate-limiting step for the absorption of MK-0476 from capsules. There was a statistically significant increase in the AUC (geometric mean ratio of fed/fast was 2.52 with 95% confidence interval of 1.25, 5.06) and in Cmax (geometric mean ratio of fed/fast was 1.36 with 95% confidence interval of 0.60, 3.04) when MK-0476 was given together with a breakfast, suggesting an increase in bioavailability.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1993

Iron-initiated tissue oxidation: lipid peroxidation, vitamin E destruction and protein thiol oxidation. Inhibition by a novel antioxidant, U-78517F.

Oxidative injury was initiated by addition of ferrous ammonium sulfate (FAS) to a suspension of whole rat brain homogenate in Krebs buffer. After FAS addition, tissue vitamin E dropped sharply over a 30-sec interval and then recovered marginally for 5 min. After 5 min, vitamin E levels dropped to a low and constant level. Also after 5 min, TBARS (thiobarbituric acid reactive substances, a color test for lipid peroxidation) showed a statistically significant (P < or = 0.05) increase that continued through the remainder of the 30-min experiment. Reduced protein thiols decreased significantly (P < or = 0.05) at 15 min post FAS addition. This suggests that, in this model of iron-initiated lipid peroxidation (LP), the endogenous antioxidant vitamin E is first depleted before membrane lipids and membrane bound proteins show evidence of oxidative injury. A novel antioxidant, U-78517F, inhibited the destruction of vitamin E, LP and protein thiol oxidation in this model. The efficacy of the compound after different times of addition is described.

Animals↗
PubMed1991

The nature and course of olfactory deficits in Alzheimer's disease.

OBJECTIVE: The aim of this study was to determine the specific nature and course of olfactory deficits in Alzheimer's disease. Previous studies had noted impaired odor identification, but there was no unanimity about the presence of odor detection deficits. METHOD: Odor identification was tested in 55 patients with Alzheimer's disease and 57 elderly control subjects by using the University of Pennsylvania Smell Identification Test. Odor detection was assessed in 46 subjects with Alzheimer's disease and 40 control subjects by using a forced-choice threshold test with geraniol as the odorant. RESULTS: Significant deficits in olfactory identification were present in subjects who were in the earliest stages of cognitive impairment, and these deficits increased as Alzheimer's disease progressed. There was some overlap in individual smell identification test scores between cognitively impaired patients and normal elderly subjects. On the other hand, odor detection deficits did not appear until Alzheimer's disease was relatively advanced. Smell identification test scores were correlated with Mini-Mental State scores, but geraniol detection was not. CONCLUSIONS: Odor identification is impaired early in Alzheimer's disease and may be more influenced by cognitive status than is acuity of odor detection, which is not altered until later in the disorder. The pattern of hyposmia in Alzheimer's disease suggests that the disorder may not "begin in the nose," as has been theorized previously. Further refinement of olfactory testing may be useful in the diagnostic evaluation of early dementia.

Aged↗