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Biomedical subjects

B L Lee

Publications and source records attributed to B L Lee.

At least 127 records · Page 7Linked to original sources
PubMed1991

Determination of thiamine and its phosphate esters by gradient-elution high-performance liquid chromatography.

A high-performance liquid chromatographic method for the determination of thiamine and its phosphate esters using gradient elution is presented. Chromatography was performed on an octadecyl C18 column with post-column derivatization using potassium ferricyanide: thiamine was oxidized to thiochrome, which was detected fluorimetrically. The gradient system avoids the use of a modifier and an ion-pairing reagent. The proposed method enables the separation of thiamine triphosphate, thiamine pyrophosphate, thiamine monophosphate and free thiamine, at concentrations of ca. 2 nM, within 10 min The within-assay precision for blood and serum total thiamine was less than 2 and 5%, respectively, and the between-day variation was less than 3 and 5%, respectively. The method is simple and rapid, and it can be used for screening of thiamine deficiency and for clinical study of various diseases related to vitamin B1 deficiency.

Chromatography, High Pressure Liquid↗
PubMed1991

Effects of dihydroavermectin B1a and analogs on stretcher muscle of the lined shore crab, Pachygrapsus crassipes.

1. Dihydroavermectin B1a (DHAVM, Ivermectin) at 1 microM reduces excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs, respectively) in stretcher muscle fibres of the lined shore crab, Pachygrapsus crassipes. IPSPs decline faster and more extensively than EPSPs and, unlike EPSPs, do not recover upon replacement of DHAVM with picrotoxinin-containing medium. 2. Intracellular recordings show DHAVM reduces membrane resistance (Rin) and hyperpolarizes muscle fibres in a concentration-dependent manner, beginning at 10 nM. The rate and magnitude of DHAVM effects on Rin mirror its effects on EPSPs. 3. The decline in Rin due to DHAVM is sustained over time (i.e. there is no tendency for desensitization); it is also irreversible and not affected by coadministration of 1 mM gamma-aminobutyric acid (GABA), 0.1 mM bicuculline methiodide or addition of 20 mM Co2+ to the recording medium. 4. Replacement of DHAVM-containing medium with medium containing Cl- channel blockers (picrotoxinin or lindane) results in partial recovery of Rin, while channel blockers specific for other ions (TTX, TEA, 4-AP or verapamil) are without effect. The decline of Rin following application of DHAVM is attenuated in Cl(-)-free medium. 5. Results of tests using compounds structurally related to DHAVM reveal that relatively minor changes in the molecule often reduce biological activity significantly. Removal of one sugar, for instance, results in a ten-fold reduction in potency. 6. In general, avermectins that stimulate conductance in shore crab muscle also possess anthelmintic activity at similar concentrations, based on studies using the free-living nematode, Caenorhabditis elegans.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effect of protein binding of daptomycin on MIC and antibacterial activity.

A higher rate of clinical failures in patients treated with daptomycin (2 mg/kg of body weight, given once daily) compared with rates in patients treated with conventional regimens caused early termination of this comparative clinical trial. One explanation for these failures could be that daptomycin is highly protein bound and that the concentration of the unbound active drug is too low for antibacterial activity. To assess this explanation, we studied the binding of daptomycin to proteins by using an ultrafiltration method. pH (7.0 to 7.4), temperature (25 or 37 degrees C), or daily freezing and thawing over 2 months had no effect on binding of daptomycin to proteins. We found that daptomycin was bound to albumin (90%) at 4 g/100 ml. Binding of daptomycin was not concentration dependent (2.5 to 80 micrograms/ml). In human serum samples spiked with daptomycin, average binding was 94% +/- 2.4%. In 6 subjects given an intravenous infusion of daptomycin (3 mg/kg), average binding was 90% +/- 2.1%. Susceptibility studies showed that a concentration in serum 20 times the unbound concentration was needed to equal the MIC of the total drug. These results indicate that daptomycin is highly bound (90 to 94%) to albumin and that clinical failure to daptomycin can in part be explained by the low concentration of the unbound drug.

Adult↗
PubMed1991

Concurrent infections with the ruminant nematodes Haemonchus contortus and Trichostrongylus colubriformis in jirds, Meriones unguiculatus, and use of this model for anthelmintic studies.

Haemonchus contortus- and Trichostrongylus colubriformis-infected jirds (Meriones unguiculatus) are useful for anthelmintic studies. With concurrent infections of these parasites established in the jird, questions of not only anthelmintic activity, but to some extent spectrum, could be assessed in a single model system. This report outlines a model using immunosuppressed (0.02% hydrocortisone in feed) jirds concurrently infected with H. contortus and T. colubriformis. Immunosuppressed jirds were inoculated with approximately 1,000 exsheathed infective larvae of each species, treated per os on day 10 postinoculation (PI), and killed on day 13 PI. Stomachs and small intestines were removed, opened longitudinally, incubated in distilled water at 37 C for 5 hr, fixed in formaldehyde solution, and stored for subsequent examination. Contents of both organs were examined using a stereomicroscope (15-45 x). Various standard anthelmintics were evaluated in the model; modern broad-spectrum ruminant anthelmintics (benzimidazoles, febantel, ivermectin, levamisole hydrochloride, and milbemycin D) are active uniformly and in most cases at doses comparable to those required for efficacy against these parasites in ruminants. This model, using worms of 2 genera living in distinct sites, allows preliminary evaluation of anthelmintic activity and spectrum for experimental compounds in a single cost- and resource-efficient experiment.

Animals↗
PubMed1991

Utility of a Haemonchus contortus/jird (Meriones unguiculatus) model for studying resistance to levamisole.

Trichostrongylid nematodes of sheep commonly are identified as exhibiting resistance to levamisole. In vitro assays have been developed to study levamisole resistance for Haemonchus contortus, but no in vivo model has been identified for this species. To determine the utility of a H. contortus/jird (Meriones unguiculatus) model for examining levamisole resistance, immunosuppressed jirds were inoculated with approximately 1,000 exsheathed infective larvae of H. contortus (resistant or susceptible to levamisole), treated per os on day 10 postinoculation (PI) with levamisole hydrochloride or analogs of the drug, and killed on day 13 PI. Stomachs were removed, opened longitudinally, incubated in distilled water at 37 C for 5 hr, fixed in formaldehyde solution, and stored for subsequent microscopic examination. Doses of levamisole and its analogs, which elicited percentage clearances of greater than or equal to 93.5 for the susceptible strain, cleared less than or equal to 68.9% of the resistant worms. These data are consistent with activities for the drugs against wild-type and levamisole-resistant strains of Caenorhabditis elegans. Thus, the H. contortus/jird model provides a useful in vivo tool to study resistance to levamisole and possibly other anthelmintics.

Animals↗
PubMed1991

Dapsone as a single agent is suboptimal therapy for Pneumocystis carinii pneumonia.

In a prospective, noncomparative study, seven patients with mild Pneumocystis carinii pneumonia, characterized by room air arterial PO2 greater than 60 mm Hg at the time of presentation, were treated with dapsone alone at a dose of 200 mg daily. Two of the seven patients required mechanical ventilation for respiratory failure on day 5 of dapsone therapy; both died. Four patients experienced major side effects during dapsone therapy. None of the seven patients successfully completed a full course of therapy with dapsone. We conclude that high-dose, single-agent dapsone is not suitable for further study as therapy for Pneumocystis carinii pneumonia.

Acquired Immunodeficiency Syndrome↗
PubMed1990

A novel anthelmintic model utilizing jirds, Meriones unguiculatus, infected with Haemonchus contortus.

Currently, no in vivo laboratory model is available for evaluating anthelmintics against the important ruminant helminth Haemonchus contortus. This report outlines a novel anthelmintic assay utilizing immunosuppressed (0.02% hydrocortisone in feed) jirds, Meriones unguiculatus, infected with H. contortus. Immunosuppressed jirds were inoculated with approximately 1,000 exsheathed infective larvae of H. contortus, treated per os on day 10 postinoculation (PI), and necropsied on day 13 PI. Each stomach was removed, opened longitudinally, incubated in distilled water at 37 C for 5 hr, fixed in formaldehyde solution, and stored for subsequent examination. Stomach contents were examined using a stereomicroscope (15-45x). A variety of standard anthelmintics has been evaluated in the model; modern broad-spectrum ruminant anthelmintics (benzimidazoles, febantel, ivermectin, levamisole hydrochloride, and milbemycin D) are active uniformly and in most cases at doses (mg/kg) comparable to those required for efficacy against H. contortus in ruminants. This model provides an important new tool to assess preliminarily the activity of experimental drugs against H. contortus in vivo prior to studies in ruminants and also may provide a useful tool for studying host-parasite interactions for H. contortus.

Animals↗
PubMed1989

Sulfonium salts as derivatizing agents. 2. Determination of theophylline in plasma by automated gas chromatography.

An automated gas chromatographic method for determination of theophylline in plasma is described. A novel feature of this assay is the use of triethylsulfonium hydroxide as an on-column alkylating agent. A simple extraction procedure together with automated sample injection and data processing has facilitated processing of large numbers of samples generated in pharmacokinetic studies. The between-run coefficient of variation was 2.2% at 5 micrograms/ml (n = 5) and 3.9% at 15 micrograms/ml (n = 6). Within-run coefficient of variation was 2.4% at 5 micrograms/ml (n = 9) and 3.3% at 15 micrograms/ml (n = 6). Accuracy was 105% at a concentration of 5 micrograms/ml and 102% at 15 micrograms/ml.

Alkylation↗
PubMed1989

Dapsone, trimethoprim, and sulfamethoxazole plasma levels during treatment of Pneumocystis pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). Evidence of drug interactions.

STUDY OBJECTIVE: To examine the interaction between dapsone and trimethoprim in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Measurement of drug levels as part of an open study of dapsone alone and randomized, double-blind comparison of trimethoprim-dapsone with trimethoprim-sulfamethoxazole in treating Pneumocystis carinii pneumonia in patients with AIDS. SETTING: County hospital and AIDS clinic. PATIENTS: Eighteen patients treated with dapsone alone, 30 with trimethoprim-dapsone, and 30 with trimethoprim-sulfamethoxazole. INTERVENTION: Dapsone, 100 mg/d; trimethoprim, 20 mg/kg body weight per day, and sulfamethoxazole, 100 mg/kg.d; administered for 21 days. MEASUREMENTS AND MAIN RESULTS: Concentrations of dapsone were 40% higher in patients treated with trimethoprim-dapsone than in those treated with dapsone alone (2.1 compared with 1.5 micrograms/mL; P less than 0.05). Trimethoprimdapsone-treated patients had fewer treatment failures but more side effects and treatment terminations due to toxicity than those treated with dapsone alone. The concentration of trimethoprim was 48.4% higher in patients treated with trimethoprim-dapsone than in those treated with trimethoprim-sulfamethoxazole, (18.4 compared with 12.4 micrograms/mL; P less than 0.05). Discontinuation of therapy due to toxicity was commoner in the trimethoprim-sulfamethoxazole group (57% compared with 30%). CONCLUSIONS: A bidirectional drug interaction exists between dapsone and trimethoprim, resulting in higher concentrations of each in the presence of the other.

Acetylation↗
PubMed1989

Urine drug screening in mothers and newborns.

A retrospective analysis of comprehensive urine drug screening was performed during a 13-month period on specimens submitted from the Neonatal Nursery and Obstetrics/Gynecology wards at San Francisco (Calif) General Hospital (mothers, N = 601; newborns, N = 339). Of mothers and newborns, respectively, 19.2% and 15.3% of all admissions during this period were screened; 68.2% and 63.1% of urine samples submitted were positive for any drug; 38.8% and 21.1% of screens were positive for more than one drug; and 45.8% and 41.6% were positive for cocaine. In mother-newborn pairs (N = 191) where urine samples were submitted within 4 days of each other, an 84% concordance was shown for cocaine and 67% for methadone, but concordance was much less for other drugs (less than 21%). These results indicate that cocaine was the most common drug detectable in the peripartum period and that both mothers and newborns should be tested to confirm the suspicion of drug effect or withdrawal in the newborn.

Cocaine↗
PubMed1989

Food and nicotine metabolism.

To examine the plausibility of the hypothesis that smoking a cigarette after a meal is motivated by accelerated metabolism of nicotine, we studied the influence of a high-protein meal on the disposition of nicotine in seven healthy smokers. Indocyanine green clearance, an estimate of hepatic blood flow, increased 31%, 50 minutes after the test meal. Consuming the meal during a steady state infusion of nicotine resulted in a small (18%) but consistent decrease in blood levels of nicotine. Our data demonstrate that food accelerates the metabolism of nicotine, but the time course and magnitude of the decline in levels of nicotine suggest that altered disposition of nicotine is not the primary motivation for smoking after meals.

Adult↗
PubMed1989

Anti-coccidial activity of human milk.

Sporozoites of Eimeria tenella, an important pathogen of poultry, were killed in vitro in a time- and concentration-dependent manner by exposure to diluted concentrations of normal human milk. Sodium cholate (bile salt stimulator) potentiated the anti-coccidial activity. The anti-coccidial activity was not found in the milk of lower mammals (cow, sheep, goat, dog). The component in human milk showing the activity was initially hypothesized to be a bile salt-stimulated lipase. However, testing of purified lipase (with or without sodium cholate) indicated no anti-coccidial activity. Consequently, we theorize that the active component may be a free fatty acid.

Animals↗
PubMed1989

Nicotine gum and theophylline metabolism.

When cigarette smokers with chronic lung disease stop smoking, they may do so with the aid of chewing nicotine gum. Smoking is known to accelerate the metabolism of theophylline, but the effects of nicotine gum on theophylline metabolism have not been determined. We studied the effects of nicotine and placebo gum on theophylline metabolism in healthy volunteers. Clearance of theophylline decreased by 32% after cessation of smoking in comparison to while chewing placebo gum. Clearance while chewing nicotine gum was similar to that measured while chewing placebo gum. Nicotine gum appears to have no effect on theophylline metabolism. For smokers who are chronically taking theophylline, the dose of theophylline will need to be reduced by one-fourth to one-third after smoking cessation and initiation of nicotine gum use.

Adult↗
PubMed1989

Anti-coccidial activity of 2-picoline, 6-amino-4-nitro-, 1-oxide.

An investigational drug (2-picoline, 6-amino-4-nitro-, 1-oxide) was evaluated to characterize the anti-coccidial spectrum of the compound. Two concentrations of the drug (125 and 250 ppm) were evaluated for bioactivity; weight gain, survival, dropping, and lesion scores were the response variables utilized to ascertain activity. The activities of the picoline derivative were compared with monensin, maduramicin, and a narasin/nicarbazin (1:1) combination. The investigational drug had significant activity against Eimeria tenella and Eimeria necatrix, and the 250-ppm level was significantly more active than 125 ppm. At 250 ppm, the E. tenella activity of the picoline derivative was comparable to both monensin (120 ppm) and the 50-ppm narasin/nicarbazin combination, significantly less effective than maduramicin (6 ppm), and significantly more efficacious than 30 ppm narasin/nicarbazin. At the same level (250 ppm), the picoline derivative had significantly less E. necatrix activity than monensin (120 ppm), maduramicin (6 ppm), and narasin/nicarbazin (50 ppm), and significantly greater activity than 30 ppm narasin/nicarbazin. At best, only extremely weak Eimeria acervulina, Eimeria brunetti, and Eimeria maxima activities were noted with the investigational drug; higher concentrations of the picoline derivative may achieve greater anti-coccidial activity against these species. The efficacy of narasin/nicarbazin compared favorably with monensin and maduramicin; the 50-ppm level of the combination appeared significantly more efficacious than 30-ppm.

Animals↗