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Biomedical subjects

L Madsen

Publications and source records attributed to L Madsen.

At least 55 records · Page 3Linked to original sources

Effect of 3-thia fatty acids on the lipid composition of rat liver, lipoproteins, and heart.

To investigate the importance of factors influencing the fatty acid composition, lipid and lipoprotein metabolism in the rat, the effect of 3-thia fatty acids of chain-length ranging from octyl- to hexadecylthioacetic acid were studied. In liver, very low density lipoprotein (VLDL), and low density lipoprotein (LDL), the hypolipidemic 3-thia fatty acids, namely C12-S-acetic acid to C14-S-acetic acid increased the amount of monoenes, especially oleic acid (18:ln-9). In contrast, the content of polyunsaturated fatty acids in liver, VLDL, and LDL decreased, mostly attributed to a reduction of eicosapentaenoic acid (EPA, 20:5n-3). Noteworthy, the hypolipidemic 3-thia fatty acids reduced the amount of arachidonic acid (AA, 20:4n-6) in LDL and HDL. 3-Thia fatty acids accumulated in the liver. In heart, as in liver, 3-thia fatty acids replaced fatty acids of chain-length homologues. In contrast to liver, we were unable to detect any changes in 18:ln-9. However, the n-3 polyunsaturated fatty acid content increased, particularly 20:5n-3 and docosahexaenoic acid (DHA, 22:6n-3) leading to an increased n-3/n-6 ratio. In conclusion, this study demonstrates that hypolipidemic 3-thia fatty acids change the fatty acid composition of organs and lipoproteins. These changes are linked to the expression and activity of hepatic delta9-desaturase, fatty acid oxidation, and displacement of normal fatty acids by 3-thia fatty acids. The fatty acid composition is regulated differently in liver and heart after administration of hypolipidemic 3-thia fatty acids.

Animals↗

Mitochondrion is the principal target for nutritional and pharmacological control of triglyceride metabolism.

Fish oil polyunsaturated fatty acids and fibrate hypolipidemic drugs are potent hypotriglyceridemic agents that act by increasing fatty acid catabolism and decreasing triglyceride synthesis and secretion by the liver. A major unresolved issue is whether this hypotriglyceridemic effect can occur independent of induction of peroxisomal beta-oxidation, a predisposing factor for hepatocarcinogenesis. The present study was undertaken to determine which component of fish oil, eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), is responsible for its triglyceride-lowering effect. We demonstrate that EPA and not DHA is the hypotriglyceridemic component of fish oil and that mitochondria and not peroxisomes are the principal target. Results obtained by fenofibrate feeding support the hypothesis that the mitochondrion is the primary site for the hypotriglyceridemic effect. In contrast to fibrates, EPA did not affect hepatic apolipoprotein C-III gene expression. Therefore, increased mitochondrial beta-oxidation with a concomitant decrease in triglyceride synthesis and secretion seems to be the primary mechanism underlying the hypotriglyceridemic effect of EPA and fibrates in rats, rabbits and possibly also in humans. In addition, these data show that lowering of plasma triglycerides can occur independently of any deleterious peroxisome proliferation.

Animals↗

Description of a geriatric medical/psychiatry unit in a small community general hospital.

This article describes a geriatric medical/psychiatry inpatient unit (GMPU) in a small community general hospital. A program description and data from the second year of the unit's operation are presented. The GMPU provides comprehensive geriatric assessment and interdisciplinary treatment for frail, medically ill elderly patients with neuropsychiatric disorders. Many of the patients have dementia or other neurobehavioral disorders, and most reside in nursing homes. The GMPU provides a valuable clinical link in the continuum of care for the elderly. Moreover, it has proven to be an economically viable financial asset for the hospital.

Adult↗

Long-term safety of ofloxacin and ciprofloxacin in the treatment of mycobacterial infections.

Ofloxacin and ciprofloxacin are potentially useful agents for treating mycobacterial infections. We retrospectively reviewed 7 years' experience with these agents in 103 patients. Ofloxacin was used primarily to treat tuberculosis (TB), dosed to achieve 2-hour postdose serum concentrations of 8-12 micrograms/ml. Ciprofloxacin was used primarily to treat Mycobacterium avium complex (MAC) infection, dosed to achieve 2-hour post-dose serum concentrations of 4-6 micrograms/ml. Despite differences in patient characteristics, underlying disease, and concurrent medications, ofloxacin and ciprofloxacin were associated with a similar spectrum and incidence of adverse reactions. Both drugs were generally well tolerated. Adverse effects led to an ofloxacin dosage change in 1 patient (3%) and discontinuation of ofloxacin in 2 patients (6%). Adverse effects led to a ciprofloxacin dosage change in 2 patients (3%) and discontinuation of ciprofloxacin in 5 patients (7%). Ofloxacin and ciprofloxacin appear to be tolerated as well as or better than other "second-line" antimycobacterial drugs.

Antitubercular Agents↗

[Low-energy laser therapy in medial tibial stress syndrome].

The effect of low-energy laser therapy on shin splints was examined in a randomized study with an unblinded design. Constripts from the Jutland Dragoon regiment with shin splints were given either active laser treatment (40 mW in 60 sec per cm tender tibia edge) or placebo laser. All patients were exempted from normal duty concerning activities like running and march. Forty-nine patients participated in the study, 23 in the laser group and 26 in the control group. From the start the study was designed to be double-blind, but by accident the code was broken towards the end of the study. We found no significant differences between the groups regarding pain visual analog score and readiness to return to active duty after 14 days.

Adult↗

Langmuir-Blodgett films.

The controlled transfer of organized monolayers of amphiphilic molecules from the airwater interface to a solid substrate was the first molecular-scale technology for the creation of new materials. However, the potential benefits of the technology envisioned by Langmuir and Blodgett in the 1930s have yet to be fully realized. Problems of reproducibility and defects and the lack of basic understanding of the packing of complex molecules in thin films have continued to thwart practical applications of Langmuir-Blodgett films and devices made from such films. However, modern high-resolution x-ray diffraction and scanning probe microscopy have proven to be ideal tools to resolve many of the basic questions involving thin organic films. Here, studies are presented of molecular order and organization in thin films of fatty acid salts, the prototypical system of Katharine Blodgett. Even these relatively simple systems present liquid, hexatic, and crystalline order; van der Waals and strained layer epitaxy on various substrates; wide variations in crystal symmetry and interfacial area with counterions; modulated superstructures; and coexisting lattice structures. The wide variety of possible structures presents both a challenge and an opportunity for future molecular design of organic thin-film devices.

Chemical Phenomena↗

Surgical management of resistant mycobacterial tuberculosis and other mycobacterial pulmonary infections.

Between August 1983 and October 1990, 42 patients with resistant Mycobacterium tuberculosis underwent 44 pulmonary resections. During the same time, 38 patients with mycobacterial infections other than tuberculosis had 41 pulmonary resections. All patients either were poor candidates for medical therapy alone or had existing complications requiring surgical intervention. There was one operative death in each group, both from adult respiratory distress syndrome (postpneumonectomy pulmonary edema). Complications were high, with bronchopleural fistula most commonly occurring after right pneumonectomy in patients infected with Mycobacterium avium with superimposed infection with nonmycobacterial pathogens. In patients undergoing pneumonectomy for resistant Mycobacterium tuberculosis, the left lung was most often resected. It is recommended that if localized disease is present and medical treatment is likely to fail, pulmonary resection should be performed for resistant Mycobacterium tuberculosis infection after 3 months of drug-specific therapy. Muscle flaps were used frequently to avoid residual space and bronchial stump problems. Earlier resection in patients with indolent nontuberculous mycobacterial pulmonary infections is advocated before extensive polymicrobial contamination and right lung destruction.

Adult↗

Sparteine and mephenytoin oxidation: genetic polymorphisms in east and west Greenland.

The oxidation of sparteine and mephenytoin was examined in a group of subjects living in Greenland: 300 in East Greenland and 171 in West Greenland. The distribution of the ratio between the chromatographic peak areas of S- and R-mephenytoin in the urine, the S/R ratio was clearly bimodal in both populations. Thus 9.3% of the East Greenlanders had S/R ratios of 0.9 or more and were phenotyped as poor metabolizers of mephenytoin. In the West Greenlanders, 2.9% of the sample had S/R ratios of 0.90 or more and were accordingly phenotyped as poor metabolizers. The intraethnic difference with regard to the frequency of the mephenytoin poor metabolizer is probably attributable in part to a much higher proportion of admixed Caucasian genes in the West Greenlanders than in the East Greenlanders. In both the East and the West Greenlanders, the sparteine metabolic ratio displayed marked interindividual differences without a clear bimodal distribution. Poor metabolizers arbitrarily defined as subjects with an metabolic ratio of 20 or more made up 3.3% of the East Greenlanders and 2.3% of the West Greenlanders, but the difference between the two groups was not statistically significant.

Adolescent↗

Surgical intervention in the treatment of pulmonary disease caused by drug-resistant Mycobacterium tuberculosis.

Of 99 patients with pulmonary disease caused by multiple-drug-resistant strains of Mycobacterium tuberculosis admitted to the National Jewish Center for Immunology and Respiratory Medicine from 1983 to 1988, 29 were selected for resection to supplement chemotherapy. All patients had organisms with high levels of resistance to all of the first line medications, including rifampin and isoniazid. Although the patients were treated preoperatively with multidrug regimens in an effort to reduce the mycobacterial burden, 20 of 29 were still sputum-culture-positive at the time of surgery. The bulk of the disease was manifest in one lung, but lesser amounts of contralateral disease were demonstrated in 27 of 29. Pneumonectomy was done in 15 patients; lobectomy or lobectomy plus was done in 14. Although physiologic studies before surgery indicated significant respiratory impairment in many of the patients, there were no operative deaths. There were two unrelated deaths in this series. Of the 27 survivors, 25 have remained sputum-culture-negative for a mean duration of 36 months. Compared with historical controls, resectional surgery appears to offer benefit to selected patients with pulmonary disease caused by M. tuberculosis with extensive levels of drug resistance.

Adult↗

Pharmacokinetics and bronchodilatory effect of proxyphylline and theophylline.

In a double-blind cross-over study, including double-dummy placebo, 8 adult asthmatics received oral sustained-release proxyphylline 900 mg (Neofyllin retard) twice daily, or 250 mg microcrystalline theophylline (Nuelin) 4 times daily for 6 days. It was found that there was a reduction in the number of bronchodilatory aerosol dosages used with both proxyphylline treatment (139 dosages) and theophylline treatment (165) dosages, but only with proxyphylline was the difference in number statistically significant when compared with the placebo period (236 dosages, p less than 0.05). Subjective side-effects occurred significantly more often during theophylline treatment than during proxyphylline treatment (p less than 0.05). Changes in lung function after intravenous infusion of proxyphylline 1400 mg and aminophylline 400 mg confirmed the potency difference between the drugs. Volume of distribution and total body clearance were comparable for the two drugs. In 2 subjects, calculations of the fraction of drug absorbed and plasma-concentration versus time curves after oral and intravenous administration, suggested saturation kinetics of theophylline.

Administration, Oral↗

Pretreatment of exercise-induced asthma in adults with aerosols and pulverized tablets.

Eighteen adult asthmatics took part in a double-blind crossover study comparing the effect on exercise-induced asthma (EIA) of pretreatment with aerosolized 1) disodium cromoglycate (DSCG), 2) ipratropium bromide (IPTB), 3) fenoterol, 4) DSCG + IPTB and 5) saline. EIA was completely blocked by pretreatment with the beta 2-agonist, fenoterol. The protective effect of nebulized DSCG and IPTB given alone could not be distinguished from that of isotonic saline. The combination of DSCG and IPTB reduced the post-exercise bronchoconstriction more than any of the two drugs given separately. Thirteen of the 18 patients went on to a double-blind cross-over study of the effect on EIA of pretreatment with the usually recommended dosages off salbutamol, theophylline and their combination administered as pulverized tablets. Seven patients were withdrawn from this part of the study because of side-effects, and in the remaining six none of the oral pretreatments could be distinguished from placebo, despite serum theophylline concentrations within or above the commonly recommended therapeutical range.

Administration, Oral↗