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Biomedical subjects

C Larsen

Publications and source records attributed to C Larsen.

At least 91 records · Page 5Linked to original sources

Hypertrophic pyloric stenosis: determination of muscle dimensions by ultrasound.

To evaluate the usefulness of ultrasound in hypertrophic pyloric stenosis (HPS) and to analyse the correlation between the dimensions of the pyloric muscle and the age and the weight of the child, 34 children with suspected HPS and 34 controls were examined. An overlap between the dimensions of the pyloric muscle in the HPS group and in the controls stresses the need to assess the muscle length, the muscle diameter, and the muscle wall thickness in establishing the sonographic diagnosis of HPS. We found the following criteria useful: muscle length greater than or equal to 19 mm, muscle diameter greater than or equal to 10 mm, and muscle wall thickness greater than or equal to 4 mm. The results did not confirm previous reports of increasing dimensions of the pyloric muscle with age and weight.

Humans↗

Chlortetracycline and aflatoxin interaction in two lines of chicks.

To determine if feed contaminants and feed additives interact, day-old chicks from lines bred for high and low antibody response to sheep erythrocytes were fed aflatoxin at a level of 3,000 ppb, chlortetracycline at a level of 550 ppm, or a combination of aflatoxin and chlortetracycline for a period of 6 wk. Weight gain in both lines of chicks was adversely affected by the aflatoxin treatment. There was a synergistic adverse effect in chicks of the low antibody response line when given chlortetracycline as well as aflatoxin, an effect not noted in chicks of the high antibody response line. Chlortetracycline alone had no effect on weight gain of low antibody response birds but increased the weight gain of chicks from the high antibody response line. Bursa to body weight ratios were adversely affected by aflatoxin in both lines of chicks, but chlortetracycline further adversely affected this parameter only in the low antibody response line. These results indicate that adverse effects of aflatoxin may be enhanced by addition of antibiotics to feed.

Aflatoxins↗

Macromolecular prodrugs. V. Simultaneous determination of high-molecular-weight dextran metronidazole monosuccinate ester prodrugs and the hydrolysis products metronidazole and the corresponding monosuccinate ester on nucleosil diol.

A high-performance size-exclusion chromatography procedure using Nucleosil Diol has been developed which provides the simultaneous determination of macromolecular dextran metronidazole monosuccinate ester prodrugs and the hydrolysis products metronidazole and metronidazole monosuccinate. Various factors influencing the chromatographic behaviour of the compounds are discussed. Baseline separation of the three substances was achieved within 8 min by using a 0.05 M phosphate buffer pH 7.5 eluent at a flow-rate of 2 ml min-1. The detection limit at 320 nm for a conjugate with a degree of substitution of 4.61 was found to be 3.5 micrograms ml-1.

Chromatography, Gel↗

Influence of experimental rhinitis on the gonadotropin response to intranasal administration of buserelin.

The influence of experimental rhinitis on the absorption of buserelin, measured as the serum luteinizing hormone (LH) response, has been investigated. A single dose of 200 micrograms buserelin was given to 24 healthy male volunteers after induction of experimental rhinitis with histamine and after use of a saline spray (placebo control). Except on one occasion, when the pump-spray apparently was incorrectly operated, serum LH concentration rose after buserelin. There was no difference in the LH response between histamine-induced rhinitis and saline controls. It was concluded that intranasal application of buserelin represents a reliable mode of application and that modification of the administration route or a change in the dosage schedule during naturally-occurring nasal inflammations, such as the common cold and allergic rhinitis, is unnecessary in patients undergoing chronic treatment with intranasal buserelin, e.g. for prostatic cancer, endometriosis, precocious puberty, and contraception.

Absorption↗

Pendred's syndrome. Acoustic, vestibular and radiological findings in 17 unrelated patients.

Seventeen unrelated Danish patients with Pendred's syndrome, whose case stories have not been published previously, are presented. Acoustic and vestibular functions were examined and endocrinological screening was performed. There was a great variation in hearing ability as well as in thyroid function. Furthermore, in contrast to previous investigations, normal caloric function was demonstrated in the majority. In all patients a Mondini malformation was demonstrated. On the basis of this investigation it is concluded that: (1) the Mondini defect is part of Pendred's syndrome; (2) the inherited Mondini malformation is the underlying cause of the sensorineural hearing impairment; and (3) the hearing sensitivity varies greatly in these patients.

Adolescent↗

Costs and benefits of medical student training to a health maintenance organization.

As health maintenance organizations (HMOs) and managed health care systems expand, they represent an increasing potential as sites for medical student teaching. Considerable difference of opinion exists about the impact of medical training on these prepaid delivery systems. This study presents a methodology for estimating the subjective and objective costs and benefits of medical student training to an independent staff model HMO with a long-standing training program. Data are derived from a provider survey, a consumer survey, and patient visit logs. Principal subjective benefits include increased perceived quality of care, improved patient satisfaction, and enhanced provider education and joy of practice. Objective impacts include a decrease in productivity of 1.1 patient visits per half day and direct physician teaching labor of 46.8 minutes per half day. Applying this methodology to the specific program of ten courses gives rise to a figure of $180 000 ($16 900 per full-time equivalent student per year) for the "opportunity cost" of medical student training to the HMO. Rules of thumb are developed for application of this method prospectively to new programs in similar relationships between staff model HMOs and academic medical centers.

Cost-Benefit Analysis↗

Pilocarpine prodrugs I. Synthesis, physicochemical properties and kinetics of lactonization of pilocarpic acid esters.

Various alkyl and aralkyl esters of pilocarpic acid were synthesized and evaluated as prodrug forms for pilocarpine with the purpose of improving the ocular bioavailability of pilocarpine through increased corneal membrane permeability. The esters were found to undergo a quantitative cyclization to pilocarpine in aqueous solution of pH 3.5-10, the rate of cyclization being a function of the polar and steric effects within the alcohol portion of the esters. The rates of lactonization increased proportionally with the hydroxide ion activity over the pH range studied which is in accord with a reaction mechanism involving intramolecular nucleophilic attack of alkoxide ion on the ester carbonyl moiety. At pH 7.4 and 37 degrees C, half-times of lactonization ranging from 30 min (p-chlorobenzyl ester) to 1105 min (n-hexyl ester) were observed for the various esters. The esters are markedly more lipophilic than pilocarpine. The results suggested that the pilocarpic acid esters may be potentially useful prodrugs, especially when further derivatized to give in vitro stable pilocarpic acid diesters.

Chemical Phenomena↗

Pilocarpine prodrugs. II. Synthesis, stability, bioconversion, and physicochemical properties of sequentially labile pilocarpine acid diesters.

Various novel diesters of pilocarpic acid were synthesized and evaluated as prodrug forms for pilocarpine with the aim of improving the ocular delivery characteristics of the drug. The pilocarpic acid monoesters previously studied cyclized spontaneously to pilocarpine in aqueous solution and although they showed enhanced corneal permeability when compared with pilocarpine these monoesters suffered from poor solution stability. The present study shows that this problem can be totally overcome by blocking the free hydroxyl group in the monoesters. Diesters of pilocarpic acid were obtained by esterification of this group. Such compounds were found to possess a high stability in aqueous solution (shelf lives of more than 5 years at 20 degrees C were estimated) but at the same time were readily converted to pilocarpine under conditions simulating those occurring in vivo through a sequential process involving enzymatic hydrolysis of the O-acyl bond followed by spontaneous lactonization of the intermediate pilocarpic acid monoester. Rate data are given for the conversion of the diesters in human plasma and in various rabbit eye homogenates. The pH-solubility profile was derived for a diester and lipophilicity parameters were determined for the compounds. All diesters were markedly more lipophilic than pilocarpine and the corresponding pilocarpic acid monoesters. The results suggest that pilocarpic acid diesters may be potentially useful pilocarpine prodrugs as they combine a high solution stability with an adequate rate of conversion to pilocarpine under in vivo conditions.

Animals↗

Effect of neurotoxic organophosphorus compounds in turkeys.

To determine the neurotoxic effects of organophosphorus compounds in turkeys, adult birds were given a single oral dose of 125, 250, 500 mg/kg triorthotolyl phosphate (TOTP) or a single subcutaneous dose of 0.4 mg/kg O,O'-diisopropyl phosphorofluoridate (DFP). At 24 h after dosing with TOTP, neurotoxic esterase activity was found to be inhibited in a dose-related manner, as were the activities of blood cholinesterase and liver cholinesterase. Clinical signs of neuropathy appeared within 2 wk in TOTP-treated groups of birds with neurotoxic esterase activities at 59 +/- 3% (125 mg/kg), 47 +/- 7% (250 mg/kg) and 33 +/- 3% (500 mg/kg) of control values (mean +/- SEM, n = 5) at 24 h after dosing. Signs appeared earlier in turkeys given DFP. Histological examination revealed only mild lesions of delayed neurotoxicity in birds given either TOTP or DFP.

Administration, Oral↗

Aflatoxin-antioxidant effects on growth of young chicks.

Butylated hydroxytoluene (BHT), an antioxidant, was provided to chicks at 8 X, 30 X and 80 X the normal concentrations in their feed beginning at 1 day of age and continuing for the next 6 weeks. The ability of these birds to resist the adverse effects of dietary aflatoxin (3000 ppb, beginning Day 8) was measured by weight gain and feed efficiency over the 6-week period of study. Birds on aflatoxin-contaminated feed did not gain weight as rapidly or as efficiently as birds on uncontaminated feed. Depression of growth caused by aflatoxin was significantly less in birds given BHT than in those fed the diet not containing antioxidant.

Aflatoxins↗