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Biomedical subjects

J Hilbert

Publications and source records attributed to J Hilbert.

At least 19 recordsLinked to original sources
PubMed2001

Evaluation of interaction between fluconazole and an oral contraceptive in healthy women.

OBJECTIVE: To evaluate the potential pharmacokinetic interaction between 2 x 150 mg fluconazole administered once weekly and an oral contraceptive (OC) containing ethinyl estradiol and norethindrone. METHODS: A placebo-controlled, double-masked, randomized, two-way crossover study was used to investigate the pharmacokinetic interaction between 300 mg fluconazole once weekly and the OC Ortho Novum 7/7/7 (Ortho-McNeil Pharmaceutical, Inc., Raritan, NJ) in 26 healthy women, 18-36 years old. In the first cycle (28 days), subjects received OC only. In the second cycle, subjects were assigned randomly to receive OC-fluconazole or OC-placebo. In the third cycle, subjects were crossed over to the opposite treatment. RESULTS: Data for 21 subjects who completed the study were included in the pharmacokinetic analysis; data for all 26 subjects were included in the safety analysis (26 OC only; 24 OC-fluconazole; 23 OC-placebo). Treatment with OC-fluconazole resulted in small but statistically significant increases in 0-24 hour area under the plasma concentration-time curve (AUC(0-24)) for both ethinyl estradiol (mean 24%, 95% confidence interval [CI] 18%, 31%) and norethindrone (mean 13%, 95% CI 8%, 18%) as compared with treatment with OC-placebo. Ethinyl estradiol maximum plasma concentration (C(max)) was slightly (mean 8%, 95% CI 2%, 15%) though statistically significantly higher for OC-fluconazole treatment as compared with OC-placebo treatment. Norethindrone C(max) was not different (95% CI -6%, 11%) between the two treatment groups. No adverse events related to treatment were seen in the fluconazole treatment group. CONCLUSION: The concomitant administration of 300 mg fluconazole once weekly, twice the recommended dose for vaginal candidiasis, to women using OCs results in a slight increase in OC concentrations. Therefore, it appears that there is no threat of contraceptive failure because of concomitant fluconazole administration.

Adolescent↗
PubMed2000

Predator-prey relations between age-1+ summer flounder (Paralichthys dentatus, Linnaeus) and age-0 winter flounder (Pseudopleuronectes americanus, Walbaum): predator diets, prey selection, and effects of sediments and macrophytes.

Laboratory experiments and weekly trammel net surveys in the Navesink River, New Jersey (USA) were used to examine the predator-prey interaction between age-1+ summer flounder (Paralichthys dentatus) and age-0 winter flounder (Pseudopleuronectes americanus). Winter flounder (24-67 mm TL) were the dominant piscine prey of summer flounder (n=95, 252-648 mm TL) collected in trammel nets. We observed a temporal shift in summer flounder diets from sand shrimp (Crangon septemspinosa) and winter flounder, dominant during June and early July, to blue crabs (Callinectes sapidus) and other fishes (primarily Atlantic silversides, Menidia menidia and Atlantic menhaden, Brevortia tyrannus) later in the summer. Variations in prey selection appeared to be related to changes in the spatial distribution of predators and spatio-temporal variation in prey availability. In laboratory experiments, summer flounder (271-345 mm total length, TL) preferred demersal winter flounder to a pelagic fish (Atlantic silversides) and a benthic invertebrate (sand shrimp) prey, and the vulnerability of winter flounder increased with increasing prey body size from 20 to 90 mm TL. Experiments testing habitat effects showed that mortality of winter flounder in three different size classes (20-29, 40-49, 60-69 mm TL) was not influenced by sediment grain sizes permitting differential burial of the prey. However, vegetation enhanced survival, with fish suffering lower mortality in eelgrass (Zostera marina, 15+/-0.04%) than in sea lettuce (Ulva lactuca, 38+/-0.04%) or bare sand (70+/-0.07%) when the macrophytes were planted to produce similar leaf surface areas (5000 cm(2) m(-2)). Prey vulnerability appeared to be related to the role of vision in the predator's attack strategy and prey activity levels.

Journal Article↗
PubMed2000

Changes in lipid composition during somatic embryogenesis in leaves of Cichorium.

The present studies were conducted to investigate the changes in lipid and fatty acid composition during the earliest stages of somatic embryogenesis in leaf tissues of the Cichorium hybrid '474'. The presence of glycerol in the culture medium during the induction step allowed to separate two phases in the embryogenic process. Firstly, cells are induced for morphogenetic competence (induction phase) and secondly, they express an embryogenic competence (expression phase). The analysis of fatty acid composition of total lipids showed that the percentage of linolenic acid (18:3) decreased while that of linoleic acid (18:2) increased throughout the culture period. A comparison with a non-embryogenic genotype of Cichorium indicated a higher increase of linoleate content in embryogenic genotype. The incorporation of [14C] glycerol into lipid classes was studied in leaf tissues. During the induction step, label was confined almost exclusively in polar lipids, particularly in phosphatidylcholine (PC). An important increase of labeled triacylglycerols (TAG) amounts was noted during the expression step. The accumulation of 18:2 was observed in PC and also in TAG. These results show that the early stages of somatic embryogenesis are associated with the increase of PC and TAG which are mainly enriched in 18:2.

Journal Article↗
PubMed1998

Pharmacokinetics of three doses of once-weekly fluconazole (150, 300, and 450 mg) in distal subungual onychomycosis of the toenail.

BACKGROUND: Preliminary clinical data suggest that fluconazole is effective in the treatment of patients with onychomycosis. To design optimum dosage regimens, a better understanding of fluconazole's distribution into and elimination from nails is needed. OBJECTIVE: The purpose of this study was to determine plasma and toenail concentrations of fluconazole. METHODS: In this multicenter, randomized, double-blind investigation, fluconazole (150 mg, 300 mg, or 450 mg) or matching placebo was administered once a week for a maximum of 12 months to patients with onychomycosis of the toenail. A total of 151 subjects participated in the pharmacokinetic assessment. Blood samples and distal toenail clippings from both affected and healthy nails were obtained for fluconazole concentration determinations at baseline, at the 2-week visit, at each monthly visit until the end of treatment, and then at 2, 4, and 6 months (nail samples only at the latter two) after fluconazole was discontinued. RESULTS: Fluconazole was detected in healthy and affected nails at the 2-week assessment in nearly all subjects. The median time to reach steady-state fluconazole concentrations in healthy nails was 4 to 5 months in the three fluconazole dose groups. In affected nails, steady-state fluconazole concentrations were achieved more slowly, with a median time of 6 to 7 months. At the 8-month assessment, affected toenail fluconazole concentrations were higher than corresponding plasma fluconazole concentrations, with ratios of 1.31 to 1.50 in the three active treatment groups. Toenail concentrations of fluconazole declined slowly after treatment was discontinued, with elimination half-lives of 2.5, 2.4, and 3.7 months for the 150, 300, and 450 mg doses, respectively. Measurable fluconazole concentrations were still present in toenails at 6 months after treatment in most subjects. CONCLUSION: Fluconazole penetrates healthy and diseased nails rapidly, yielding detectable concentrations after two weekly doses. Once it penetrates nail, fluconazole persists for up to 6 months or longer after therapy is stopped. These favorable pharmacokinetic characteristics support a once-weekly fluconazole dosage regimen for the treatment of patients with onychomycosis.

Antifungal Agents↗
PubMed1998

Pharmacokinetics of three once-weekly dosages of fluconazole (150, 300, or 450 mg) in distal subungual onychomycosis of the fingernail.

BACKGROUND: Fluconazole has proven to be safe and effective for a variety of superficial and systemic fungal infections. Preliminary analysis of extensive Phase III studies suggests that it is very effective for the treatment of onychomycosis. Its pharmacokinetic properties, including low molecular weight and high water-solubility, suggest a unique ability to penetrate the nail. This feature is likely to account in part for fluconazole's effectiveness in the treatment of onychomycosis. OBJECTIVE: Determinations of plasma and fingernail concentrations of fluconazole were performed as part of a larger study comparing the safety and efficacy of once-weekly fluconazole (150, 300, and 450 mg) to placebo in the treatment of distal subungual onychomycosis of the fingernails caused by dermatophytes. The relationship between fluconazole concentrations and efficacy was also examined. METHODS: Pharmacokinetic studies were performed by means of plasma and fingernail samples from 133 patients, a subset of 349 patients participating in a double-blind, placebo-controlled clinical trial of fluconazole administered in once-weekly doses of 150, 300, or 450 mg until cure of onychomycosis or for a maximum of 9 months. Blood and fingernail samples for pharmacokinetic analysis were taken at baseline, at week 2, and at monthly intervals during the treatment phase of the study. Patients considered clinically cured or improved also participated in a 6-month follow-up study. During this phase, patients were monitored and samples taken every 2 months. RESULTS: Significant amounts of fluconazole were detected in the earliest fingernail samples taken (after 2 weeks of treatment). After two weekly doses, 30% to 33% of steady-state concentrations had been achieved in healthy nails and 22% to 29% in affected nails. Steady state was achieved in 3 to 5 months. Fluconazole concentration in nails as well as plasma followed dose-proportional pharmacokinetics. Nail:plasma ratios in affected nails were 0.4 to 0.6 at 2 weeks and 1.7 to 1.8 at 6 months. Fluconazole concentrations fell slowly after drug discontinuation and were still detectable 4 months after end of treatment. A statistically significant correlation was found between steady-state concentration and clinical and global outcomes. CONCLUSION: Fluconazole rapidly penetrates the fingernail, where it is retained at detectable levels for at least 4 months after drug discontinuation. A significant correlation exists between fluconazole concentration in the fingernails and clinical and global outcomes.

Adult↗
PubMed1998

Linear correlates in the speech signal: the orderly output constraint.

Neuroethological investigations of mammalian and avian auditory systems have documented species-specific specializations for processing complex acoustic signals that could, if viewed in abstract terms, have an intriguing and striking relevance for human speech sound categorization and representation. Each species forms biologically relevant categories based on combinatorial analysis of information-bearing parameters within the complex input signal. This target article uses known neural models from the mustached bat and barn owl to develop, by analogy, a conceptualization of human processing of consonant plus vowel sequences that offers a partial solution to the noninvariance dilemma--the nontransparent relationship between the acoustic waveform and the phonetic segment. Critical input sound parameters used to establish species-specific categories in the mustached bat and barn owl exhibit high correlation and linearity due to physical laws. A cue long known to be relevant to the perception of stop place of articulation is the second formant (F2) transition. This article describes an empirical phenomenon--the locus equations--that describes the relationship between the F2 of a vowel and the F2 measured at the onset of a consonant-vowel (CV) transition. These variables, F2 onset and F2 vowel within a given place category, are consistently and robustly linearly correlated across diverse speakers and languages, and even under perturbation conditions as imposed by bite blocks. A functional role for this category-level extreme correlation and linearity (the "orderly output constraint") is hypothesized based on the notion of an evolutionarily conserved auditory-processing strategy. High correlation and linearity between critical parameters in the speech signal that help to cue place of articulation categories might have evolved to satisfy a preadaptation by mammalian auditory systems for representing tightly correlated, linearly related components of acoustic signals.

Humans↗
PubMed1998

Pharmacokinetic interaction between finasteride and terazosin, but not finasteride and doxazosin.

The alpha 1-adrenoceptor antagonists doxazosin and terazosin and the 5 alpha-reductase inhibitor finasteride are used in the treatment of benign prostatic hyperplasia. The aim of this study was to assess the potential pharmacokinetic interaction of doxazosin or terazosin when coadministered with finasteride. This was a randomized, placebo-controlled, multi-center study. Ninety healthy men were assigned to one of six treatment groups: doxazosin; doxazosin plus finasteride; terazosin; terazosin plus finasteride; placebo; and placebo plus finasteride. Plasma concentrations, maximum plasma concentration (Cmax), time to maximum concentration (tmax), and area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) of doxazosin, terazosin, and finasteride were determined. Ratios of Cmax and AUC for doxazosin and terazosin were not significantly altered by coadministration with finasteride. The Cmax and AUC0-24 of finasteride were not significantly altered by coadministration with doxazosin. However, Cmax and AUC0-24 of finasteride were significantly higher after coadministration with terazosin. There is no statistically significant pharmacokinetic interaction between finasteride and doxazosin; however, there is a statistically significant interaction between finasteride and terazosin, which affects the pharmacokinetics of finasteride but not those of terazosin. The clinical significance of this interaction remains to be determined.

Adrenergic alpha-Antagonists↗
PubMed1997

Employee response to a company-sponsored program of colorectal and prostate cancer screening.

Studies done in the mid-1970s documented increased risk for respiratory cancer and leukemia among employees in a chemical company manufacturing plant where chloromethyl ethers were used in production from 1948 to 1971. In the late 1980s, the company informed current and former employees about the results of follow-up studies which showed a moderation of risk of respiratory cancer and leukemia. New data showing elevated rates of mortality from colorectal, prostate, bladder, and pancreatic cancer in the population were also reported. Via mailed correspondence, the company made a no-cost program of colorectal and prostate cancer screening available to employees upon request; and information about bladder and pancreatic cancer was made available. Thirteen percent of employees in the population indicated interest in colorectal and prostate cancer screening (response). Thirty-one percent of these responders were screened (adherence). Multivariate analyses showed that education and length of employment in the plant were positively associated with response. Being white was positively associated with response for younger workers; while among older workers being male was positively associated with response. In terms of adherence, we found that older, more highly educated workers were more likely to have a screening examination. Findings indicate that employee participation in workplace-sponsored colorectal and prostate cancer screening can vary according to worker sociodemographic factors and length of employment in areas of potential exposure.

Age Factors↗
PubMed1996

Adaptation of lung antioxidants to cigarette smoking in humans.

We investigated the effect of free radical scavengers, micronutrient antioxidants, on antioxidant enzyme activities in cigarette smokers. We measured the intracellular superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities and vitamin E and beta-carotene levels in the bronchoalveolar cells of 14 smokers before and after 6 weeks of supplementation with vitamins E and C and beta-carotene. Eight nonsmokers served as control subjects. CAT and GPx activities were higher in BAL cells from smokers compared with nonsmokers (20.5 +/- 2.3 vs 9.6 +/- 1.3 U/10(6) cells; p = 0.027; 0.90 +/- 0.10 vs 0.46 +/- 0.12 U/10(6) cells; p = 0.049, respectively), while there was no difference in SOD activity between the two groups. Likewise, vitamin E and beta-carotene concentrations were markedly higher in smokers' lung lavage cells (403.3 +/- 81.0 in smokers vs 16.6 +/- 5.3 ng/10(6) cells in nonsmokers, and 1.23 +/- 0.21 in smokers vs 0.15 +/- 0.04 ng/10(6) cells in nonsmokers, respectively). The serum levels of vitamin E and C and beta-carotene increased by 2.0-, 1.6-, and 8.9-fold in smokers after supplementation, which were similar to nonsmokers. Similarly, BAL cell vitamin E increased from 403.3 +/- 81.0 to 477.4 +/- 97.7 ng/10(6) cells and beta-carotene increased from 1.23 +/- 0.21 to 4.32 +/- 0.45 ng/10(6) cells (p < 0.05). Despite increased concentrations of vitamins in serum as well as beta-carotene levels in BAL cells, there was no significant down regulation in SOD, CAT, or GPx activities in the lung lavage cells. These data suggest that augmentation of micronutrient antioxidants in smokers and nonsmokers does not appear to have an effect on antioxidant enzyme activities, suggesting a differential regulation of these defenses.

Adaptation, Physiological↗
PubMed1994

Daytime oxygen saturation does not predict nocturnal oxygen desaturation in patients with chronic obstructive pulmonary disease.

Nocturnal hypoxemia occurs commonly in patients with chronic obstructive pulmonary disease (COPD). Because pulmonary hypertension and cardiac arrhythmias are associated with this phenomenon, the detection and treatment of nocturnal hypoxemia should be part of the management of COPD patients. The ability to predict nocturnal hypoxemia by evaluating an awake patient would be desirable economically and logistically because continuous nocturnal oximetry is not widely available and because it is costly and labor intensive. We sought to determine whether awake oximetry would be precise enough to be clinically useful in predicting the degree of nocturnal oxygen desaturation in patients with COPD. We studied 71 patients with COPD. During sleep, the arterial oxygen saturation (SaO2) decreased by an average of 9% with a maximum decrease of 21% (awake SaO2 93.0 +/- 0.4% vs nocturnal lowest SaO2 84.0 +/- 0.7%, p = 0.0001). The nocturnal oxygen desaturation in each patient, however, was poorly predicted from awake SaO2. The standard error of estimate was large with a value of 5.3%. These data suggest that awake SaO2 is not a good predictor of nocturnal oxygen desaturation in individual patients. The lack of a simple relationship between awake SaO2 and nocturnal SaO2 is due to a complex interplay of various physiologic and pathologic mechanisms involved in the control of breathing and oxygenation during sleep.

Aged↗
PubMed1990

Pharmacokinetics of loratadine in patients with renal insufficiency.

The disposition of loratadine, a new orally active histamine H1 receptor antagonist and its primary metabolite descarboethoxyloratadine were characterized in adult volunteers with normal renal function (group I), patients with chronic renal failure, i.e., creatinine clearance less than 30 mL/min (group II), as well as chronic hemodialysis patients (group III). The effect of hemodialysis on the disposition of loratadine and descarboethoxyloratadine was also assessed. Subjects in groups I and II were given a single oral 40 mg dose of loratadine while the patients in Group III received two single 40 mg doses of loratadine (during an interdialytic period and just prior to hemodialysis). Loratadine was rapidly absorbed and the decline of plasma concentrations after attainment of the Cmax was biexponential in all subjects. No significant differences in t1/2 beta were observed between the three groups (8.7 +/- 5.9, 7.6 +/- 6.9, 8.6 +/- 1.6 hrs: in groups I, II, and III, respectively). The apparent total body clearance and apparent volume of distribution of loratadine also did not differ significantly among the three groups. No significant differences in the Cmax or tmax of the metabolite were observed. The metabolite AUC infinity 0 however was significantly greater in group II subjects: (212.4 +/- 37.8, 469.5 +/- 95.4, 325.2 +/- 114.6 ng.hr/mL; groups I, II, and III, respectively). No significant relationship was observed between the terminal elimination half-life of loratadine or descarboethoxyloratadine and creatinine clearance. Hemodialysis augmented endogenous clearance by less than 1%. The disposition of loratadine is not significantly altered in patients with severe renal insufficiency nor is hemodialysis an effective means of removing loratadine or descarboethoxyloratadine from the body.

Adult↗
PubMed1988

Excretion of loratadine in human breast milk.

The excretion of loratadine, a new nonsedating antihistamine, into human breast milk was studied in six lactating nonpregnant volunteers. Each volunteer received one 40-mg loratadine capsule. Milk and blood were collected before and at specified times (to 48 hours) after dosing. Plasma and milk loratadine concentrations were determined by a specific radioimmunoassay, and those of an active but minor metabolite, descarboethoxyloratadine, by high performance liquid chromatography (HPLC). Breast milk concentration-time curves of both loratadine and descarboethoxyloratadine paralleled the plasma concentration-time curves. For loratadine, the plasma Cmax was 30.5 ng/mL at 1.0 hour after dosing and the milk Cmax was 29.2 ng/mL in the 0 to 2 hour collection interval. Through 48 hours, the loratadine milk-plasma AUC ratio was 1.2 and 4.2 micrograms of loratadine was excreted in breast milk, which was 0.010% of the administered dose. For descarboethoxyloratadine, the plasma Cmax was 18.6 ng/mL at 2.2 hours after dosing, whereas the milk Cmax was 16.0 ng/mL, which was in the 4 to 8-hour collection interval. Through 48 hours, the mean milk-plasma descarboethoxyloratadine AUC ratio was 0.8 and a mean of 6.0 micrograms of descarboethoxyloratadine (7.5 micrograms loratadine equivalents) were excreted in the breast milk, or 0.019% of the administered loratadine dose. Thus, a total of 11.7 micrograms loratadine equivalents or 0.029% of the administered dose were excreted as loratadine and its active metabolite. A 4-kg infant ingesting the loratadine and descarboethoxyloratadine excreted would receive a dose equivalent to 0.46% of the loratadine dose received by the mother on a mg/kg basis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Loratadine: multiple-dose pharmacokinetics.

The steady-state pharmacokinetics of loratadine (L), a new long-acting antihistamine devoid of CNS activity, was investigated in 12 healthy male volunteers. Each volunteer received 40-mg L capsules q24h for ten days. Blood samples were collected at various times on day 1, 5, 7, and 10 and assayed for L by radioimmunoassay (RIA) and for descarboethoxyloratadine (DCL), a known active metabolite, by high-performance liquid chromatography (HPLC). The plasma L and DCL concentration-time data in the disposition phases were fitted to a biexponential equation for pharmacokinetic analysis. Steady-state plasma L Cmax concentrations were reached at 1.5 hour (Tmax) after each dose. DCL steady-state Cmax values ranged 26 to 29 ng/mL at a Tmax ranging from 1.8 to 3 hours. The AUC at steady state, AUC tau, was 80 to 96 and 349 to 421 h X ng/mL for L and DCL, respectively. The accumulation indexes (Ra) based on AUC tau ratios, did not change for either compound after day 5. Ra values for L and DCL after the fifth dose were 1.4 and 1.9, respectively, indicating that there is little accumulation of either L or DCL after a multiple (once-a-day) dosage regimen. The t1/2 beta at steady state were 14.4 and 18.7 hours for L and DCL, respectively, which were similar to those reported following a single-dose L administration. Observed plasma drug concentrations were in good agreement with predicted values derived for pharmacokinetic parameters.

Adult↗
PubMed1987

Pharmacokinetics and dose proportionality of loratadine.

The dose proportionality and pharmacokinetics of loratadine, a new nonsedating antihistamine, were studied in 12 normal volunteers. In a three-way cross-over, each volunteer received a single 10-, 20-, or 40-mg loratadine capsule. Blood was collected up to 96 hours after dosing. Plasma loratadine concentrations were determined by radioimmunoassay (RIA), and those of a minor, but active metabolite, descarboethoxyloratadine, by high performance liquid chromatography (HPLC). Concentrations in the disposition phase were fitted to a biexponential equation for pharmacokinetic analysis. For dose proportionality, AUC- and Cmax-dose relationships were evaluated by linear regression. Also, pharmacokinetic parameters and dose-adjusted AUCs were compared by analysis of variance. Loratadine was rapidly absorbed, reaching Cmax values (4.7, 10.8, and 26.1 ng/mL) at 1.5, 1.0 and 1.2 hours for the 10-, 20-, and 40-mg doses, respectively. The loratadine t1/2 beta ranged from 7.8 to 11.0 hours. Descarboethoxyloratadine reached Cmax values (4.0, 9.9, and 16.0 ng/mL) at 3.7, 1.5, and 2.0 hours for the 10-, 20-, and 40-mg doses, respectively. Its t1/2 beta ranged from 17 to 24 hours. For both compounds, AUC- and Cmax-dose relationships were linear and there were no differences in the t1/2 beta, CL/F, or dose-adjusted AUC values among the treatments. Loratadine and descarboethoxyloratadine plasma concentrations and pharmacokinetics were not dose dependent.

Administration, Oral↗
PubMed1981

[Detection of haemoglobinopathies at birth, using isoelectric focalization (author's transl)].

The incidence and nature of haemoglobinopathies were investigated at birth in Martinique, where 4635 samples of umbilical cord blood were examined. Conventional blood values were determined, and a new, extremely simple and highly selective test was performed: isoelectric focalization. Abnormalities were found in 14.3% of blood samples, viz: A/S 7.25%, A/C 3.17%, S/S 0.17%, S/C 0.24%, C/C 0.04%, other mutations 0.63% alpha-thalassaemia minor (alpha 1-thal) 1.72% and isolated microcytosis 1.01%. Unusual abnormalities included 7 different mutations of the 4a-chain, 3 of the beta-chain and 3 of the gamma-chain. The clinical and epidemiological importance of such investigations is emphasized.

Fetal Blood↗