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Biomedical subjects

N Nair

Publications and source records attributed to N Nair.

At least 55 records · Page 3Linked to original sources

Effect of nedocromil on antigen-induced bronchoconstriction in asthmatic subjects.

Nedocromil sodium, a pyranoquinoline decarboxylic acid derivative, is a new antiasthma compound undergoing clinical investigation. It has been shown to be effective in the management of asthma and to attenuate exercise-induced bronchoconstriction. We performed a randomized, double-blind, placebo-controlled, crossover study in 12 ragweed-sensitive subjects known to respond to inhaled ragweed antigen. On two study days, four to ten days apart, ragweed challenges were performed using a standard protocol 30 minutes after a single dose (two puffs of 2 mg/puff) of either active drug or placebo. The PD20 (20% fall in FEV1) for each treatment day was compared by parametric and nonparametric 2-period crossover analyses. Baseline FEV1 pre-drug and post-drug administration did not differ significantly between study days. On the nedocromil day, the mean +/- SD for log PD20 was 2.25 +/- 0.561 and on the placebo day, 1.73 +/- 1.048 (P = 0.04). There were no side effects associated with either treatment. These results demonstrate that nedocromil is effective in shifting the stimulus response curve to inhaled antigen in some ragweed-sensitive subjects. Its wide spectrum of efficacy against bronchoprovocation suggests it is useful in the treatment of hyperreactive airway disorders.

Administration, Inhalation↗

Workshop on schizophrenia, PET, and dopamine D2 receptors in the human neostriatum.

Recently, two research groups published numbers for D2 receptor sites in the neostriatum of drug-naive schizophrenic patients, obtained in vivo by positron emission tomography (PET). One study appeared to confirm the increase of D2 receptor numbers, while the other study did not. A workshop was convened in Montreal to examine the reasons for the discrepancy between the results obtained by the two groups. The workshop considered patient populations, PET instrumentation and scanning methods, pharmacology, and modeling. The workshop identified differences between the approaches of the two groups that could contribute to the divergent results, including age and chronicity of the patient samples, brain region selected for study, metabolism of the different radioligands in blood and brain, reversibility of binding, PET instrumentation, and complexity of data analysis. The workshop concluded that these initial efforts had made considerable progress in establishing the role of PET in the understanding of the biochemical processes underlying mental illness. In particular, the unique ability to quantify regional neuroreceptor density at different stages in the evolution of the disease has been implemented. At the same time, the work so far and this conference served to identify the main sources contributing to the different findings from the two centers. This information will be important in designing the next phase of the research which will build upon and reconcile these apparent discrepancies.

Adult↗

Effect of administration of diethylhexyl phthalate on the function and turnover of rat hepatic mitochondria.

Administration of the widely used plasticizer di(2-ethylhexyl)phthalate (2% w/w) in the diet to the rat caused proliferation of mitochondria in the liver. The number of mitochondria as well as the amount of protein recovered in the organellar fraction was doubled. Mitochondria isolated from the livers of treated animals showed decreased (50%) respiratory activity. The content and activity of cytochrome oxidase were also decreased. The specific incorporation of amino acids into the proteins of whole liver and of mitochondria was not increased in plasticizer-treated animals. Isolated mitochondria also did not show any difference in the rate of incorporation of amino acids into proteins. The half-lives of whole liver proteins and of mitochondria were increased in plasticizer-fed animals. The half-life of cytochrome oxidase, however, was unaffected by the treatment. The pattern of double labeling of mitochondrial proteins confirmed decreased turnover in plasticizer-treated animals.

Amino Acids↗

Investigations on the mechanism of the hypocholesterolemic action of diethylhexyl phthalate in rats.

The plasticizer di(2-ethylhexyl)phthalate (DEHP), used widely in the manufacture of food packages and medical plastic devices, depressed serum cholesterol (40%) and proliferated hepatic mitochondria (100%) when administered in the diet (2%, w/w) to the rat. Microsomes isolated from the livers of animals administered DEHP showed lowered specific activity of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (50%). The incorporation of acetate but not of mevalonate into hepatic cholesterol was decreased (52%) in these animals. The release of bile acids was greatly enhanced (100%), and the activity of cholesterol 7 alpha-hydroxylase, the regulatory enzyme in the pathway of bile acid formation, was stimulated (70%) on DEHP administration. Even though the capacity of mitochondria to oxidize the side chain of cholesterol was not enhanced in DEHP-fed animals, the larger population of mitochondria would ensure that the amount of cholesterol oxidized per gram of liver was significantly higher.

Acetates↗

Segregation analysis of bronchial response to methacholine inhalation challenge in families with and without asthma.

A segregation analysis was performed on the bronchial response to a standardized methacholine inhalation challenge obtained from members of 83 families that were part of a Natural History of Asthma study population. Each bronchial response was expressed as the area under the best fitting parabolic dose-response curve. Standard methods of statistical analysis demonstrated that age, sex, and recent respiratory infection had a significant effect on the bronchial response to methacholine inhalation. Segregation analysis indicated that, although a familial component exists in the transmission of bronchial response to methacholine, the bimodal distribution of the bronchial response is not due to segregation at a single autosomal locus.

Asthma↗

A group comparative study of the safety and efficacy of nedocromil sodium (Tilade) in reversible airways disease: a preliminary report.

Nedocromil sodium in a dose of 4 mg b.i.d. or q.i.d. by inhalation was used to treat asthmatic patients in a double-blind, placebo-controlled, randomized, parallel study. 80 patients (39 active drug and 41 placebo) received q.i.d. dosage and 87 patients (45 active drug and 42 placebo) received b.i.d. dosage. The patients selected were not on oral or inhaled steroids but required oral sustained-release theophylline with or without an inhaled beta-agonist aerosol. There was a significant reduction in daytime asthma symptoms (p = 0.04) and asthma severity (p less than 0.01) 6 weeks after the onset of therapy in the nedocromil sodium q.i.d. treated group as compared with placebo. In the nedocromil sodium b.i.d. treated group, the following variables showed statistically significant improvements compared with placebo: daytime and night-time asthma (p = 0.002 in both instances), wheezing assessed by auscultation (p = 0.03) and overall asthma severity (p less than 0.01). All these variables showed improvements within 2 weeks of the onset of therapy and became statistically significant at 6 weeks. Side-effects were minor and occurred only in a small number of patients. It can be concluded from this study that nedocromil sodium is a safe and effective drug in the management of asthma.

Adrenal Cortex Hormones↗

Correlation of methacholine-induced non-specific bronchial reactivity and cold air hyperventilation challenge.

The degree of bronchoconstriction seen with cold air hyperventilation challenge was determined in 48 adult subjects with known degrees of methacholine-induced bronchial reactivity. The degree of bronchial reactivity as determined by the cold air hyperventilation challenge significantly correlated with the non-specific bronchial reactivity determined by a methacholine inhalation challenge. Cold air hyperventilation challenge can accurately confirm the presence of reactive airway disease.

Adult↗

Bone scanning in Ewing's sarcoma.

This is a retrospective analysis of bone scans in 72 patients with Ewing's sarcoma. Sites of primary disease were found to be evenly distributed among the axial skeleton and the proximal and distal extremities. Primary disease sites in the axial skeleton were more frequently associated with metastases. Fifty-three of these patients had their first scans done at presentation; among them, 25 were found to have metastases. Unsuspected metastases were picked up in 28 of all the patients. Metastases at presentation were seen to be associated with a poorer prognosis.

Adolescent↗

Protection by ipratropium bromide and metaproterenol against methacholine and histamine bronchoconstriction.

To establish relative protection against methacholine and histamine, 40 micrograms of ipratropium bromide, an anticholinergic compound, 1.3 mg of metaproterenol or placebo aerosols were administered by metered-dose inhaler prior to inhalation challenge with methacholine or histamine in nine asthmatic subjects. Double-blind, randomized challenges were performed. Subjects required a mean methacholine dose of 1.72 +/- 0.73 and 2.46 +/- 0.72 (Ln inhalation units), and mean histamine dose of 2.16 +/- 0.65 and 2.68 +/- 0.49, to cause a drop of 20% and 35% respectively in the FEV1 following the placebo. In the methacholine challenges, both ipratropium bromide and metaproterenol had significant protection as compared to placebo (P less than 0.001). There was no statistical difference in the degree of protection against methacholine between ipratropium bromide and metaproterenol. In histamine challenges, metaproterenol had significant protection as compared to the placebo, while ipratropium bromide did not protect against histamine.

Adolescent↗

Safety of nifedipine in subjects with bronchial asthma and COPD.

This prospective study was undertaken to evaluate the safety of nifedipine, a calcium channel blocking agent, on 60 subjects with asthma, chronic obstructive pulmonary disease (COPD), angina, and normal subjects. All subjects received nifedipine, 20 mg, sublingually. Spirometry was done pre-drug administration and every 20 minutes after for two hours. Parameters measured were forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and forced expiratory flow at 25 percent to 75 percent of total volume (FEF25-75%). Subjects with asthma and COPD were also given nifedipine 20 mg three times daily, orally for two weeks, and tested biweekly during this period. All bronchodilators, beta-blockers, and long acting nitrates were withheld for five half-lives of the drug prior to test day. There was no adverse effect on the pulmonary function. We found a statistically significant improvement (p less than 0.05) in FEV1 after nifedipine. There was no tachyphylaxis at the end of two weeks. Nifedipine is safe in patients with asthma and/or chronic bronchitis.

Adult↗

Electroporation: a novel approach to enhance the radioiodine uptake in a human thyroid cancer cell line.

Radioiodine has been the best choice of treatment for differentiated thyroid cancer. Loss of the ability to concentrate iodide makes thyroid cancer cells refractory to radioiodine therapy. Therefore, the methods that enhance the uptake of radioiodine may have significant therapeutic effect. Electroporation involves the application of short high-voltage electric pulses which transiently permeabilize the plasma membrane, allowing entry of the otherwise impermeable molecules. The aim of our study was to use electroporation for incorporating radioiodine into a non-iodine concentrating thyroid cell line. Cultured WRO thyroid cancer cells that do not incorporate iodine due to the lack of the specific transporter protein incorporated significant amounts of radioiodine after electroporation. The uptake of radioiodine by electroporation showed dependence on the electric field, external concentration of the iodine, time and the temperature of incubation. The incorporated radioiodine was retained over a period of 24 h. The retainability of the incorporated iodine may have a significant effect on the tumoricidal properties if validated in vivo.

Cell Line, Tumor↗

Splenic metastases from cervical carcinoma: a case report.

Splenic metastasis from squamous cell carcinoma of the uterine cervix is an unusual event in the natural history of the disease. The authors report one such uncommon occurrence in a 41-year-old female who presented initially with cervical carcinoma (stage IIB) and was treated with radical radiotherapy with concurrent weekly chemotherapy. Following a disease-free interval of less than a year, she developed hepatosplenic metastases despite being locally controlled. The literature relevant to the report is also discussed. This report reaffirms the notion that splenic metastases from cervical carcinoma are rare events but can occur as part of widespread dissemination.

Adult↗